bluuebunny/crossref_metadata_2025 huggingface dataset:
Paediatric rhombencephalitis presenting with bradycardia: a good recovery despite cardiac involvement
Authors: Stokes Victoria , Milner Sarah , Surridge Julia
Published: November 2021

Rhombencephalitis is a rare condition, often caused by infection, commonly presenting with myoclonic jerks, ataxia and cranial nerve palsy. Typically, it has a high morbidity and mortality, with worse prognosis associated with cardiopulmonary involvement. Herein, we present the case of a 10-year-old boy, presenting with headache, vomiting, symptomatic bradycardia and rapidly progressing ophthalmoplegia from a sixth nerve palsy, without additional brainstem symptoms. Previously, pericarditis, myocarditis and heart failure have been associated with rhombencephalitis, but not bradycardia. The cause of his rhombencephalitis was presumed viral, but despite extensive screening, the virus responsible was never isolated. Following treatment with intravenous antibiotics and antivirals in a high dependency unit, he recovered well with no neurological deficit on discharge and marked radiological improvement on MRI 4 weeks later. Although rare, rhombencephalitis should be considered in a child presenting with neurological symptoms, particularly alongside a cranial nerve palsy, developing over a rapid time course.
Identifying low-risk chest pain in the emergency department without troponin testing: a validation study of the HE-MACS and HEAR risk scores
Authors: Todd Fraser , Duff James , Carlton Edward
Published: November 2021

Introduction

Patients presenting to EDs with chest pain of possible cardiac origin represent a substantial and challenging cohort to risk stratify. Scores such as HE-MACS (History and Electrocardiogram-only Manchester Acute Coronary Syndromes decision aid) and HEAR (History, ECG, Age, Risk factors) have been developed to stratify risk without the need for troponin testing. Validation of these scores remains limited.

Methods

We performed a post hoc analysis of the Limit of Detection and ECG discharge strategy randomised-controlled trial dataset (n=629; June 2018 to March 2019; 8 UK hospitals) to calculate HEAR and HE-MACS scores. A <4% risk of major adverse cardiac events (MACE) at 30 days using HE-MACS and a score of <2 calculated using HEAR defined ‘very low risk’ patients suitable for discharge. The primary outcome of MACE at 30 days was used to assess diagnostic accuracy.

Results

MACE within 30 days occurred in 42/629 (7%) of the cohort. HE-MACS and HEAR scores identified 85/629 and 181/629 patients as ‘very low risk’, with MACE occurring in 0/85 and 1/181 patients, respectively. The sensitivities of each score for ruling out MACE were 100% (95% CI: 91.6% to 100%) for HE-MACS and 97.6% (95% CI: 87.7% to 99.9%) for HEAR. Presenting symptoms within these scores were poorly predictive, with only diaphoresis reaching statistical significance (OR: 4.99 (2.33 to 10.67)). Conventional cardiovascular risk factors and clinician suspicion were related to the presence of MACE at 30 days.

Conclusion

HEAR and HE-MACS show potential as rule out tools for acute myocardial infarction without the need for troponin testing. However, prospective studies are required to further validate these scores.
25 Potential role of serum proteome in predicting immune-related adverse events from immunotherapy in non-small cell lung cancer
Authors: Kim Leeseul , Chae Young Kwang , Lee Dong-Uk
Published: November 2021

Background

Predicting immune-related adverse events (irAEs) in early stage is being emphasized even more. Host response to disease is reflected in serum proteome level and that allows serum proteome level as a new marker to explore response to immunotherapy. With the help of a serum-based proteomics test, Primary Immune Response (PIR), we are accessing the correlations between developing irAEs and immunotherapy in non-small cell lung cancer (NSCLC) patients.

Methods

Data of 48 consented NSCLC patients with baseline PIR test done within one week prior to the start of immunotherapy were collected. Samples were grouped into either sensitive or intermediate/resistant (not sensitive) by PIR classification. We analyzed the durations from the immunotherapy initiation to the first episode of irAE. IrAEs were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

Results

Among the 48 NSCLC patients, 19 patients (39%) experienced one or more irAEs with the majority classified as either grade 1 (n=7, 36%) or grade 2 (n=10, 52%). PIR-sensitive group showed no difference in irAE free period compared to PIR-not sensitive (p=0.92, HR=0.95, 95% CI=00.3212 to 2.834). The median ‘Time to first irAE’ were undefined and 24 in PIR-sensitive and PIR-not sensitive, respectively.

Conclusions

Our results demonstrated PIR-sensitive patients are not likely to tolerate immunotherapy longer without developing irAEs.
31 Serum LAG-3 is associated with improved patient prognosis in high grade serous ovarian cancer
Authors: James Nicole , Eurich Katrin , Lips Erin , Cruz Payton De La , Woodman Morgan , Ribeiro Jennifer
Published: November 2021

Background

High grade serous ovarian cancer (HGSOC) is a lethal gynecologic malignancy with a five-year survival rate of only 39 percent.1 Despite the fact that ovarian tumors are considered immunologic, HGSOC patients respond poorly to PD-1 based immunotherapy. Hence, the need to identify novel prognostic and therapeutic immunologic factors is crucial. Our previous investigation uncovered intratumoral levels of immune co-inhibitory receptor LAG-3 as a marker of improved HGSOC patient survival. For this current study we sought to evaluate the prognostic utility of serum-based LAG-3, as well as determine how these circulating levels change in response to HGSOC standard of care therapy.

