bluuebunny/crossref_metadata_2025 huggingface dataset:
Promiscuous molecules for smarter file operations in DNA-based data storage
Authors: Tomek Kyle J. , Volkel Kevin , Indermaur Elaine W. , Tuck James M. , Keung Albert J.
Published: June 2021

DNA holds significant promise as a data storage medium due to its density, longevity, and resource and energy conservation. These advantages arise from the inherent biomolecular structure of DNA which differentiates it from conventional storage media. The unique molecular architecture of DNA storage also prompts important discussions on how data should be organized, accessed, and manipulated and what practical functionalities may be possible. Here we leverage thermodynamic tuning of biomolecular interactions to implement useful data access and organizational features. Specific sets of environmental conditions including distinct DNA concentrations and temperatures were screened for their ability to switchably access either all DNA strands encoding full image files from a GB-sized background database or subsets of those strands encoding low resolution, File Preview, versions. We demonstrate File Preview with four JPEG images and provide an argument for the substantial and practical economic benefit of this generalizable strategy to organize data.
Targeted PI3K/AKT-hyperactivation induces cell death in chronic lymphocytic leukemia
Authors: Ecker Veronika , Stumpf Martina , Brandmeier Lisa , Neumayer Tanja , Pfeuffer Lisa , Engleitner Thomas , Ringshausen Ingo , Nelson Nina , Jücker Manfred , Wanninger Stefan , Zenz Thorsten , Wendtner Clemens , Manske Katrin , Steiger Katja , Rad Roland , Müschen Markus , Ruland Jürgen , Buchner Maike
Published: June 2021

Current therapeutic approaches for chronic lymphocytic leukemia (CLL) focus on the suppression of oncogenic kinase signaling. Here, we test the hypothesis that targeted hyperactivation of the phosphatidylinositol-3-phosphate/AKT (PI3K/AKT)-signaling pathway may be leveraged to trigger CLL cell death. Though counterintuitive, our data show that genetic hyperactivation of PI3K/AKT-signaling or blocking the activity of the inhibitory phosphatase SH2-containing-inositol-5′-phosphatase-1 (SHIP1) induces acute cell death in CLL cells. Our mechanistic studies reveal that increased AKT activity upon inhibition of SHIP1 leads to increased mitochondrial respiration and causes excessive accumulation of reactive oxygen species (ROS), resulting in cell death in CLL with immunogenic features. Our results demonstrate that CLL cells critically depend on mechanisms to fine-tune PI3K/AKT activity, allowing sustained proliferation and survival but avoid ROS-induced cell death and suggest transient SHIP1-inhibition as an unexpectedly promising concept for CLL therapy.
Antibody-drug conjugates with dual payloads for combating breast tumor heterogeneity and drug resistance
Authors: Yamazaki Chisato M. , Yamaguchi Aiko , Anami Yasuaki , Xiong Wei , Otani Yoshihiro , Lee Jangsoon , Ueno Naoto T. , Zhang Ningyan , An Zhiqiang , Tsuchikama Kyoji
Published: June 2021

Breast tumors generally consist of a diverse population of cells with varying gene expression profiles. Breast tumor heterogeneity is a major factor contributing to drug resistance, recurrence, and metastasis after chemotherapy. Antibody-drug conjugates (ADCs) are emerging chemotherapeutic agents with striking clinical success, including T-DM1 for HER2-positive breast cancer. However, these ADCs often suffer from issues associated with intratumor heterogeneity. Here, we show that homogeneous ADCs containing two distinct payloads are a promising drug class for addressing this clinical challenge. Our conjugates show HER2-specific cell killing potency, desirable pharmacokinetic profiles, minimal inflammatory response, and marginal toxicity at therapeutic doses. Notably, a dual-drug ADC exerts greater treatment effect and survival benefit than does co-administration of two single-drug variants in xenograft mouse models representing intratumor HER2 heterogeneity and elevated drug resistance. Our findings highlight the therapeutic potential of the dual-drug ADC format for treating refractory breast cancer and perhaps other cancers.
Giant phonon anomalies in the proximate Kitaev quantum spin liquid α-RuCl3
Authors: Li Haoxiang , Zhang T. T. , Said A. , Fabbris G. , Mazzone D. G. , Yan J. Q. , Mandrus D. , Halász Gábor B. , Okamoto S. , Murakami S. , Dean M. P. M. , Lee H. N. , Miao H.
Published: June 2021

The Kitaev quantum spin liquid epitomizes an entangled topological state, for which two flavors of fractionalized low-energy excitations are predicted: the itinerant Majorana fermion and the Z2 gauge flux. It was proposed recently that fingerprints of fractional excitations are encoded in the phonon spectra of Kitaev quantum spin liquids through a novel fractional-excitation-phonon coupling. Here, we detect anomalous phonon effects in α-RuCl3 using inelastic X-ray scattering with meV resolution. At high temperature, we discover interlaced optical phonons intercepting a transverse acoustic phonon between 3 and 7 meV. Upon decreasing temperature, the optical phonons display a large intensity enhancement near the Kitaev energy, JK~8 meV, that coincides with a giant acoustic phonon softening near the Z2 gauge flux energy scale. These phonon anomalies signify the coupling of phonon and Kitaev magnetic excitations in α-RuCl3 and demonstrates a proof-of-principle method to detect anomalous excitations in topological quantum materials.
Asymmetric benzylic C(sp3)−H acylation via dual nickel and photoredox catalysis
Authors: Huan Leitao , Shu Xiaomin , Zu Weisai , Zhong De , Huo Haohua
Published: June 2021

