bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and Safety of Tramadol for Knee or Hip Osteoarthritis: A Systematic Review and Network Meta‐Analysis of Randomized Controlled Trials
Authors: Zhang Xiurui , Li Xiaoxiao , Xiong Yilin , Wang Yilun , Wei Jie , Zeng Chao , Sha Tingting , Lei Guanghua
Published: July 2021

Objective

To examine efficacy and safety of tramadol for knee or hip osteoarthritis (OA).

Methods

PubMed, Embase, Cochrane Library, and Web of Science were searched up to May 2020 for randomized controlled trials (RCTs) comparing any of the following interventions: tramadol 100 mg/day, 200 mg/day, and 300 mg/day, and placebo for knee or hip OA. Pain and function were measured at or near 12 weeks for efficacy. Gastrointestinal, cardiovascular, and central nervous system (CNS) adverse events (AEs), and withdrawals were measured for safety. Bayesian network meta‐analysis was conducted.

Results

Six RCTs (3,611 participants) were included. Tramadol 100 mg/day (standardized mean difference [SMD] –0.16 [95% confidence interval (95% CI) –0.34, 0.00]), 200 mg/day (SMD –0.21 [95% CI –0.37, –0.06]), and 300 mg/day (SMD –0.30 [95% CI –0.48, –0.14]) were statistically more effective than placebo in pain relief, but only tramadol 300 mg/day was better than placebo in functional improvement (SMD –0.24 [95% CI –0.47, –0.03]). Tramadol 100 mg/day (relative risk [RR] 2.29 [95% credible interval (CrI) 1.22, 4.25]), 200 mg/day (RR 4.35 [95% CrI 2.31, 8.01]), and 300 mg/day (RR 6.02 [95% CrI 3.22, 11.1]) involved a higher risk of gastrointestinal AEs. Similarly, tramadol 100–300 mg/day showed a higher risk of CNS AEs and withdrawals. However, the risk of cardiovascular AEs remained unclear.

Conclusion

Only tramadol 300 mg/day showed minimal improvement in pain and function but with increasing AEs compared with placebo. Tramadol may not be sufficiently recommended for knee or hip OA based on the presented evidence, especially in patients with the risk of gastrointestinal and CNS AEs.
Engineering Microdomains of Oxides in High‐Entropy Alloy Electrodes toward Efficient Oxygen Evolution
Authors: Chen Zheng‐Jie , Zhang Tao , Gao Xiao‐Yu , Huang Yong‐Jiang , Qin Xiao‐Hui , Wang Yi‐Fan , Zhao Kai , Peng Xu , Zhang Cheng , Liu Lin , Zeng Ming‐Hua , Yu Hai‐Bin
Published: July 2021

One important goal of the current electrocatalysis is to develop integrated electrodes from the atomic level design to multilevel structural engineering in simple ways and low prices. Here, a series of oxygen micro‐alloyed high‐entropy alloys (O‐HEAs) is developed via a metallurgy approach. A (CrFeCoNi)97O3 bulk O‐HEA shows exceptional electrocatalytic performance for the oxygen evolution reaction (OER), reaching an overpotential as low as 196 mV and a Tafel slope of 29 mV dec−1, and with stability longer than 120 h in 1 m KOH solution at a current density of 10 mA cm−2. It is shown that the enhanced OER performance can be attributed to the formation of island‐like Cr2O3 microdomains, the leaching of Cr3+ ions, and structural amorphization at the interfaces of the domains. These findings offer a technological‐orientated strategy to integrated electrodes.
Boosting the Electrochemical Performance of All‐Solid‐State Batteries with Sulfide Li6PS5Cl Solid Electrolyte Using Li2WO4‐Coated LiCoO2 Cathode
Authors: Sun Zhen , Lai Yanqing , lv Na , Hu Yaqi , Li Bingqin , Jing Shenghao , Jiang Liangxing , Jia Ming , Li Jie , Chen Shiyou , Liu Fangyang
Published: July 2021

Solid‐state batteries exhibit promising prospects due to their potential in terms of safety and energy density. Sulfide solid electrolytes have received much attention due to their high ionic conductivity (about 10−2 S cm−1). However, high side reactions between solid sulfide electrolytes and oxide cathodes, such as LiCoO2, have hampered the development of all‐solid‐state sulfide batteries. Here, first‐principles calculations and experiments are combined to demonstrate a novel protective layer to cope with the Li6PS5Cl electrolyte and LiCoO2 cathode interface problem. By uniformly coating LiCoO2 with a layer of Li2WO4, the interfacial resistance (the 100th cycle) between the sulfide electrolyte and LiCoO2 is reduced to about 68 Ω cm2, which is nearly 15 times lower than the premodified 1061 Ω cm2. The 2 wt% Li2WO4‐coated LiCoO2(2%LWO‐LCO)/Li6PS5Cl/Li‐In all‐solid‐state battery exhibits satisfactory capacity and excellent cycling stability at room temperature (93% capacity retention after 100 cycles). Furthermore, the ab initio molecular dynamics based on the Perdew, Burke, and Ernzerhof density functional theory calculations show that Li2WO4 can effectively prevent the diffusion of Co and O from LiCoO2 into the Li6PS5Cl solid electrolyte. It is shown that molecular dynamics help predict the interfacial reactions in all‐solid‐state sulfide batteries.
Modeling of Deformable Cell Separation in a Microchannel with Sequenced Pillars
Authors: Hymel Scott J. , Fujioka Hideki , Khismatullin Damir B.
Published: July 2021

