bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutritional supplements for neuropsychiatric symptoms in people with dementia: A systematic review and meta‐analysis
Authors: Haider Sandra , Schwarzinger Angela , Stefanac Sinisa , Soysal Pinar , Smith Lee , Veronese Nicola , Dorner Thomas E. , Grabovac Igor
Published: August 2020

Objectives

The aim of the present study was to assess the effects of nutritional supplementation on neuropsychiatric symptoms among people with dementia.

Methods/Design

Randomized controlled trials (RCTs) were searched in the Databases PubMed, EMBASE, SCOPUS, Cochrane Central Register of Controlled Trials and Clinicaltrials.gov from inception until January 31, 2020. Studies of RCTs carried out on people with any type of dementia who were taking nutritional supplements and had neuropsychiatric symptoms were included in this systematic review and meta‐analysis. Neuropsychiatric symptoms were assessed with the validated Neuropsychiatric Inventory (NPI). Effect sizes were calculated with standardized mean differences (SMD) and 95% confidence intervals (95%CI), applying a random effect model.

Results

The search yielded 1034 studies with four studies being included in the meta‐analysis with a total of 377 people with dementia (mean age 69.3 [SD: 7.7] years). The diagnoses comprised mild to late Alzheimer's disease and frontotemporal dementia. Two studies included a multicomponent supplementation, one an omega‐3, and one a special supplement tailored for cognitive impairment. The median follow‐up was 18 weeks, with a range from 12 to 24 weeks. Pooled data showed that nutritional supplementation did not improve NPI (SMD = −0.33; [95%CI: −0.74 to 0.08]; P = 0.11; I2 = 45%).

Conclusions

The findings of this meta‐analysis demonstrated no significant impact on NPI through nutritional supplementation. However, the generalization of the results is limited, as different supplements were used in different stages of dementia with a short follow‐up time.
Effect of immunoadsorption alone or combined with membrane filtration on hemostasis parameters
Authors: Marlu Raphaël , Bennani Hamza Naciri , Seyve Landry , Malvezzi Paolo , Janbon Bénédicte , Noble Johan , Christophe Maryvonne , Motte Lionel , Imerzoukene Farida , Chevallier Eloi , Rostaing Lionel , Jouve Thomas
Published: August 2020

Introduction

ABO‐ or HLA‐incompatible kidney transplantation is possible thanks to pretransplant antibody‐depletion achieved by extracorporeal‐treatment modalities. These methods induce depletion of some plasma proteins and may also impact on proteins involved in hemostasis.

Methods

To determine the impact of one session of immunoadsorption (IA) alone or combined with membrane filtration (MF) on clotting factors and natural anticoagulants, we performed a prospective, observational study on 13 patients waiting for HLA‐/ABO‐incompatible kidney transplants. Plasma hemostasis parameters were measured before and immediately after a first session of IA alone in six patients and of IA + MF in seven patients.

Results

IA alone induced depletion of fibrinogen and factor XIII (FXIII) whereas IA + MF caused greater depletion of all high‐molecular‐weight hemostatic proteins (fibrinogen, FV, FVIII, FXI, FXIII, von‐Willebrand factor [VWF]). After an IA session, median reductions were 30% for fibrinogen and 43% for FXIII compared to baseline values. After a session of IA + MF, median decreases were 70% for fibrinogen, 54% for FV, 56% for FVIII, 37% for FXI, 78% for FXIII, and 62% for VWF. Noticeably, levels of low‐molecular‐weight factors (<100 kDa) were far less decreased than high‐molecular‐weight proteins with IA + MF, except for protein S and the tissue factor pathway inhibitor, which are known to be partially physiologically bound to high‐molecular‐weight molecules.

Conclusions

IA and IA + MF induced significant depletion of some proteins implicated in the hemostatic process; however, IA + MF resulted in stronger modifications to hemostasis parameters than IA alone. This may have potential clinical implications regarding bleeding risk, and particularly depletion of fibrinogen and FXIII.
Inhibitory effects of biochanin A on titanium particle‐induced osteoclast activation and inflammatory bone resorption via NF‐κB and MAPK pathways
Authors: Liao Shijie , Feng Wenyu , Liu Yun , Wang Ziyi , Ding Xiaofei , Song Fangming , Lin Xixi , Song Huijie , KC Anil , Su Yuangang , Liang Jiamin , Xu Jiake , Liu Qian , Zhao Jinmin
Published: August 2020

Revision operations have become a new issue after successful artificial joint replacements, and periprosthetic osteolysis leading to prosthetic loosening is the main cause of why the overactivation of osteoclasts (OCs) plays an important role. The effect of biochanin A (BCA) has been examined in osteoporosis, but no study on the role of BCA in prosthetic loosening osteolysis has been conducted yet. In this study, we utilised enzyme‐linked immunosorbent assay, computed tomography imaging, and histological analysis. Results showed that BCA downregulated the secretion levels of tumor necrosis factor‐α, interleukin‐1α (IL‐1α), and IL‐1β to suppress inflammatory responses. The secretion levels of receptor‐activated nuclear factor‐κB ligand, CTX‐1, and osteoclast‐associated receptor as well as Ti‐induced osteolysis were also reduced. BCA effectively inhibited osteoclastogenesis and suppressed hydroxyapatite resorption by downregulating OC‐related genes in vitro. Analysis of mechanisms indicated that BCA inhibited the signalling pathways of mitogen‐activated protein kinase (P38, extracellular signal‐regulated kinase, and c‐JUN N‐terminal kinase) and nuclear factor‐κB (inhibitor κB‐α and P65), thereby downregulating the expression of nuclear factor of activated T cell 1 and c‐Fos. In conclusion, BCA may be an alternative choice for the prevention of prosthetic loosening caused by OCs.
lncRNA ZNF667‐AS1 (NR_036521.1) inhibits the progression of colorectal cancer via regulating ANK2/JAK2 expression
Authors: Zhuang Lin , Ding Wenbin , Ding Wei , Zhang Qi , Xu Xuezhong , Xi Dong
Published: August 2020