Asymmetric C(sp3)−H functionalization is a persistent challenge in organic synthesis. Here, we report an asymmetric benzylic C−H acylation of alkylarenes employing carboxylic acids as acyl surrogates for the synthesis of α-aryl ketones via nickel and photoredox dual catalysis. This mild yet straightforward protocol transforms a diverse array of feedstock carboxylic acids and simple alkyl benzenes into highly valuable α-aryl ketones with high enantioselectivities. The utility of this method is showcased in the gram-scale synthesis and late-stage modification of medicinally relevant molecules. Mechanistic studies suggest a photocatalytically generated bromine radical can perform benzylic C−H cleavage to activate alkylarenes as nucleophilic coupling partners which can then engage in a nickel-catalyzed asymmetric acyl cross-coupling reaction. This bromine-radical-mediated C−H activation strategy can be also applied to the enantioselective coupling of alkylarenes with chloroformate for the synthesis of chiral α-aryl esters.
Circulating tumor cell number and endocrine therapy index in ER positive metastatic breast cancer patients
Authors: Paoletti Costanza , Regan Meredith M. , Niman Samuel M. , Dolce Emily M. , Darga Elizabeth P. , Liu Minetta C. , Marcom P. Kelly , Hart Lowell L. , Smith John W. , Tedesco Karen L. , Amir Eitan , Krop Ian E. , DeMichele Angela M. , Goodwin Pamela J. , Block Margaret , Aung Kimberly , Brown Martha E. , McCormack Robert T. , Hayes Daniel F.
Published: June 2021

Circulating tumor cells (CTC) are prognostic in metastatic breast cancer (MBC). The CTC-endocrine therapy index (CTC-ETI), consisting of CTC-ER (estrogen receptor), BCL2, human epidermal growth factor receptor (HER2), and Ki67 expression, might predict resistance to endocrine therapy (ET) in patients with ER-positive MBC. One hundred twenty-one patients with ER-positive/HER2-negative MBC initiating a new ET after ≥1 lines of ET were enrolled in a prospective, multi-institutional clinical trial. CTC-ETI and clinical/imaging follow-up were performed at baseline and serial time points. Progression-free survival (PFS) and rapid progression (RP; determined at the 3-month time point) were primary endpoints. Associations with clinical outcomes used logrank and Fisher’s exact tests. At baseline, 36% (38/107) of patients had ≥5 CTC/7.5 ml whole blood (WB). Patients with ≥5 vs. <5 CTC/7.5 ml WB had significantly worse PFS (median 3.3 vs. 5.9 months, P = 0.03). Elevated CTC at 1 month was associated with even worse PFS (1.9 vs. 5.0 months from the 1-month sample, P < 0.001). Low, intermediate, and high CTC-ETI were observed in 71 (66%), 8 (8%), and 28 (26%) patients, with median PFS of 6.9, 8.5, and 2.8 months, respectively (P = 0.008). Patients with high vs. low CTC and CTC-ETI more frequently experienced RP (CTC: 66% vs. 41%; P = 0.03; CTC-ETI: 79% vs. 40%; P = 0.002). In conclusion, CTC enumeration and the CTC-ETI assay are prognostic at baseline and follow-up in patients with ER-positive/HER2-negative MBC starting new ET. CTC at first follow-up might identify a group of patients with ER-positive MBC that could forego ET, but CTC-ETI did not contribute further.
Senolytics improve bone forming potential of bone marrow mesenchymal stem cells from aged mice
Authors: Zhou Yueying , Xin Xiaonan , Wang Lichao , Wang Binsheng , Chen Li , Liu Ousheng , Rowe David W. , Xu Ming
Published: June 2021

The osteogenic potential of bone marrow mesenchymal stem cells (BMSCs) declines dramatically with aging. By using a calvarial defect model, we showed that a senolytic cocktail (dasatinib+quercetin; D + Q) improved osteogenic capacity of aged BMSC both in vitro and in vivo. The study presented a model to assess strategies to improve bone-forming potential on aged BMSCs. D + Q might hold promise for improving BMSC function in aged populations.
The effect of endurance and endurance-strength training on body composition and cardiometabolic markers in abdominally obese women: a randomised trial
Authors: Jamka Małgorzata , Mądry Edyta , Krzyżanowska-Jankowska Patrycja , Skrypnik Damian , Szulińska Monika , Mądry Radosław , Lisowska Aleksandra , Batyrova Gulnara , Duś-Żuchowska Monika , Gotz-Więckowska Anna , Bogdański Paweł , Walkowiak Jarosław
Published: June 2021

Studies comparing the effect of endurance and endurance-strength training on cardiometabolic markers provided inconsistent results. Therefore, the study aimed to compare the effect of endurance and endurance-strength training on body composition and cardiometabolic parameters in abdominally obese women. In this randomised trial, 101 subjects were included and divided into endurance (n = 52) and endurance-strength (n = 49) training. During the 12-week intervention, participants performed supervised one-hour training three times a week. Body composition, blood pressure (BP), markers of glucose and lipid homeostasis, and myoglobin levels were measured before and after the intervention. In total, 85 subjects completed the trial. Both interventions decreased fat mass and visceral adipose tissue and increased free fat mass, appendicular lean mass index and lean mass index. Neither endurance training nor endurance-strength training affected glucose and lipid metabolism. However, only endurance training significantly decreased paraoxonase and myoglobin levels. Both training programmes significantly decreased BP, with a more reduction of diastolic BP noted in the endurance group. In conclusion, both training programmes had a favourable effect on body composition but did not improve glucose and lipid homeostasis. Besides, endurance training decreased paraoxonase activity and myoglobin levels and was more effective in reducing BP.

