bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparable diagnostic accuracy of SARS-CoV-2 Spike RBD and N-specific IgG tests to determine pre-vaccination nation-wide baseline seroprevalence in Mexico
Authors: Martínez-Barnetche Jesús , Carnalla Martha , Gaspar-Castillo Carlos , Basto-Abreu Ana , Lizardi Ricardo , Antonio Rodrigo Aparicio , Martinez Irma López , Escamilla Anais Cortes , Ramirez Octavio T. , Palomares Laura A. , Barreto-Cabrera Daniel , Rivera-Castro Juan Carlos , Segura-Sánchez Carlos , Ávila Mauricio Hernández , Barrientos-Gutiérrez Tonatiuh , Aranda Celia M. Alpuche
Published: October 2022

A major challenge for developing countries during the COVID-19 pandemic is affordable and adequate monitoring of disease progression and population exposure as the primary source relevant epidemiological indicators. Serology testing enables assessing population exposure and to guide vaccination strategies but requires rigorous accuracy validation before population-wide implementation. We adapted a two-step ELISA protocol as a single-step protocol for detection of IgG against the Receptor Binding Domain (RBD) of SARS-CoV-2 spike protein and compared its diagnostic accuracy with a commercial immunoassay anti-nucleoprotein IgG. Both methods yielded adequate and comparable diagnostic accuracy after 3 weeks post-symptom onset and were implemented in a nation-wide population based serological survey during August–November 2020. Anti-RBD National seroprevalence was 23.6%, 1.3% lower, but not significantly, than for anti-N. Double positive seroprevalence was 19.7%. Anti-N single-positive seroprevalence was 3.72% and anti-RBD single-positive seroprevalence was 1.98%. Discrepancies in the positivity to either single marker may be due to different kinetics of each antibody marker as well as the heterogeneity of the sampling time in regards to local epidemic waves. Baseline single positivity prevalence will be useful to assess the serological impact of vaccination and natural infection in further serosurveillance efforts.
Environmentally-relevant concentrations of the antipsychotic drugs sulpiride and clozapine induce abnormal dopamine and serotonin signaling in zebrafish brain
Authors: Zhang Bo , Peng Xijian , Sun Xiumei , Guo Yuanming , Li Tiejun
Published: October 2022

The presence of drugs in surface and groundwaters adversely affects the physiological function of non-target organisms due special activities that can pose a serious threats to various forms of aquatic life. Psychotropic drugs are one of the most commonly used drugs in the world. Hence, the aim of this study was to investigate the effect of environmentally-relevant concentrations of the antipsychotic drugs, sulpiride and clozapine, on dopaminergic (DAergic) and serotonergic (5-HTergic) neurotransmitter systems in the brain of zebrafish. Adult zebrafish (AB strain) were exposed to the environmentally-relevant concentrations of sulpiride, clozapine, or a mixture of sulpiride and clozapine. The effects of the drugs on the mRNA and protein levels of major functional molecules in DAergic and 5-HTergic systems were then analyzed in the telencephalon and diencephalon. Both drugs induced abnormal mRNA and protein levels of important functional molecules of the DA and 5-HT signaling pathways in both telencephalon and diencephalon, as shown by the abnormal transcriptional levels of TH, DAT, DR D1, DR D2, MAO, TPH, serotonin transporter (SERT), 5-HTR 1AA, 5-HTR 1B, 5-THR 2AA, and 5-HTR 2B, and the abnormal translational levels of DAT, DR D2, SERT, 5-HTR 1A, 5-HTR 1B, and 5-HTR 2B. In addition, we observed a specificity in the adverse effects of these antipsychotic drugs, in terms of doses and brain parts. Compared to their effects alone, the drug mixture had a weaker effect on the DA and 5-HT systems, suggesting an antagonistic interaction between sulpiride and clozapine. Our findings suggest that sulpiride and clozapine interfere with DAergic and 5-HTergic neurotransmitter systems in the telencephalon and diencephalon of zebrafish, resulting in possible effects on brain functions and posing a serious threat to the health of zebrafish.
Micro-scale aerosol jet printing of superparamagnetic Fe3O4 nanoparticle patterns
Authors: Taccola Silvia , da Veiga Tomas , Chandler James H. , Cespedes Oscar , Valdastri Pietro , Harris Russell A.
Published: October 2022

The opportunity to create different patterns of magnetic nanoparticles on surfaces is highly desirable across many technological and biomedical applications. In this paper, this ability is demonstrated for the first time using a computer-controlled aerosol jet printing (AJP) technology. AJP is an emerging digitally driven, non-contact and mask-less printing process which has distinguishing advantages over other patterning technologies as it offers high-resolution and versatile direct-write deposition of a wide range of materials onto a variety of substrates. This research demonstrates the ability of AJP to reliably print large-area, fine-feature patterns of superparamagnetic iron oxide nanoparticles (SPIONs) onto both rigid material (glass) and soft and flexible materials (polydimethylsiloxane (PDMS) films and poly-L-lactic acid (PLLA) nanofilms). Investigation identified and controlled influential process variables which permitted feature sizes in the region of 20 μm to be realised. This method could be employed for a wide range of applications that require a flexible and responsive process that permits high yield and rapid patterning of magnetic material over large areas. As a first proof of concept, we present patterned magnetic nanofilms with enhanced manipulability under external magnetic field gradient control and which are capable of performing complex movements such as rotation and bending, with applicability to soft robotics and biomedical engineering applications.
Direct current stimulation modulates gene expression in isolated astrocytes with implications for glia-mediated plasticity
Authors: Cancel Limary M. , Silas Dharia , Bikson Marom , Tarbell John M.
Published: October 2022