Embedded pillar microstructures are an efficient approach for controlling and sculpting shear flow in a microchannel but have not yet demonstrated to be effective for deformability‐based cell separation and sorting. Although simple pillar configurations (lattice, line sequence) work well for size‐based separation of rigid particles, these have a low separation efficiency for circulating cells. The objective of this study is to optimize sequenced microstructures for separation of deformable cells. This is achieved by numerical analysis of pairwise cell migration in a microchannel with multiple pillars, where size, longitudinal spacing, and lateral location as well as the cell elasticity and size vary. This study reveals two basic pillar configurations optimized for deformability‐based separation: “duplet” that consists of two closely spaced pillars positioned far below the centerline and above the centerline halfway to the wall; and “triplet” composed of three widely spaced pillars located below, above and at the centerline, respectively. The duplet configuration is well suited for deformable cell separation in short channels, whereas the triplet or a combination of duplets and triplets provides even better separation in long channels. These optimized pillar microstructures can dramatically improve microfluidic methods for sorting and isolation of blood and rare circulating tumor cells.
Outcome assessment of medical education fellowships in emergency medicine
Authors: Jordan Jaime , Ahn James , Diller David , Riddell Jeffrey , Pedigo Ryan , Tolles Juliana , Gisondi Michael A.
Published: July 2021

Objectives

Medical education fellowships in emergency medicine (EM) provide training in teaching, assessment, educational program administration, and scholarship. The longitudinal impact of this training is unknown. Our objective was to characterize the career outcomes of medical education fellowship graduates.

Methods

We solicited curriculum vitae (CV) from graduates of U.S. EM education fellowships by email. We abstracted data from CVs with a standard instrument that included program characteristics, employment history, leadership positions, awards, and scholarly productivity. We calculated and reported descriptive statistics.

Results

A total of 71 of 91 (78%) graduates participated. Thirty‐three completed a 1‐year fellowship and 38 completed a 2‐year fellowship. Nineteen (27%) completed an advanced degree during fellowship. Median (range) graduation year was 2016 (1997–2020). The majority, 63 of 71 (89%), work in an academic setting. Graduates held leadership positions in continuing medical education, graduate medical education, and undergraduate medical education. Forty‐eight (68%) served on national medical education committees. The mean ± SD number of national medical education awards was 1.27 ± 2.03. The mean ± SD number of national medical education presentations was 7.63 ± 10.83. Graduates authored a mean ± SD of 3.63 ± 5.81 book chapters and a mean ± SD of 4.99 ± 6.17 peer‐reviewed medical education research publications. Ten (14%) served on journal editorial boards, 34 (48%) were journal reviewers, and 31 (44%) had received a medical education grant.

Conclusion

EM medical education fellowship graduates are academically productive and hold education leadership positions.
A New and Effective One‐Pot Synthesis of Polysubstituted Carbazoles Starting from β‐Nitro‐β,γ‐Unsaturated‐Ketones and Indoles
Authors: Lupidi Gabriele , Bassetti Benedetta , Ballini Roberto , Petrini Marino , Palmieri Alessandro
Published: July 2021

Herein, we report a new one‐pot synthesis of polysubstituted carbazoles starting from β‐nitro‐β,γ‐unsaturated‐ketones and indoles. The process is based on a Friedel‐Crafts reaction of indoles to nitroolefins supported by 2,2,2‐trifluoroethanol (TFE) followed by an acidic‐promoted and microwave‐assisted intramolecular cyclization, that involves the elimination of both nitrous acid and water molecules. Products were obtained in satisfactory to good overall yields (55–78%).
One‐step Annulation/Chlorination towards Chlorinated Diphenanthro, Dibenzophenanthro, and Dichrysenothiophens
Authors: Venkateswarlu Samala , Kumar Sushil , Tao Yu‐Tai
Published: July 2021

One‐step Scholl and chlorination reactions on fourteen polyaryl thiophenes offered regioselective preparations of chlorinated diphenanthro‐, dibenzophenanthro‐, dichrysenothiophenes derivatives. Specific annulating patterns and the positions of chlorination in these polyheteroaromatics were confirmed by single‐crystal X‐ray analyses for the selected ones. Despite being twisted in their molecular frameworks, these derivatives packed into near‐perfect face‐to‐face styles.
Stressful social environment and financial strain drive depressive symptoms, and reveal the effects of a FKBP5 variant and male sex, in African Americans living in Tallahassee
Authors: Fuller Kia , Gravlee Clarence C. , McCarty Christopher , Mitchell Miaisha M. , Mulligan Connie J.
Published: July 2021

Objectives

The World Health Organization estimates that almost 300 million people suffer from depression worldwide. African Americans are understudied for depression‐related phenotypes despite widespread racial disparities. In our study of African Americans, we integrated information on psychosocial stressors with genetic variation in order to better understand how these factors associated with depressive symptoms.

Methods

Our research strategy combined information on financial strain and social networks with genetic data to investigate variation in symptoms of depression (CES‐D scores). We collected self‐report data on depressive symptoms, financial strain (difficulty paying bills) and personal social networks (a model of an individual's social environment), and we genotyped genetic variants in five genes previously implicated in depressive disorders (HTR1a, BDNF, GNB3, SLC6A4, and FKBP5) in 128 African Americans residing in Tallahassee, Florida. We tested for direct and gene–environment interactive effects of the psychosocial stressors and genetic variants on depressive symptoms.

Results

Significant associations were identified between high CES‐D scores and a stressful social environment (i.e., a high percentage of people in participants' social network who were a source of stress) and high financial strain. Only one genetic variant (rs1360780 in FKBP5) was significantly associated with CES‐D scores and only when psychosocial stressors were included in the model; the T allele had an additive effect on depressive symptoms. Sex was also significantly associated with CES‐D score in the model with psychosocial stressors and genetic variants; males had higher CES‐D scores. No significant interactive effects were detected.