The study was registered with the German Clinical Trials Register (DRKS) within the number: DRKS00019832 (retrospective registration), date of registration: 26/02/2020.
Vertical and seasonal changes in soil carbon pools to vegetation degradation in a wet meadow on the Qinghai-Tibet Plateau
Authors: Wu Jiangqi , Wang Haiyan , Li Guang , Wu Jianghua , Ma Weiwei
Published: June 2021

Wet meadows provide opportunities to decrease carbon dioxide (CO2) and methane (CH4) released into the atmosphere by increasing the soil organic carbon (SOC) stored in wetland systems. Although wet meadows serve as the most important and stable C sinks, there has been very few investigations on the seasonal distributions of SOC fractions in high-altitude wet meadows. Here, we studied the effects of four vegetation degradation levels, non-degraded (ND), lightly degraded (LD), moderately degraded (MD), and heavily degraded (HD), on the measured vertical and seasonal changes of SOC and its different fractions. Among these vegetation degradation levels, 0–10 and 10–20 cm soil depths in ND plots had significantly higher SOC contents than the other degradation levels had throughout the year. This is attributed to the relatively greater inputs of aboveground plant litter and richer fine-root biomass in ND plots. Particulate organic carbon (POC) and light fraction organic carbon (LFOC) showed similar vertical and seasonal variations in autumn, reaching a minimum. Moreover, microbial biomass (MBC) and easily oxidizable organic carbon (EOC) contents were highest in summer and the smallest in winter, while dissolved organic carbon (DOC) content was highest in spring and lowest in summer, and were mainly concentrated in the 0–20 cm layer. Pearson correlation analysis indicated that soil properties and aboveground biomass were significantly related to different SOC fractions. The results indicate that vegetation degradation reduces the accumulation of total SOC and its different fractions, which may reduce carbon sink capacity and soil quality of alpine wet meadows, and increase atmospheric environmental pressure. In addition, vegetation biomass and soil characteristics play a key role in the formation and transformation of soil carbon. These results strengthen our understanding of soil C dynamics, specifically related to the different C fractions as affected by vegetation degradation levels and soil depth, in wet meadow systems.
Listening to speech with a guinea pig-to-human brain-to-brain interface
Authors: Richter Claus-Peter , La Faire Petrina , Tan Xiaodong , Fiebig Pamela , Landsberger David M. , Micco Alan G.
Published: June 2021

Nicolelis wrote in his 2003 review on brain-machine interfaces (BMIs) that the design of a successful BMI relies on general physiological principles describing how neuronal signals are encoded. Our study explored whether neural information exchanged between brains of different species is possible, similar to the information exchange between computers. We show for the first time that single words processed by the guinea pig auditory system are intelligible to humans who receive the processed information via a cochlear implant. We recorded the neural response patterns to single-spoken words with multi-channel electrodes from the guinea inferior colliculus. The recordings served as a blueprint for trains of biphasic, charge-balanced electrical pulses, which a cochlear implant delivered to the cochlear implant user’s ear. Study participants completed a four-word forced-choice test and identified the correct word in 34.8% of trials. The participants' recognition, defined by the ability to choose the same word twice, whether right or wrong, was 53.6%. For all sessions, the participants received no training and no feedback. The results show that lexical information can be transmitted from an animal to a human auditory system. In the discussion, we will contemplate how learning from the animals might help developing novel coding strategies.
Social Network Research contribution to evaluating process in a feasibility study of a peer-led and school-based sexual health intervention
Authors: Broccatelli Chiara , Wang Peng , McDaid Lisa , McCann Mark , Simpson Sharon Anne , Elliott Lawrie , Moore Laurence , Mitchell Kirstin
Published: June 2021

There is growing interest in social network-based programmes to improve health, but rigorous methods using Social Network research to evaluate the process of these interventions is less well developed. Using data from the “STis And Sexual Health” (STASH) feasibility trial of a school-based, peer-led intervention on sexual health prevention, we illustrate how network data analysis results can address key components of process evaluations for complex interventions—implementation, mechanisms of impacts, and context. STASH trained students as Peer Supporters (PS) to diffuse sexual health messages though face-to-face interactions and online Facebook (FB) groups. We applied a Multilevel Exponential Random Graph modelling approach to analyse the interdependence between offline friendship relationships and online FB ties and how these different relationships align. Our results suggest that the creation of online FB communities mirrored offline adolescent groups, demonstrating fidelity of intervention delivery. Data on informal friendship networks related to student’s individual characteristics (i.e., demographics, sexual health knowledge and adherence to norms, which were included for STASH), contributed to an understanding of the social relational ‘building’ mechanisms that sustain tie-formation. This knowledge could assist the selection of opinion leaders, improving identification of influential peers situated in optimal network positions. This work provides a novel contribution to understanding how to integrate network research with the process evaluation of a network intervention.
Global historic pandemics caused by the FAM-1 genotype of Phytophthora infestans on six continents
Authors: Saville Amanda C. , Ristaino Jean B.
Published: June 2021

The FAM-1 genotype of Phytophthora infestans caused late blight in the 1840s in the US and Europe and was responsible for the Irish famine. We sampled 140 herbarium specimens collected between 1845 and 1991 from six continents and used 12-plex microsatellite genotyping (SSR) to identify FAM-1 and the mtDNA lineage (Herb-1/Ia) present in historic samples. FAM-1 was detected in approximately 73% of the historic specimens and was found on six continents. The US-1 genotype was found later than FAM-1 on all continents except Australia/Oceania and in only 27% of the samples. FAM-1 was the first genotype detected in almost all the former British colonies from which samples were available. The data from historic outbreak samples suggest the FAM-1 genotype was widespread, diverse, and spread to Asia and Africa from European sources. The famine lineage spread to six continents over 144 years, remained widespread and likely spread during global colonization from Europe. In contrast, modern lineages of P. infestans are rapidly displaced and sexual recombination occurs in some regions.
Dispersion of metallic/ceramic matrix nanocomposite material through porous surfaces in magnetized hybrid nanofluids flow with shape and size effects
Authors: Qureshi M. Zubair Akbar , Bilal S. , Malik M. Y. , Raza Qadeer , Sherif El-Sayed M. , Li Yong-Min
Published: June 2021