While the applications of transcranial direct current stimulation (tDCS) across brain disease and cognition are diverse, they rely on changes in brain function outlasting stimulation. The cellular mechanisms of DCS leading to brain plasticity have been studied, but the role of astrocytes remains unaddressed. We previously predicted that during tDCS current is concentrated across the blood brain-barrier. This will amplify exposure of endothelial cells (ECs) that form blood vessels and of astrocytes that wrap around them. The objective of this study was to investigate the effect of tDCS on the gene expression by astrocytes or ECs. DCS (0.1 or 1 mA, 10 min) was applied to monolayers of mouse brain ECs or human astrocytes. Gene expression of a set of neuroactive genes were measured using RT-qPCR. Expression was assessed immediately or 1 h after DCS. Because we previously showed that DCS can produce electroosmotic flow and fluid shear stress known to influence EC and astrocyte function, we compared three interventions: pressure-driven flow across the monolayer alone, pressure-driven flow plus DCS, and DCS alone with flow blocked. We show that DCS can directly modulate gene expression in astrocytes (notably FOS and BDNF), independent of but synergistic with pressure-driven flow gene expression. In ECs, pressure-driven flow activates genes expression with no evidence of further contribution from DCS. In ECs, DCS alone produced mixed effects including an upregulation of FGF9 and downregulation of NTF3. We propose a new adjunct mechanism for tDCS based on glial meditated plasticity.
Heavy metal ecological-health risk assessment under wheat–maize rotation system in a high geological background area in eastern China
Authors: Wan Fang , Jiang Nan , Yu Linsong , Zang Kai , Liu Shuming , He Wei , Hu Zunfang , Fan Haiyin , Li Haosong , Wang Hui , Pan Hong , Yang Quangang , Lou Yanhong , Zhuge Yuping
Published: October 2022

A high geological background can increase the ecological and health risks associated with crop production; therefore, it is essential to assess the heavy metals and their impact. In this study, ecological and health risk impacts of heavy metal contamination, in combination with positive matrix factorization was assessed for an area with high geological background with wheat–maize cropping system, to provide a quantitative understanding of the effects of heavy metals, enabling its prevention and control. This study revealed that the comprehensive ecological risk (RIwheat–maize) is 56.21 (low), with industries being the biggest contributors (34.22%). Comprehensive health risk (non-carcinogenic) assessment showed that industrial (40.98–49.30%) and natural (23.96–37.64%) factors were the primary (particularly of Cd and Zn) and secondary (particularly of Cr and Ni) contributors, respectively in eastern China. Comprehensive health risk (HIwheat–maize) for children and adults were 0.74 and 0.42, respectively, indicating that non-carcinogenic risks were at an acceptable level. Soil ingestion was the primary pathway for health risks (62.23–73.00%), especially for children. Based on soil heavy metal sources and crop systems, source-ecological risk assessment and source-health risk assessment were used to provided valuable insights on making strategies to protect human health in high geological background areas.
The electrochemical corrosion behaviour of compacted (Bi, Pb)-2223 superconductors in aqueous solutions
Authors: Abdel-Gaber Ashraf M. , Najem Ahmad , Awad Ramadan
Published: October 2022

The corrosion behaviour of (Bi, Pb)-2223 samples compacted at 0.3–1.9 GPa in 0.5 M of HCl, NaCl, and NaOH solutions at 30 °C was investigated using potentiodynamic polarization curves measurements and electrochemical impedance spectroscopy (EIS) technique as well as scanning electron microscopy (SEM) and energy dispersive X-ray emission spectroscopy (EDX). Polarization results showed that the increase in compaction decreases both cathodic hydrogen evolution or oxygen reduction and anodic (BiPb)-2223 superconductor dissolution in 0.5 M HCl, and 0.5 M NaOH. On the other hand, compaction mainly affects the anodic part of the polarization curves of (Bi, Pb)-2223 in 0.5 M NaCl solution. EIS measurements revealed that the highest protection of the superconductors was achieved in 0.5 M NaCl, while the lowest degree of protection was observed in 0.5 M HCl. SEM images show a random plate-like morphology fitted with the marker of (Bi, Pb)-2223 material. The compacted sample at 1.9 GPa indicates deformation of the grains and the formation of a micro-crack. The corrosion mechanism of the superconductor at different pH values was also discussed.
Parasympathetic tonus in type 2 diabetes and pre-diabetes and its clinical implications
Authors: Hadad Rakin , Akobe Sarah F. , Weber Philip , Madsen Christoffer V. , Larsen Bjørn Strøier , Madsbad Sten , Nielsen Olav W. , Dominguez Maria Helena , Haugaard Steen B. , Sajadieh Ahmad
Published: October 2022

Autonomic imbalance reflected by higher resting heart rate and reduced parasympathetic tone may be driven by low-grade inflammation (LGI) and impaired glycemic control in type 2 diabetes mellitus (T2DM) and pre-diabetes. We examined the interaction of parasympathetic components of heart rate variability (HRV), variables of LGI, and glucose metabolism in people with T2DM, pre-diabetes, and normal glucose metabolism (NGM). We recorded HRV by Holter (48 h) in 633 community-dwelling people of whom T2DM n = 131, pre-diabetes n = 372, and NGM n = 130 and mean HbA1c of 7.2, 6.0 and 5.3%, respectively. Age was 55–75 years and all were without known cardiovascular disease except from hypertension. Fasting plasma glucose, fasting insulin, HOMA-IR, HbA1c and LGI (CRP, Interleukin-18 (IL-18), and white blood cells) were measured. Root-mean-square-of-normal-to-normal-beats (RMSSD), and proportion of normal-to-normal complexes differing by more than 50 ms (pNN50) are accepted measures of parasympathetic activity. In univariate analyses, RMSSD and pNN50 were significantly inversely correlated with level of HbA1c and CRP among people with T2DM and pre-diabetes, but not among NGM. RMSSD and pNN50 remained significantly inversely associated with level of HbA1c after adjusting for age, sex, smoking, and BMI among people with T2DM (β = − 0.22) and pre-diabetes (β = − 0.11); adjustment for LGI, HOMA-IR, and FPG did not attenuate these associations. In backward elimination models, age and level of HbA1c remained associated with RMSSD and pNN50. In people with well controlled diabetes and pre-diabetes, a lower parasympathetic activity was more related to age and HbA1c than to markers of LGI. Thus, this study shows that the driver of parasympathetic tonus may be more the level of glycemic control than inflammation in people with prediabetes and well controlled diabetes.
Clinical predictors of recovery of COVID-19 associated-abnormal liver function test 2 months after hospital discharge
Authors: Lu Justin Y. , Ho Scott L. , Buczek Alexandra , Fleysher Roman , Hou Wei , Chacko Kristina , Duong Tim Q.
Published: October 2022

