bluuebunny/crossref_metadata_2025 huggingface dataset:
Tight Adherence (Tad) Pilus Genes Indicate Putative Niche Differentiation in Phytoplankton Bloom Associated Rhodobacterales
Authors: Isaac Ashley , Francis Ben , Amann Rudolf I. , Amin Shady A.
Published: August 2021

The multiple interactions of phytoplankton and bacterioplankton are central for our understanding of aquatic environments. A prominent example of those is the consistent association of diatoms with Alphaproteobacteria of the order Rhodobacterales. These photoheterotrophic bacteria have traditionally been described as generalists that scavenge dissolved organic matter. Many observations suggest that members of this clade are specialized in colonizing the microenvironment of diatom cells, known as the phycosphere. However, the molecular mechanisms that differentiate Rhodobacterales generalists and phycosphere colonizers are poorly understood. We investigated Rhodobacterales in the North Sea during the 2010–2012 spring blooms using a time series of 38 deeply sequenced metagenomes and 10 metaproteomes collected throughout these events. Rhodobacterales metagenome assembled genomes (MAGs) were recurrently abundant. They exhibited the highest gene enrichment and protein expression of small-molecule transporters, such as monosaccharides, thiamine and polyamine transporters, and anaplerotic pathways, such as ethylmalonyl and propanoyl-CoA metabolic pathways, all suggestive of a generalist lifestyle. Metaproteomes indicated that the species represented by these MAGs were the dominant suppliers of vitamin B12 during the blooms, concomitant with a significant enrichment of genes related to vitamin B12 biosynthesis suggestive of association with diatom phycospheres. A closer examination of putative generalists and colonizers showed that putative generalists had persistently higher relative abundance throughout the blooms and thus produced more than 80% of Rhodobacterales transport proteins, suggesting rapid growth. In contrast, putative phycosphere colonizers exhibited large fluctuation in relative abundance across the different blooms and correlated strongly with particular diatom species that were dominant during the blooms each year. The defining feature of putative phycosphere colonizers is the presence of the tight adherence (tad) gene cluster, which is responsible for the assembly of adhesive pili that presumably enable attachment to diatom hosts. In addition, putative phycosphere colonizers possessed higher prevalence of secondary metabolite biosynthetic gene clusters, particularly homoserine lactones, which can regulate bacterial attachment through quorum sensing. Altogether, these findings suggest that while many members of Rhodobacterales are competitive during diatom blooms, only a subset form close associations with diatoms by colonizing their phycospheres.
Impact of Prior Infection on Severe Acute Respiratory Syndrome Coronavirus 2 Transmission in Syrian Hamsters
Authors: Zhang Cheng , Guo Zhendong , Li Nan , Cui Huan , Meng Keyin , Liu Lina , Zhao Li , Zhang Shanshan , Qin Chengfeng , Liu Juxiang , Gao Yuwei , Zhang Chunmao
Published: August 2021

Prior infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provides protective immunity against reinfection. However, whether prior infection blocks SARS-CoV-2 transmission is not yet clear. Here, we evaluated the impact of prior infection on SARS-CoV-2 transmission in Syrian hamsters. Our results showed that prior infection significantly reduced SARS-CoV-2 replication in Syrian hamsters, but sterilizing immunity was not achieved. Prior infection blocked the airborne transmission of SARS-CoV-2 from previously infected Syrian hamsters to naïve Syrian hamsters and previously infected Syrian hamsters. Moreover, prior infection substantially reduced the efficiency of direct contact transmission between previously infected Syrian hamsters. However, prior infection had limited impact on SARS-CoV-2 transmission from previously infected Syrian hamsters to naïve Syrian hamsters via direct contact in the early course of infection. Human reinfection and SARS-CoV-2 transmission between a previously infected population and a healthy population would be likely, and a higher vaccination coverage rate was needed to reach herd immunity. Our work will aid the implementation of appropriate public health and social measures to control coronavirus infectious disease 2019 (COVID-19) pandemic.
Reactivity of Thiol-Rich Zn Sites in Diacylglycerol-Sensing PKC C1 Domain Probed by NMR Spectroscopy
Authors: Cole Taylor R. , Igumenova Tatyana I.
Published: August 2021

Conserved homology 1 (C1) domains are peripheral zinc finger domains that are responsible for recruiting their host signaling proteins, including Protein Kinase C (PKC) isoenzymes, to diacylglycerol-containing lipid membranes. In this work, we investigated the reactivity of the C1 structural zinc sites, using the cysteine-rich C1B regulatory region of the PKCα isoform as a paradigm. The choice of Cd2+ as a probe was prompted by previous findings that xenobiotic metal ions modulate PKC activity. Using solution NMR and UV-vis spectroscopy, we found that Cd2+ spontaneously replaced Zn2+ in both structural sites of the C1B domain, with the formation of all-Cd and mixed Zn/Cd protein species. The Cd2+ substitution for Zn2+ preserved the C1B fold and function, as probed by its ability to interact with a potent tumor-promoting agent. Both Cys3His metal-ion sites of C1B have higher affinity to Cd2+ than Zn2+, but are thermodynamically and kinetically inequivalent with respect to the metal ion replacement, despite the identical coordination spheres. We find that even in the presence of the oxygen-rich sites presented by the neighboring peripheral membrane-binding C2 domain, the thiol-rich sites can successfully compete for the available Cd2+. Our results indicate that Cd2+ can target the entire membrane-binding regulatory region of PKCs, and that the competition between the thiol- and oxygen-rich sites will likely determine the activation pattern of PKCs.
Lateral Habenula Inactivation Alters Willingness to Exert Physical Effort Using a Maze Task in Rats
Authors: Sevigny Joshua P. , Bryant Emily N. , Encarnacion Érica , Smith Dylan F. , Acosta Rudith , Baker Phillip M.
Published: August 2021