Matrix nanocomposites are high performance materials possessing unusual features along with unique design possibilities. Due to extraordinary thermophysical characteristic contained by these matrix nanocomposites materials they are useful in several areas ranging from packaging to biomedical applications. Being an environment friendly, utilization of nanocomposites offer new technological opportunities for several sectors of aerospace, automotive, electronics and biotechnology. In this regards, current pagination is devoted to analyze thermal features of viscous fluid flow between orthogonally rotating disks with inclusion of metallic matrix nanocomposite (MMNC) and ceramic matrix nanocomposites (CMNC) materials. Morphological aspects of these nanomaterials on flow and heat transfer characteristics has been investigated on hybrid viscous fluid flow. Mathematical structuring of problem along with empirical relations for nanocomposites materials are formulated in the form of partial differential equations and later on converted into ordinary differential expressions by using suitable variables. Solution of constructed coupled differential system is found by collaboration of Runge–Kutta and shooting methods. Variation in skin friction coefficient at lower and upper walls of disks along with measurement about heat transfer rate are calculated against governing physical parameters. Impact of flow concerning variables on axial, radial components of velocity and temperature distribution are also evaluated. Contour plots are also drawn to explore heat and thermal profiles. Comparison and critical analysis of MMNc and CMNc have been presented at lower and upper porous disks. Our computed analysis indicates that hybrid nanofluids show significant influence as compared to simple nanofluids with the permutation of the different shape factors.
Dinosaur senescence: a hadrosauroid with age-related diseases brings a new perspective of “old” dinosaurs
Authors: Słowiak Justyna , Szczygielski Tomasz , Rothschild Bruce M. , Surmik Dawid
Published: June 2021

Senile vertebrates are extremely rare in the fossil record, making their recognition difficult. Here we present the largest known representative of the Late Cretaceous hadrosauriformGobihadros mongoliensisshowing features of cessation of growth indicating attainment of the terminal size. Moreover, this is the first non-avian dinosaur with an age-related pathology recognized as primary calcium pyrophosphate deposition disease indicating its advanced age. Because senile dinosaurs are so rare and thus “senescence” in dinosaurs is unclear, we also propose a new unified definition of a senile dinosaur: an individual which achieved the terminal size as revealed by the presence of the external fundamental system and closed transcortical channels, has completely secondary remodeled weight-bearing bones and possesses non-traumatic, non-contagious bone pathologies correlated with advanced age.
Anthropometric﻿ accuracy of three-dimensional average faces compared to conventional facial measurements
Authors: Shan Zhiyi , Hsung Richard Tai-Chiu , Zhang Congyi , Ji Juanjuan , Choi Wing Shan , Wang Wenping , Yang Yanqi , Gu Min , Khambay Balvinder S.
Published: June 2021

This study aimed to evaluate and compare the accuracy of average faces constructed by different methods. Original three-dimensional facial images of 26 adults in Chinese ethnicity were imported into Di3DView and MorphAnalyser for image processing. Six average faces (Ave_D15, Ave_D24, Ave_MG15, Ave_MG24, Ave_MO15, Ave_MO24) were constructed using “surface-based registration” method with different number of landmarks and template meshes. Topographic analysis was performed, and the accuracy of six average faces was assessed by linear and angular parameters in correspondence with arithmetic means calculated from individual original images. Among the six average faces constructed by the two systems, Ave_MG15 had the highest accuracy in comparison with the conventional method, while Ave_D15 had the least accuracy. Other average faces were comparable regarding the number of discrepant parameters with clinical significance. However, marginal and non-registered areas were the most inaccurate regions using Di3DView. For MorphAnalyser, the type of template mesh had an effect on the accuracy of the final 3D average face, but additional landmarks did not improve the accuracy. This study highlights the importance of validating software packages and determining the degree of accuracy, as well as the variables which may affect the result.
Structure-based redesigning of pentoxifylline analogs against selective phosphodiesterases to modulate sperm functional competence for assisted reproductive technologies
Authors: Satish Mutyala , Kumari Sandhya , Deeksha Waghela , Abhishek Suman , Nitin Kulhar , Adiga Satish Kumar , Hegde Padmaraj , Dasappa Jagadeesh Prasad , Kalthur Guruprasad , Rajakumara Eerappa
Published: June 2021

