bluuebunny/crossref_metadata_2025 huggingface dataset:
Promising Technologies in the Field of Helminth Vaccines
Authors: Perera Dilhan J. , Ndao Momar
Published: August 2021

Helminths contribute a larger global burden of disease than both malaria and tuberculosis. These eukaryotes have caused human infections since before our earliest recorded history (i.e.: earlier than 1200 B.C. forSchistosomaspp.). Despite the prevalence and importance of these infections, helminths are considered a neglected tropical disease for which there are no vaccines approved for human use. Similar to other parasites, helminths are complex organisms which employ a plethora of features such as: complex life cycles, chronic infections, and antigenic mimicry to name a few, making them difficult to target by conventional vaccine strategies. With novel vaccine strategies such as viral vectors and genetic elements, numerous constructs are being defined for a wide range of helminth parasites; however, it has yet to be discussed which of these approaches may be the most effective. With human trials being conducted, and a pipeline of potential anti-helminthic antigens, greater understanding of helminth vaccine-induced immunity is necessary for the development of potent vaccine platforms and their optimal design. This review outlines the conventional and the most promising approaches in clinical and preclinical helminth vaccinology.
Leveraging NKG2D Ligands in Immuno-Oncology
Authors: Fuertes Mercedes Beatriz , Domaica Carolina Inés , Zwirner Norberto Walter
Published: August 2021

Immune checkpoint inhibitors (ICI) revolutionized the field of immuno-oncology and opened new avenues towards the development of novel assets to achieve durable immune control of cancer. Yet, the presence of tumor immune evasion mechanisms represents a challenge for the development of efficient treatment options. Therefore, combination therapies are taking the center of the stage in immuno-oncology. Such combination therapies should boost anti-tumor immune responses and/or target tumor immune escape mechanisms, especially those created by major players in the tumor microenvironment (TME) such as tumor-associated macrophages (TAM). Natural killer (NK) cells were recently positioned at the forefront of many immunotherapy strategies, and several new approaches are being designed to fully exploit NK cell antitumor potential. One of the most relevant NK cell-activating receptors is NKG2D, a receptor that recognizes 8 different NKG2D ligands (NKG2DL), including MICA and MICB. MICA and MICB are poorly expressed on normal cells but become upregulated on the surface of damaged, transformed or infected cells as a result of post-transcriptional or post-translational mechanisms and intracellular pathways. Their engagement of NKG2D triggers NK cell effector functions. Also, MICA/B are polymorphic and such polymorphism affects functional responses through regulation of their cell-surface expression, intracellular trafficking, shedding of soluble immunosuppressive isoforms, or the affinity of NKG2D interaction. Although immunotherapeutic approaches that target the NKG2D-NKG2DL axis are under investigation, several tumor immune escape mechanisms account for reduced cell surface expression of NKG2DL and contribute to tumor immune escape. Also, NKG2DL polymorphism determines functional NKG2D-dependent responses, thus representing an additional challenge for leveraging NKG2DL in immuno-oncology. In this review, we discuss strategies to boost MICA/B expression and/or inhibit their shedding and propose that combination strategies that target MICA/B with antibodies and strategies aimed at promoting their upregulation on tumor cells or at reprograming TAM into pro-inflammatory macrophages and remodeling of the TME, emerge as frontrunners in immuno-oncology because they may unleash the antitumor effector functions of NK cells and cytotoxic CD8 T cells (CTL). Pursuing several of these pipelines might lead to innovative modalities of immunotherapy for the treatment of a wide range of cancer patients.
Decreased USP2a Expression Inhibits Trophoblast Invasion and Associates With Recurrent Miscarriage
Authors: Wang Jiayu , Ding Jinli , Zhang Sainan , Chen Xin , Yan Sisi , Zhang Yan , Yin Tailang
Published: August 2021