An impairment in willingness to exert physical effort in daily activities is a noted aspect of several psychiatric conditions. Previous studies have supported an important role for the lateral habenula (LHb) in dynamic decision-making, including decisions associated with discounting costly high value rewards. It is unknown whether a willingness to exert physical effort to obtain higher rewards is also mediated by the LHb. It also remains unclear whether the LHb is critical to monitoring the task contingencies generally as they change, or whether it also mediates choices in otherwise static reward environments. The present study indicates that the LHb might have an integrative role in effort-based decision-making even when no alterations in choice contingencies occur. Specifically, pharmacological inactivation of the LHb showed differences in motivational behavior by reducing choices for the high effort (30cm barrier) high reward (2 pellets) choice versus the low effort (0 cm) low reward (1 pellet) choice. In sessions where the barrier was removed, rats demonstrated a similar preference for the high reward arm under both control and LHb inactivation. Further, no differences were observed when accounting for sex as a biological variable. These results support that effort to receive a high-value reward is considered on a trial-by-trial basis and the LHb is part of the circuit responsible for integrating this information during decision-making. Therefore, it is likely that previously observed changes in the LHb may be a key contributor to changes in a willingness to exert effort in psychiatric conditions.
Dysregulated Microglial Cell Activation and Proliferation Following Repeated Antigen Stimulation
Authors: Prasad Sujata , Sheng Wen S. , Hu Shuxian , Chauhan Priyanka , Lokensgard James R.
Published: August 2021

Upon reactivation of quiescent neurotropic viruses antigen (Ag)-specific brain resident-memory CD8+ T-cells (bTRM) may respond tode novo-produced viral Ag through the rapid release of IFN-γ, which drives subsequent interferon-stimulated gene expression in surrounding microglia. Through this mechanism, a small number of adaptive bTRMmay amplify responses to viral reactivation leading to an organ-wide innate protective state. Over time, this brain-wide innate immune activation likely has cumulative neurotoxic and neurocognitive consequences. We have previously shown that HIV-1 p24 Ag-specific bTRMpersist within the murine brain using a heterologous prime-CNS boost strategy. In response to Ag restimulation, these bTRMdisplay rapid and robust recall responses, which subsequently activate glial cells. In this study, we hypothesized that repeated challenges to viral antigen (Ag) (modeling repeated episodes of viral reactivation) culminate in prolonged reactive gliosis and exacerbated neurotoxicity. To address this question, mice were first immunized with adenovirus vectors expressing the HIV p24 capsid protein, followed by a CNS-boost using Pr55Gag/Env virus-like particles (HIV-VLPs). Following the establishment of the bTRMpopulation [>30 days (d)], prime-CNS boost animals were then subjected toin vivochallenge, as well as re-challenge (at 14 d post-challenge), using the immunodominant HIV-1 AI9 CD8+ T-cell epitope peptide. In these studies, Ag re-challenge resulted in prolonged expression of microglial activation markers and an increased proliferative response, longer than the challenge group. This continued expression of MHCII and PD-L1 (activation markers), as well as Ki67 (proliferative marker), was observed at 7, 14, and 30 days post-AI9 re-challenge. Additionally,in vivore-challenge resulted in continued production of inducible nitric oxide synthase (iNOS) with elevated levels observed at 7, 14 and 30 days post re-challenge. Interestingly, iNOS expression was significantly lower among challenged animals when compared to re-challenged groups. Furthermore,in vivospecific Ag re-challenge produced lower levels of arginase (Arg)-1 when compared with the challenged group. Taken together, these results indicate that repeated Ag-specific stimulation of adaptive immune responses leads to cumulative dysregulated microglial cell activation.
Clopidogrel Resistance in Patients With Stroke Recurrence Under Single or Dual Antiplatelet Treatment
Authors: Kang Hyun Goo , Lee Seung Jae , Heo Sung Hyuk , Chang Dae-il , Kim Bum Joon
Published: August 2021

Background: The factors associated with clopidogrel resistance in patients with stroke recurrence receiving single or dual antiplatelet treatment (SAPT or DAPT) may differ. This study compared the high on-treatment platelet reactivities (HPRs) and the factors associated with clopidogrel resistance in recurrent ischemic stroke patients receiving clopidogrel or aspirin and clopidogrel.

Methods: We enrolled and allocated 275 recurrent ischemic stroke patients to the clopidogrel and DAPT groups and compared their demographics, conventional risk factors, and P2Y12 reaction units (PRUs). Clopidogrel resistance was categorized as PRU higher than 275. We performed a multivariate logistic regression analysis to determine the factors underlying clopidogrel resistance during SAPT and DAPT.

Results: In total, 145 (52.7%) and 130 (47.3%) patients received clopidogrel and DAPT, respectively at recurrence. The risk factors of the two groups were not significantly different, except that coronary artery disease was more frequent in the DAPT group. The PRU was higher (255 ± 91 vs. 221 ± 84; p = 0.002) and clopidogrel resistance was more frequent (45.5 vs. 31.5%; p = 0.018) in the SAPT than in the DAPT group. Hyperlipidemia was associated with clopidogrel resistance during SAPT, and smoking (Odds ratio = 0.426, 95% confidence interval 0.210–0.861; p = 0.018) had a protective effect against clopidogrel resistance. For those receiving DAPT, old age, female, low hemoglobin A1c level, and high ARU were associated with clopidogrel resistance.