Phosphodiesterase (PDE) inhibitors, such as pentoxifylline (PTX), are used as pharmacological agents to enhance sperm motility in assisted reproductive technology (ART), mainly to aid the selection of viable sperm in asthenozoospermic ejaculates and testicular spermatozoa, prior to intracytoplasmic sperm injection (ICSI). However, PTX is reported to induce premature acrosome reaction (AR) and, exert toxic effects on oocyte function and early embryo development. Additionally, in vitro binding studies as well as computational binding free energy (ΔGbind) suggest that PTX exhibits weak binding to sperm PDEs, indicating room for improvement. Aiming to reduce the adverse effects and to enhance the sperm motility, we designed and studied PTX analogues. Using structure-guided in silico approach and by considering the physico-chemical properties of the binding pocket of the PDEs, designed analogues of PTX. In silico assessments indicated that PTX analogues bind more tightly to PDEs and form stable complexes. Particularly, ex vivo evaluation of sperm treated with one of the PTX analogues (PTXm-1), showed comparable beneficial effect at much lower concentration—slower AR, higher DNA integrity and extended longevity of  spermatozoa and  superior embryo quality. PTXm-1 is proposed to be a better pharmacological agent for ART than PTX for sperm function enhancement.
Author Correction: Genome-wide identification of Argonautes in Solanaceae with emphasis on potato
Authors: Liao Zhen , Hodén Kristian Persson , Singh Ravi Kumar , Dixelius Christina
Published: June 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Delayed elimination communication on the prevalence of children's bladder and bowel dysfunction
Authors: Xu Peng Chao , Wang Yi He , Meng Qing Jun , Wen Yi Bo , Yang Jing , Wang Xi Zheng , Chen Yan , He Yu Lin , Wang Qing Wei , Wang Yan , Cui Lin Gang , Sihoe Jennifer D. , Franco Israel , Lang Jing He , Wen Jian Guo
Published: June 2021

To determine the prevalence of bladder and bowel dysfunction (BBD) and its relationship with delayed elimination communication (EC) in children. A cross-sectional study was carried out in kindergartens and primary schools in mainland China. A total of 10,166 children ranging from 4 to 10 years old were included. A total of 10,166 valid questionnaires were collected, and 409 children were diagnosed with BBD. The overall prevalence was 4.02% (409/10,166) and decreased with age, from 6.19% at age 4 to 1.96% at age 10. With the prolonged use of disposable diapers (DDs), the commencement of usage of EC in a child was significantly put off or delayed by parents, and the prevalence of BBD amongst these children increased (P < 0.001). The prevalence of BBD among children who stopped using DDs within the first 12 months and after more than 24 months was 2.79% and 4.38% respectively. Additionally, the prevalence among children who started EC within 12 months after birth and those who never engaged in EC was 1.36% and 15.71% respectively. Early introduction of EC and weaning of DD usage has a positive correlation with lower prevalence of BBD in children in China.
Dendritic spines are lost in clusters in Alzheimer’s disease
Authors: Mijalkov Mite , Volpe Giovanni , Fernaud-Espinosa Isabel , DeFelipe Javier , Pereira Joana B. , Merino-Serrais Paula
Published: June 2021

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by a deterioration of neuronal connectivity. The pathological accumulation of tau in neurons is one of the hallmarks of AD and has been connected to the loss of dendritic spines of pyramidal cells, which are the major targets of cortical excitatory synapses and key elements in memory storage. However, the detailed mechanisms underlying the loss of dendritic spines in individuals with AD are still unclear. Here, we used graph-theory approaches to compare the distribution of dendritic spines from neurons with and without tau pathology of AD individuals. We found that the presence of tau pathology determines the loss of dendritic spines in clusters, ruling out alternative models where spine loss occurs at random locations. Since memory storage has been associated with synaptic clusters, the present results provide a new insight into the mechanisms by which tau drives synaptic damage in AD, paving the way to memory deficits through alterations of spine organization.
High-performance dialyzers and mortality in maintenance hemodialysis patients
Authors: Abe Masanori , Masakane Ikuto , Wada Atsushi , Nakai Shigeru , Kanda Eiichiro , Nitta Kosaku , Nakamoto Hidetomo
Published: June 2021

Few data are available regarding the association of dialyzer type with prognosis. In Japan, dialyzers are classified as types I, II, III, IV, and V based on β2-microglobulin clearance rates of < 10, < 30, < 50, < 70, and ≥ 70 mL/min, respectively. We investigated the relationship of the 5 dialyzer types with 1-year mortality. This nationwide cohort study used data collected at the end of 2008 and 2009 by the Japanese Society for Dialysis Therapy Renal Data Registry. We enrolled 203,008 patients on maintenance hemodialysis who underwent hemodialysis for at least 1 year and were managed with any of the 5 dialyzer types. To evaluate the association of dialyzer type with 1-year all-cause mortality, Cox proportional hazards models and propensity score-matched analyses were performed. After adjustment of the data with clinicodemographic factors, the type I, II, and III groups showed significantly higher hazard ratios (HRs) than the type IV dialyzers (reference). After adjustment for Kt/V and β2-microglobulin levels, the HRs were significantly higher in the type I and II groups. After further adjustment for nutrition- and inflammation-related factors, the HRs were not significantly different between the type IV and type I and II groups. However, type V dialyzers consistently showed a significantly lower HR. With propensity score matching, the HR for the type V dialyzer group was significantly lower than that for the type IV dialyzer group. Additional long-term trials are required to determine whether type V dialyzers, which are high-performance dialyzers, can improve prognosis.
Author Correction: Genetic analysis and QTL mapping of yield and fruit traits in bitter gourd (Momordica charantia L.)
Authors: Rao P. Gangadhara , Behera T. K. , Gaikwad Ambika B. , Munshi A. D. , Srivastava Arpita , Boopalakrishnan G. , Vinod
Published: June 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The impact of socio-demographic factors on the survival of cancer patients in Zimbabwe
Authors: Okorie Idika E. , Moyo Ricardo , Nadarajah Saralees
Published: June 2021

We provide a survival analysis of cancer patients in Zimbabwe. Our results show that young cancer patients have lower but not significant hazard rate compared to old cancer patients. Male cancer patients have lower but not significant hazard rate compared to female cancer patients. Race and marital status are significant risk factors for cancer patients in Zimbabwe.
Antibody-dependent enhancement representing in vitro infective progeny virus titer correlates with the viremia level in dengue patients
Authors: Yamanaka Atsushi , Imad Hisham Ahmed , Phumratanaprapin Weerapong , Phadungsombat Juthamas , Konishi Eiji , Shioda Tatsuo
Published: June 2021