This study investigated whether acute liver injury (ALI) persisted and identified predictors of ALI recovery [as indicated by alanine aminotransferase (ALT) level] at hospital discharge and 2 months post-discharge for 7595 hospitalized COVID-19 patients from the Montefiore Health System (03/11/2020–06/03/2021). Mild liver injury (mLI) was defined as ALT = 1.5–5 ULN, and severe livery injury (sLI) was ALT ≥ 5 ULN. Logistic regression was used to identify predictors of ALI onset and recovery. There were 4571 (60.2%), 2306 (30.4%), 718 (9.5%) patients with no liver injury (nLI), mLI and sLI, respectively. Males showed higher incidence of sLI and mLI (p < 0.05). Mortality odds ratio was 4.15 [95% CI 3.41, 5.05, p < 0.001] for sLI and 1.69 [95% CI 1.47, 1.96, p < 0.001] for mLI compared to nLI. The top predictors (ALT, lactate dehydrogenase, ferritin, lymphocytes) accurately predicted sLI onset up to three days prior. Only 33.5% of mLI and 17.1% of sLI patients (survivors) recovered completely at hospital discharge. Most ALI patients (76.7–82.4%) recovered completely ~ 2 months post-discharge. The top predictors accurately predicted recovery post discharge with 83.2 ± 2.2% accuracy. In conclusion, most COVID-19 patients with ALI recovered completely ~ 2 months post discharge. Early identification of patients at-risk of persistent ALI could help to prevent long-term liver complications.
Experimental confirmation of self-imaging effect between guided light and surface plasmon polaritons in hybrid plasmonic waveguides
Authors: Okamoto Hiroyuki , Kamada Shun , Yamaguchi Kenzo , Haraguchi Masanobu , Okamoto Toshihiro
Published: October 2022

We fabricated a hybrid plasmonic device using self-imaging effect between guided light and surface plasmon polaritons in the hybrid plasmonic waveguide. The hybrid plasmonic device was fabricated by evaporating gold on the part of the silicon waveguide. Self-imaging was generated at the gold-covered section in the waveguide. Self-imaging of guided light and surface plasmon polaritons in hybrid plasmonic waveguides affect the output intensity of the hybrid plasmonic waveguide. The length of the hybrid plasmonic waveguide changes self-imaging conditions. We confirmed that the output intensity was affected by the length of the hybrid plasmonic waveguide. These findings contribute to the development of hybrid plasmonic devices and potentially improve integration density of hybrid photonic integrated circuits.
GABAA receptor function is enhanced by Interleukin-10 in human epileptogenic gangliogliomas and its effect is counteracted by Interleukin-1β
Authors: Ruffolo Gabriele , Alfano Veronica , Romagnolo Alessia , Zimmer Till , Mills James D. , Cifelli Pierangelo , Gaeta Alessandro , Morano Alessandra , Anink Jasper , Mühlebner Angelika , Vezzani Annamaria , Aronica Eleonora , Palma Eleonora
Published: October 2022

Gangliogliomas (GGs) are low-grade brain tumours that cause intractable focal epilepsy in children and adults. In GG, as in epileptogenic focal malformations (i.e.,tuberous sclerosis complex, TSC), there is evidence of sustained neuroinflammation with involvement of the pro-inflammatory cytokine IL-1β. On the other hand, anti-inflammatory mediators are less studied but bear relevance for understanding seizure mechanisms. Therefore, we investigated the effect of the key anti-inflammatory cytokine IL-10 on GABAergic neurotransmission in GG. We assessed the IL-10 dependent signaling by transcriptomic analysis, immunohistochemistry and performed voltage-clamp recordings onXenopusoocytes microtransplanted with cell membranes from brain specimens, to overcome the limited availability of acute GG slices. We report that IL-10-related mRNAs were up-regulated in GG and slightly in TSC. Moreover, we found IL-10 receptors are expressed by neurons and astroglia. Furthermore, GABA currents were potentiated significantly by IL-10 in GG. This effect was time and dose-dependent and inhibited by blockade of IL-10 signaling. Notably, in the same tissue, IL-1β reduced GABA current amplitude and prevented the IL-10 effect. These results suggest that in epileptogenic tissue, pro-inflammatory mechanisms of hyperexcitability prevail over key anti-inflammatory pathways enhancing GABAergic inhibition. Hence, boosting the effects of specific anti-inflammatory molecules could resolve inflammation and reduce intractable seizures.
A new periocular dataset collected by mobile devices in unconstrained scenarios
Authors: Zanlorensi Luiz A. , Laroca Rayson , Lucio Diego R. , Santos Lucas R. , Britto Alceu S. , Menotti David
Published: October 2022