Conclusions

A stressful social environment and material disadvantage increase depressive symptoms in the study population. Additional associations with FKBP5 and male sex were revealed in models that included both psychosocial and genetic data. Our results suggest that incorporating psychosocial stressors may empower future genetic association studies and help clarify the biological consequences of social and financial stress.
Biologics for chronic rhinosinusitis with nasal polyps: Economics and ethics
Authors: Roland Lauren T. , Regenberg Alan , Luong Amber U. , Wise Sarah K. , Toskala Elina , Lam Kent K. , Levy Joshua M. , Franzese Christine B. , Smith Kristine , Kim Jean
Published: July 2021

Biologics have recently been approved for use in chronic rhinosinusitis with nasal polyps patients. While effective in controlling disease on subjective and objective short‐term outcome measures, limited data suggest that biologics have the potential to be used long term. The current wholesale acquisition costs for biologics are quite high. Widespread, prolonged use of these medications may create a large burden to our healthcare system. Cost‐effectiveness analyses, particularly for specific patient cohorts, are needed to determine appropriate use of these medications. The ethics of patient preference of various treatment options, counseling regarding side effect profiles, and healthcare economics also need to be addressed.
Phage‐Derived and Aberrant HaloTag Peptides Immobilized on Magnetic Microbeads for Amperometric Biosensing of Serum Autoantibodies and Alzheimer's Disease Diagnosis
Authors: Valverde Alejandro , Montero‐Calle Ana , Arévalo Beatriz , San Segundo‐Acosta Pablo , Serafín Verónica , Alonso‐Navarro Miren , Solís‐Fernández Guillermo , Pingarrón José M. , Campuzano Susana , Barderas Rodrigo
Published: July 2021

An electrochemical biosensing platform for serum autoantibodies (AAbs) detection is reported in this work, exploiting for the first time six Alzheimer's disease (AD)‐specific phage‐derived and frameshift aberrant HaloTag peptides as receptors, immobilized on magnetic microbeads (MBs) surface and captured on disposable electrodes to perform amperometric detection. Operational analytical characteristics and clinical diagnostic ability of the bioplatform were probed in optimized key experimental conditions by analysing serum AAbs of AD patients and healthy subjects. The value of 100 % obtained for AUC, sensitivity, and selectivity from the all peptides combined ROC curve, indicate full AD‐diagnostic capability of the methodology, which was further implemented, as proof of concept, in a POC multiplexing platform to detect the signature in a single test over clinically actionable times (1 h 15 min), opening great promise for the type of diagnosis and AD patients’ monitoring follow‐up currently pursued.
Decrease in viscosity of styrene‐isoprene‐styrene filling systems induced by micro elastic phase
Authors: Chi Houfang , Han Hui , Tian Guannan , Luo Hengyu , Hong Song , Li Junyu , Hu Haiqing
Published: July 2021

The melt viscosity of triblock copolymer styrene‐isoprene‐styrene (SIS) filling systems decreased in some sense by adding 0.1 wt% fillers. The types of fillers included both nano‐ and non‐nano fillers. It was insufficient to explain the phenomenon of viscosity reduction only from the view of nanoscale effects of particles. The results of SAXS and TEM enabled us to relate this behavior to the damage of PS microphase in SIS. The PS microphase acted as a strong entanglement point in the SIS system. When it was damaged, the entanglement among molecular chains weakened greatly, resulting in a decrease in viscosity. The dynamic viscoelasticity (complex viscosity, storage modulus, and loss modulus) of the filling systems was also studied.
Role of autophagy in midgut stem cells of silkworm Bombyx mori, during larval–pupal metamorphosis
Authors: Gunay Busra , Goncu Ebru
Published: July 2021

Autophagy is a critical mechanism for the self‐renewal, proliferation, and differentiation of stem cells. Bombyx mori midgut has stem cells that play a role in the regeneration of the larval epithelium in larval stages and the formation of the pupal midgut epithelium during larval–pupal metamorphosis. In this study, the role of the autophagy mechanism in midgut stem cells during the formation of the pupal midgut was investigated. For this purpose, two different doses of autophagy inhibitor chloroquine were administered to B. mori larvae on days 7 and 8 of the fifth larval stage. Morphological changes during the formation process of the pupal epithelium, expression levels of autophagy‐related genes Atg8 and Atg12 in stem cells, and the amounts of lysosomal enzyme acid phosphatase were determined after the application. The obtained findings were evaluated in comparison with the control groups. Abnormalities in the formation of the pupal midgut after inhibition of autophagy showed the significance of the autophagy mechanism during this period.
Substantial changes in the probability of future annual temperature extremes
Authors: Slater Ross , Freychet Nicolas , Hegerl Gabriele
Published: July 2021

Extreme temperature events causing significant environmental and humanitarian impacts are expected to increase in frequency and magnitude due to global warming. The latest generation of climate model projections, Coupled Model Intercomparison Project Phase Six (CMIP6), provides a new and improved database to investigate change in future daily scale extreme temperature events. This study examines the changes in 1, 3, and 5 day averaged annual maximum temperature in four large CMIP6 ensembles. It analyses, using a generalized extreme value (GEV) method, the change in extreme daily mean temperatures at 1.5 and 2°C of global warming, levels highlighted by the 2016 Paris Agreement, and additionally at 3°C. Extremely hot events are characterized using the annual maxima of daily near surface air temperature in the SSP370 scenario. Global changes in the mode of the distributions (location parameter) follow long‐term summer warming and show very similar spatial patterns. Changes in variability (scale parameter) show a clear trend of increases over the tropics and decreases over higher latitudes, while changes to the tails of distributions (shape parameter) show less globally consistent trends but clear signals over the Arctic sea ice, behaviour also seen in variability. Risk ratios (RRs) indicating the change in probability of hot daily extremes that currently have a 10 year return period increase globally with mean temperature change, with greater increases over the tropics. Globally averaged changes in RR over land range from 3.1–3.6 to 7.9–8.3 for 1.5 and 3°C of warming, respectively. For the latter case, this indicates previously rare, once‐in‐a‐decade summer extremes will occur almost annually in the future under high warming.
Rhodol‐derived turn‐on fluorescent probe for copper ions with high selectivity and sensitivity
Authors: Zeng Xiaodan , Gao Song , Jiang Cheng , Duan Qingxia , Ma Mingshuo , Liu Zhigang , Chen Jie
Published: July 2021