Methods

This study was approved by the Women and Infants Institutional Review Board; approval number 1057626. HGSOC serum samples were obtained from the Department of Special Testing and the Program in Women’s Oncology Gynecologic Tissue Bank at Women and Infants Hospital. A total of 43 HGSOC treatment naïve serum samples were tested for serum LAG-3 and in 20 of these patients, samples from on- and post- frontline platinum-based chemotherapy were also analyzed. A commercially available ELISA kit was employed to detect serum LAG-3.

Results

There was no statistically significant change in pre-, on-, and post- serum LAG-3 levels following frontline chemotherapy, however median levels of LAG-3 decreased once patients initiated therapy and remained stable post-treatment. Spearman Rank Correlation analysis revealed a significant relationship between progression-free survival (PFS) and pre-treatment serum LAG-3 levels (r=0.36, p=0.017). Furthermore, it was found that patients with a PFS of 6 months or less exhibited a significantly (p=0.0031) lower mean rank of pre-treatment serum LAG-3 levels, compared to patients with a PFS of 18 months or longer. Finally, Kaplan Meier curve analysis revealed a statistically significant association between longer patient PFS and higher pre-treatment LAG-3 concentrations, when stratified by both median(HR=0.4916, log-rank p=0.022) and quartile LAG-3 serum levels (HR=0.2679, log-rank p=0.0031).

Conclusions

This study demonstrates for the first time that circulating immune checkpoint receptors have prognostic capabilities in ovarian cancer. Our findings suggest that LAG-3 is a marker for improved patient PFS. Future directions include an expansion of this original cohort in order to validate and further assess the clinical prognostic utility of serum LAG-3 in HGSOC.

Reference

Survival Rates for Ovarian Cancer, American Cancer Society, [https://www.cancer.org/cancer/ovarian-cancer/detection-diagnosis-staging/survival-rates.html]
35 Chemokine-driven spatial organization of immune cell microaggregates marks oropharyngeal squamous cell carcinomas containing tumor-specific T cells
Authors: Abdulrahman Ziena , Santegoets Saskia , Sturm Gregor , Charoentong Pornpimol , Ijsselsteijn Marieke , Somarakis Antonios , Höllt Thomas , Finotello Francesca , Trajanoski Zlatko , Egmond Sylvia van , Mustafa Dana , Welters Marij , Miranda Noel de , Burg Sjoerd van der
Published: November 2021

Background

Oropharyngeal squamous cell carcinoma (OPSCC) is the most prevalent type of head and neck cancer. The survival of patients with OPSCC is tightly linked to the intratumoral presence of tumor-specific CD4+ and CD8+ T cells. Yet, immunotherapy is currently far from effective in OPSCC partly due to our limited understanding of its immune microenvironment.

Methods

Here a multi-modal, high-dimensional approach was used to dissect the immune landscape in a unique cohort of pre-therapy OPSCC patient samples (n=20) in which intratumoral tumor-specific T cells were either detected (immune response positive, IR+) or not (IR-). This included imaging mass cytometry (Hyperion) for high-dimensional phenotyping, spatial localization and interaction analyses of the cells in the tumor mircoenvironment with our newly developed imaging processing pipeline employing machine learning, Nanostring PanCancer IO360 panel analysis of immune signaling pathways, and combined single-cell gene expression profiling and T cell receptor sequencing (scRNAseq) to characterize the transcriptional states of clonally expanded tumor-infiltrating T cells.

Results

Immune cell infiltration in IR+ tumors is stronger and highly coordinated, with a distinct spatial phenotypic signature characterized by microaggregates of tumor-resident (CD103+) CD8+ and CD4+ T cells and dendritic cells within the tumor cell beds, which retained after permutation based correction for differences in cell frequencies. Furthermore, the increased expression of CXCL12 and LTB produced by CD4+ T cells, both involved in the spatial organization of immune cell infiltration, and the clonal expansion of CD8+ T cells producing the DC-attracting chemokines CCL4 or XCL1 in IR+ OPSCC, indicate that tumor-reactive T cells act as a positive feedback loop in the formation of these aggregates. The impact of these chemokines on local immunity and clinical outcome was confirmed in an independent TCGA OPSCC cohort. In contrast, the IR- OPSCC signature comprised spatial interactions between lymphocytes and different subpopulations of immunosuppressive myeloid cells.

Conclusions

Our study reveals that the chemokine-driven spatial immune signature of OPSCC has strong potential as a prognostic and predictive biomarker. While the immune signature of IR+ OPSCC suggests potential benefit from neoadjuvant immunotherapeutic approaches to limit the side effects of current radio(chemo)therapy, that of IR- OPSCC calls for strategies focused on stimulating T cells and counteracting immune suppressive mechanisms.
42 The role of tissue stiffness in predicting the immunotherapy response in hepatocellular carcinoma
Authors: Yavuz Betul Gok , Hasanov Elshad , Xiao Lianchun , Mohamed Yehia , Lee Sunyoung , Rashid Asif , Kaseb Ahmed , Qayyum Aliya
Published: November 2021

Background

Currently, there is no standard biomarker that predict immunotherapy response in hepatocellular carcinoma (HCC). Here, we aim to investigate the role of tissue stiffness measured by magnetic resonance elastography (MRE) in predicting neoadjuvant immunotherapy response in patients with resectable HCC.