An appropriate development of the placenta consisting of trophoblast cell migration, invasion, proliferation, and apoptosis, is essential to establishing and maintaining a successful pregnancy. Ubiquitin‐specific protease 2a (USP2a) regulates the processes of metastasis in multiple tumor cells. Yet, no known research has focused on exploring the effect of USP2a on trophoblasts and its possible mechanism in the pathogenies of recurrent miscarriage (RM). In this study, we first detected the decreased mRNA levels and the protein levels of USP2a in placental villous tissue samples from the RM patients. In vitro assays verified that overexpression of USP2a promoted human trophoblast proliferation, migration, invasion, whereas knockdown of USP2a inhibited these processes. Mechanistically, USP2a activated PI3K/Akt/GSK3β signaling pathway to promote nuclear translocation of β‐catenin and further activated epithelial-mesenchymal transition (EMT) in the trophoblasts. Moreover, transforming growth factor-beta (TGF-β) up-regulated USP2a expression in trophoblasts. Interestingly, M2 macrophage secreted TGF-β induced trophoblast migration and invasion, and an anti-TGF-β antibody alleviated this effect. Collectively, this study indicated that USP2a regulated trophoblast invasion and that abnormal USP2a expression might lead to aberrant trophoblast invasion, thus contributing to RM.
Detection of Anti-SARS-CoV-2-S2 IgG Is More Sensitive Than Anti-RBD IgG in Identifying Asymptomatic COVID-19 Patients
Authors: Liao Baolin , Chen Zhao , Zheng Peiyan , Li Linghua , Zhuo Jianfen , Li Fang , Li Suxiang , Chen Dingbin , Wen Chunyan , Cai Weiping , Wu Shanhui , Tang Yanhong , Duan Linwei , Wei Peilan , Chen Fangli , Yuan Jinwei , Yang Jinghong , Feng Jiaxin , Zhao Jingxian , Zhao Jincun , Sun Baoqing , Zhu Airu , Li Yimin , Tang Xiaoping
Published: August 2021

Characterizing the serologic features of asymptomatic SARS-CoV-2 infection is imperative to improve diagnostics and control of SARS-CoV-2 transmission. In this study, we evaluated the antibody profiles in 272 plasma samples collected from 59 COVID-19 patients, consisting of 18 asymptomatic patients, 33 mildly ill patients and 8 severely ill patients. We measured the IgG against five viral structural proteins, different isotypes of immunoglobulins against the Receptor Binding Domain (RBD) protein, and neutralizing antibodies. The results showed that the overall antibody response was lower in asymptomatic infections than in symptomatic infections throughout the disease course. In contrast to symptomatic patients, asymptomatic patients showed a dominant IgG-response towards the RBD protein, but not IgM and IgA. Neutralizing antibody titers had linear correlations with IgA/IgM/IgG levels against SARS-CoV-2-RBD, as well as with IgG levels against multiple SARS-CoV-2 structural proteins, especially with anti-RBD or anti-S2 IgG. In addition, the sensitivity of anti-S2-IgG is better in identifying asymptomatic infections at early time post infection compared to anti-RBD-IgG. These data suggest that asymptomatic infections elicit weaker antibody responses, and primarily induce IgG antibody responses rather than IgA or IgM antibody responses. Detection of IgG against the S2 protein could supplement nucleic acid testing to identify asymptomatic patients. This study provides an antibody detection scheme for asymptomatic infections, which may contribute to epidemic prevention and control.
Integration of Molecular Inflammatory Interactome Analyses Reveals Dynamics of Circulating Cytokines and Extracellular Vesicle Long Non-Coding RNAs and mRNAs in Heroin Addicts During Acute and Protracted Withdrawal
Authors: Zhang Zunyue , Wu Hongjin , Peng Qingyan , Xie Zhenrong , Chen Fengrong , Ma Yuru , Zhang Yizhi , Zhou Yong , Yang Jiqing , Chen Cheng , Li Shaoyou , Zhang Yongjin , Tian Weiwei , Wang Yuan , Xu Yu , Luo Huayou , Zhu Mei , Kuang Yi-Qun , Yu Juehua , Wang Kunhua
Published: August 2021