Dengue virus (DENV) causes dengue fever (DF) and dengue hemorrhagic fever in humans. Some DF patients suddenly develop severe symptoms around the defervescent period. Although the pathogenic mechanism of the severe symptoms has not been fully elucidated, the viremia level in the early phase has been shown to correlate with the disease severity. One of the hypotheses is that a phenomenon called antibody-dependent enhancement (ADE) of infection leads to high level of viremia. To examine the plausibility of this hypothesis, we examined the relationship between in vitro ADE activity and in vivo viral load quantity in six patients with dengue diseases. Blood samples were collected at multiple time points between the acute and defervescent phases, and the balance between neutralizing and enhancing activities against the autologous and prototype viruses was examined. As the antibody levels against DENV were rapidly increased, ADE activity was decreased over time or partially maintained against some viruses at low serum dilution. In addition, positive correlations were observed between ADE activity representing in vitro progeny virus production and viremia levels in patient plasma samples. The measurement of ADE activity in dengue-seropositive samples may help to predict the level of viral load in the subsequent DENV infection.
The role of pattern electroretinograms and optical coherence tomography angiography in the diagnosis of normal-tension glaucoma
Authors: Lee Sang Yeop , Son Nak-Hoon , Bae Hyoung Won , Seong Gong Je , Kim Chan Yun
Published: June 2021

In this study, we investigated the correlation between pattern electroretinogram (PERG) and optical coherence tomography angiography (OCTA) parameters for diagnosis in patients with normal-tension glaucoma (NTG). Forty-nine normal individuals (49 eyes) and 60 patients with NTG (60 eyes) were enrolled. OCTA and PERG parameters, such as macular vessel density (VD) and the amplitude of N35–P50 and P50–N95, were measured. Correlation analyses were performed between the parameters, and the area under the curve (AUC) was used to identify their diagnostic ability for NTG. Macular VD and the amplitude of N35–P50 and P50–N95 showed significant differences between the normal individuals and patients with NTG. Correlation between P50 and N95 amplitude and macular VD was significant in the normal and early glaucoma groups. Macular VD showed a higher AUC value (0.730) than that of P50–N95 amplitude (0.645) in the early glaucoma group. In the moderate to severe glaucoma group, the AUC value of the amplitude of P50–N95 (0.907) was higher than that of macular VD (0.876). The results indicate that PERG and OCTA parameters may identify glaucoma in its early stage, based on the severity of glaucomatous damage in patients with NTG.
Early-phase 18F-FP-CIT and 18F-flutemetamol PET were significantly correlated
Authors: An Young-Sil , Yoon Jung Han , Son Sang Joon , Hong Chang Hyung , Lee Su Jin , Yoon Joon-Kee
Published: June 2021

Little is known about whether early-phase PET images of 18F-FP-CIT match those of amyloid PET. Here, we compared early-phase 18F-FP-CIT and 18F-flutemetamol PET images in patients who underwent both within a 1-month interval. The SUVR on early-phase 18F-FP-CIT PET (median, 0.86) was significantly lower than that of 18F-flutemetamol PET (median, 0.91, p < 0.001) for total brain regions including all cerebral lobes and central structures. This significant difference persisted for each brain region except central structures (p = 0.232). The SUVR of total brain regions obtained from early 18F-FP-CIT PET showed a very strong correlation with that of 18F-flutemetamol PET (rho = 0.80, p < 0.001). Among the kinetic parameters, only R1 showed a statistically significant correlation between the two techniques for all brain regions (rho = 0.89, p < 0.001). R1 from 18F-FP-CIT (median, 0.77) was significantly lower in all areas of the brain compared to R1 from 18F-flutemetamol PET (median, 0.81, p < 0.001).18F-FP-CIT demonstrated lower uptake in cortical brain regions than 18F-flutemetamol on early-phase PET. However, both early-phase PETs demonstrated significant correlation of uptake.
Expression of purinergic receptors on microglia in the animal model of choroidal neovascularisation
Authors: Li Lu , Liu Juejun , Xu Amin , Heiduschka Peter , Eter Nicole , Chen Changzheng
Published: June 2021

To investigate the effect of P2 receptor on microglia and its inhibitor PPADS on choroidal neovascularization. Forty CX3CR1GFP/+mice were randomly divided into 8 groups. In addition to the normal group, the rest of groups were receiving laser treatment. The retina and choroid from the second, third, fourth and fifth group of mice were taken in the 1, 4, 7, 14 days after laser treatment. The mice in the sixth and seventh group received intravitreal injection of 2 µl PPADS or PBS respectively immediately after laser treatment. The mice in the eighth group received topical application of PPADS once per day of three days. The mice in sixth, seventh and eighth group received AF and FFA examination on the fourth day after laser treatment. Immunofluorescence histochemical staining and real-time quantitative PCR were used to evaluate P2 expression and its effect on choroidal neovascularization. After laser treatment, activated microglia can express P2 receptors (P2X4, P2X7, P2Y2 and P2Y12). The expression of P2 increased on the first day after laser damage, peaked on the fourth day (tP2X4 = 6.05, tP2X7 = 2.95, tP2Y2 = 3.67, tP2Y12 = 5.98, all P < 0.01), and then decreased. After PPADS inhibition, compared with the PBS injection group, the mRNA of P2X4, P2X7, P2Y2 and P2Y12 were decreased significantly in the PPADS injection group (tP2X4 = 5.54, tP2X7 = 9.82, tP2Y2 = 3.86, tP2Y12 = 7.91, all P < 0.01) and the PPADS topical application group (tP2X4 = 3.24, tP2X7 = 5.89, tP2Y2 = 6.75, tP2Y12 = 4.97, all P < 0.01). Compared with the PBS injection group, not only the activity of microglia cells but also the leakage of CNV decreased significantly (P < 0.01) in the PPADS injection group and the PPADS topical application group. But between two PPADS groups, the leakage of CNV had no difference (P = 0.864). After laser induced CNV, activated microglia can express P2 receptors. The P2 receptor inhibitor, PPADS, can significantly affect the function of microglia and inhibit the formation of choroidal neovascularization.
CHIMs are versatile cholesterol analogs mimicking and visualizing cholesterol behavior in lipid bilayers and cells
Authors: Matos Anna L. L. , Keller Fabian , Wegner Tristan , del Castillo Carla Elizabeth Cadena , Grill David , Kudruk Sergej , Spang Anne , Glorius Frank , Heuer Andreas , Gerke Volker
Published: June 2021