Methods

This was a study of 15 patients with HCC treated with immune checkpoint blockade (ICB) therapy, nivolumab ± ipilimumab, followed by surgical resection. HCC MRE assessment was performed at baseline and after 6 weeks of therapy. HCC stiffness (kPa) was measured on MRE elastograms (liver stiffness maps). Baseline stiffness and changes in stiffness were compared with treatment response to ICB. Treatment response was defined as a tumor with more than 60% necrosis which was the major pathological response. Analysis was performed using descriptive statistics, Fisher’s exact test, and Wilcoxon rank sum test; p-value <0.05 was considered statistically significant.

Results

Fifteen patients were evaluable for MRE assessment. The median age was 67 years. Etiology of liver disease was NASH (n=4), HCV (n=3), HBV (n=2) and unknown (n=6). Three out of 15 patients (20%) achieved a major pathological response (MPR). Median baseline HCC stiffness and change in stiffness were 4.6 kPa and –0.2 kPa, respectively. Among the 4 patients with stiffness increase, 3 (75%) of them achieved MPR and 1 (25%) did not achieve MPR. Among the patients without stiffness increase, none of them achieved MPR. Fisher’s exact test indicates that increase in stiffness was associated with a higher chance to achieve MPR than patients without stiffness increase (p=0.0088). Median baseline HCC stiffness for responders and non-responders was 6.8 (5.4, 9) kPa and 3.9 (2.2, 9.7) kPa, respectively (p=0.09). The median change in HCC stiffness for responders and non-responders was 1 (1, 1.4) kPa and -0.4 (-2.2, 0.7) kPa, respectively (p=0.02).

Conclusions

Patients who achieved MPR inclined to have a higher baseline stiffness than patients who did not achieve MPR. Regarding the changes in stiffness between the two arms, patients with MPR group had a greater increase than that in the non-MPR group. In conclusion, baseline and change in MRE stiffness may be a useful biomarkers in predicting response to ICB therapy in HCC.

Ethics Approval

This was an Institutional Review Board approved study (MDACC 2017–0972). All patients provided written informed consent.
69 Immunophenotyping of TCR and BCR clonotypes
Authors: Chenchik Alex , Makhanov Michael , Darst Russell , Liu Tianbing , Kobzik Lester
Published: November 2021

Background

T-cell receptor (TCR) and B-cell receptor (BCR) repertoire profiling holds great potential for understanding disease mechanisms and for the development of new therapeutics in infectious diseases, autoimmunity and in immuno-oncology. However, this potential could be greatly improved by combining information about receptor clonotypes with immuno-phenotypes of T and B cells.

Methods

To facilitate these studies, we developed a novel technology for combined profiling of all human TCR and BCR variable regions and phenotypic characterization of immune cells in bulk and at the single-cell level in PBMC and immune cell fraction samples. The developed TCR/BCR Immunophenotyping method involves multiplex RT-PCR amplification and sequencing of CDR3 regions of TCR and BCR genes and a set of the most informative T- and B-cell phenotyping genes. Bioinformatics analysis of NGS data allows profiling of TCR/BCR clonotypes, and identification of major immune cell subtypes and their activation status.

Results

Data will be presented showing how combined TCR/BCR clonotype analysis combined with targeted expression profiling of immune cells can be applied for large-scale discovery of novel cell typing and activation biomarkers in several immune-responsive model systems.

Conclusions

Preliminary studies demonstrate the assay has unparalleled throughput, sensitivity, and improved cost-effectiveness for high-throughput immunity biomarker discovery applications.
211 SQZ™ eAPCs generated from PBMCs by delivery of multiple mRNAs encoding for antigens, costimulatory proteins, and engineered cytokines
Authors: Maloney Michael , Ozay Emrah Ilker , Merino Amy , Silva Andrea , Martin Amber , Manja Sanjana , Upadhyay Madhav , Trumpfheller Christine , Umana Pablo , Sharei Armon , Bernstein Howard , Loughhead Scott
Published: November 2021

Background

Antigen-specific CD8+ T cells are critical components of mounting an effective immune response against tumors. Generation of antigen-specific T cells require interactions with multiple signals produced by antigen presenting cells (APCs). These signals are comprised of three components: (signal 1) the peptide-MHC complex binding to the T cell receptor, (signal 2) costimulatory molecules on the surface of APCs, and (signal 3) inflammatory cytokines binding to cognate receptors on T cells.

Methods

To engineer all major cell subsets of human peripheral blood mononuclear cells (PBMCs) to become enhanced APCs (eAPCs), we used Cell Squeeze® technology to deliver multiple mRNA encoding for non-self-antigens (signal 1), CD86 (signal 2), and/or membrane-bound cytokines (signal 3). The signal 3 molecules, membrane-bound IL-12 (mbIL-12) and membrane-bound IL-2 (mbIL-2), are chimeric proteins designed to increase the localized concentration of the cytokines and limit off-target effects. Flow cytometry and western blots were used to confirm the translation of each of the delivered mRNA. The increased capabilities of these enhanced APCs were assessed in vitro by culturing the APCs with antigen-specific T cells for multiple days before measuring the functionality of antigen-specific T cells via intracellular cytokine staining or ELISA.

Results

We demonstrate that Cell Squeeze® processing of PBMCs with mRNA encoding for signals 1, 2, and 3 results in highly effective enhanced APCs in vitro. In a single squeeze process, efficient delivery and translation of up to five mRNA is observed in all major PBMC cell subsets including T cells, B cells, NK cells, and monocytes. Once translated, the chimeric mbIL-2 and mbIL-12 can bind to their cognate receptors and exhibit minimal shedding from the surface. We show that enhanced APCs can present antigenic peptides derived from mRNA encoding for a foreign antigen on MHC complexes in an HLA agnostic manner, which drives antigen-specific T cell responses. The addition of CD86, mbIL-2, and mbIL-12 further enhance the activation and potency of antigen-specific T cells, as measured by an increase in the secretion of inflammatory cytokines upon restimulation (i.e. IFNγ).