Conclusions: HPR and clopidogrel resistance were more frequent in recurrent ischemic stroke patients receiving clopidogrel than in those receiving DAPT. Smoking was independently associated with less clopidogrel resistance among those receiving clopidogrel SAPT but not in those receiving DAPT.
Case Report: Paraneoplastic Hashimoto's Encephalopathy Associated With Lymphomatosis Cerebri With Periodic Synchronous Discharges Resembling Creutzfeldt–Jakob Disease
Authors: Amano Ryota , Tsukada Setsuro , Kosuge Shota , Yano Satoshi , Ono Kenjiro , Yoneda Makoto , Taki Katsumi
Published: August 2021

Hashimoto's encephalopathy (HE) is an autoimmune encephalopathy that presents with various clinical symptoms, including cognitive deterioration, convulsive seizures, and personality changes. HE is associated with thyroid autoimmunity; however, few cases have been reported to develop as paraneoplastic syndrome. Herein, we report the case of a 73-year-old woman with onset of rapidly progressive dementia. Brain magnetic resonance imaging showed diffuse T2 hyperintensity areas involving the bilateral cerebral white matter, right midbrain tegmental area, left cerebral peduncle, and right middle cerebellar peduncle without clear diffusion hyperintensities and gadolinium enhancement. Her neurological symptoms worsened rapidly, and she presented with the apallic syndrome. Electroencephalogram showed periodic synchronous discharge, suggestive of Creutzfeldt–Jakob disease. However, a brain biopsy revealed infiltration of atypical lymphoid cells expressing CD20, and the anti-NH2 terminal of the α-enolase antibody was detected, diagnosing the complication with lymphomatosis cerebri and HE. High-dose intravenous methylprednisolone therapy and oral prednisolone with whole cranial irradiation enabled her to have simple conversations and consume food orally; however, severe cognitive impairment persisted. Although HE is a rare complication of malignant lymphoma, clinicians should be aware that it could be strongly suspected if the clinical symptoms worsen in the absence of imaging changes.
Neural Correlates of Garment Fit and Purchase Intention in the Consumer Decision-Making Process and the Influence of Product Presentation
Authors: Kim Hesun Erin , Kwon Joon Hee , Kim Jae-Jin
Published: August 2021

In today’s competitive e-commerce markets, it is crucial to promote product satisfaction and to quickly identify purchase intention in decision-making consumers. The present investigation examined the relationship between perceived garment fit and purchase intention, together with how product presentation methods (mannequin versus self-model) contribute to decision-making processes of clothing. Thirty-nine female volunteers were scanned using fMRI while performing an online shopping task. In Part 1, univariate analysis was conducted between garment fit and product presentation factors to assess their effects on purchase deliberation. In Part 2, univariate, multivariate pattern, and psychophysiological interaction analyses were carried out to examine the predictive ability of fit evaluation and product presentation on purchase intention. First, garment fit × product presentation interaction effects on purchase deliberation were observed in the frontopolar cortex, superior frontal gyrus, anterior cingulate cortex, and posterior cingulate cortex. Part 2 demonstrated neural signals of the dorsomedial prefrontal cortex, premotor cortex, supplementary motor area, superior parietal lobule, supramarginal gyrus, superior temporal sulcus, fusiform gyrus, and insula to distinguish subsequent purchase intentions. Overall, the findings denote directed exploration, visual and action processing as key neural processes in decision-making that uniquely reflect garment fit and product presentation type during purchase deliberation. Additionally, with respect to the effects of purchase intention on product evaluation, the evidence conveys that mental interactions with products and social cognition are fundamental processes that capture subsequent purchase intention at the product evaluation stage.
Functional Connectivity Within the Fronto-Parietal Network Predicts Complex Task Performance: A fNIRS Study
Authors: Chenot Quentin , Lepron Evelyne , De Boissezon Xavier , Scannella Sébastien
Published: August 2021

Performance in complex tasks is essential for many high risk operators. The achievement of such tasks is supported by high-level cognitive functions arguably involving functional activity and connectivity in a large ensemble of brain areas that form the fronto-parietal network. Here we aimed at determining whether the functional connectivity at rest within this network could predict performance in a complex task: the Space Fortress video game. Functional Near Infrared Spectroscopy (fNIRS) data from 32 participants were recorded during a Resting-State period, the completion of a simple version of Space Fortress (monotask) and the original version (multitask). The intrinsic functional connectivity within the fronto-parietal network (i.e., during the Resting-State) was a significant predictor of performance at Space Fortress multitask but not at its monotask version. The same pattern was observed for the functional connectivity during the task. Our overall results suggest that Resting-State functional connectivity within the fronto-parietal network could be used as an intrinsic brain marker for performance prediction of a complex task achievement, but not for simple task performance.
Nanopesticides: A Systematic Review of Their Prospects With Special Reference to Tea Pest Management
Authors: Deka Bhabesh , Babu Azariah , Baruah Chittaranjan , Barthakur Manash
Published: August 2021

Background: Tea is a natural beverage made from the tender leaves of the tea plant (Camellia sinensis Kuntze). Being of a perennial and monoculture nature in terms of its cultivation system, it provides a stable micro-climate for various insect pests, which cause substantial loss of crop. With the escalating cost of insect pest management and increasing concern about the adverse effects of the pesticide residues in manufactured tea, there is an urgent need to explore other avenues for pest management strategies.