Cholesterol is an essential component of cellular membranes regulating the structural integrity and fluidity of biological bilayers and cellular processes such as signal transduction and membrane trafficking. However, tools to investigate the role and dynamics of cholesterol in live cells are still scarce and often show limited applicability. To address this, we previously developed a class of imidazolium-based cholesterol analogs, CHIMs. Here we confirm that CHIM membrane integration characteristics largely mimic those of cholesterol. Computational studies in simulated phospholipid bilayers and biophysical analyses of model membranes reveal that in biologically relevant systems CHIMs behave similarly to natural cholesterol. Importantly, the analogs can functionally replace cholesterol in membranes, can be readily labeled by click chemistry and follow trafficking pathways of cholesterol in live cells. Thus, CHIMs represent chemically versatile cholesterol analogs that can serve as a flexible toolbox to study cholesterol behavior and function in live cells and organisms.
Simultaneous determination of chito-oligosaccharides in rat plasma by the LC-MS/MS method: application to a pharmacokinetic study
Authors: Zhang Pengpeng , Liu Shuai , Yang Shuang , Wang Yuanhong , Jiang Tingfu , Yu Mingming , Lv Zhihua
Published: June 2021

A simple and sensitive method for the simultaneous determination of chito-oligosaccharides (COSs) with degrees of polymerization (DPs) from 2 to 7 was developed and used for COS quantification in rat plasma.
Plant-wide systems microbiology for the wastewater industry
Authors: Cerruti Marta , Guo Bing , Delatolla Robert , de Jonge Nadieh , Hommes - de Vos van Steenwijk Aleida , Kadota Paul , Lawson Christopher E. , Mao Ted , Oosterkamp Margreet J. , Sabba Fabrizio , Stokholm-Bjerregaard Mikkel , Watson Ian , Frigon Dominic , Weissbrodt David G.
Published: June 2021

Infiltrating systems microbiology concepts in the water industry requires the development of a language of love and shared endpoints in analytical bioscience and process engineering at the (waste)water line.
Alhagi honey polysaccharides attenuate intestinal injury and immune suppression in cyclophosphamide-induced mice
Authors: Cai Gaofeng , Wu Yu , Wusiman Adelijiang , Gu Pengfei , Mao Ningning , Xu Shuwen , Zhu Tianyu , Feng Zian , Liu Zhenguang , Wang Deyun
Published: June 2021

Cyclophosphamide (CY), extensively used as an anti-cancer agent, could cause diverse side effects, such as immunosuppression and intestinal barrier damage.
Anti-osteoporosis effect and purification of peptides with high calcium-binding capacity from walnut protein hydrolysates
Authors: Sun Xiaodong , Ruan Shiyan , Zhuang Yongliang , Sun Liping
Published: June 2021

The walnut protein hydrolysate (WPH) was prepared via simulated gastrointestinal digestion.
Improved performance of lithium–sulfur batteries by employing a sulfonated carbon nanoparticle-modified glass fiber separator
Authors: Ponnada Srikanth , Kiai Maryam Sadat , Gorle Demudu Babu , Nowduri Annapurna
Published: June 2021

Lithium–sulfur batteries with novel sulfonated coating glass fiber separator with high energy density and theoretical capacity.
The enhanced water splitting activity of a ZnO-based photoanode by modification with self-doped lanthanum ferrite
Authors: Long Xuefeng , Wang Tong , Jin Jun , Zhao Xinhong , Ma Jiantai
Published: June 2021

In this work, the Fe self-doped LaFeO3 film modification has double advantages in charge tranfer behavior of composite ZnO-based photoanode. The target photoanode obtained excellent PEC water oxidation properties.
Deuteration mechanistic studies of hydrogenase mimics
Authors: Gómez-Gallego Mar , Sierra Miguel A.
Published: June 2021

The role of deuterium in disentangling key steps of the mechanisms of H2 activation by mimics of hydrogenases is presented. These studies have allowed to a better understanding of the mode of action of the natural enzymes and their mimics.
Recent developments in the difunctionalization of alkenes with C–N bond formation
Authors: Chen Xiang , Xiao Fang , He Wei-Min
Published: June 2021

Various alkene difunctionalization reactions involving nitridization, diamination, azidation, oxyamination, carboamination, aminohalogenation, and nitration are introduced in this review.
Methionine epimerization in cyclic peptides
Authors: Jadhav Pramodkumar D. , Shen Jianheng , Burnett Peta-Gaye , Yang Jian , Sammynaiken Ramaswami , Reaney Martin J. T.
Published: June 2021