Conclusions

Cell squeezing of human PBMCs with mRNA encoding for signals 1, 2, and 3 has the potential to generate enhanced APCs that drive robust CD8+ T cell response against multiple targets across several disease areas. The versatility of the Cell Squeeze® technology potentially enables rapid exchange of mRNA to other antigens or T cell activation signals.
370 Time course of treatment-related adverse events (TRAEs) during dostarlimab therapy in the GARNET trial
Authors: Pothuri Bhavana , Berton Dominique , Moreno Victor , Oaknin Ana , Trigo Perez Jose Manuel , Curigliano Giuseppe , Ellard Susan , Pikiel Joanna , Banerjee Susana , Barretina-Ginesta Maria-Pilar , Miller Rowan , Tinker Anna , Jewell Andrea , Plummer Ruth , Joly Florence , Veneris Jennifer , Duan Tao , Andre Thierry
Published: November 2021

Background

Dostarlimab is a humanized programmed death 1 (PD-1) receptor monoclonal antibody that blocks interaction with the ligands PD-L1 and PD-L2. Dostarlimab is approved as a monotherapy in adult patients (pts) with mismatch repair deficient (dMMR; US) or dMMR/microsatellite-instability high (EU) recurrent or advanced endometrial cancer that has progressed progressing on or following prior treatment with a platinum-containing regimen. GARNET is a phase 1 study assessing antitumor activity and safety of dostarlimab monotherapy in pts with solid tumors.

Methods

Pts with dMMR solid tumors, mismatch repair proficient endometrial cancer, and non-small cell lung cancer that progressed on or after prior therapy received 500 mg of dostarlimab IV every 3 weeks (Q3W) for 4 cycles, then 1000 mg IV every 6 weeks (Q6W) for up to 2 years or until disease progression or discontinuation. Here, we report TRAEs by cycle.

Results

A total of 515 pts were included. Of these pts, 60 (11.7%) experienced TRAEs leading to treatment interruption, and 25 (4.9%) experienced TRAEs leading to discontinuation. TRAEs of any grade with overall incidence of ≥10% of pts are shown (table 1). The majority of TRAEs occurred during cycles 1–3, with highest incidence during cycle 1. Grade 3 or 4 TRAEs were rare; those seen in ≥1% of pts are shown. Immune-related (ir) TRAEs of any grade with overall incidence of ≥2% of pts are shown. Most cases (96.9%) of irTRAEs occurred during cycles 1–8. The peak incidence of hypothyroidism occurred during cycle 4; in addition, frequency was increased during cycles 5–8, compared with cycles 1–4. No deaths were attributed to dostarlimab.

Abstract 370 Table 1

Time course of adverse events in the GARNET trial

Conclusions

No new safety signals were detected with dostarlimab compared to other anti–PD-1 inhibitors. Most TRAEs were low grade. The majority of TRAEs and grade ≥3 TRAEs occurred in the first 3 cycles (first 12 weeks), but some cases occurred later, suggesting a need for ongoing monitoring. Few increases in the incidence of TRAEs were seen during cycle 5 following the transition to the 1000-mg Q6W dosing schedule; the TRAEs with increased incidence after the transition were fatigue and lipase increased. An increase in the frequency of the irTRAE hypothyroidism was seen after transitioning to the 1000-mg Q6W schedule.
Proximity of IQOS and JUUL points of sale to schools in Israel: a geospatial analysis
Authors: Elbaz Daniel , Bar Zeev Yael , Berg Carla J , Abroms Lorien C , Levine Hagai
Published: November 2021

Significance

Exploring proximity and density of heated tobacco product (HTP) and electronic nicotine delivery system (ENDS) points of sale (POS) to schools is critical for understanding youth marketing exposure and informing policy and enforcement to protect youth. This study examined IQOS and JUUL POS (prominent HTPs and ENDS), specifically their proximity to and density around schools in Israel.

Methods

Using geospatial analysis and IQOS/JUUL website data, distance matrices were used to calculate distance from each school in Israel (grades 1–12) to the nearest POS and number of POS within 1 km, accounting for schools’ neighbourhood socioeconomic status (SES) ranking.

Results

An average of 8.7 IQOS POS and 5.2 JUUL POS were within walking distance (1 km) from schools. Average distances from schools to nearest IQOS and JUUL POS were 954 m (median=365 m) and 1535 m (median=579 m), respectively. The percentages of schools with at least one IQOS or JUUL POS within 1 km were 86% and 74%, respectively. The average numbers of POS within 1 km of schools in low-SES, middle-SES, and high-SES neighbourhoods were 7.5, 9.9, and 7.6 for IQOS and 4.1, 5.9, and 5.5 for JUUL, respectively. Median distances from schools in low-SES, middle-SES, and high-SES neighbourhoods to nearest POS were 428 m, 325 m, and 403 m for IQOS and 1044 m, 483 m, and 525 m for JUUL.