Long noncoding RNAs (lncRNAs) participate in many biological processes by affecting gene expression at the posttranscriptional level. lncRNAs are dysregulated in colorectal cancer (CRC) and this dysregulation is closely related to tumorigenesis, metastasis, and prognosis. Although many lncRNAs have been identified in CRC, the relation between ZNF667 antisense RNA 1 (head to head; ZNF667‐AS1, accession: NR_036521.1) and CRC remains unclear. In this study, a total of 2,218 differentially expressed genes and 428 differentially expressed lncRNAs were identified between tumor and pericarcinous tissues. They were mainly enriched in cancer pathways, chemokine signaling, phosphoinositide 3‐kinase–protein kinase B signaling pathway, and others. Key lncRNAs, including ZNF667‐AS1, and their corresponding genes, such as ankyrin 2 (ANK2), were downregulated in CRC tumor tissues. In addition, downregulated ZNF667‐AS1 (NR_036521.1) expression is associated with poor prognosis and disease progression. Overexpression of ZNF667‐AS1 (NR_036521.1) inhibited the proliferation, migration, and invasion of VOLO cells both in vitro and in vivo. Moreover, Janus kinase 2 (JAK2) and ANK2 were significantly down‐ and upregulated in the overexpressed ZNF667‐AS1 VOLO cells compared to those in the negative‐control group. Knockdown of ANK2 or overexpression of JAK2 significantly counteracted the inhibitory effects of overexpression of ZNF667‐AS1 on LOVO cell proliferation and migration. Taken together, it is indicated in our research that ZNF667‐AS1 interaction with ANK2/JAK2 maybe important in CRC progression. Overexpression of ZNF667‐AS1 could inhibit the proliferation, migration, and invasion of CRC cells, which may be related with the high ANK2 and low JAK2 levels.
Release of ATP by TRPV4 activation is dependent upon the expression of AQP2 in renal cells
Authors: Pizzoni Alejandro , Bazzi Zaher , Di Giusto Gisela , Alvarez Cora L. , Rivarola Valeria , Capurro Claudia , Schwarzbaum Pablo J. , Ford Paula
Published: August 2020

Increasing evidence indicates that aquaporins (AQPs) exert an influence in cell signaling by the interplay with the transient receptor potential vanilloid 4 (TRPV4) channel. We previously found that TRPV4 physically and functionally interacts with AQP2 in cortical collecting ducts (CCD) cells, favoring cell volume regulation and cell migration. Because TRPV4 was implicated in ATP release in several tissues, we investigated the possibility that TRPV4/AQP2 interaction influences ATP release in CCD cells. Using two CCD cell lines expressing or not AQP2, we measured extracellular ATP (ATPe) under TRPV4 activation and intracellular Ca2+ under ATP addition. We found that AQP2 is critical for the release of ATP induced by TRPV4 activation. This ATP release occurs by an exocytic and a conductive route. ATPe, in turn, stimulates purinergic receptors leading to ATPe‐induced ATP release by a Ca2+‐dependent mechanism. We propose that AQP2 by modulating Ca2+ and ATP differently could explain AQP2‐increased cell migration.
The prognostic value and potential subtypes of immune activity scores in three major urological cancers
Authors: Shi Bowen , Qi Jun
Published: August 2020

Immune‐based rather than cancer‐based classification systems are becoming an important additional component for prognostic prediction. Herein, we investigate the status of tumor–immune interaction and prognostic value of immune activity scores in bladder urothelial carcinoma (BLCA), kidney renal clear cell carcinoma (KIRC), and prostate adenocarcinoma (PRAD) from The Cancer Genome Atlas dataset and tracking the tumor immunophenotype platform. Traditional clinicopathological parameters still are effective predictors for prognosis. Comparison of 23‐set, seven‐step immune activity scores, and its distribution between favorable and adverse outcome groups within each cancer type and among cancer types show that each cancer has a distinct tumor–immune pattern. Adjusted overall immune activity scores based on the binary logistic regression analysis show a great discrimination ability in the progression‐free survival (p = .0056 in BLCA, p < .0001 in KIRC, and p < .0001 in PRAD). K‐mean cluster method and principal component analysis were performed to explore the cancer subtype. The results reveal that certain immune activity scores pattern such as high nature killer (NK) cell, T cell, macrophage, T helper type 1 (Th1) cell, and dendritic cell recruiting scores in BLCA, low NK cell, CD8 T cell, macrophage, T cell, Th1 cell recruiting scores in KIRC have a favorable clinical outcome comparing to other subtypes. Also, It is remarkable that a relatively small subtype of patients has a poor clinical prognosis in PRAD and this subtype features high CD4 T cell, macrophage, T cell, and regulatory T cell recruiting scores.
The crosstalk between gut bacteria and host immunity in intestinal inflammation
Authors: Yang Qiuli , Wang Yuexin , Jia Anna , Wang Yufei , Bi Yujing , Liu Guangwei
Published: August 2020