Aim: Integrated pest management (IPM) in tea invites an multidisciplinary approach owing to the high pest diversity in the perennial tea plantation system. In this review, we have highlighted current developments of nanotechnology for crop protection and the prospects of nanoparticles (NPs) in plant protection, emphasizing the control of different major pests of tea plantations.

Methods: A literature search was performed using the ScienceDirect, Web of Science, Pubmed, and Google Scholar search engines with the following terms: nanotechnology, nanopesticides, tea, and insect pest. An article search concentrated on developments after 1988.

Results: We have described the impact of various pests in tea production and innovative approaches on the use of various biosynthesized and syntheric nanopesticides against specific insect pest targets. Simultaneously, we have provided support for NP-based technology and their different categories that are currently employed for the management of pests in different agro-ecosystems. Besides the broad categories of active ingredients (AI) of synthetic insecticides, pheromones and natural resource-based molecules have pesticidal activity and can also be used with NPs as a carriers as alternatives to traditional pest control agents. Finally, the merits and demerits of incorporating NP-based nanopesticides are also illustrated.

Conclusions: Nanopesticides for plant protection is an emerging research field, and it offers new methods to design active ingredients amid nanoscale dimensions. Nanopesticide-based formulations have a potential and bright future for the development of more effective and safer pesticide/biopesticides.
The Role of Polydimethylsiloxane in Suppressing the Evolution of Lipid Oxidation Products in Thermo-Oxidised Sunflower Oil: Influence of Stirring Processes
Authors: Ampem Gilbert , Le Gresley Adam , Grootveld Martin , Naughton Declan P.
Published: August 2021

Suppressing the evolution of lipid oxidation products (LOPs) in commercially available culinary oils is considered to represent a valuable health-promoting incentive since these agents have cytotoxic and genotoxic properties and have been implicated in the pathogenesis of several chronic disease states. One agent used to suppress LOPs formation is polydimethylsiloxane (PDMS). In this study, proton nuclear magnetic resonance (1H NMR) analysis was employed to evaluating the influence of increasing PDMS concentrations (6.25 × 10−7, 1.0 × 10−5, 0.025, 0.05, 0.1, 0.5, 1.0, 5.0, and 10.0 ppm) in either stirred or unstirred refined sunflower oil exposed to thermal stressing episodes continuously at 180°C for 300 min with no oil replenishment. Results acquired showed that the extent of blockage of LOPs generation was correlated with increasing concentrations of PDMS. The minimal level of added PDMS required to provide a statistically significant protective role for both stirred and unstirred culinary oils when exposed to high frying temperatures was only 6.25 × 10−7 ppm. Furthermore, stirring at 250 rpm was experimentally determined to reduce the functional role PDMS. This is vital in a real world setting since the boiling process of frying may ultimately reduce the LOPs suppression activity of PDMS.
EGFR DNA Methylation Correlates With EGFR Expression, Immune Cell Infiltration, and Overall Survival in Lung Adenocarcinoma
Authors: Xu Zhanyu , Qin Fanglu , Yuan Liqiang , Wei Jiangbo , Sun Yu , Qin Junqi , Deng Kun , Zheng Tiaozhan , Li Shikang
Published: August 2021

Background

The epidermal growth factor receptor (EGFR) is a primary target of molecular targeted therapy for lung adenocarcinoma (LUAD). The mechanisms that lead to epigenetic abnormalities of EGFR in LUAD are still unclear. The purpose of our study was to evaluate the abnormal methylation of EGFR CpG sites as potential biomarkers for LUAD.

Methods

To assess the differentially methylation CpG sites of EGFR in LUAD, we used an integrative study of Illumina HumanMethylation450K and RNA-seq data from The Cancer Genome Atlas (TCGA). We evaluated and compared EGFR multiple-omics data to explore the role of CpG sites located in EGFR promoter regions and gene body regions and the association with transcripts, protein expression levels, mutations, and somatic copy number variation. We calculated the correlation coefficients between CpG sites of EGFR and immune infiltration fraction (by MCPcounter and ESTIMATE) and immune-related pathways in LUAD. Finally, we validated the differential methylation of clinically and prognostically relevant CpG sites using quantitative methylation-specific PCR (qMSP).

Results

We found that the methylation level of many EGFR CpGs in the promoter region was negatively correlated with the transcription level, protein expression, and SCNV, while the methylation at the gene body region was positively correlated with these features. The methylation level of EGFR CpGs in the promoter region was positively correlated with the level of immune infiltration and IFN-γ signature, while the opposite was found for methylation of the gene body region. The qMSP results showed that cg02316066 had a high methylation level, while cg02166842 had a low methylation level in LUAD. There was a high degree of co-methylation between cg02316066 and cg03046247.