Conclusions

Youth experience high environmental exposure to IQOS and JUUL POS, particularly IQOS. POS were more densely located near schools in middle-SES neighbourhoods. Thus, regulating HTP and ENDS POS near schools and in certain neighbourhoods is key to reducing youth population impact in Israel and elsewhere.
Photoelectric properties and stability of the single-layer transition metal dichalcogenides under three stress states
Authors: Wang Duo , Yang Lu
Published: November 2021

In this paper, the electrical and optical properties of single-layer MoS2 and single-layer WS2 in three strain states: biaxial tension, biaxial compression, biaxial tension and compression are systematically studied. All calculations are based on the first-principle of density functional theory. The results show that after biaxial tension strain, biaxial compression strain, and biaxial tension-compression strain are applied, the atomic structure, energy band structure, and optical absorption coefficient will show disparate changing trends. When the biaxial tension and compression strain intensity is less than 15%, the bond length, bond angle, and light absorption peak will have little fluctuation with the increase of strain intensity. However, compared with the other two strain states, these two crystal structures are the most volatile at this time. In addition, when 15% biaxial tensile strain is applied, the two crystals can still maintain their kinetic stability.
Dynamical analysis, FPGA implementation and synchronization for secure communication of new chaotic system with hidden and coexisting attractors
Authors: Lai Qiang , Wang Ziling , Kuate Paul Didier Kamdem
Published: November 2021

This paper proposes an interesting autonomous chaotic system with hidden attractors and coexisting attractors. The system has no equilibrium, one equilibrium, three equilibria and line equilibria for different parameter regions. The existence of hidden attractors and coexisting attractors of the system has been revealed by using simulation analysis. The bifurcation diagram shows the period-doubling bifurcation route to chaos with the variation of parameters. The analog circuit and FPGA implementation of the system are presented. The synchronization for secure communication of the system is investigated. The synchronization conditions are established by using the adaptive control method.
Buffer Placement and Sizing for High-Performance Dataflow Circuits
Authors: Josipović Lana , Sheikhha Shabnam , Guerrieri Andrea , Ienne Paolo , Cortadella Jordi
Published: November 2021

Commercial high-level synthesis tools typically produce statically scheduled circuits. Yet, effective C-to-circuit conversion of arbitrary software applications calls for dataflow circuits, as they can handle efficiently variable latencies (e.g., caches), unpredictable memory dependencies, and irregular control flow. Dataflow circuits exhibit an unconventional property: registers (usually referred to as “buffers”) can be placed anywhere in the circuit without changing its semantics, in strong contrast to what happens in traditional datapaths. Yet, although functionally irrelevant, this placement has a significant impact on the circuit’s timing and throughput. In this work, we show how to strategically place buffers into a dataflow circuit to optimize its performance. Our approach extracts a set of choice-free critical loops from arbitrary dataflow circuits and relies on the theory of marked graphs to optimize the buffer placement and sizing. Our performance optimization model supports important high-level synthesis features such as pipelined computational units, units with variable latency and throughput, and if-conversion. We demonstrate the performance benefits of our approach on a set of dataflow circuits obtained from imperative code.
Adaptations and Diversity of Antarctic Fishes: A Genomic Perspective
Authors: Daane Jacob M. , Detrich H. William
Published: November 2021

Antarctic notothenioid fishes are the classic example of vertebrate adaptive radiation in a marine environment. Notothenioids diversified from a single common ancestor ∼22 Mya to between 120 and 140 species today, and they represent ∼90% of fish biomass on the continental shelf of Antarctica. As they diversified in the cold Southern Ocean, notothenioids evolved numerous traits, including osteopenia, anemia, cardiomegaly, dyslipidemia, and aglomerular kidneys, that are beneficial or tolerated in their environment but are pathological in humans. Thus, notothenioids are models for understanding adaptive radiations, physiological and biochemical adaptations to extreme environments, and genetic mechanisms of human disease. Since 2014, 16 notothenioid genomes have been published, which enable a first-pass holistic analysis of the notothenioid radiation and the genetic underpinnings of novel notothenioid traits. Here, we review the notothenioid radiation from a genomic perspective and integrate our insights with recent observations from other fish radiations.
Accumulating Knowledge in the Organizational Sciences
Authors: Bosco Frank A.
Published: November 2021

In some fields, research findings are rigorously curated in a common language and made available to enable future use and large-scale, robust insights. Organizational researchers have begun such efforts [e.g., metaBUS ( http://metabus.org/ )] but are far from the efficient, comprehensive curation seen in areas such as cognitive neuroscience or genetics. This review provides a sample of insights from research curation efforts in organizational research, psychology, and beyond—insights not possible by even large-scale, substantive meta-analyses. Efforts are classified as either science-of-science research or large-scale, substantive research. The various methods used for information extraction (e.g., from PDF files) and classification (e.g., using consensus ontologies) is reviewed. The review concludes with a series of recommendations for developing and leveraging the available corpus of organizational research to speed scientific progress.
The Structure of Intrinsic Motivation
Authors: Fishbach Ayelet , Woolley Kaitlin
Published: November 2021

Intrinsic motivation (IM) is key for persistence at work. When they are intrinsically motivated, people experience work activities as an end in itself, such that the activity and its goal collide. The result is increased interest and enjoyment of work activities. In this article, we review the current state of knowledge on IM, including studies within organizational, cognitive, and social psychology. We distinguish our structural perspective, which defines IM as the overlap between means and ends (e.g., the means-ends fusion model), from content-based approaches to study IM. We specifically discuss three questions: ( a) What is IM and why does it matter, ( b) how can individuals and organizations increase IM, and ( c) what biases and misconceptions do employees and managers hold about IM?
The Cellular and Molecular Basis of Sour Taste
Authors: Turner Heather N. , Liman Emily R.
Published: November 2021