Recently, ocular biometrics in unconstrained environments using images obtained at visible wavelength have gained the researchers’ attention, especially with images captured by mobile devices. Periocular recognition has been demonstrated to be an alternative when the iris trait is not available due to occlusions or low image resolution. However, the periocular trait does not have the high uniqueness presented in the iris trait. Thus, the use of datasets containing many subjects is essential to assess biometric systems’ capacity to extract discriminating information from the periocular region. Also, to address the within-class variability caused by lighting and attributes in the periocular region, it is of paramount importance to use datasets with images of the same subject captured in distinct sessions. As the datasets available in the literature do not present all these factors, in this work, we present a new periocular dataset containing samples from 1122 subjects, acquired in 3 sessions by 196 different mobile devices. The images were captured under unconstrained environments with just a single instruction to the participants: to place their eyes on a region of interest. We also performed an extensive benchmark with several Convolutional Neural Network (CNN) architectures and models that have been employed in state-of-the-art approaches based on Multi-class Classification, Multi-task Learning, Pairwise Filters Network, and Siamese Network. The results achieved in the closed- and open-world protocol, considering the identification and verification tasks, show that this area still needs research and development.
New objective timbre parameters for classification of voice type and fach in professional opera singers
Authors: Müller Matthias , Wang Zehui , Caffier Felix , Caffier Philipp P.
Published: October 2022

Voice timbre is defined as sound color independent of pitch and volume, based on a broad frequency band between 2 and 4 kHz. Since there are no specific timbre parameters, previous studies have come to the very general conclusion that the center frequencies of the singer’s formants are somewhat higher in the higher voice types than in the lower ones. For specification, a database was created containing 1723 sound examples of various voice types. The energy distribution in the frequency bands of the singer’s formants was extracted for quantitative analysis. When the energy distribution function reached 50%, the corresponding absolute frequency in Hz was defined as Frequency of Half Energy (FHE). This new parameter quantifies the timbre of a singing voice as a concrete measure, independent of fundamental frequency, vowel color and volume. The database allows assigning FHE means ± SD as characteristic or comparative values for sopranos (3092 ± 284 Hz), tenors (2705 ± 221 Hz), baritones (2454 ± 206 Hz) and basses (2384 ± 164 Hz). In addition to vibrato, specific timbre parameters provide another valuable feature in vocal pedagogy for classification of voice type and fach according to the lyric or dramatic character of the voice.
Prevention of Shiga toxin 1-caused colon injury by plant-derived recombinant IgA
Authors: Nakanishi Katsuhiro , Takase Taichi , Ohira Yuya , Ida Ryota , Mogi Noriko , Kikuchi Yuki , Matsuda Minami , Kurohane Kohta , Akimoto Yoshihiro , Hayakawa Junri , Kawakami Hayato , Niwa Yasuo , Kobayashi Hirokazu , Umemoto Eiji , Imai Yasuyuki
Published: October 2022

Immunoglobulin A (IgA) is a candidate antibody for oral passive immunization against mucosal pathogens like Shiga toxin-producing Escherichia coli (STEC). We previously established a mouse IgG monoclonal antibody (mAb) neutralizing Shiga toxin 1 (Stx1), a bacterial toxin secreted by STEC. We designed cDNA encoding an anti-Stx1 antibody, in which variable regions were from the IgG mAb and all domains of the heavy chain constant region from a mouse IgA mAb. Considering oral administration, we expressed the cDNA in a plant expression system aiming at the production of enough IgA at low cost. The recombinant-IgA expressed in Arabidopsis thaliana formed the dimeric IgA, bound to the B subunit of Stx1, and neutralized Stx1 toxicity to Vero cells. Colon injury was examined by exposing BALB/c mice to Stx1 via the intrarectal route. Epithelial cell death, loss of crypt and goblet cells from the distal colon were observed by electron microscopy. A loss of secretory granules containing MUC2 mucin and activation of caspase-3 were observed by immunohistochemical methods. Pretreatment of Stx1 with the plant-based recombinant IgA completely suppressed caspase-3 activation and loss of secretory granules. The results indicate that a plant-based recombinant IgA prevented colon damage caused by Stx1 in vivo.
Characterizing phenotypic diversity in marine populations of the threespine stickleback
Authors: Fraser Ainsley Lilias , El-Sabaawi Rana
Published: October 2022

The threespine stickleback (Gasterosteus aculeatus) is an important model for studying the evolution of vertebrate morphology. Sticklebacks inhabit freshwater, brackish, and marine northern hemisphere waters. Anadromous and marine populations (hereafter marine) are assumed to have remained unchanged morphologically from ancestral marine sticklebacks, despite marine environments varying on regional and local scales. Recent studies suggest that genetic and phenotypic structure exists in marine populations, yet the scale of this variation, and its ecological causes remain unclear. Our goal was to assess morphological trait variation in marine stickleback populations around Southern British Columbia (BC) and determine if oceanographic and habitat characteristics were associated with this variation. Between May–July 2019, we sampled 534 sticklebacks from 15 sites around Vancouver Island, a region characterized by a large diversity of oceanographic and habitat features. We characterized trait variation using two-dimensional (2D) geometric morphometric analysis, comparing individuals between oceanographic regions and habitats. We focused on head and body shape. We found that marine sticklebacks varied morphologically among and between regions and habitats, but the variation did not appear to be related to environmental variation. Sexual dimorphism was the largest source of variation, but oceanographic and habitat variables influenced differences between sexes. We concluded that marine sticklebacks offer abundant opportunities for expanding our knowledge of drivers of morphology.
Eco-friendly method for construction of superhydrophobic graphene-based coating on copper substrate and its corrosion resistance performance
Authors: Ragheb D. M. , Abdel-Gaber A. M. , Mahgoub F. M. , Mohamed M. E.
Published: October 2022