Heroin addiction and withdrawal influence multiple physiological functions, including immune responses, but the mechanism remains largely elusive. The objective of this study was to investigate the molecular inflammatory interactome, particularly the cytokines and transcriptome regulatory network in heroin addicts undergoing withdrawal, compared to healthy controls (HCs). Twenty-seven cytokines were simultaneously assessed in 41 heroin addicts, including 20 at the acute withdrawal (AW) stage and 21 at the protracted withdrawal (PW) stage, and 38 age- and gender-matched HCs. Disturbed T-helper(Th)1/Th2, Th1/Th17, and Th2/Th17 balances, characterized by reduced interleukin (IL)-2, elevated IL-4, IL-10, and IL-17A, but normal TNF-α, were present in the AW subjects. These imbalances were mostly restored to the baseline at the PW stage. However, the cytokines TNF-α, IL-2, IL-7, IL-10, and IL-17A remained dysregulated. This study also profiled exosomal long non-coding RNA (lncRNA) and mRNA in the plasma of heroin addicts, constructed co-expression gene regulation networks, and identified lncRNA-mRNA-pathway pairs specifically associated with alterations in cytokine profiles and Th1/Th2/Th17 imbalances. Altogether, a large amount of cytokine and exosomal lncRNA/mRNA expression profiling data relating to heroin withdrawal was obtained, providing a useful experimental and theoretical basis for further understanding of the pathogenic mechanisms of withdrawal symptoms in heroin addicts.
Endoplasmic Reticulum Stress Disturbs Lipid Homeostasis and Augments Inflammation in the Intestine and Isolated Intestinal Cells of Large Yellow Croaker (Larimichthys crocea)
Authors: Fang Wei , Chen Qiuchi , Li Jiamin , Liu Yongtao , Zhao Zengqi , Shen Yanan , Mai Kangsen , Ai Qinghui
Published: August 2021

The small intestine is crucial for lipid homeostasis and immune regulation of the whole body. Endoplasmic reticulum (ER) stress may affect lipid metabolism and inflammation in the intestine, but the potential mechanism is not completely understood. In the present study, intraperitoneal injection of tunicamycin (TM) induced ER stress in the intestine of large yellow croaker (Larimichthys crocea). ER stress induced excessive accumulation of triglyceride (TG) in the intestine by promoting lipid synthesis. However, it also enhanced lipid secretion and fatty acid β-oxidation. In addition, ER stress augmented inflammation in the intestine by promoting p65 into the nucleus and increasing proinflammatory genes expression. In the isolated intestinal cells, the obtained results showed that TM treatment significantly upregulated the mRNA expression of lipid synthesis and inflammatory response genes, which were consistent with those in vivo. Moreover, overexpression of unfolded protein response (UPR) sensors significantly upregulated promoter activities of lipid synthesis and proinflammatory genes. In conclusion, the results suggested that ER stress disturbed lipid metabolism and augmented inflammation in the intestine and isolated intestinal cells of large yellow croaker, which may contribute to finding novel therapies to tackle lipid dysregulation and inflammation in the intestine of fish and human beings.
Environmental Factors Affecting Spatial Dinoflagellate Cyst Distribution in Surface Sediments Off Aveiro-Figueira da Foz (Atlantic Iberian Margin)
Authors: García-Moreiras Iria , Oliveira Anabela , Santos Ana I. , Oliveira Paulo B. , Amorim Ana
Published: August 2021