The gut of mammals is considered as a harmonious ecosystem mediated by intestinal microbiota and the host. Both bacteria and mammalian immune cells show region‐related distribution characteristics, and the interaction between the two could be demonstrated by synergetic roles in maintaining intestinal homeostasis and dysregulation in intestinal inflammation. The harmonious interplay between bacteria and host requires fine‐tuned regulations by environmental and genetic factors. Thus, the disturbed immune response to microbial components or metabolites and dysbiosis related to immunodeficiency are absolute risk factors to intestinal inflammation and cancer. In this review, we discuss the crosstalk between bacteria and host immunity in the gut and highlight the critical roles of bidirectional regulation between bacteria and the mammalian immune system involved in intestinal inflammation.
Postnatal growth retardation is associated with deteriorated intestinal mucosal barrier function using a porcine model
Authors: Qi Ming , Tan Bie , Wang Jing , Liao Simeng , Li Jianjun , Cui Zhijuan , Shao Yirui , Ji Peng , Yin Yulong
Published: August 2020

Individuals with postnatal growth retardation (PGR) are prone to developing chronic diseases. Abnormal development in small intestine is casually implicated in impaired growth. However, the exact mechanism is still implausible. In this present study, PGR piglets (aged 42 days) were employed as a good model to analyze developmental changes in intestinal mucosal barrier function. Our data demonstrated that PGR piglets exhibited impaired jejunal and ileal epithelial villous morphology and permeability, accompanied by decreased cell proliferation ability and increased apoptosis rate. In addition, the expression of tight junction proteins (ZO‐1, claudin 1, and occludin) and E‐cadherin was markedly inhibited by PGR. The expression of P‐glycoprotein was significantly reduced in PGR piglets, as well as decreased activity of lysozyme. Moreover, the mRNA abundance and content of inflammatory cytokines were significantly increased in the intestinal mucosa and plasma of PGR piglets, respectively. PGR also contributed to lower level of sIgA, and higher level of CD68‐positive rate, β‐defensins, and protein expression involved p38 MAPK/NF‐κB pathway. Furthermore, PGR altered the intestinal microbial community such as decreased genus Alloprevotella and Oscillospira abundances, and led to lower microbial‐derived butyrate production, which may be potential targets for treatment. Collectively, our findings indicated that the intestinal mucosal barrier function of PGR piglets could develop the nutritional intervention strategies in prevention and treatment of the intestinal mucosal barrier dysfunction in piglets and humans.
Virtual brain endocast of Antifer (Mammalia: Cervidae), an extinct large cervid from South America
Authors: Fontoura Emmanuelle , Ferreira José Darival , Bubadué Jamile , Ribeiro Ana Maria , Kerber Leonardo
Published: August 2020

A diverse fossil record of Cervidae (Mammalia) has been documented in the South American Pleistocene, when these animals arrived during the Great American Biotic Interchange. Using computed tomography‐scanning techniques, it is possible to access the endocranial morphology of extinct species. Here, we studied the brain endocast of the extinct late Pleistocene cervid Antifer ensenadensis from southern Brazil, one of the largest forms that lived on this continent, using comparative morphology, geometric morphometrics, and encephalization quotients. The analyzed endocasts demonstrate that A. ensenadensis had a gyrencephalic brain, showing a prominent longitudinal sinus (=sagittal superior sinus), which is also observed in the large South American cervid Blastocerus dichotomus. The encephalization quotient is within the variation of extant cervids, suggesting maintenance of the pattern of encephalization from at least the late Pleistocene. Geometric morphometric analysis suggested a clear and linear allometric trend between brain endocast size and shape, and highlights A. ensenadensis as an extreme form within the analyzed cervids regarding brain morphology.
Transitions in functional morphology from “large branchiopods” to Cladocera: Video and confocal microscopic studies of Cyclestheria hislopi (Cyclestherida) and Sida crystallina (Cladocera: Ctenopoda)
Authors: Sigvardt Zandra M. S. , Worsaae Katrine , Savatenalinton Sukonthip , Kerbl Alexandra , Olesen Jørgen
Published: August 2020

Great diversity is found in morphology and functionality of arthropod appendages, both along the body axis of individual animals and between different life‐cycle stages. Despite many branchiopod crustaceans being well known for displaying a relatively simple arrangement of many serially post‐maxillary appendages (trunk limbs), this taxon also shows an often unappreciated large variation in appendage morphology. Diplostracan branchiopods exhibit generally a division of labor into locomotory antennae and feeding/filtratory post‐maxillary appendages (trunk limbs). We here study the functionality and morphology of the swimming antennae and feeding appendages in clam shrimps and cladocerans and analyze the findings in an evolutionary context (e.g., possible progenetic origin of Cladocera). We focus on Cyclestheria hislopi (Cyclestherida), sister species to Cladocera and exhibiting many “large” branchiopod characters (e.g., many serially similar appendages), and Sida crystallina (Cladocera, Ctenopoda), which likely exhibits plesiomorphic cladoceran traits (e.g., six pairs of serially similar appendages). We combine (semi‐)high‐speed recordings of behavior with confocal laser scanning microscopy analyses of musculature to infer functionality and homologies of locomotory and filtratory appendages in the two groups. Our morphological study shows that the musculature in all trunk limbs (irrespective of limb size) of both C. hislopi and S. crystallina comprises overall similar muscle groups in largely corresponding arrangements. Some differences between C. hislopi and S. crystallina, such as fewer trunk limbs and antennal segments in the latter, may reflect a progenetic origin of Cladocera. Other differences seem related to the appearance of a specialized type of swimming and feeding in Cladocera, where the anterior locomotory system (antennae) and the posterior feeding system (trunk limbs) have become fully separated functionally from each other. This separation is likely one explanation for the omnipresence of cladocerans, which have conquered both freshwater and marine free water masses and a number of other habitats.
Change in intersegmental foot and ankle motion after a high tibial osteotomy in genu varum patients
Authors: Kyung Min Gyu , Cho Yun Jae , Hwang Sunghyun , Lee Dong‐Oh , Lee Myung Chul , Lee Dong Yeon
Published: August 2020