In this work, Ni and Ni-graphene, Ni-G, films were electrodeposited on copper substrate by potentiostatic deposition. To achieve superhydrophobicity, myristic acid, MA, was used to modify the surface of the electrodeposited coatings. The manufactured Ni film modified with myristic acid, Ni-MA, and the Ni-G film modified with myristic acid, Ni-G-MA, show excellent superhydrophobic, SHP, properties with a water contact angle of 159° and 162°, respectively. The surface morphology of the prepared SHP films was investigated using a Scanning Electron Microscope, and the results revealed micro-nano structures in both Ni-MA and Ni-G-MA films. The Fourier Transform Infrared Spectrophotometer data showed that the Ni-MA and Ni-G-MA films were successfully grafted on the copper metal. The Ni-G-MA film possessed higher chemical stability and mechanical abrasion resistance than Ni-MA. The Ni-MA and Ni-G-MA films exhibit long-term durability in the outdoor environment for more than four months. The potentiodynamic polarization and electrochemical impedance spectroscopy results demonstrated that the SHP films on the copper substrate exhibit remarkable corrosion resistance in 0.5 M NaCl.
Deep learning-based diagnosis of Alzheimer’s disease using brain magnetic resonance images: an empirical study
Authors: Kim Jun Sung , Han Ji Won , Bae Jong Bin , Moon Dong Gyu , Shin Jin , Kong Juhee Eliana , Lee Hyungji , Yang Hee Won , Lim Eunji , Kim Jun Yup , Sunwoo Leonard , Cho Se Jin , Lee Dongsoo , Kim Injoong , Ha Sang Won , Kang Min Ju , Suh Chong Hyun , Shim Woo Hyun , Kim Sang Joon , Kim Ki Woong
Published: October 2022

The limited accessibility of medical specialists for Alzheimer’s disease (AD) can make obtaining an accurate diagnosis in a timely manner challenging and may influence prognosis. We investigated whether VUNO Med-DeepBrain AD (DBAD) using a deep learning algorithm can be employed as a decision support service for the diagnosis of AD. This study included 98 elderly participants aged 60 years or older who visited the Seoul Asan Medical Center and the Korea Veterans Health Service. We administered a standard diagnostic assessment for diagnosing AD. DBAD and three panels of medical experts (ME) diagnosed participants with normal cognition (NC) or AD using T1-weighted magnetic resonance imaging. The accuracy (87.1% for DBAD and 84.3% for ME), sensitivity (93.3% for DBAD and 80.0% for ME), and specificity (85.5% for DBAD and 85.5% for ME) of both DBAD and ME for diagnosing AD were comparable; however, DBAD showed a higher trend in every analysis than ME diagnosis. DBAD may support the clinical decisions of physicians who are not specialized in AD; this may enhance the accessibility of AD diagnosis and treatment.
Development of a bispecific antibody targeting PD-L1 and TIGIT with optimal cytotoxicity
Authors: Zhong Zhenwei , Zhang Mengyao , Ning Yanan , Mao Guanchao , Li Xiaopei , Deng Qi , Chen Xiaorui , Zuo Dongliang , Zhao Xiangyu , Xie Ermin , Wang Huajing , Guo Lina , Li Bohua , Xiao Kai , He Xiaowen
Published: October 2022

Programmed death-ligand 1 (PD-L1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) are two potential targets for cancer immunotherapy, early clinical studies showed the combination therapy of anti-PD-L1 and anti-TIGIT had synergistic efficacy both in the terms of overall response rate (ORR) and overall survival (OS). It is rational to construct bispecific antibodies targeting PD-L1 and TIGIT, besides retaining the efficacy of the combination therapy, bispecific antibodies (BsAbs) can provide a new mechanism of action, such as bridging between tumor cells and T/NK cells. Here, we developed an IgG1-type bispecific antibody with optimal cytotoxicity. In this study, we thoroughly investigated 16 IgG-VHH formats with variable orientations and linker lengths, the results demonstrated that (G4S)2 linker not only properly separated two binding domains but also had the highest protein yield. Moreover, VHH-HC orientation perfectly maintained the binding and cytotoxicity activity of the variable domain of the heavy chain of heavy‐chain‐only antibody (VHH) and immunoglobulin G (IgG). Following treatment with BiPT-23, tumor growth was significantly suppressed in vivo, with more cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells infiltration, and selective depletion of Regulatory T cells (Tregs). BiPT-23 represents novel immunotherapy engineered to prevent hyperprogression of cancer with PD-1 blockade, and preferentially killed PD-L1+ tumor cells, and TIGIT+ Tregs but maintained CD11b+F4/80+ immune cells within the tumor microenvironment (TME).
Metabolic alterations in dairy cattle with lameness revealed by untargeted metabolomics of dried milk spots using direct infusion-tandem mass spectrometry and the triangulation of multiple machine learning models
Authors: He Wenshi , Cardoso Ana S. , Hyde Robert M. , Green Martin J. , Scurr David J. , Griffiths Rian L. , Randall Laura V. , Kim Dong-Hyun
Published: October 2022

Metabolic alteration and metabolite indicators associated with cattle lameness were discovered by untargeted metabolomics analysis of dried milk spots using direct infusion mass spectrometry and triangulation of statistical models.
A novel electrochemical sensor based on AuPd/UiO-66-NH2/GN composites for sensitive dopamine detection
Authors: Zhou Ying , Li Ruichun , Zhang Guomei , Zhang Yan , Zhang Caihong , Shuang Shaomin
Published: October 2022

The AuPd/UiO-66-NH2/GN composites were successfully synthesized. And they were used to modify a glassy carbon electrode to construct a novel electrochemical sensor for sensitive dopamine detection.
Synthesis of conjugated bisallenes by cooperative Cu/Pd-catalysed borylallenylation of 2-trifluoromethyl-1,3-enynes
Authors: Yu Shang-Hai , Gong Tian-Jun , Fu Yao
Published: October 2022