A new rhodol‐derived fluorescent probe 1 with picolinate as the recognition receptor was designed and simply synthesized using a one‐step reaction. With the concentration of added Cu2+ increases, it gradually turns pink, so the effect of naked eye detection can be achieved. The detection limit of probe 1 for Cu2+ is 42 nM, and the linear detection range was 0–2 μM. The experimental results showed that 1 was a fluorescent probe with high selectivity, good water solubility, and high sensitivity to Cu2+.

Probe 1 was successfully applied in cell imaging experiments and can detect the concentration of Cu2+ in water samples. All these indicate that probe 1 has the potential to be applied to the detection of Cu2+ concentration in the real environment.
Estrogen receptor‐low breast cancer: Biology chaos and treatment paradox
Authors: Yu Ke‐Da , Cai Yu‐Wen , Wu Song‐Yang , Shui Ruo‐Hong , Shao Zhi‐Ming
Published: July 2021

Hormone receptor testing mainly serves the purpose of guiding treatment choices for breast cancer patients. Patients with estrogen receptor (ER)‐positive breast cancers show significant response to endocrine therapy. However, the methods to define ER status and eligibility for treatment remain controversial. Despite recent guidelines considering staining ≥1% of tumor nuclei by immunohistology as ER‐positive, it has raised concerns on the benefit of endocrine therapy for tumors with ER 1%‐10% expression, termed “ER‐low positive”. This subgroup accounts for 3% to 9% of all patients and is likely to have unique molecular features, and therefore distinct therapeutic response to endocrine therapy compared with ER‐high positive tumors. The latest guidelines did not provide detailed descriptions for those patients, resulting in inconsistent treatment strategies. Consequently, we aimed to resolve this dilemma comprehensively. This review discusses molecular traits and recent ER‐low positive breast cancer innovations, highlighting molecular‐targeted treatment rather than traditional unified endocrine therapy for future basic and clinical research.
Parallel realistic visualization of particle‐based fluid
Authors: Chen Qiaorui , Zhang Shuai , Zheng Yao
Published: July 2021

In this article, an entirely parallel pipeline for creating realistic visualization of particle‐based fluid is presented, which significantly improves surface reconstruction and foam generation performance. Firstly, we develop a spatial hashing grid‐based strategy. Based on this strategy, a novel narrow band surface reconstruction method is presented, which could even discard the detection of surface particles methods to achieve the effect of accurate identification of surface vertices. And a novel narrow band like diffuse particle classification method is proposed, which ensures less memory access and less computation. Furthermore, in order to obtain a best performance, we put forward several parallel schemes to avoid potential race conditions and invalid threads. Experiments are conducted to verify that our developed method and code efficiently improve the particle‐based visualization.
Forward Chemical Genetic Screen for Oxygen‐Dependent Cytotoxins Uncovers New Covalent Fragments that Target GPX4
Authors: Cordon Marie B. , Jacobsen Kristian M. , Nielsen Cecilie S. , Hjerrild Per , Poulsen Thomas B.
Published: July 2021

The identification of growth inhibitory compounds with the ability to selectively target the cellular oxygenation state may be of therapeutic interest. Here, a phenotypic screen of a covalent fragment library revealed diverse compounds containing propiolamide warheads with selective toxicity for liver cancer cells in normoxic conditions. Target identification and validation through CETSA and direct pulldown experiments demonstrated that several compounds target glutathione peroxidase 4 (GPX4) and induce ferroptotic cell death. Although being an oxidative cell death mechanism, ferroptosis can be induced also under hypoxic conditions. Prompted by the selective toxicity discovered in the screen, we mapped the oxygen‐dependence of several ferroptosis‐inducing compounds across three different cell lines. These studies revealed combinations with notable reductions in sensitivity under hypoxic conditions. These observations are mechanistically interesting and may be relevant for the use of ferroptosis‐inducers as anti‐cancer agents.
Origin of Stability and Inhibition of Cooperative Alkyne Hydrofunctionalization Catalysts
Authors: Chapple Devon E. , Boyle Paul D. , Blacquiere Johanna M.
Published: July 2021

New entries to the [Ru(Cp/Cp*)(PR2NR′2)(MeCN)]PF6 catalyst family were synthesized, including a Cp complex (R=Cy; R′=Ph) and two Cp* complexes (R=Cy, Ph; R′=Ph). These and other derivatives were used for the intramolecular hydroamination of 2‐ethynylaniline to elucidate trends in catalytic lifetime and rate. The readily accessible [Ru(Cp)(PCy2NPh2)(MeCN)]PF6 derivative showed comparable lifetime to [Ru(Cp)(Pt−Bu2NPh2)(MeCN)]PF6, the previous optimal catalyst. Donor‐free ‘active’ catalysts, [Ru(Cp/Cp*)(PCy2NPh2)]PF6, were prepared and their thermal stability was assessed. The relatively high stability of the Cp derivative was explained by the capacity of the PCy2NPh2 ligand to coordinate in a κ3‐(P,P,Ar) mode, which protects the low‐coordinate species. This coordination mode is inaccessible with the Cp* derivative. Additionally, [Ru(Cp*)(PCy2NPh2)]PF6 readily activated the C−Cl bond of the solvent dichloromethane. Variable time normalization analysis (VTNA) revealed that the indole product inhibited the catalyst [Ru(Cp)(PCy2NPh2)(MeCN)]PF6, which slowed catalytic rates.
Additive hazard regression of event history studies with intermittently measured covariates
Authors: Sun Xiaowei , Song Xinyuan , Sun Liuquan
Published: July 2021