High tibial osteotomy (HTO) is a well‐established treatment for medial compartment knee osteoarthritis (OA), which shifts the weight‐bearing axis from the medial to the lateral side of the knee. As the adjacent ankle joint may be directly affected by the change in biomechanics, this study aimed to evaluate the change in the intersegmental foot and ankle motion after HTO in patients with genu varum. The study included 24 patients who underwent HTO, and 48 older healthy participants as a control group. Segmental foot kinematics were evaluated using a 3D multisegment foot model, and gait data of temporal and spatial parameters were obtained. After HTO, normalized stride length significantly increased with a tendency for increases in gait speed. In hallux kinematics relative to the forefoot, the sagittal motions of both the patients and the control group were similar throughout the majority of the gait cycle. In forefoot kinematics relative to the hindfoot, the pre‐HTO state revealed significant pronation throughout the gait cycle, while the post‐HTO state showed a similar position and motion to the control group. In hindfoot kinematics relative to the tibia, coronal motions of the pre‐HTO state showed supination throughout the gait cycle, while supination during the stance phase decreased after HTO. Genu varum patients with medial compartment knee OA showed different gait parameters and intersegmental motion during gait when compared with age‐ and gender‐matched controls. The effect of HTO was demonstrated by the normalization of midfoot compensation in patients with genu varum.
Technical Choices in Pediatric Living Donor Liver Transplantation: The Path to Reduce Vascular Complications and Improve Survival
Authors: Neto João Seda , Fonseca Eduardo A. , Vincenzi Rodrigo , Pugliese Renata , Benavides Marcel R. , Roda Karina , Porta Gilda , Miura Irene K. , Porta Adriana , Borges Christian , Baggio Vera , Feier Flavia H. , Teng Hsiang , Rodrigues Mônica L. , Iwase Fernanda C. , Kondo Mário , Chapchap Paulo
Published: August 2020

Pediatric living donor liver transplantation (PLDLT) is a successful therapeutic option for children with chronic and acute liver disease. After early transplant results, many technical advancements were introduced in the field to reduce the rate of complications and improve survival. The aim of this study is to present the outcomes of 975 primary PLDLTs in 3 periods: initial practice (period 1, 29 patients, January 1995 to December 1999), second period (period 2, 331 patients, January 2000 to December 2009), and third period (period 3 [P3], 615 patients, January 2010 to September 2019). Among the technical refinements introduced in P3 are the use of hyperreduced left lateral segment grafts, abdominal wall prosthetic mesh closure, double hepatic artery anastomosis, and increased use of vascular grafts for portal vein reconstruction. The outcomes included significant reductions of hepatic artery thrombosis (HAT), early portal vein thrombosis (EPVT), and retransplantation, with better patient and graft survival in P3. Additional analyses showed that the factors independently associated with worse 90‐day patient survival were HAT, EPVT, and increasing Pediatric End‐Stage Liver Disease score. In conclusion, the introduction of technical refinements in P3, in addition to improvements in patient care, determined a reduction in EPVT, HAT, and retransplantation. Consequently, patient and graft survival rates increased in all time points studied.
Electrical Writing to Three‐Dimensional Pattern Dynamic Polysaccharide Hydrogel for Programmable Shape Deformation
Authors: Zhu Xinyi , Wu Si , Yang Chen , Deng Hongbing , Du Yumin , Shi Xiaowen
Published: August 2020

The ability to pattern and actuate hydrogels is essential for biomimetics, soft robotics, and biosensors. Here an electrical writing technique with the capability to create both surface and across thickness patterns in dynamic chitosan‐H+/agarose hydrogel by electronically generated pH gradient is introduced. The diffusible pH cues deprotonate and re‐assemble chitosan chains by hydrogen bonds, changing the electrical writing domains from original loose structure to a dense layer and resulting in different mechanical stress and swell ability that causes the hydrogel to deform. The deformable trend can be modulated by writing depth and selective writing area on the surface, and significantly enhanced by temperature increment. Finally, a dual electrical writing process to create three‐dimensional patterns and demonstrate programmable shape transition by differing patterns is performed.
N‐Acyl Dibenzazepine Chemistry as Versatile Approach for Photoreversible Thiol‐Ene Networks
Authors: Bener Semira , Aydogan Cansu , Yagci Yusuf
Published: August 2020

It is herein reported that a facile application of N‐acyl dibenzazepine (ADBA) photochemistry for preparing photoreversible ADBA based thiol‐ene networks. Crosslinking of the ADBA thiol‐ene networks is successfully achieved by UV induced dimerization of ADBA groups at wavelengths above 300 nm while a subsequent deep UV exposure (λ = 250 nm) results in a well‐defined cleavage of the crosslinks. The photochemical bonding and cleavage of the process has been determined and studied in detail by spectroscopic measurements.
Optimization of weld bead geometry of laser welded ANSI 304 austenitic stainless steel using grey‐based Taguchi method
Authors: Gencalp Irizalp S. , Koroglu B.K.
Published: August 2020