Conclusion

Our data indicate that EGFR is an epigenetic regulator in LUAD acting through DNA methylation. Our research provides a theoretical basis for the further detection of EGFR DNA methylation as a predictive biomarker for LUAD survival and immunotherapy.
Mutational Analysis of PBRM1 and Significance of PBRM1 Mutation in Anti-PD-1 Immunotherapy of Clear Cell Renal Cell Carcinoma
Authors: Aili Abudureyimujiang , Wen Jie , Xue Lixiang , Wang Junjie
Published: August 2021

Renal cell carcinoma is a common solid tumor. PBRM1 is one of the most mutation-prone genes in clear cell renal cell carcinoma (ccRCC) with the occurrence of mutation in 40% of ccRCC patients. Mutations in PBRM1 have been correlated with the efficacy of immunotherapy. However, the mutation types of PBRM1 are not well characterized. The effects of PBRM1 expression levels in the tumor microenvironment are not well studied. In addition, the mechanism and effect of anti-PD-1 immunotherapy in ccRCC tumor microenvironments are not well clarified. In this study, using bioinformatics methods we analyzed the alternation frequency and expression levels of PBRM1 in various tumors. Next, we experimentally validated their expression levels in ccRCC tissues from human and mouse models. We attempted to clarify the mechanisms of anti-PD-1 immunotherapy in ccRCC with various PBRM1 expression levels. Our results showed that deficiency of PBRM1 protein is correlated with CD4 T cell reduction in human and mouse ccRCC tissues. We also showed that anti-PD-1 Immunotherapy can increase the infiltration of T cells in both PBRM1 high and PBRM1 low tumors but to different degrees. Our study indicates that the reduction of CD4 cells in tumor tissues with low expression of PBRM1 may explain the compromised efficacy of anti-PD-1 immunotherapy in patients with PBRM1 mutated ccRCC. Our study sheds light on the potential of PBRM1 as a therapeutic target in ccRCC.
Case Report: Immune Dysregulation Due to Toxoplasma gondii Reactivation After Allogeneic Hematopoietic Cell Transplant
Authors: Lindell Robert B. , Wolf Michael S. , Alcamo Alicia M. , Silverman Michael A. , Dulek Daniel E. , Otto William R. , Olson Timothy S. , Kitko Carrie L. , Paueksakon Paisit , Chiotos Kathleen
Published: August 2021

Disseminated toxoplasmosis is an uncommon but highly lethal cause of hyperferritinemic sepsis after hematopoietic cell transplantation (HCT). We report two cases of disseminated toxoplasmosis from two centers in critically ill adolescents after HCT: a 19-year-old who developed fever and altered mental status on day +19 after HCT and a 20-year-old who developed fever and diarrhea on day +52 after HCT. Both patients developed hyperferritinemia with multiple organ dysfunction syndrome and profound immune dysregulation, which progressed to death despite maximal medical therapies. Because disseminated toxoplasmosis is both treatable and challenging to diagnose, it is imperative that intensivists maintain a high index of suspicion for Toxoplasma gondii infection when managing immunocompromised children, particularly in those with known positive T. gondii serologies.
Trends in Topical Prescriptional Therapy for Old Patients With Dry Eye Disease in Six Major Areas of China: 2013–2019
Authors: Yu Zhenwei , Wu Xiaoyan , Zhu Jianping , Jin Jiayi , Zhao Yuhua , Yu Lingyan
Published: August 2021

The prevalence of dry eye disease (DED) in old patients are high, corresponding to a substantial economic burden. In this cross-sectional study, we analyzed the trends in the topical prescriptional treatment of old patients with DED in six major areas of China. Information on topical drug prescriptions for DED patients aged above 60 years was extracted from the Hospital Prescription Analysis Cooperative Program of China database. Trends in yearly prescriptions and cost were analyzed. The data were further stratified by patient age and sex, drug class, and specific drug. A total of 130,734 prescriptions from 52 hospitals located in six major areas of China were analyzed. The number of prescripptions per year for patients with DED increased from 13,308 in 2013 to 22,074 in 2019, with a corresponding increase in cost of all topical drugs from 1,490,014 Chinese Yuan (CNY) to 2,618,206 CNY. Drugs for the treatment of DED accounted for the largest proportion of the total cost in each year. Ocular lubricants were the main pharmacotherapy agent. Sodium hyaluronate use increased over time, and the drug was used by 65.9% of patients by the end of the study. Pranoprofen was the second most frequently used drug. The most frequently used drugs for co-incident disease were antimicrobials. Treatment patterns for DED haven’t changed, and the most frequently used drug combination was sodium hyaluronate and pranoprofen. In summary, prescription for old patients with DED and the cost of treatment are increasing. Ocular lubricants are the main treatment option, while sodium hyaluronate is the most frequently used drug. The observed trends can lead to more efficient allocation of health care resources in China.
An Overview of Cell-Based Assay Platforms for the Solute Carrier Family of Transporters
Authors: Dvorak Vojtech , Wiedmer Tabea , Ingles-Prieto Alvaro , Altermatt Patrick , Batoulis Helena , Bärenz Felix , Bender Eckhard , Digles Daniela , Dürrenberger Franz , Heitman Laura H. , IJzerman Adriaan P. , Kell Douglas B. , Kickinger Stefanie , Körzö Daniel , Leippe Philipp , Licher Thomas , Manolova Vania , Rizzetto Riccardo , Sassone Francesca , Scarabottolo Lia , Schlessinger Avner , Schneider Vanessa , Sijben Hubert J. , Steck Anna-Lena , Sundström Hanna , Tremolada Sara , Wilhelm Maria , Wright Muelas Marina , Zindel Diana , Steppan Claire M. , Superti-Furga Giulio
Published: August 2021

The solute carrier (SLC) superfamily represents the biggest family of transporters with important roles in health and disease. Despite being attractive and druggable targets, the majority of SLCs remains understudied. One major hurdle in research on SLCs is the lack of tools, such as cell-based assays to investigate their biological role and for drug discovery. Another challenge is the disperse and anecdotal information on assay strategies that are suitable for SLCs. This review provides a comprehensive overview of state-of-the-art cellular assay technologies for SLC research and discusses relevant SLC characteristics enabling the choice of an optimal assay technology. The Innovative Medicines Initiative consortium RESOLUTE intends to accelerate research on SLCs by providing the scientific community with high-quality reagents, assay technologies and data sets, and to ultimately unlock SLCs for drug discovery.
Processing Non-at-Issue Meanings of Conditional Connectives: The wenn/falls Contrast in German
Authors: Liu Mingya
Published: August 2021