In the analysis of event history data, some covariates may vary over time. Such covariates are typically sparse and measured intermittently in many longitudinal settings. This article considers additive hazard regression models with intermittently measured covariates and proposes kernel weighting methods to estimate the model parameters. Two scenarios are investigated: half kernel estimation for data in which observation ceases at an event, and full kernel estimation in which observation may continue after an event, such as in recurrent event data. The asymptotic properties of the resulting estimators are established. Simulation studies show that the proposed estimators perform satisfactorily. An application to a study on primary biliary cirrhosis is illustrated.
Novel Phenyl‐Based Bis‐quaternary Ammonium Compounds as Broad‐Spectrum Biocides
Authors: Frolov Nikita A. , Fedoseeva Ksenia A. , Hansford Karl A. , Vereshchagin Anatoly N.
Published: July 2021

Herein we report the synthesis and microbiological evaluation of novel phenyl based bis‐quaternary ammonium compounds (bis‐QACs). Using a simple 2‐step synthetic route from dibromo‐ and dihydroxybenzenes, we obtained a structurally diverse broad panel of bis‐QACs with topologically distinct bridging connections between pyridinium heads. Selected analogs possessed potent broad‐spectrum biocidal activity against both bacterial and fungal pathogens: methicillin‐resistant Staphylococcus aureus (ATCC 43300); Escherichia coli (ATCC 25922), Klebsiella pneumonia (ATCC 700603), Acinetobacter baumannii (ATCC 19606), Pseudomonas aeruginosa (ATCC 27853), Candida albicans (ATCC 90028), Cryptococcus neoformans var. grubii (ATCC 208821). Promising compounds displayed minimum inhibitory concentrations (MIC) values ≤0.25 μg/mL alongside improved cytotoxicity and hemolytic profiles compared to modern antiseptics. Thus, synthesized bis‐QACs represent a promising class of biocides with the potential to replace existing household sanitizers.
An efficient privacy‐preserving model based on OMFTSA for query optimization in crowdsourcing
Authors: Renukadevi M. , Anita E. A. Mary , Mohana Geetha D.
Published: July 2021

Crowdsourcing is now one of the most important and transformative paradigms, with great success in a variety of application tasks. Crowdsourcing obtains knowledge and information to solve cognitive or intelligence‐intensive tasks from an evolving group of participants via the Internet. Unfortunately, providing a hard privacy guarantee and query optimization is incompatible when a higher task acceptance rate needs to be accomplished and this case is common in most existing crowdsourcing solutions. The state of art systems suffered from different complexities such as lack of crowdsourcing optimization techniques, increased cost, latency, security, and scalability issues. In this paper, we have proposed a crowdsourcing model to optimize the cost and latency, issues that occur while query optimization using the Moth Flame and Tunicate Swarm Algorithm (MF‐TSA). The TSA algorithm is added to the MF algorithm to enhance its exploitation capability and yield fast convergence. The data privacy concerns of the worker and the requestor are addressed using homomorphic encryption that simultaneously enhances the efficiency of the crowdsourcing framework. The main aim of this work is to optimize the cost and latency for query plan selection along with security. Initially, the homomorphic encryption model is used to encrypt the data. In query design, two kinds of crowd‐controlled administrators, that is, Crowd Powered Selection (CSelect) and Crowd Powered Join (CJoin) are connected for assessing query. The proposed framework utilizes MF‐TSA to optimize the selection and join queries with low cost and latency. Finally, the experimental results demonstrate better query optimization performance than other existing algorithms such as sequential, parallel, and CrowdOp.
Squaramide‐Based Self‐Associating Amphiphiles for Anion Recognition
Authors: Kumawat Lokesh K. , Wynne Conor , Cappello Emanuele , Fisher Peter , Brennan Luke E. , Strofaldi Alessandro , McManus Jennifer J. , Hawes Chris S. , Jolliffe Katrina A. , Gunnlaugsson Thorfinnur , Elmes Robert B. P.
Published: July 2021

The synthesis and characterisation of two novel self‐assembled amphiphiles (SSAs) SQS‐1 and SQS‐2 are reported. Both compounds, based on the squaramide motif, were fully soluble in a range of solvents and were shown to undergo self‐assembly through a range of physical techniques. Self‐assembly was shown to favour the formation of crystalline domains on the nanoscale but also fibrillar film formation, as suggested by SEM analysis. Moreover, both SQS‐1 and SQS‐2 were capable of anion recognition in DMSO solution as demonstrated using 1H NMR and UV/Vis absorption spectroscopy, but displayed lower binding affinities for various anions when compared against other squaramide based receptors. In more competitive solvent mixtures SQS‐1 gave rise to a colourimetric response in the presence of HPO42− that was clearly visible to the naked eye. We anticipate that the observed response is due to the basic nature of the HPO42− anion when compared against other biologically relevant anions.
Peripheral autoreactive CD8 T‐cell frequencies are too variable to be a reliable predictor of disease progression of human type 1 diabetes
Authors: Wesley Johnna D , Pfeiffer Susanne , Schneider Darius , Friedrich David , Perdue Nikole , Sehested‐Hansen Birgit , Hagopian William , von Herrath Matthias G
Published: July 2021

Objectives

The detection of a peripheral immune cell signature that specifically reflects autoimmunity in type 1 diabetes would enable the prediction and staging of disease on an individual basis. However, defining such a signature is technically challenging. Reliable interpretation of immune cell‐related biomarkers depends on their inherent variability and, to understand this variability, longitudinal analyses are required.