This paper investigates the quality characteristics of the welding geometry of the laser welding process for the ANSI 304 austenitic stainless steel, with the use of a pulsed Nd:YAG laser welding system. Laser welding of 2 mm thick ANSI 304 stainless steel is performed at three different levels of three factors, i. e., peak power, welding speed and pulse duration. In this study, a multi‐response optimization problem is developed to achieve weld bead geometry with full penetration as well as a narrow bead width and minimum crater. Grey relational analysis based on Taguchi orthogonal array is used to present an effective approach for the optimization of laser welding process parameters. Regression equations between the welding parameters and the bead dimensions for laser welded austenitic stainless steels are developed, which are used in predicting the penetration, width and crater. Finally, the equations are tested for values different from the levels of the parameters in the orthogonal array. It will be beneficial to engineers for continuous improvement in laser welded product quality.
Exploring the relationship between health concerns and high‐risk behaviours in Medical Sciences' students
Authors: Arabi‐Mianrood Hoda , Hamzehgardeshi Zeinab , Jahanfar Shayesteh , Moosazadeh Mahmood , Khoori Elham , Shahhosseini Zohreh
Published: August 2020

Aim

The need to cope with life concerns may drive an individual to resort to high‐risk behaviours. This study aimed to determine the relationship between health concerns and high‐risk behaviours.

Design

A cross‐sectional study.

Methods

We sampled 926 Medical Sciences' students from the North of Iran from September–December 2017 using the stratified sampling method.

Results

The most and less common high‐risk behaviour was physical inactivity (97.5%) and high‐risk sexual behaviour (15.7%), respectively. In multivariate logistic regression analysis, participants' concerns about human sexuality (AOR: 1.39; CI: 1.22, 1.57), injury prevention and control (AOR: 1.12; CI: 1.01, 1.20), nutrition (AOR: 1.13; CI: 1.02, 1.26) and emotional health (AOR: 1.08; CI: 1.02, 1.15) increased the odds of risky behaviours. Among Medical Sciences' students, health concerns are linked with risky behaviours. The result of this study can be used to develop relevant interventions targeting mental health to reduce risky behaviour among youth.
The Effects of Employee Hours‐of‐Service Regulations on the U.S. Airline Industry
Authors: Luttmann Alexander , Nehiba Cody
Published: August 2020

Maximum employee work‐hour restrictions are implemented to reduce accidents. However, because they decrease the stock of work hours available to employers in the short run, they may also have detrimental effects. A quasi‐experiment suggests that pilot hours‐of‐service reforms, which decreased the number of flights and hours a pilot may work, reduced consumer choice and increased fares in the airline industry. We find that regional and low‐cost carriers reduced scheduled flight frequency, while less constrained legacy carriers (and potentially their wholly owned subsidiaries) were unaffected. Further, we find evidence that market concentration increased on many routes, implying that fare increases may be due to a decrease in competition. These findings suggest a situation where a policy implemented to correct one market failure, airlines not internalizing the full social costs of accidents by allowing dangerously fatigued pilots to fly, exacerbated another market failure by decreasing competition.
How Managers Can Reduce Household Water Use Through Communication: A Field Experiment
Authors: Hodges Heather , Kuehl Colin , Anderson Sarah E. , Ehret Phillip J. , Brick Cameron
Published: August 2020

As populations increase and droughts intensify, water providers are using tools such as persuasive messaging to decrease residential water use. However, district‐led messaging campaigns are rarely informed by psychological science, evaluated for effectiveness, or strategically disseminated. In collaboration with a water district, we report a field experiment among single‐family households using persuasive messaging based on the information‐motivation‐behavioral skills model (IMB). We randomly assigned 10,000 households to receive different mailings and measured household water use. All messaging reduced water consumption relative to the control. On average, water use dropped 0.68 hundred cubic feet (HCF) (509 gallons) per household in the first month. Had all 10,000 single‐family, occupied, non‐agricultural residences been mailed the IMB messaging, more than five million gallons would have been saved in the first month. The effects declined but persisted for approximately three months and were three to six times greater in households with high water use (75th to 90th percentiles) relative to average water use. These findings suggest that combining message elements from the IMB model can reduce residential water use and that targeting high‐use households is particularly cost‐effective.
Safety concerns reported by consumers, manufacturers and healthcare professionals: A detailed evaluation of opioid‐related adverse drug reactions in the FDA database over 15 years
Authors: Andreaggi Christian A. , Novak Emily A. , Mirabile Mitchell E. , Sampathkumar Shivani , Gray Matthew P. , He Meiqi , Kane‐Gill Sandra L.
Published: August 2020