Logical connectives in natural language pose challenges to truth-conditional semantics due to pragmatics and gradience in their meaning. This paper reports on a case study of the conditional connectives (CCs)wenn/falls‘if/when, if/in case’ in German. Using distributional evidence, I argue thatwennandfallsdiffer in lexical pragmatics: They express different degrees of speaker commitment (i.e., credence) toward the modified antecedent proposition at the non-at-issue dimension. This contrast can be modeled using the speaker commitment scale (Giannakidou and Mari, 2016), i.e.,More committedLess committed. Four experiments are reported which tested thewenn/fallscontrast, as well as the summary of an additional one fromLiu (2019). Experiment 1 tested the naturalness of sentences containing the CCs (wennorfalls) and conditional antecedents with varying degrees of likelihood (very likely/likely/unlikely). The starting prediction was thatfallsmight be degraded in combination with very likely and likely events in comparison to the other conditions, which was not borne out. Experiment 2 used the forced lexical choice paradigm, testing the choice betweenwennandfallsin the doxastic agent’s conditional thought, depending on their belief or disbelief in the antecedent. The finding was that subjects chosefallssignificantly more often thanwennin the disbelief-context, and vice versa in the belief-context. Experiment 3 tested the naturalness of sentences with CCs and an additional relative clause conveying the speaker’s belief or disbelief in the antecedent. An interaction was found: While in the belief-context,wennwas rated more natural thanfalls, the reverse pattern was found in the disbelief-context. While the results are mixed, the combination of the findings in Experiment 2, Experiment 3 and that of Experiment 4a fromLiu (2019)thatfallsled to lower speaker commitment ratings thanwenn, provide evidence for the CC scale. Experiment 4b tested the interaction between two speaker commitment scales, namely, one of connectives (includingweil‘because’ andwenn/falls) and the other of adverbs (factive vs. non-factive,Liu, 2012). While factive and non-factive adverbs were rated equally natural for the factive causal connective, non-factive adverbs were preferred over factive ones by both CCs, with no difference betweenwennandfalls. This is discussed together with the result inLiu (2019), where thewenn/fallsdifference occurred in the absence of negative polarity items (NPIs), but disappeared in the presence of NPIs. This raises further questions on how different speaker commitment scales interact and why.
A Just Assemblage in Mental Health Services—the Necessity of and Possibilities for Service Diversity
Authors: Sundet Rolf
Published: August 2021

Basic to the Norwegian welfare state is the principle of universality; every citizen has the right to equal health care and social services. Experiences from a family team in mental health care for children and adolescents exemplify challenges for mental health work in this welfare state. These experiences indicate an ongoing process of dismantling the welfare state, disguised as managerial changes and reorganizations. The argument is put forth that these changes and reorganizations that are claimed to benefit service users actually have negative consequences for many of them. These negative consequences are related to how psychological research on and knowledge of mental health and treatment are combined with organizational principles. The concept of an assemblage is introduced as a manner of describing the dominating relationships in health care between the medical model, the randomized controlled trial and new public management in order to provide responsible health care practices. Rooted in a supposition that how we look upon, describe and understand causation defines our views of science in general, how to produce knowledge, what kind of scientific knowledge is most productive, and how it should be implemented in practice, an alternative assemblage is suggested that better realizes the principle of universality. Here justice is about equal opportunities and equal rights to treatments and sets of practices that fit people as unique individuals. Such an assemblage would bring together diverse models of mental health care, a network of multiple research-based knowledges, and service organizations that include the differences and diversity of the population.
Effect of Virtual Reality on Stress Reduction and Change of Physiological Parameters Including Heart Rate Variability in People With High Stress: An Open Randomized Crossover Trial
Authors: Kim Hyewon , Kim Dong Jun , Kim Seonwoo , Chung Won Ho , Park Kyung-Ah , Kim James D. K. , Kim Dowan , Kim Min Ji , Kim Kiwon , Jeon Hong Jin
Published: August 2021

Introduction: Although, attempts to apply virtual reality (VR) in mental healthcare are rapidly increasing, it is still unclear whether VR relaxation can reduce stress more than conventional biofeedback.

Methods: Participants consisted of 83 healthy adult volunteers with high stress, which was defined as a score of 20 or more on the Perceived Stress Scale-10 (PSS-10). This study used an open, randomized, crossover design with baseline, stress, and relaxation phases. During the stress phase, participants experienced an intentionally generated shaking VR and serial-7 subtraction. For the relaxation phase, participants underwent a randomly assigned relaxation session on day 1 among VR relaxation and biofeedack, and the other type of relaxation session was applied on day 2. We compared the State-Trait Anxiety Inventory-X1 (STAI-X1), STAI-X2, the Numeric Rating Scale (NRS), and physiological parameters including heart rate variability (HRV) indexes in the stress and relaxation phases.

Results: A total of 74 participants were included in the analyses. The median age of participants was 39 years, STAI-X1 was 47.27 (SD = 9.92), and NRS was 55.51 (SD = 24.48) at baseline. VR and biofeedback significantly decreased STAI-X1 and NRS from the stress phase to the relaxation phase, while the difference of effect between VR and biofeedback was not significant. However, there was a significant difference in electromyography, LF/HF ratio, LF total, and NN50 between VR relaxation and biofeedback.