We report a cooperative Cu/Pd-catalysed borylallenylation of 2-trifluoromethyl-1,3-enynes with diboron reagents and propargylic carbonates access to a series of conjugated bisallenes with excellent functional group compatibility.
The eutectic point in choline chloride and ethylene glycol mixtures
Authors: Hayler Hannah J. , Perkin Susan
Published: October 2022

We present measurements that contrast the reported eutectic point of choline chloride and ethylene glycol mixtures, and confirm the non-deep and non-1:2 nature of the eutectic point.
A disulfide-induced supra-amphiphilic co-assembly for glycosylated pro-drug-photosensitizer nanoparticles in combination therapies
Authors: Jin Wenjuan , Chen Zelong , Yang Senyu , Qu Yun , Pei Yuxin , Pei Zhichao
Published: October 2022

We reported an intermolecular chalcogen bonding interaction (S⋯S contacts) induced supra-amphiphilic co-assembly strategy to construct glycosylated pro-drug-photosensitizer nanoparticles (BG-L NPs) in combination therapies.
First observation of [Pu6(OH)4O4]12+ cluster during the hydrolytic formation of PuO2 nanoparticles using H/D kinetic isotope effect
Authors: Cot-Auriol Manon , Virot Matthieu , Dumas Thomas , Diat Olivier , Menut Denis , Moisy Philippe , Nikitenko Sergey I.
Published: October 2022

New insights are provided about the formation mechanism of PuO2 nanoparticles (NPs) by investigating an unprecedented kinetic isotope effect observed during their hydrolytic synthesis in H2O or D2O media.
Non-seed chemical bath deposition of ZnO films in a rotating continuous flow reactor with various carboxylic acids and their application to transparent conductive films
Authors: Wagata Hajime , Shioiri Naoya , Tanaka Yuya , Yokogawa Ryo , Ogura Atsushi
Published: October 2022

The effect of various carboxylic acids on non-seed-CBD fabricated ZnO films and their optical and electrical properties were investigated and discussed.
Multi-faceted elastic flexibility of 1-naphthyl and 9-anthryl 2,2′:6′,2′′-terpyridine crystals
Authors: Kusumoto Sotaro , Oishi Karin , Nakaya Manabu , Suzuki Ryo , Tachibana Masaru , Kim Yang , Koide Yoshihiro , Hayami Shinya
Published: October 2022

We report two organic crystals of 2,2′:6′,2′′-terpyridine derivatives each substituted with luminescent naphthyl and anthryl moieties, displaying multi-faceted flexible bending with elasticity in response to mechanical stress.
Solubility and permeability enhancement of BCS class IV drug ribociclib through cocrystallization
Authors: Mannava M. K. Chaitanya , Garai Abhijit , Bommaka Manish K. , Solomon K. Anand , Nangia Ashwini K.
Published: October 2022

Cocrystallization improves the solubility and permeability of BCS class IV anticancer drug ribociclib as a cocrystal with resorcinol and as a salt hydrate with vanillic acid.
An electrodeposition model with surface relaxation predicts temperature and current effects in compact and dendritic film morphologies
Authors: Carrasco Ismael S. S. , Alves Sidiney G. , Aarão Reis Fábio D. A.
Published: October 2022

The model produces compact or dendritic (self-organized) films by changing the cation flux and connects adsorbed atom diffusion with temperature and current, whose increase respectively leads to larger and smaller low-energy configurations.
Computational identification of bifunctional metal-modified ZSM-5 catalysts to boost methane–methanol coupling
Authors: Sun Mengnan , Nie Xiaowa , Zhang Xinwei , Liu Sirui , Song Chunshan , Guo Xinwen
Published: October 2022

Zn/ZSM-5 exhibits superior catalytic activity for reactant activation and C–C coupling in methane–methanol coupling revealed by DFT calculations. Introducing Co, Ni or Pd into Zn/ZSM-5 further promotes the reaction by reducing C–C coupling barriers.
An ultra-thin flexible wearable sensor with multi-response capability prepared from ZIF-67 and conductive metal–organic framework composites for health signal monitoring
Authors: Zhao Youwei , Li Xiang , Yuan Tian , Huang Shuhong , Jiang Ronghui , Duan Xuefei , Li Ling , Li Xiaoting , Zhang Wenming
Published: October 2022

The first synthesized cZIF-67@Cu-CAT nanoparticles were used as sensitive materials to prepare a dual response mode sensor.
Engineering surface Mn-enriched species and regulating active oxygen species over LaMnO3 catalysts by synergistic modification of acid etching and potassium support for soot removal
Authors: Dai Wenyue , Li Congcong , Wang Fang , Zhang Changsen , Liu Panpan , Qiao Haonan , Li Zihan
Published: October 2022

A highly efficient K-supported synergistically modified LaMnO3 catalyst was prepared by acid etching for soot oxidation.
Enhancing the photoluminescence and cellular uptake of fluorescent carbon nanodots via cubosome lipid nanocarriers
Authors: Zhai Jiali , Bao Lei , Walduck Anna K. , Dyett Brendan P. , Cai Xudong , Li Miaosi , Nasa Zeyad , Drummond Calum J.
Published: October 2022

C-dots loaded cubosome is green fluorescent for cell imaging.
Equation learning to identify nano-engineered particle–cell interactions: an interpretable machine learning approach
Authors: Johnston Stuart T. , Faria Matthew
Published: October 2022

Equation learning and biologically-informed neural networks are used to identify and quantify particle-cell interactions from a diverse collection of experimental data.
Coupling solute interactions with functionalized graphene membranes: towards facile membrane-level engineering
Authors: Arya Vinay , Chaudhuri Abhirup , Bakli Chirodeep
Published: October 2022