Sour taste, the taste of acids, is one of the most enigmatic of the five basic taste qualities; its function is unclear and its receptor was until recently unknown. Sour tastes are transduced in taste buds on the tongue and palate epithelium by a subset of taste receptor cells, known as type III cells. Type III cells express a number of unique markers, which allow for their identification and manipulation. These cells respond to acid stimuli with action potentials and release neurotransmitters onto afferent nerve fibers, with cell bodies in geniculate and petrosal ganglia. Here, we review classical studies of sour taste leading up to the identification of the sour receptor as the proton channel OTOP1.
Comprehensive Analysis of the Immune Implication of TEX41 in Skin Cutaneous Melanoma
Authors: Chen Zhi-yong , Huang Jie-qing , Zhu Yu , Chen Yong-song , Yu Xue-feng
Published: November 2021

Enhancer RNAs (eRNAs), a subclass of noncoding RNAs from enhancers, have been demonstrated to exhibit important regulatory effects on the expressions of various genes. However, the role of eRNAs in skin cutaneous melanoma (SKCM) remained largely unclear. In this study, we aimed to explore the expression and prognostic value of an enhancer RNA TEX41 in SKCM as well as the associations between TEX41 and tumor-infiltrating immune cells (TICs). We observed that TEX41 expression was distinctly increased in SKCM specimens compared with normal skin specimens using GEPIA. Survival assays based on TGCA datasets revealed that patients with low TEX41 expressions displayed a longer overall survival than those with high TEX41 expression. CIBERSORT datasets revealed that TEX41 was related to 8 types of TICs (macrophages M1, T cells regulatory, plasma cells, mast cells resting, T cells CD8, dendritic cells resting, and T cells follicular helper). Three kinds of TICs were negatively related to TEX41 expressions, including macrophages M2, NK cells resting, and macrophages M0. The expressions of TEX41 were involved in five KEGG pathways, including transcriptional misregulation in cancer, SNARE interactions in vesicular transport, mitophagy-animal, melanoma, melanogenesis, and progesterone-mediated oocyte maturation. Overall, TEX41 can be used as a novel biomarker for the prognosis of SKCM patients and is associated with TICs, indicating it as a therapeutic target for SKCM.
Numerical Approximation of Generalized Burger’s-Fisher and Generalized Burger’s-Huxley Equation by Compact Finite Difference Method
Authors: Kaur Ravneet , Shallu  , Kumar Sachin , Kukreja V. K.
Published: November 2021

In this work, computational analysis of generalized Burger’s-Fisher and generalized Burger’s-Huxley equation is carried out using the sixth-order compact finite difference method. This technique deals with the nonstandard discretization of the spatial derivatives and optimized time integration using the strong stability-preserving Runge-Kutta method. This scheme inculcates four stages and third-order accuracy in the time domain. The stability analysis is discussed using eigenvalues of the coefficient matrix. Several examples are discussed for their approximate solution, and comparisons are made to show the efficiency and accuracy of CFDM6 with the results available in the literature. It is found that the present method is easy to implement with less computational effort and is highly accurate also.
Aspirin Exerts Neuroprotective Effects by Reversing Lipopolysaccharide-Induced Secondary Brain Injury and Inhibiting Matrix Metalloproteinase-3 Gene Expression
Authors: Feng Depeng , Chen Dezhe , Chen Tuanzhi , Sun Xiaoqian
Published: November 2021

Objective. This study is aimed at exploring the possible neuroprotective mechanism of aspirin and the effect of bacterial endotoxin lipopolysaccharide (LPS) during cerebral ischaemia-reperfusion (CIRP) injury. Methods. We established three animal models: the CIRP, LPS, and CIRP+LPS models. Mortality, the injured brain area, and the beam walking test were used to estimate the degree of cerebral injury among the rats. Immunohistochemistry and immunofluorescence were used to detect activated microglia, matrix metalloproteinase-3 (MMP-3), and osteopontin (OPN). Results. The injured brain area and mortality were dramatically reduced (

p
<
0.01

), and the beam walking test scores were elevated (

p
<
0.01

) in the acetylsalicylic acid (ASA) group compared to the control group. The number of microglia-, MMP-3-, and OPN-positive cells also increased. Furthermore, the number of GSI-B4, OPN, and MMP-3 cells decreased in the ASA group compared to the control group. After LPS stimulation, the number of microglia reached a peak at 24 h; at 7 d, these cells disappeared. In the ASA group, the number of microglia was significantly smaller (

p
<
0.05

), especially at 24 h (

p
<
0.01

), compared to the LPS group. Moreover, the injured brain area and the mortality were dramatically increased and the beam walking test scores were reduced (

p
<
0.01

) after LPS simulation following CIRP. The degree of injury in the ASA group resembled that in the control group. However, the number of MMP-3-immunoreactive neurons or microglia was significantly larger than that of the control group (

p
<
0.05

). In the ASA group, the MMP-3 expression was also considerably decreased (

p
<
0.05

). Conclusions. After CIRP, microglia were rapidly activated and the expression of MMP-3 and OPN significantly increased. For rats injected with LPS at reperfusion, the injured brain area and mortality also dramatically increased and the neurologic impairment worsened. However, ASA exhibited a neuroprotective effect during CIRP injury. Furthermore, ASA can reverse LPS-induced cerebral injury and inhibit the inflammatory reaction after CIRP injury.
The Activity of Plant Crude Extracts against Schistosoma mansoni
Authors: Basha Hirut , Mamo Hassen
Published: November 2021