Methods

We performed a longitudinal observational study in which 40 individuals with elevated genetic risk of type 1 diabetes and persistent islet autoantibodies provided a blood sample every 4–6 weeks for > 1 year.

Results

Peripheral immune cell composition (T cells, NK cells and monocytes) was assessed using well‐validated flow cytometry panels and demonstrated that, while non‐antigen‐specific immune cell subsets were stable over time, autoantigen‐reactive T‐cell frequencies were highly variable in and between individuals. Neither the frequency nor phenotype of non‐antigen‐specific subsets or autoreactive CD8+ T cells associated with clinical onset of T1D.

Conclusion

The findings from the Type 1 Diabetes Longitudinal BIomarker Trial underscore the inherent challenge of evaluating changes in peripheral immune cell populations as surrogates of organ‐specific disease activity. The variability of peripheral antigen‐specific T cells precludes their use as a prognostic marker and clearly demonstrates that a reliable prognostic cell signature remains elusive.
Cardiorespiratory fitness mitigates brain atrophy and cognitive decline in adults at risk for Alzheimer's disease
Authors: Dougherty Ryan J. , Jonaitis Erin M. , Gaitán Julian M. , Lose Sarah R. , Mergen Brandon M. , Johnson Sterling C. , Okonkwo Ozioma C. , Cook Dane B.
Published: July 2021

Introduction

Cardiorespiratory fitness (CRF) may mitigate Alzheimer's disease (AD) progression. This study examined the longitudinal associations of CRF with brain atrophy and cognitive decline in a late‐middle‐aged cohort of adults at risk for AD.

Methods

One hundred ten cognitively unimpaired adults (66% female, mean age at baseline 64.2 ± 5.7 years) completed a baseline graded treadmill exercise test, two brain magnetic resonance imaging scans (over 4.67 ± 1.17 years), and two to three cognitive assessments (over 3.26 ± 1.02 years). Linear mixed effects models examined the longitudinal associations adjusted for covariates.

Results

Participants with higher baseline CRF had slower annual decline in total gray matter volume (P = .013) and cognitive function (P = .048), but not hippocampal volume (P = .426). Exploratory analyses suggested these effects may be stronger among apolipoprotein E ε4 carriers.

Discussion

CRF is a modifiable physiological attribute that may be targeted during the preclinical phase of AD in effort to delay disease progression, perhaps most effectively among those with genetic risk.
Hydromorphone and codeine concentrations in oral fluid specimens from patients receiving substitution therapy with Substitol™ (morphine sulfate)
Authors: Lierheimer Stefan , Beck Olof , Keller Thomas , Monticelli Fabio Carlo , Böttcher Michael
Published: July 2021

This study aimed to determine whether hydromorphone and codeine can be detected in oral fluid specimens following administration of Substitol™, a slow‐release formulation of morphine. This is of interest for those monitoring treatment compliance using drug testing. Oral fluid specimens collected for compliance assessment in routine clinical practice or as part of a clinical trial were subjected to quantitative analysis of hydromorphone, morphine, codeine, and 6‐acetylmorphine using highly sensitive mass spectrometric methods. Oral fluid was collected using a Greiner Bio‐One saliva collection system. Patients undergoing substitution treatment with Substitol™, methadone, or buprenorphine were included, together with patients undergoing pain treatment with hydromorphone. Hydromorphone was detected in 642 of the 663 (97%) samples from substitol‐treated patients. Concentrations were not higher in methadone‐ and buprenorphine‐treated patients who relapsed into heroin use, or in patients on hydromorphone therapy. Codeine was detected in 29% of the samples. These concentrations were lower than those in patients who had relapsed to heroin use. Clinical administration of morphine can lead to detectable concentrations of both hydromorphone and codeine in oral fluids. This should be taken into consideration when using drug testing in oral fluid samples for compliance assessment in this patient group.
Speeding‐up Thermally Activated Delayed Fluorescence in Cu(I) Complexes Using Aminophosphine Ligands
Authors: Toigo Jéssica , Farias Giliandro , Salla Cristian A. M. , Duarte Luís Gustavo Teixeira Alves , Bortoluzzi Adailton J. , Zambon Atvars Teresa Dib , de Souza Bernardo , Bechtold Ivan H.
Published: July 2021

Luminescent copper(I) complexes presenting thermally activated delayed fluorescence (TADF) have drawn attention as emitters for organic light emitting diodes (OLEDs). While the majority of ligands used have nitrogen as donor atoms, in this work, we report the synthesis and characterization of three copper(I) complexes with the diimine ligand 1,10‐phenanthroline and aminophosphine‐derived ligands containing the piperazine and N,N’‐dimethylethylenediamine to evaluate their effect into the emission properties. The photophysical studies as a function of temperature suggested TADF and phosphorescence emission, supported by detailed density functional theory (DFT) calculations. The use of aminophosphine ligands enhance the TADF decay pathway in comparison with copper complex containing the usual POP ligand. These properties, combined with the appropriate HOMO‐LUMO energy levels and thermal stability, make these compounds a promising alternative for application in OLEDs.
Additional Studies on the Electrochemical Behaviour of Three Macrolides on Pt and Carbon Based Electrodes
Authors: Veseli Albana , Švorc Ľubomír , Sopaj Flamur
Published: July 2021