Conclusion: VR relaxation was effective in reducing subjectively reported stress in individuals with high stress.
Adversity Over the Life Course: A Comparison Between Women and Men Who Died by Suicide
Authors: Séguin Monique , Beauchamp Guy , Notredame Charles-Édouard
Published: August 2021

Purpose: This study sets out to compare the presence of life events across different domains throughout the life course which may contribute to the burden of adversity experienced differently among men and women who died by suicide.

Method: In a sample of 303 individuals (213 men and 90 women), data was derived from extensive clinical interviews conducted with informants. Models allowed the identification of patterns of life trajectories.

Results: Overall, the burden of adversity was similar across the life course except for the 5–9, 25–29, and 30–34 age ranges, where a significant difference appeared between genders [t-test = 2.13 (p < 0.05), 2.16 (p < 0.05) and 3.08 (p < 0.005), respectively] that seems to disadvantage women. The early adversities of violence and neglect, between 0 and 19 years old, are important for both groups. During the life course, women were more exposed to interpersonal adverse events such as being victims of negligence and violence, relational difficulties or abuse from their spouse, as well as tension with their own children. Men encountered more academic difficulties, legal entanglements and financial difficulties, and were more than three times more likely to develop an alcohol/drug abuse problem than women.

Conclusions: The data suggests some gender differences in exposure to longstanding and severe life problems contributing to suicide vulnerability. For women, the continuing burden emerges from chronic interpersonal adversities, whereas, for men, the adverse events are to a larger degree socially exposed, compounded with alcohol misuse. The adversities, especially those of a public or social nature, may be witnessed by others, which should favor the detection of vulnerability over the life course, and psychosocial or mental health services should be offered and provided earlier during the life course. Yet more men die by suicide than women. Resiliency and protective factors may benefit women to a greater degree. Future research should tackle the challenge of investigating these important elements. Meanwhile, from a public health perspective, access to psychosocial and mental health services and social acceptability of seeking services should be part of an ongoing effort in all institutional structures as a way of decreasing downstream mental health problems and vulnerability to suicide.
Comparison of the Efficacy of Disinfectant Pre-impregnated Wipes for Decontaminating Stainless Steel Carriers Experimentally Inoculated With Ebola Virus and Vesicular Stomatitis Virus
Authors: Cutts Todd A. , Kasloff Samantha B. , Krishnan Jay , Nims Raymond W. , Theriault Steven S. , Rubino Joseph R. , Ijaz M. Khalid
Published: August 2021

The authors evaluated four disinfectant pre-impregnated wipes (DPW) for efficacy against Ebola virus Makona variant (EBOV) and vesicular stomatitis virus (VSV), Indiana serotype. Steel carriers were inoculated with the infectious virus and then were wiped with DPW in the Wiperator instrument per ASTM E2967-15. Following the use of J-Cloth impregnated with medium (negative control wipes) or the use of activated hydrogen peroxide (AHP)-, ethanol-, sodium hypochlorite (NaOCl)-, or single or dual quaternary ammonium compound (QAC)-based DPW, virus recovery from the carriers was assayed by titration assay and by two passages on Vero E6 cells in 6-well plates. The Wiperator also enabled the measurement of potential transfer of the virus from the inoculated carrier to a secondary carrier by the DPW or control wipes. The J-Cloth wipes wetted with medium alone (no microbicidal active) removed 1.9–3.5 log10 of virus from inoculated carriers but transferred ~4 log10 of the wiped virus to secondary carriers. DPW containing AHP, ethanol, NaOCl, or single or dual QAC as active microbicidal ingredients removed/inactivated ~6 log10 of the virus, with minimal EBOV or no VSV virus transfer to a secondary surface observed. In Ebola virus outbreaks, a DPW with demonstrated virucidal efficacy, used as directed, may help to mitigate the unintended spread of the infectious virus while performing surface cleaning.
Reduced Graphene Oxide Carbon Yarn Electrodes for Drug Sensing
Authors: Sriprasertsuk Sutthima , Zhang Shuai , Wallace Gordon , Chen Jun , Varcoe John R. , Crean Carol
Published: August 2021

A modified carbon fibre yarn sensor was developed for the voltammetric determination of paracetamol and its interferents (dopamine and ascorbic acid). Reduced graphene oxide (rGO) was electrochemically deposited onto a carbon fibre yarn. Further modification was achieved using polypyrrole (PPy) coated onto the rGO carbon fibre yarn via electropolymerisation of pyrrole with cyclic voltammetry (CV). The surface of the rGO and PPy-rGO carbon fibre electrodes were characterised using Raman spectroscopy and scanning electron microscopy. The rGO and PPy-rGO carbon fibres had a 3.5-fold and 7-fold larger electrochemical surface area compared to bare carbon fibre (calculated using the Randles-Sevcik equation). Two clearly distinguished oxidation peaks at 0.49 and 0.25 V (vs. Ag/AgCl) were observed at the rGO fibre electrode during the simultaneous detection of paracetamol and dopamine, respectively, by CV. The detection limit (3σ S/N) of the rGO carbon fibre electrode for differential pulse voltammetry (DPV) determination of paracetamol was at 21.1 and 6.0 µM for dopamine. In comparison, the simultaneous determination of paracetamol and dopamine by CV at the PPy-rGO fibre electrode gave oxidation peaks of paracetamol and dopamine at 0.55 and 0.25 V (vs. Ag/AgCl), respectively. The detection limit (3σ S/N) for paracetamol was notably improved to 3.7 µM and maintained at 6.0 µM for dopamine at the PPy-rGO carbon fibre electrode during DPV.
Head and Body Dyskinesia During Gait in Tactical Athletes With Vestibular Deficit Following Concussion
Authors: Fraser John J. , VanDehy Jacob , Bodell Dawn M. , Gottshall Kim R. , Sessoms Pinata H.
Published: August 2021

Background: Vestibular deficit is common following concussion and may affect gait. The purpose of this study was to investigate differences in head and pelvic center of mass (COM) movement during gait in military tactical athletes with and without concussion-related central vestibular impairment.