Tuning ion-water transport steered by membrane-level functionalization of graphene at the nanoscale.
Insights into the importance of WPD-loop sequence for activity and structure in protein tyrosine phosphatases
Authors: Shen Ruidan , Crean Rory M. , Olsen Keith J. , Corbella Marina , Calixto Ana R. , Richan Teisha , Brandão Tiago A. S. , Berry Ryan D. , Tolman Alex , Loria J. Patrick , Johnson Sean J. , Kamerlin Shina C. L. , Hengge Alvan C.
Published: October 2022

Protein tyrosine phosphatases have a key catalytic residue on a mobile loop (the WPD-loop), making the connections between this loop sequence and its dynamics, together with the dynamics of other mobile loops, particularly important.
Electro-optic crosslinkable chromophores with ultrahigh electro-optic coefficients and long-term stability
Authors: Zeng Ziying , Liu Jianhua , Luo Tongyu , Li Zhibei , Liao Juanfei , Zhang Weijun , Zhang Lian , Liu Fenggang
Published: October 2022

Ultrahigh electro-optic activity and high long-term alignment stability were achieved with crosslinkable binary chromophores QLD1 and QLD2 or crosslinkable single chromophore QLD3 and multichromophore QLD4 with large hyperpolarizability using tetrahydroquinoline as the donor.
Intrinsic-water desorption induced thermomechanical response of hydrogels
Authors: Debta Sanghamitra , Bhutia Sonam Zangpo , Satapathy Dillip K. , Ghosh Pijush
Published: October 2022

Desorption of different types of water from the hydrogel at different temperature ranges resulting in different mechanical properties and relaxation behaviour.
Carbon dots as an electron extractant for enhanced photocatalytic antibacterial activity of covalent organic frameworks
Authors: Liang Jiarong , Li Wei , Chen Jianying , Huang Xiaoman , Liu Yingliang , Zhang Xuejie , Shu Wei , Lei Bingfu , Zhang Haoran
Published: October 2022

An intramolecular charge transfer system was constructed to extract π-electrons from photosensitive D–A COF semiconductors to CDs through hydrogen bonding for more ROS evolution, which demonstrated high-efficiency bactericidal mechanism.
Polyamide-imide/polyimide alloy with enhanced energy density and efficiency
Authors: Liu Man , Song Yiheng , Qin Hongmei , Li Ziwei , Fu Yuheng , Xiong Chuanxi , Liu Feihua
Published: October 2022

Strong intermolecular forces of PAI/PI alloy decrease the possibilities of imperfect voids, contributing to much improved dielectric constant and breakdown strength, thus leading to much increased discharged energy density and efficiency.
Evolution of pits at the surface of 67P/Churyumov-Gerasimenko
Authors: Benseguane Selma , Guilbert-Lepoutre Aurélie , Lasue Jérémie , Besse Sébastien , Leyrat Cédric , Beth Arnaud , Costa Sitjà Marc , Grieger Björn , Capria Maria Teresa
Published: October 2022

Context. The observation of pits at the surface of comets offers the opportunity to take a glimpse into the properties and the mechanisms that shape a nucleus through cometary activity. If the origin of these pits is still a matter of debate, multiple studies have recently suggested that known phase transitions (such as volatile sublimation or amorphous water ice crystallization) alone could not have carved these morphological features on the surface of 67P/Churyumov-Gerasimenko (hereafter 67P).

Aims. We want to understand how the progressive modification of 67P’s surface due to cometary activity might have affected the characteristics of pits and alcoves. In particular, we aim to understand whether signatures of the formation mechanism of these surface morphological features can still be identified.

Methods. To quantify the amount of erosion sustained at the surface of 67P since it arrived on its currently observed orbit, we selected 380 facets of a medium-resolution shape model of the nucleus, sampling 30 pits and alcoves across the surface. We computed the surface energy balance with a high temporal resolution, including shadowing and self-heating contributions. We then applied a thermal evolution model to assess the amount of erosion sustained after ten orbital revolutions under current illumination conditions.

Results. We find that the maximum erosion sustained after ten orbital revolutions is on the order of 80 m, for facets located in the southern hemisphere. We thus confirm that progressive erosion cannot form pits and alcoves, as local erosion is much lower than their observed depth and diameter. We find that plateaus tend to erode more than bottoms, especially for the deepest depressions, and that some differential erosion can affect their morphology. As a general rule, our results suggest that sharp morphological features tend to be erased by progressive erosion.

Conclusions. This study supports the assumption that deep circular pits, such as Seth_01, are the least processed morphological features at the surface of 67P, or the best preserved since their formation.
On r-hued coloring of product graphs
Authors: Liang Lingmei , Liu Fengxia , Wu Baoyindureng
Published: October 2022

A (k,r)-coloring of a graph G is a proper coloring with k colors such that for every vertex v with degree d(v) in G, the color number of the neighbors of v is at least min{d(v),r}. The smallest integer k such that G has a (k,r)-coloring is called the r-hued chromatic number and denoted by χr(G). In Kaliraj et al. [Taibah Univ. Sci. 14 (2020) 168–171], it is determined the 2-hued chromatic numbers of Cartesian product of complete graph and star graph. In this paper, we extend its result and determine the r-hued chromatic number of Cartesian product of complete graph and star graph.
Synthesis of (S)-Nyasol through a Copper-Catalyzed Propargylic Substitution
Authors: Kobayashi Yuichi , Hirotsu Takayuki
Published: October 2022