To perform an in‐depth analysis of opioid‐related ADRs reported by consumers, manufacturers and healthcare professionals. Delving into the depth and breadth of reported opioid‐related adverse drug reactions (ADRs) provides an opportunity to strategize better clinical management and alleviate safety concerns. Retrospective pharmacovigilance disproportionality analysis for opioid‐related ADRs in the FDA Adverse Event Reporting System (FAERS) database was performed. Detailed analysis of patient (sex, age) and report (year of report; reporter: healthcare worker vs consumer) characteristics were conducted using reports from 2004 quarter 1 to 2018 quarter 4. Reporting odds ratios and confidence intervals (RORs,CI) were calculated. Of the 1 916 674 ADR reports, 300 985 indicated opioids as the primary medication. There was a surge in opioid‐related ADRs reported in 2018 with six times more reports compared to 2004 and twice the number of reports compared to 2017. The largest ROR among the 20 common ADRs was depression and suicide‐self‐injury (ROR 3.12, 95% CI 3.01‐3.22) for reports in age group ≥65 compared to age group 18 to 64, and lack of efficacy (ROR 6.80, 95% CI 6.61‐7.00) for males compared to females. ADRs with the largest RORs for consumers included lack of efficacy/effect (ROR 3.37, 95% CI 3.28‐3.46), administration site reactions (ROR 3.21, 95% CI 3.11‐3.32), depression and suicide self‐injury (ROR 2.26, 95% CI 2.14‐2.38) compared to healthcare professionals. Important aspects of opioid ADR voluntary reporting included suicidal ideation in elderly patients and lack of efficacy, especially in male patients. This examination provides insight to better manage safety concerns of opioids.
Applying modified hyperbranched polyester in hydroxyl‐terminated polyether/ammonium perchlorate/aluminium/cyclotrimethylenetrinitramine (HTPE/AP/Al/RDX) composite solid propellant
Authors: Wen Xiaomu , Chen Keke , Sang Chao , Yuan Shen , Luo Yunjun
Published: August 2020

Composite solid propellants demand fine and stable mechanical properties, creep resistance and stress relaxation performance during their long storage and usage time. In this study, modified hyperbranched polyester (MHBPE) was prepared and introduced into HTPE/AP/Al/RDX (HTPE, hydroxyl‐terminated polyether; AP, ammonium perchlorate; RDX, cyclotrimethylenetrinitramine) solid propellant as an effective additive. The static tensile and dynamic mechanical properties of this propellant before and after the introduction of MHBPE were evaluated. The elevated interfacial interaction by using MHBPE between the binder and RDX fillers improved the toughness and elasticity of the propellant. The enhancement mechanisms were also confirmed by the influence on the fracture surface morphology of the binder which was investigated by SEM. In addition, some influence on the dynamic mechanical properties of HTPE/AP/Al/RDX propellant caused by MHBPE was investigated by dynamic mechanical analysis. The creep behaviors of the HTPE/AP/Al/RDX propellants with and without MHBPE were also investigated at different stresses and temperatures. Reduced creep strain rate and strain were obtained for the modified propellant, implying enhanced creep resistance performance. The creep properties were quantitatively evaluated using a six‐element model and the long‐term creep performance of the propellant was predicted using the time–temperature superposition principle. A creep behavior of nearly 106 s at 30 °C could be acquired in a short‐term experiment (800 s) at 30–70 °C. Moreover, the stress relaxation investigation of the propellants with and without MHBPE at −40 °C, 20 °C and 70 °C suggested that MHBPE/HTPE/AP/Al/RDX propellant possessed better response ability to deformation. Thus, the application of MHBPE provides an efficient route of reinforcement to enhance the creep resistance and stress relaxation properties. © 2020 Society of Chemical Industry
On the solvent‐ and temperature‐driven stereoselectivity of the Diels–Alder cycloaddition reactions of furan with maleic anhydride and maleimide
Authors: Yadav Veejendra K. , Prasad Dasari L.V.K. , Yadav Arpita , Yadav Kedar
Published: August 2020

In quantum chemical calculations, the Diels–Alder (DA) cycloaddition reaction of furan with maleic anhydride favors the endo‐isomer kinetically in the gas phase. This preference, however, changes in favor of the exo‐isomer on inclusion of solvent effects. For example, in acetonitrile, the exo‐isomer was calculated to form twice as fast as the endo‐isomer at room temperature, an observation that corroborates well with the experiments. The free energy change of the reaction is such that it allows faster reversal of the endo‐isomer to the reactants in an equilibrium process and, thus, the predominance of the more stable exo‐isomer eventually. The reaction of furan with maleimide is similar to that with maleic anhydride. However, it predominantly favors endo‐selectivity at temperatures below 320 K, which is also in excellent agreement with the experimental studies of temperature dependence of this DA reaction. Further, a gedanken calculation of the DA reaction of furan with cyclopropene has been investigated to delineate the effect of the retro‐pathway on stereoselectivity.
GLUT1‐Targeting and GSH‐Responsive DOX/L61 Nanodrug Particles for Enhancing MDR Breast Cancer Therapy
Authors: Wang Xin , Yang Lu , Fang Qin , Xu Jiaxi , Cheng Xu , Xue Yanbing , Tang Rupei
Published: August 2020