Material and Methods: 24 patients with post-concussion vestibular impairment (20 males, 4 females; age: 31.7 ± 7.9 years; BMI: 27.3 ± 3.3) and 24 matched controls (20 males, 4 females; age: 31.8 ± 6.4 years; BMI: 27.2 ± 2.6) were included in the analyses. Three-dimensional head and pelvic displacement and velocities were collected at a 1.0 m/s standardized treadmill walking speed and assessed using Statistical Parametric Mapping t-tests. Maximum differences (dmax) between groups were reported for all significant kinematic findings.

Results: The Vestibular group demonstrated significantly diminished anteroposterior head excursions (dmax = 2.3 cm, p = 0.02) and slower anteroposterior (dmax = 0.37 m/s, p = 0.01), mediolateral (dmax = 0.47 m/s, p = 0.02) and vertical (dmax = 0.26 m/s, p < 0.001) velocities during terminal stance into pre-swing phases compared to the Control group. Vertical pelvic excursion was significantly increased in midstance (dmax = 2.4 cm, p = 0.03) and mediolaterally during pre- to initial-swing phases (dmax = 7.5 cm, p < 0.001) in the Vestibular group. In addition, pelvic velocities of the Vestibular group were higher mediolaterally during midstance (dmax = 0.19 m/s, p = 0.02) and vertically during post-initial contact (dmax = 0.14 m/s, p < 0.001) and pre-swing (dmax = 0.16 m/s, p < 0.001) compared to the Control group.

Significance: The Vestibular group demonstrated a more constrained head movement strategy during gait compared with Controls, a finding that is likely attributed to a neurological impairment of visual-vestibular-somatosensory integration.
Interactive Video Simulation for Remote Healthcare Learning
Authors: Musa Dahlia , Gonzalez Laura , Penney Heidi , Daher Salam
Published: August 2021

Simulation is an essential component of healthcare education as it enables educators to replicate clinical scenarios in a controlled learning environment. Simulation has traditionally been conducted in-person through the use of manikins, however, the COVID-19 pandemic has challenged the practice of manikin simulation. Social distance constraints were enforced during the pandemic to reduce the potential spread of the virus and as a result, many educators and students were denied physical access to their universities' simulation facilities. Healthcare educators sought remote alternatives to manikin simulation and many resorted to instructional videos to educate their learners. While the use of videos increases safety, passively watching videos lacks interactivity which is an important component of simulation learning. In response to these challenges, we developed an interactive video simulation software that uses educators' existing video content to conduct a simulation remotely, thereby promoting safety during the pandemic while also meeting the interactivity standards of best practice for healthcare simulation. In this paper, we compare the interactive video simulation to the current practice of watching non-interactive video of a simulation using the same content. We found that interactivity promotes higher order learning, increases teamwork and enhances the perception of authenticity. Additionally, the majority of participants demonstrated positive reception of the interactive simulation. The simulation software provides the safety desired of a remote simulation during the pandemic while also engaging students in interactive learning experiences.
Effect of Lactobacillus johnsonii Strain SQ0048 on the TLRs-MyD88/NF-κB Signaling Pathway in Bovine Vaginal Epithelial Cells
Authors: Cheng Chao , Zhang Linchong , Mu Junxiang , Tian Qiaozhen , Liu Yanming , Ma Xiaohong , Fu Yanru , Liu Zhiguo , Li Zhenjun
Published: August 2021

Vaginal inflammation is a common disease of the dairy cows' reproductive tract. Lactic acid bacteria can combat purulent inflammation caused by pathogenic bacteria and regulate the NF-κB signaling pathway mediated by toll-like receptors (TLRs) in the inflammatory response. We studied the effect of Lactobacillus johnsonii SQ0048, an isolate with antibacterial activity, on the NF-κB signaling pathway in cow vaginal epithelial cells. The expression levels of serial effectors related to the TLRs-MyD88/NF-κB signaling pathway (TLR2, TLR4, MyD88, IKK, NF-κB, IL-1β, IL-6, TNF-α, and IL-10) were measured with real-time polymerase chain reaction (RT-PCR), ELISA, and Western blot analyses. TLR2 and TLR4 were activated by SQ0048 cells, as noted by increased mRNA expression levels of TLR2 and TLR4 in SQ0048-treated bovine vaginal epithelial cells relative to control cells (P <0.01). SQ0048 treatment also significantly increased MyD88 and IKK expression, and activated NF-κB in vaginal epithelial cells (P <0.01). In addition, SQ0048 treatment also significantly increased mRNA expression levels of IL-1β, IL-6, and TNF-α, but decreased IL-10 mRNA expression levels (P <0.01). These data indicate that strain SQ0048 presence can improve the immune functions of cow vaginal epithelial cells by activating TLRs-MyD88/NF-κB signaling pathways. However, further in vivo studies are required to confirm these findings.