Resting cysts of planktonic dinoflagellates, once produced, sink to the seabed where they can remain viable for a long time. These cysts have important ecological roles, such as acting as the inoculum for the development of planktonic populations. Moreover, dinoflagellate cyst records from depth sediment cores are broadly used as a proxy to infer past environmental conditions. In this study, the main objective was to obtain information on the relationships between the spatial distribution of modern dinoflagellate cysts and present-day hydrography in the NW Iberian shelf. Cyst assemblages were analyzed in 51 surface sediment samples with varying grain sizes, collected at different water depths, following nine transects perpendicular to the coast, between Aveiro and Figueira da Foz (Atlantic Iberian margin). Multivariate statistical analyses revealed marked land-sea and latitudinal gradients in the distribution of cysts, and helped investigate how environmental factors [water depth, grain size, sea-surface temperature (SST), sea-surface salinity (SSS), bottom temperature (BTT) and surface chlorophyll-a concentration (CHL)] influence modern dinoflagellate cyst composition and abundances. Three main ecological signals were identified in the modern dinoflagellate cyst assemblages: (1) the heterotroph signal as the main upwelling signal; (2) the dominance of P. reticulatum and L. polyedra signal, indicative of warm stratified conditions, possibly reflecting transitional environments between more active inshore upwelling and warmer offshore waters; and (3) the G. catenatum signal for the presence of mid-shelf upwelling fronts. The almost absence of viable cysts of the toxic and potentially toxic species G. catenatum L. polyedra and P. reticulatum suggests that in the study area, for these species, there is no build-up of significant cyst beds and thus planktonic populations must depend on other seeding processes. These results are the first detailed modern distribution of dinoflagellate cysts in the NW Iberian Atlantic margin (off Portugal), and show a good correspondence with hydrographic features of summer upwelling season in the study area, meaning that they are reflecting water column characteristics and therefore may be used as supporting evidence for the interpretation of stratigraphic cyst records and reconstruction of past marine ecosystems in W Iberia.
Loss of Giant Kelp, Macrocystis pyrifera, Driven by Marine Heatwaves and Exacerbated by Poor Water Clarity in New Zealand
Authors: Tait Leigh W. , Thoral François , Pinkerton Matthew H. , Thomsen Mads S. , Schiel David R.
Published: August 2021

Marine heatwaves (MHW) are becoming stronger and more frequent across the globe. MHWs affect the thermal physiology of all biological organisms, but wider ecosystem effects are particularly impactful when large habitat-forming foundation species such as kelps are affected. Many studies on impacts from MHWs on kelps have focused on temperature effects in isolation, except for a few studies that have integrated co-occurring stress from grazers, wave exposure and nutrient limitation. It is likely that many stressors act in concert with MHWs and exacerbate their effects. Here we analyzed satellite images over 60 months to assess temporal changes in abundance of surface canopies of the giant kelp Macrocystis pyrifera in the New Zealand coastal zone. The analysis encompassed the most extreme MHW on record (2017/18), across a 6° latitudinal gradient of four regions southward from the northern distributional limit of Macrocystis along mainland New Zealand. We tested the association of surface canopy cover of Macrocystis with sea surface temperature, temperature anomalies, chlorophyll-a (a proxy for nutrient availability) and water clarity (diffuse attenuation coefficient). We found a reduced cover of Macrocystis across all regions during and after the 2017/18 MHW, with least impact at the most southern region where the maximum temperatures did not exceed 18°C. There was also an important and significant interaction between temperature and water clarity, showing that temperature-induced kelp loss was greater when water clarity was poor. These results show that notable negative effects occurred across the coastal range of this foundation species and highlight the importance of studying MHW effects across latitudinal gradients and in concert with other co-occurring stressors.
Experimental Study of Compressive Properties and Environmental Impact of Recycled Aggregate
Authors: Xuetong Ma , Debin Gao
Published: August 2021