Efficient targeting to tumor tissues and subsequent rapid drug release in cancer cells remains a major challenge for nanodrug delivery systems. Herein, smart nanodrug particles with reduction‐sensitive and active tumor‐targeting ability are constructed based on the nanoprecipitation of glucosamine‐grafted pluronic L61 (GA‐L61) and disulphide‐linked doxorubicin dimer (DOXSSDOX) to overcome tumor multidrug resistance (MDR). These nanoparticles show proper size and excellent stability under neutral conditions, while quickly release DOX due to the breakage of disulfide bonds under reductive medium. In vitro cellular uptake and drug efflux demonstrate that L61 can efficiently increase DOX concentration in MCF/ADR resistant cells by inhibiting the function of drug resistance proteins. In vivo biodistribution reveals that glucose transporter 1 (GLUT1)‐mediated tumor‐targeting significantly improves tumor accumulation of the glucosamine‐contained nanoparticles. Finally, the combination of GLUT1‐targeting, glutathione (GSH)‐responsive, and MDR‐reversal effects in nanoparticles achieve superior antitumor effects, which can provide an efficient, safe, and economic approach for drug delivery and cancer chemotherapy.
Structural analysis and reaction mechanism of the disproportionating enzyme (D‐enzyme) from potato
Authors: Imamura Kayo , Matsuura Takanori , Nakagawa Atsushi , Kitamura Shinichi , Kusunoki Masami , Takaha Takeshi , Unno Hideaki
Published: August 2020

Starch produced by plants is a stored form of energy and is an important dietary source of calories for humans and domestic animals. Disproportionating enzyme (D‐enzyme) catalyzes intramolecular and intermolecular transglycosylation reactions of α‐1, 4‐glucan. D‐enzyme is essential in starch metabolism in the potato. We present the crystal structures of potato D‐enzyme, including two different types of complex structures: a primary Michaelis complex (substrate binding mode) for 26‐meric cycloamylose (CA26) and a covalent intermediate for acarbose. Our study revealed that the acarbose and CA26 reactions catalyzed by potato D‐enzyme involve the formation of a covalent intermediate with the donor substrate. HPAEC of reaction substrates and products revealed the activity of the potato D‐enzyme on acarbose and CA26 as donor substrates. The structural and chromatography analyses provide insight into the mechanism of the coupling reaction of CA and glucose catalyzed by the potato D‐enzyme. The enzymatic reaction mechanism does not involve residual hydrolysis. This could be particularly useful in preventing unnecessary starch degradation leading to reduced crop productivity. Optimization of this mechanism would be important for improvements of starch storage and productivity in crops.
TheAutoDocksuite at 30
Authors: Goodsell David S. , Sanner Michel F. , Olson Arthur J. , Forli Stefano
Published: August 2020

The AutoDock suite provides a comprehensive toolset for computational ligand docking and drug design and development. The suite builds on 30 years of methods development, including empirical free energy force fields, docking engines, methods for site prediction, and interactive tools for visualization and analysis. Specialized tools are available for challenging systems, including covalent inhibitors, peptides, compounds with macrocycles, systems where ordered hydration plays a key role, and systems with substantial receptor flexibility. All methods in the AutoDock suite are freely available for use and reuse, which has engendered the continued growth of a diverse community of primary users and third‐party developers.
Designing “Metamolecules” for Photonic Function: Reduced Backscattering
Authors: Deng Tian-Song , Parker John , Hirai Yutaro , Shepherd Nolan , Yabu Hiroshi , Scherer Norbert F.
Published: August 2020

Metamaterials, subwavelength nanostructured materials, can exhibit novel optical properties such as a negative index of refraction. Dielectric core–nanoparticle satellite clusters, termed “metamolecules,” can have strong optical magnetic resonances in the visible wavelength range—a requirement to achieve negative refractive index materials. However, achieving the desired photonic properties is challenging due to limited control in forming the metamolecule structures. Here, polystyrene (PS) core–gold nanoparticle (AuNP) satellite metamolecules with highly ordered single layers (monolayers) of AuNPs are fabricated and single particle spectroscopy, electron tomography structural measurements, and electrodynamics simulations are conducted to study the photonic properties of metamolecules constituted of ≈100 AuNPs. The simulated and experimental spectra of the many metamolecules studied, including excitation with azimuthally and radially polarized light, are in excellent agreement. It is shown that the scattering properties of the metamolecules are dominated by the AuNPs near the “equator” of the cluster, and that backscattering is strongly suppressed when different multipolar modes (e.g., dipolar and quadrupolar) of electric or optical magnetic character have comparable intensity due to the π‐phase shift of their scattering. Both the optical excitation fields and the ordering of the nanoparticles within metamolecules affect their optical excitation and scattering properties, providing new insights into designing novel photonic metamaterials.
Physical Properties and Electronic Structure of Cr2B Under Pressure
Authors: Zhang Yongmei , Liu Dong , Zhao Yuhong , Li Wu , Gao Yanqin , Duan Meiling , Hou Hua
Published: August 2020

The physical properties of Cr2B with I4/m symmetry under pressure are investigated by the first‐principles method. With the increase in pressure, the hardness decreases first and then slightly increases, whereas the bulk modulus, shear modulus, Young's modulus, fracture toughness, minimum thermal conductivity, and Debye temperature monotonically increase. Pressure induces the transition from brittleness to toughness at ≈30 GPa. When P > 30 GPa, the hardness and toughness increase simultaneously with pressure. The analysis of electronic structure indicates that the variation of BB covalent bonds may be responsible for the abnormous increase in hardness when P > 30 GPa.
Synthesizing independent stagewise trials for optimal dynamic treatment regimes
Authors: Chen Yuan , Wang Yuanjia , Zeng Donglin
Published: August 2020