One step regioselective methionine epimerization in cyclic peptides followed by selective functionalization leads to chemical novelty.
Highly-active platinum nanoparticle-encapsulated alumina-doped resorcinol–formaldehyde carbon composites for asymmetric hydrogenation
Authors: Yao Wei , Zhang Na , Xiong Renjie , Kankala Ranjith Kumar , Liu Yongjun , Wang Shile , Zhang Xueqin , McBreen Peter H.
Published: June 2021

Alumina-doped resorcinol–formaldehyde carbon supported Pt nanoparticles were synthesized and employed in asymmetric hydrogenation with high enantioselectivity, good reusability, and unprecedentedly high TOF.
Chiral assembly of organic luminogens with aggregation-induced emission
Authors: Liu Chenchen , Yang Jun-Cheng , Lam Jacky W. Y. , Feng Hai-Tao , Tang Ben Zhong
Published: June 2021

This review highlights the recent development of chiral materials with aggregation-induced emission properties, including their molecular structures, self-assembly and functions.
Thermal- and light-responsive programmable shape-memory behavior of liquid crystalline polyurethanes with pendant photosensitive groups
Authors: Shen Wenbo , Liu Jiaoshi , Du Bin , Zhuo Haitao , Chen Shaojun
Published: June 2021

A liquid crystalline polyurethane bearing side-chain photosensitive moieties prepared via the quaternization reaction exhibits thermal- and light-responsive programmable shape-memory behavior.
A tailored graft-type polymer as a dopant-free hole transport material in indoor perovskite photovoltaics
Authors: Opoku Henry , Kim Yun Hoo , Lee Ji Hyeon , Ahn Hyungju , Lee Jae-Joon , Baek Se-Woong , Jo Jea Woong
Published: June 2021

A new graft-type polymer which exhibits dual functionality of efficient charge transport and interfacial passivation was synthesized as a dopant-free hole transport material for indoor perovskite photovoltaics.
High-entropy oxynitride as a low-bandgap and stable photocatalyst for hydrogen production
Authors: Edalati Parisa , Shen Xiao-Feng , Watanabe Motonori , Ishihara Tatsumi , Arita Makoto , Fuji Masayoshi , Edalati Kaveh
Published: June 2021

High-entropy oxynitride photocatalysts have the advantages of high-etropy alloys (high stability) and of oxynitrides (narrow bandgap).
Correction: Performance optimization and fast rate capabilities of novel polymer cathode materials through balanced electronic and ionic transport
Authors: Gannett Cara N. , Peterson Brian M. , Melecio-Zambrano Luis , Trainor Colleen Q. , Fors Brett P. , Abruña Héctor D.
Published: June 2021

Correction for ‘Performance optimization and fast rate capabilities of novel polymer cathode materials through balanced electronic and ionic transport’ by Cara N. Gannett et al., J. Mater. Chem. A, 2021, 9, 5657–5663, DOI: 10.1039/D0TA11099J.
Machine morality, moral progress, and the looming environmental disaster
Authors: Kenward Ben , Sinclair Thomas
Published: June 2021

The creation of artificial moral systems requires making difficult choices about which of varying human value sets should be instantiated. The industry‐standard approach is to seek and encode moral consensus. Here the authors' argue, based on evidence from empirical psychology, that encoding current moral consensus risks reinforcing current norms, and thus inhibiting moral progress. However, so do efforts to encode progressive norms. Machine ethics is thus caught between a rock and a hard place. The problem is particularly acute when progress beyond prevailing moral norms is particularly urgent, as is currently the case due to the inadequacy of prevailing moral norms in the face of the climate and ecological crisis.
Computing morality: Synthetic ethical decision making and behaviour
Authors: Crook Nigel , Nugent Selin , Rolf Matthias , Baimel Adam , Raper Rebecca
Published: June 2021

We find ourselves at a unique point of time in history. Following over two millennia of debate amongst some of the greatest minds that ever existed about the nature of morality, the philosophy of ethics and the attributes of moral agency, and after all that time still not having reached consensus, we are coming to a point where artificial intelligence (AI) technology is enabling the creation of machines that will possess a convincing degree of moral competence. The existence of these machines will undoubtedly have an impact on this age old debate, but we believe that they will have a greater impact on society at large, as AI technology deepens its integration into the social fabric of our world. The purpose of this special issue on Computing Morality is to bring together different perspectives on this technology and its impact on society. The special issue contains four very different and inspiring contributions.
Synthesis design of dual‐path coupled line circular ring resonator filter with tunable characteristic impedances and transmission zeros
Authors: Nordin Siti Aminah , Hairuddin Muhammad Asraf , Khirul Ashar Nur Dalila , Khan Zuhani Ismail
Published: June 2021

A dual‐path coupled‐line circular ring resonator filter synthesis is presented. The topology comprises identical coupled lines in series duplicated to form dual‐path coupled‐line interconnections. A bandpass response of nth order equal to (n/2) + 1, corresponds to controllable transmission zeros (TZs) found on both sides of the passband by varying the values of the even‐ and odd‐mode impedances of the coupled lines, denoted Zoe and Zoo, respectively. Concerning the efficiency of controllable electrical characteristics of the resonator filter, such as in‐band matching level, high selective response, and wide bandwidth, and fixing the position of the TZ frequencies, the proposed method using asymmetrical quarter‐wavelength coupled lines in a circular ring resonator filter is superior to existing methods. Ultimately, the proposed bandpass filter is implemented on contrast dielectric substrate FR‐4 and Taconic TRF‐45 substrates using a planar form of microstrip technology to verify the synthesis equation. The measurement results indicate that the filter achieved more than 40% fractional bandwidth with excellent in‐band matching levels and a controllable filter order. Both measurement and simulation results are in good agreement regarding return and insertion loss values, thus validating the proposed designs.