The voltammetric behaviour of the macrolide based antibiotic: Erythromycin (ERT), Clarithromycin (CLA) and Azithromycin (AZT) was presented in this work. Carbon electrodes and platinum (Pt) electrode were applied as working electrodes. Cyclic voltamograms of each molecule in each electrode were recorded and similar electrochemical behaviour of macrolides was observed for all carbon based electrodes, which gave more defined current intensity peaks than platinum. Other organic compounds were tested trying to clarify electro‐active groups of macrolides. Experiments on mechanism of electrochemical reaction were performed, and studies on the influence of pH on peak current and peak potential were also carried out.
Performance of ECG‐based seizure detection algorithms strongly depends on training and test conditions
Authors: Jahanbekam Amirhossein , Baumann Jan , Nass Robert D. , Bauckhage Christian , Hill Holger , Elger Christian E. , Surges Rainer
Published: July 2021

Objective

To identify non‐EEG‐based signals and algorithms for detection of motor and non‐motor seizures in people lying in bed during video‐EEG (VEEG) monitoring and to test whether these algorithms work in freely moving people during mobile EEG recordings.

Methods

Data of three groups of adult people with epilepsy (PwE) were analyzed. Group 1 underwent VEEG with additional devices (accelerometry, ECG, electrodermal activity); group 2 underwent VEEG; and group 3 underwent mobile EEG recordings both including one‐lead ECG. All seizure types were analyzed. Feature extraction and machine‐learning techniques were applied to develop seizure detection algorithms. Performance was expressed as sensitivity, precision, F1 score, and false positives per 24 hours.

Results

The algorithms were developed in group 1 (35 PwE, 33 seizures) and achieved best results (F1 score 56%, sensitivity 67%, precision 45%, false positives 0.7/24 hours) when ECG features alone were used, with no improvement by including accelerometry and electrodermal activity. In group 2 (97 PwE, 255 seizures), this ECG‐based algorithm largely achieved the same performance (F1 score 51%, sensitivity 39%, precision 73%, false positives 0.4/24 hours). In group 3 (30 PwE, 51 seizures), the same ECG‐based algorithm failed to meet up with the performance in groups 1 and 2 (F1 score 27%, sensitivity 31%, precision 23%, false positives 1.2/24 hours). ECG‐based algorithms were also separately trained on data of groups 2 and 3 and tested on the data of the other groups, yielding maximal F1 scores between 8% and 26%.

Significance

Our results suggest that algorithms based on ECG features alone can provide clinically meaningful performance for automatic detection of all seizure types. Our study also underscores that the circumstances under which such algorithms were developed, and the selection of the training and test data sets need to be considered and limit the application of such systems to unseen patient groups behaving in different conditions.
The three‐dimensional bioconvective flow of Sisko nanofluid under Robin's conditions
Authors: Puneeth Venkatesh , Manjunatha Sarpabhushana , Gireesha Bijjanal Jayanna , Shehzad Sabir A.
Published: July 2021

The proposed model investigates three‐dimensional bioconvective Sisko nanofluid flow under Robin's conditions. The Sisko nanofluid has versatile implications in drilling fluids, cement slurries, waterborne coatings, and so on. Furthermore, the inclusion of gyrotactic microorganisms prevents the deposition and agglomeration of the nanoparticles in the base fluid. Buongiorno's model is included to explore the behavior of Brownian motion and thermophoretic factors. The energy and mass transmissions along with the gyrotactic microorganism density are illustrated by the partial differential expression system with Robin's conditions. These are further reframed into an ordinary differential equation system with the aid of similarity transformation. The developing model is tackled by using the MAPLE inbuilt package BVP. The nanofluid acts as a good cooling agent for higher values of the thermophoresis parameter. Furthermore, the pseudoplastic nanofluid performs better than the dilatant nanofluid. The developed model is very useful in energy production and engineering products.
A physically constrained wavelet‐aided statistical model for multi‐decadal groundwater dynamics predictions
Authors: Gordu Fatih , Nachabe Mahmood H.
Published: July 2021

A physically constrained wavelet‐aided statistical model (PCWASM) is presented to analyse and predict monthly groundwater dynamics on multi‐decadal or longer time scales. The approach retains the simplicity of regression modelling but is constrained by temporal scales of processes responsible for groundwater level variation, including aquifer recharge and pumping. The methodology integrates statistical correlations enhanced with wavelet analysis into established principles of groundwater hydraulics including convolution, superposition and the Cooper–Jacob solution. The systematic approach includes (1) identification of hydrologic trends and correlations using cross‐correlation and multi‐time scale wavelet analyses; (2) integrating temperature‐based evapotranspiration and groundwater pumping stresses and (3) assessing model prediction performances using fixed‐block k‐fold cross‐validation and split calibration‐validation methods. The approach is applied at three hydrogeologicaly distinct sites in North Florida in the United States using over 40 years of monthly groundwater levels. The systematic approach identifies two patterns of cross‐correlations between groundwater levels and historical rainfall, indicating low‐frequency variabilities are critical for long‐term predictions. The models performed well for predicting monthly groundwater levels from 7 to 22 years with less than 2.1 ft (0.7 m) errors. Further evaluation by the moving‐block bootstrap regression indicates the PCWASM can be a reliable tool for long‐term groundwater level predictions. This study provides a parsimonious approach to predict multi‐decadal groundwater dynamics with the ability to discern impacts of pumping and climate change on aquifer levels. The PCWASM is computationally efficient and can be implemented using publicly available datasets. Thus, it should provide a versatile tool for managers and researchers for predicting multi‐decadal monthly groundwater levels under changing climatic and pumping impacts over a long time period.
Infiltration reduction characteristics and a simplified calculation model of film hole irrigation during interference infiltration*
Authors: Fan Yanwei , Shi Wen , Shao Xiaoxia , Zhang Changyan , Yin Weifan
Published: July 2021