Dynamic treatment regimes (DTRs) adaptively prescribe treatments based on patients' intermediate responses and evolving health status over multiple treatment stages. Data from sequential multiple assignment randomization trials (SMARTs) are recommended to be used for learning DTRs. However, due to re‐randomization of the same patients over multiple treatment stages and a prolonged follow‐up period, SMARTs are often difficult to implement and costly to manage, and patient adherence is always a concern in practice. To lessen such practical challenges, we propose an alternative approach to learn optimal DTRs by synthesizing independent trials over different stages. Specifically, at each stage, data from a single randomized trial along with patients' natural medical history and health status in previous stages are used. We use a backward learning method to estimate optimal treatment decisions at a particular stage, where patients' future optimal outcome increments are estimated using data observed from independent trials with future stages' information. Under some conditions, we show that the proposed method yields consistent estimation of the optimal DTRs and we obtain the same learning rates as those from SMARTs. We conduct simulation studies to demonstrate the advantage of the proposed method. Finally, we learn optimal DTRs for treating major depressive disorder (MDD) by stagewise synthesis of two randomized trials. We perform a validation study on independent subjects and show that the synthesized DTRs lead to the greatest MDD symptom reduction compared to alternative methods.
Variance formulae for multiphase stepped wedge cluster randomized trial
Authors: Zhang Pengyue , Shoben Abigail , Jackson Rebecca , Fernandez Soledad
Published: August 2020

In a multiphase stepped wedge cluster randomized trial (MSW‐CRT), more than one intervention will be initiated on each sequence in a fixed order. Hence, with the MSW‐CRT design, the effect of the first intervention can be evaluated when compared to control, as well as the added‐on effects of the subsequent interventions. Studies that use MSW‐CRT have been proposed, but properties of this design have not been explicitly studied. We derive closed‐form variance formulae to test the interventions' effects, which can be readily used for sample size and power calculation. Additionally, we provide relationships between variances to test the interventions' effects and design parameters. Under special conditions, some important properties include: (i) the variances to test different interventions' effects (ie, the first intervention effect and the second intervention effect) may be same; (ii) as the cluster‐period mean autocorrelation increases, the variance to test an intervention effect may first increase and then decrease; (iii) as the amount of periods between the initiations of two interventions (ie, lag) increases, the variance to test an intervention effect may remain unchanged. We illustrate the relationships between power and design parameters using the variance formulae. From a few illustrative examples, we observe that the statistical test that uses data only relevant to a specific intervention has inferior power (relative power loss <15%) compared to the test when using all the study data. Also, power is reduced when both the total number of periods and lag are decreased simultaneously (relative power loss <20%).
Statistical inference for missing data mechanisms
Authors: Zhao Yang
Published: August 2020

In the literature of statistical analysis with missing data there is a significant gap in statistical inference for missing data mechanisms especially for nonmonotone missing data, which has essentially restricted the use of the estimation methods which require estimating the missing data mechanisms. For example, the inverse probability weighting methods (Horvitz & Thompson, 1952; Little & Rubin, 2002), including the popular augmented inverse probability weighting (Robins et al, 1994), depend on sufficient models for the missing data mechanisms to reduce estimation bias while improving estimation efficiency. This research proposes a semiparametric likelihood method for estimating missing data mechanisms where an EM algorithm with closed form expressions for both E‐step and M‐step is used in evaluating the estimate (Zhao et al, 2009; Zhao, 2020). The asymptotic variance of the proposed estimator is estimated from the profile score function. The methods are general and robust. Simulation studies in various missing data settings are performed to examine the finite sample performance of the proposed method. Finally, we analysis the missing data mechanism of Duke cardiac catheterization coronary artery disease diagnostic data to illustrate the method.
Influence of curing temperature on the mechanical properties and microstructure of limestone powder mass concrete
Authors: Jin Weizhun , Jiang Linhua , Han Lin , Chen Lei , Yan Xiancui , Chen Chen
Published: August 2020

This study investigates the influence of different percentages: 10, 30, and 50% of limestone powder (LS) and different curing temperatures: 50, 20, and 5°C on mechanical properties and microstructure of mass concrete. The microstructure is studied by X‐ray diffraction, thermogravimetric, and scanning electron microscopy. The results show that the mechanical strength of concrete gradually decreases with the increase of LS. Curing temperature 50°C enhances mechanical strength of LS concrete at ages of 3 and 7 days, but slightly reduces that at age of 28 days. While curing temperature 5°C significantly reduces the mechanical strength at ages of 3, 7, and 28 days. The microstructure results indicate that LS has weak chemical effect and can participate in cement hydration. Different curing temperatures can significantly influence the hydration products and microstructure of LS composite cement pastes.
The utilization of walnut shells as a partial replacement of sand in mortar mixes
Authors: Abdulwahid Mohanad Yaseen , Abdullah Sarmad Fadhil
Published: August 2020

The effect of walnut shells on different properties of mortar was investigated through several experimental tests. The investigated properties include dry density, thermal conductivity, compressive and flexural strengths. Percentage replacements of the walnut shells to sand ratio were 5, 10, and 15%. The walnut shells used in this study were treated by soaking in boiling water for two periods: 1/2 hr and 1 hr. All mortar mixes have same proportion of 1:3:0.7 by weight for cement, sand, and water, respectively. The test results showed that the use of 15% walnut shells treated for 1/2 hr lead to decrease of the density and thermal conductivity of mortar by 15 and 31%, respectively. On the contrary, the compressive and flexural strengths of mortar were decreased by 17 and 25%, respectively, in comparison to the control mortar after 28 days of moist curing. This study leads to a conclusion that by soaking the walnut shells in boiling water for 1/2 hr enhanced the behavior of mortar compared to the un‐soaked ones. This results in achieving an acceptable strength, good thermal insulator, and environmentally friendly mortar.