(S)-Nyasol was selected as a target to demonstrate the efficiency of a copper-catalyzed substitution of secondary propargylic phosphates. The key phosphate (R)-TBDPSO(CH2)2CH[C≡C(C6H4-4-OTBS)]OP(O)(OEt)2 was synthesized from TBDPSO(CH2)2CO2H in four steps. Substitution of the phosphate with 4-TBSOC6H4MgBr in the presence of CuBr·Me2S as a catalyst in THF–DME proceeded with both stereo- and regioselectivity at the propargylic position. All the silyl groups in the propargylic product, TBDPSO(CH2)2CH[C≡C(C6H4-4-OTBS)](C6H4-4-OTBS) were removed, and the acetylene bond was reduced by using active Zn to produce the cis-olefin. Finally, the HO(CH2)2 moiety was converted into CH2=CH, giving (S)-nyasol with 97% cis selectivity, 94.5% ee, and >99% enantiospecificity. Similarly, dihydronyasol was synthesized through hydrogenation of the substitution product, followed by construction of the terminal olefin.
Sequential 1,3-Dipole Cycloaddition of Nitrile Imines with Alkenyl Isoxazoles and Aromatization: A One-Pot Access to 1,3,4-Triarylpyrazoles
Authors: Li Mei-Mei , Huang Hui , Lu Jun
Published: October 2022

A novel one-pot two-step process for the preparation of 1,3,4-triarylpyrazoles is disclosed. This process involves a 1,3-dipolar cycloaddition reaction of alkenyl isoxazoles with nitrile imines generated in situ, followed by SnCl2-promoted aromatization/elimination reaction to give a range of 1,3,4-triarylpyrazoles in a fully regioselective manner. This protocol features mild reaction conditions, easily available raw materials, and excellent regioselectivity.
The Influence of Male- and Female-Spoken Vowel Acoustics on Envelope-Following Responses
Authors: Easwar Vijayalakshmi , Purcell David , Eeckhoutte Maaike Van , Aiken Steven J.
Published: October 2022

The influence of male and female vowel characteristics on the envelope-following responses (EFRs) is not well understood. This study explored the role of vowel characteristics on the EFR at the fundamental frequency (f0) in response to the vowel /ε/ (as in “head”). Vowel tokens were spoken by five males and five females and EFRs were measured in 25 young adults (21 females). An auditory model was used to estimate changes in auditory processing that might account for talker effects on EFR amplitude. There were several differences between male and female vowels in relation to the EFR. For male talkers, EFR amplitudes were correlated with the bandwidth and harmonic count of the first formant, and the amplitude of the trough below the second formant. For female talkers, EFR amplitudes were correlated with the range of f0 frequencies and the amplitude of the trough above the second formant. The model suggested that the f0 EFR reflects a wide distribution of energy in speech, with primary contributions from high-frequency harmonics mediated from cochlear regions basal to the peaks of the first and second formants, not from low-frequency harmonics with energy near f0. Vowels produced by female talkers tend to produce lower-amplitude EFR, likely because they depend on higher-frequency harmonics where speech sound levels tend to be lower. This work advances auditory electrophysiology by showing how the EFR evoked by speech relates to the acoustics of speech, for both male and female voices.
Real-Time User Feedback to Support Clinical Decision Support System Improvement
Authors: Rubins David , McCoy Allison B. , Dutta Sayon , McEvoy Dustin S. , Patterson Lorraine , Miller Amy , Jackson John G. , Zuccotti Gianna , Wright Adam
Published: October 2022

Objectives To improve clinical decision support (CDS) by allowing users to provide real-time feedback when they interact with CDS tools and by creating processes for responding to and acting on this feedback.

Methods Two organizations implemented similar real-time feedback tools and processes in their electronic health record and gathered data over a 30-month period. At both sites, users could provide feedback by using Likert feedback links embedded in all end-user facing alerts, with results stored outside the electronic health record, and provide feedback as a comment when they overrode an alert. Both systems are monitored daily by clinical informatics teams.

Results The two sites received 2,639 Likert feedback comments and 623,270 override comments over a 30-month period. Through four case studies, we describe our use of end-user feedback to rapidly respond to build errors, as well as identifying inaccurate knowledge management, user-interface issues, and unique workflows.

Conclusion Feedback on CDS tools can be solicited in multiple ways, and it contains valuable and actionable suggestions to improve CDS alerts. Additionally, end users appreciate knowing their feedback is being received and may also make other suggestions to improve the electronic health record. Incorporation of end-user feedback into CDS monitoring, evaluation, and remediation is a way to improve CDS.
Studying fusion-born alpha particles in the ITER experiment
Authors: Thompson Avery
Published: October 2022

Details of ITER’s Collective Thomson Scattering diagnostic, which will monitor the dynamics of energetic alpha particles and other fast ions
Electro-optic Bdot probe measurement of magnetic fluctuations in plasma
Authors: Saitoh H. , Nishiura M. , Nakazawa T. , Morikawa J. , Yoshida Z. , Osawa R.
Published: October 2022

We propose a combined use of a Pockels electro-optic sensor with a pickup loop coil (Bdot probe) for the measurement of magnetic fluctuations in plasmas. In this method, induced fluctuating voltage on the coil loop is converted into an optical signal by a compact electro-optic sensor in the vicinity of the measurement point and is transferred across optical fiber that is unaffected by electric noise or capacitive load issues. Compared with conventional Bdot probes, the electro-optic Bdot probe (1) is electrically isolated and free from noise pickup caused by the metallic transmission line and (2) can be operated at a higher-frequency range because of the smaller capacitance of the operation circuit, both of which are suitable for many plasma experiments. Conversely, the sensitivity of the current electro-optic Bdot probe arrangement is still significantly lower than that of conventional Bdot probes. A preliminary measurement result with the electro-optic Bdot probe showed the detection of a magnetic fluctuation signal around the cyclotron frequency range in the RT-1 magnetospheric plasma experiment.