Background. Schistosoma mansoni remains a significant health problem in low-income countries. Praziquantel (PZQ) is the only drug available to treat schistosomiasis, and PZQ resistance is a potential threat towards control of the disease although PZQ is currently effective against all species of schistosomes. Moreover, PZQ is less efficacious against larval stages. In response to these challenges, multiple in vivo/in vitro studies evaluated the anti-S. mansoni activity of crude plant extracts in a bid for novel drug(s). However, these studies appear fragmented and patchy. This systematic review explored the extent of such studies in the past 11 years (2010-2020). Methods. A systematic web search analysis and review of the literature on crude plant extracts tested against S. mansoni was done. Data from 17 articles meeting eligibility criteria were extracted and analyzed. Forty-three plant species have been tested by the 17 studies. The leaves, barks, stems, flowers, rhizomes, and roots of the plants as well as the whole plant part were used for the experiments. Conclusion. Nearly all of the plants significantly reduced schistosome egg output, killed adult worms, and improved liver histology and function. Further studies are required to assess the therapeutic potential of more promising plant species.
Wireless Network Communication in the XML Metadata Storage of Wushu Historical Archives
Authors: Liu Xin
Published: November 2021

The wireless communication network has a huge promotion effect on data processing. As an important standard for internet data transmission, XML markup language is currently widely used in the internet. The rapid development of XML has brought fresh blood to the research of database. This article is aimed at studying the application of wireless network communication in the storage of the XML metadata database of Wushu Historical Archives. One part uses data load‐balancing algorithms and two‐way path constraint algorithms to conduct research on the metadata storage of XML databases, such as document size, document loading, and document query. Combining wireless technology and comparing with SGML and HTML, it highlights the flexibility and importance of XML database. The other part analyzes the XML database of Wushu Historical Archives itself and uses questionnaire surveys combined with the experience of 30 users randomly checked to provide constructive suggestions for the construction of XML database, such as strengthening the operation page design, text, and graphics. The experimental results show that the time consumed by the XML database in the case of bidirectional path indexing is 0.37 s, and the time consumed in the case of unidirectional path indexing is 0.27 s. This data shows that the application of wireless network communication technology has played an important role in the easy update and flexibility of the XML database. The data load capacity presented by the two path indexes is inconsistent; the current experience of XML database mainly focuses on the copy of the database quantity.
The 7-Round Subspace Trail-Based Impossible Differential Distinguisher of Midori-64
Authors: Liu Wenhao , Yang Yang
Published: November 2021

This paper analyzes the subspace trail of Midori-64 and uses the propagation law and mutual relationship of the subspaces of Midori-64 to provide a 6-round Midori-64 subspace trail-based impossible differential key recovery attack. The data complexity of the attack is

2

54.6

chosen plaintexts, and the computational complexity is

2

58.2

lookup operations. Its overall complexity is less than that of the known 6-round truncated impossible differential distinguisher. This distinguisher is also applicable to Midori-128 with a secret

S

-box. Additionally, utilizing the properties of subspaces, we prove that a subspace trail-based impossible differential distinguisher of Midori-64 contains at most 7 rounds. This is 1 more than the upper bound of Midori-64’s truncated impossible differential distinguisher which is 6. According to the Hamming weights of the starting and ending subspaces, we classify all 7-round Midori-64 subspace trail-based impossible differential distinguishers into two types and they need

2

59.6

and

2

51.4

chosen plaintexts, respectively.
Optimization of Intelligent Tuning System for Stringed Instruments Based on Wireless Sensor Network
Authors: Zhuo Pin
Published: November 2021

With the increasing abundance of material civilization, people’s pursuit of spiritual civilization is also higher and higher. Although tuning is the analysis and processing of sound signal, the string signal is also a kind of sound signal, which follows the basic law of acoustics. In the field of wireless sensor network, this paper introduces the status quo of tuning tools for stringed instruments, analyses the existing problems of tuning tools for mainstream stringed instruments, and puts forward an automatic tuning system based on wireless sensor network. The hardware design of intelligent tuning system based on wireless sensor network includes audio acquisition module, tuning control module driver circuit design and voice broadcast module, and network communication module selection analysis. The software design of intelligent tuning system based on wireless sensor network includes embedded software design and mobile software design. Embedded software design mainly includes system flow design and automatic tuning function design. In this paper, an improved endpoint detection algorithm is used to separate the chord tone from the nonchord tone, and an improved pitch detection algorithm is used to get the accurate pitch frequency of the chord tone signal. The function and performance of the tuning system are tested to verify the reliability of the optimized intelligent tuning system.
Antimicrobial Effect of Calcium Hydroxide Combined with Electrolyzed Superoxidized Solution at Neutral pH on Enterococcus faecalis Growth
Authors: Jimenez-Gonzalez Héctor Armando , Nakagoshi-Cepeda María Argelia Akemi , Nakagoshi-Cepeda Sergio Eduardo , Urrutia-Baca Víctor Hugo , De La Garza-Ramos Myriam Angélica , Solis-Soto Juan Manuel , Gomez-Flores Ricardo , Tamez-Guerra Patricia
Published: November 2021