The infiltration types of film hole irrigation (FHI) can be divided into film hole free infiltration (FHFI) and film hole interference infiltration (FHII). Numerical simulations were carried out with HYDRUS to investigate the influence of soil texture (ST), film hole diameter (D), film hole spacing (S) and water depth above the film hole (H) on the cumulative infiltration under two infiltration types of FHFI and FHII. The results showed that the amount of FHII was reduced significantly compared to that of FHFI. ST, D and S are the dominant factors affecting the infiltration reduction volume (ΔI). The relationship between ΔI and the time after interference (t − t0) is a proportional function (R2 ≥ 0.96), and its proportional coefficient has a good power function relationship with D and S. The power function coefficients have large differences for different ST, and the range of variation is 0.1–191, whereas there is little difference between the power function index of D and S; the average values were 2.6 and −2.5, respectively. A simplified calculation model of infiltration reduction was established, and the estimation accuracy was high (RMSE = 0.017 L, EF = 0.980). This research can provide a reference for the calculation of the irrigation water volume of the FHI.
Photobiomodulation at a wavelength of 633 nm leads to faster functional recovery than 804 nm after facial nerve injury
Authors: Lee Jae‐Hun , Carpena Nathaniel T. , Kim Sehwan , Lee Min Young , Jung Jae Yun , Choi Ji Eun
Published: July 2021

We analyzed the effects of photobiomodulation (PBM) of various wavelengths on regeneration of the facial nerve using in vitro and in vivo experimental models. We assessed the antioxidative effect of PBM in geniculate ganglion neurons irradiated with a diode laser at 633 nm, 780 nm and 804 nm. Wavelengths of 633 and 780 nm but not 804 nm inhibited cell death by oxidative stress. We assessed the effects of PBM on functional and morphologic recovery in rats divided into control, facial nerve damage (FND) and FND irradiated with a 633 nm or 804 nm lasers. Injured rats treated with 633‐nm light had better facial palsy scores, larger axon diameter and higher expression of Schwann cells compared with the FND group. No positive results were observed in rats irradiated at 804‐nm light. These findings indicate that 633‐nm PBM promotes accelerated nerve regeneration and improved functional recovery in an injured facial nerve.
Correlation analysis of long non‐coding RNA TUG1 with disease risk, clinical characteristics, treatment response, and survival profiles of adult Ph− Acute lymphoblastic leukemia
Authors: Zeng Pengyun , Chai Ye , You Chongge , Yue Lingling , Wu Chongyang , Chen Huiling , Li Liangliang , Li Jingjing , Liu Huan , Zhang Yurong , Cao Tingyong , Li Yaru , Hu Wanli
Published: July 2021

Background

Long non‐coding RNA taurine‐upregulated gene 1 (lncRNA TUG1) is reported to be involved in the progression and development of several malignancies; however, its role in Philadelphia chromosome‐negative acute lymphoblastic leukemia (Ph−ALL) is unknown. The present study aimed to explore the correlation of lncRNA TUG1 with disease risk, disease condition, and prognosis of adult Ph−ALL.

Methods

Total 101 adult Ph− ALL patients and 40 bone marrow (BM) donors were included, followed by detection of BM monocyte cell lncRNA TUG1 expression by reverse transcription‐quantitative polymerase chain reaction. According to the quantiles of lncRNA TUG1 expression in Ph− ALL patients, these patients were divided into four tiers: tier 1 (ranked in 0%~25%), tier 2 (ranked in 25%~50%), tier 3 (ranked in 50%~75%), and tier 4 (ranked in 75%~100%).

Results

LncRNA TUG1 was upregulated in Ph− ALL patients compared with healthy donors. Further analysis indicated that in Ph− ALL patients, higher lncRNA TUG1 tier was correlated with the presence of central nervous system leukemia, increased white blood cell level, and bone marrow blasts. Furthermore, higher lncRNA TUG1 tier was negatively associated with complete remission (CR) within 4 weeks, total CR, and allogeneic hematopoietic stem cell transplant achievement. In addition, higher lncRNA TUG1 tier was associated with decreased disease‐free survival and overall survival, which was further verified to be an independent factor by Cox's regression analysis.

Conclusion

lncRNA TUG1 presents potential to be a novel biomarker for disease risk assessment and survival surveillance in Ph− ALL management.
Learning the subtle dance: The experience of therapists who deliver mentalisation‐based therapy for borderline personality disorder
Authors: Gardner Kathryn Jane , Wright Karen M. , Elliott Alison , Lamph Gary , Graham Simon , Parker Lucy , Fonagy Peter
Published: July 2021

Objectives

This study aimed to understand therapists' lived experiences of delivering mentalisation‐based therapy (MBT), including their experiences of service user change.

Method

One‐to‐one semi‐structured interviews or focus groups were conducted with 14 MBT therapists and analysed using interpretative phenomenological analysis (IPA).

Results

Four superordinate themes were identified: (1) experiencing the challenges and complexities of being with service users during MBT; (2) being on a journey of discovery and change; (3) being an MBT therapist: a new way of working and developing a new therapeutic identity; and (4) being a therapist in the group: seeing it all come together.

Conclusion

Our findings highlight the complexity, challenges and individualised experience of working therapeutically with service users with a diagnosis of BPD. The study provides a perspective of service use change that is enriched by idiosyncrasies within the therapeutic encounter. We conclude with a consideration of implications for MBT research and clinical practice.