Objective. To evaluate the effect of the combination of calcium hydroxide (Ca(OH)2) and a novel electrolyzed superoxidized solution at neutral pH, known as OxOral® on Enterococcus faecalis growth in root canals. Methods. Sixty human teeth were used, from which root canals were infected and randomly divided into the following treatment groups: saline solution, saline solution plus Ca(OH)2, OxOral®, and OxOral® plus Ca(OH)2. Results. A permanent reduction in bacterial growth was observed at days 1, 6, 12, and 18 after OxOral® plus Ca(OH)2 treatment from 4.4 ± 0.074 log10 CFU/mL to 0.0 ± 0.001 log10 CFU/mL. In addition, alkaline conditions maintenance was observed from application time (pH = 12.2 ± 0.033) to 18 d posttreatment (pH = 12.6 ± 0.083). Conclusion. The combination of OxOral® and Ca(OH)2 provides an alkaline pH and inhibits E. faecalis growth into the root canals. Our study opens the possibility for further research on the use of OxOral® in endodontic therapy.
mtDNA in the Pathogenesis of Cardiovascular Diseases
Authors: Wang Lili , Zhang Qianhui , Yuan Kexin , Yuan Jing
Published: November 2021

The incidence rate of cardiovascular disease (CVD) has been increasing year by year and has become the main cause for the increase of mortality. Mitochondrial DNA (mtDNA) plays a crucial role in the pathogenesis of CVD, especially in heart failure and ischemic heart diseases. With the deepening of research, more and more evidence showed that mtDNA is related to the occurrence and development of CVD. Current studies mainly focus on how mtDNA copy number, an indirect biomarker of mitochondrial function, contributes to CVD and its underlying mechanisms including mtDNA autophagy, the effect of mtDNA on cardiac inflammation, and related metabolic functions. However, no relevant studies have been conducted yet. In this paper, we combed the current research status of the mechanism related to the influence of mtDNA on the occurrence, development, and prognosis of CVD, so as to find whether these mechanisms have something in common, or is there a correlation between each mechanism for the development of CVD?
Obtaining Solutions of a Vakhnenko Lattice System by N-Fold Darboux Transformation
Authors: Zhang Ning , Xu Xi-Xiang
Published: November 2021

Using a suitable gauge transformation matrix, we present a

N

-fold Darboux transformation for a Vakhnenko lattice system. This transformation preserves the form of Lax pair of the Vakhnenko lattice system. Applying the obtained Darboux transformation, we arrive at an exact solution of the Vakhnenko lattice system.
Identification of Autophagy‐Related Prognostic Signature and Analysis of Immune Cell Infiltration in Low‐Grade Gliomas
Authors: Quan Qingli , Xiong Xinxin , Wu Shanyun , Yu Meixing
Published: November 2021

Autophagy plays an important role in cancer. Many studies have demonstrated that autophagy‐related genes (ARGs) can act as a prognostic signature for some cancers, but little has been known in low‐grade gliomas (LGG). In our study, we aimed to establish a prognostical model based on ARGs and find prognostic risk‐related key genes in LGG. In the present study, a prognostic signature was constructed based on a total of 8 ARGs (MAPK8IP1, EEF2, GRID2, BIRC5, DLC1, NAMPT, GRID1, and TP73). It was revealed that the higher the risk score, the worse was the prognosis. Time‐dependent ROC analysis showed that the risk score could precisely predict the prognosis of LGG patients. Additionally, four key genes (TGFβ2, SERPING1, SERPINE1, and TIMP1) were identified and found significantly associated with OS of LGG patients. Besides, they were also discovered to be strongly related to six types of immune cells which infiltrated in LGG tumor. Taken together, the present study demonstrated the promising potential of the ARG risk score formula as an independent factor for LGG prediction. It also provided the autophagy‐related signature of prognosis and potential therapeutic targets for the treatment of LGG.
Genotoxicity Assessment and Protective Effect of Anogeissus leiocarpus Roots against Cyclophosphamide-Induced DNA Damage In Vivo
Authors: Motto Aku Enam , Lawson-Evi Povi , Diallo Aboudoulatif , Eklu-Gadegbeku Kwashie
Published: November 2021

Background. Belonging to the family of Combretaceae, the roots of Anogeissus leiocarpus are traditionally used to treat diabetes, wounds, infections, pain, and gastrointestinal diseases. To our knowledge, no genotoxicity assessment of the plant was reported. Hence, this study was designed to evaluate the potential genotoxic and protective effects of extract of Anogeissus leiocarpus roots using the micronucleus test on mice bone marrow cells in vivo. Methods. Three different concentrations (250, 500, and 1000 mg·kg−1) of hydroalcoholic extract of roots of A. leiocarpus were administered daily for 7 days per os to mice, and the genotoxicity was induced by the administration ip of cyclophosphamide. Genotoxicity and cytotoxicity were evaluated by counting, respectively, the number of micronucleated polychromatic erythrocytes and polychromatic erythrocytes to total erythrocytes in the bone marrow of mice. Results. The administration of A. leiocarpus did neither increase the ratio of the polychromatic erythrocyte (PCE) nor the frequency of micronucleated PCE (MNPCE) significantly in the bone marrow cells of the mice, compared to the vehicle control animals. However, a significant increase in the incidence of MNPCE in the bone marrow cell of the cyclophosphamide-treated mice was found. Moreover, in the groups treated with the total extract of A. leiocarpus at different doses plus cyclophosphamide, there was a significant decrease

p
<
0.0001

in MNPCEs compared to the positive controls, in a dose-dependent manner. Conclusion. This first finding reports that the extract of A. leiocarpus was neither genotoxic nor cytotoxic. However, it shows a protective effect against the genotoxicity and cytotoxicity induced by cyclophosphamide.