As the main component of fiber-reinforced recycled aggregate concrete, the properties of recycled aggregate determine whether recycled aggregate concrete can be used in engineering applications. To study the compressive properties and environmental impact of recycled aggregate, large-scale indoor compression tests were carried out on recycled aggregate under different moisture contents, concrete aggregate ratios, dry-wet cycles, and loads. The results showed that the crushing rate and settlement first increased and then decreased upon increasing the moisture content. Upon increasing the concrete aggregate ratio, the settlement continuously decreased, and the crushing rate decreased from 157.2 to 82.5%. Upon increasing the number of dry-wet cycles, the settlement continued to increase to an upper limit of about 17.5%, and the crushing rate increased to 35%. Upon increasing the load, the settlement and crushing rate of the aggregate increased. These results show that the effects of aggregate ratio, moisture content, and dry-wet cycles on settlement were caused by crushing the aggregate. Based on this, a formula was constructed to predict the final settlement of reclaimed aggregate. The leaching amount of Cr in recycled aggregate was 0.0175–0.0375 mg/L under normal conditions, but under extreme conditions, the leaching amount of some sampling points was greater than in the standard requirements. This means that recycled aggregate may pose environmental risks that should be mitigated during use. Recycled aggregate can be used to construct sponge city storage and reuse facilities, as well as fiber-reinforced recycled aggregate concrete, but its sources need to be determined to ensure that it does not pose environmental risks.
Algorithm for Detection and Quantification of Hyperreflective Dots on Optical Coherence Tomography in Diabetic Macular Edema
Authors: Huang Haifan , Zhu Liangjiu , Zhu Weifang , Lin Tian , Los Leonoor Inge , Yao Chenpu , Chen Xinjian , Chen Haoyu
Published: August 2021

Purpose: To develop an algorithm to detect and quantify hyperreflective dots (HRDs) on optical coherence tomography (OCT) in patients with diabetic macular edema (DME).

Materials and Methods: Twenty OCTs (each OCT contains 128 b scans) from 20 patients diagnosed with DME were included in this study. Two types of HRDs, hard exudates and small HRDs (hypothesized to be activated microglia), were identified and labeled independently by two raters. An algorithm using deep learning technology was developed based on input (in total 2,560 OCT b scans) of manual labeling and differentiation of HRDs from rater 1. 4-fold cross-validation was used to train and validate the algorithm. Dice coefficient, intraclass coefficient (ICC), correlation coefficient, and Bland–Altman plot were used to evaluate agreement of the output parameters between two methods (either between two raters or between one rater and proposed algorithm).

Results: The Dice coefficients of total HRDs, hard exudates, and small HRDs area of the algorithm were 0.70 ± 0.10, 0.72 ± 0.11, and 0.46 ± 0.06, respectively. The correlations between rater 1 and proposed algorithm (range: 0.95–0.99, all p < 0.001) were stronger than the correlations between the two raters (range: 0.84–0.96, all p < 0.001) for all parameters. The ICCs were higher for all the parameters between rater 1 and proposed algorithm (range: 0.972–0.997) than those between the two raters (range: 0.860–0.953).

Conclusions: Our proposed algorithm is a good tool to detect and quantify HRDs and can provide objective and repeatable information of OCT for DME patients in clinical practice and studies.
Systematic Review and Recommendations to Combine Newer Therapies With Conventional Therapy in Psoriatic Disease
Authors: Arora Sandeep , Das Pankaj , Arora Gulhima
Published: August 2021

Background: Psoriasis continues to have unmet needs in its management despite introduction of newer molecules. Monotherapy with these newer agents may not achieve therapeutic goals in all cases, hence necessitating their combinations with other molecules. Improved understanding of newer as well as conventional treatment modalities and experiences in their combinations hence necessitates therapeutic guidelines for their use in psoriasis.

Objective: To review the combinations of treatments reported in literature and recommendations for their use based on best current evidence in literature.

Methods: A literature review of MEDLINE database for studies evaluating combinations of newer therapies with conventional therapies in psoriasis was done. Newer therapies were identified as biologic disease modifying anti rheumatic drugs and other molecules such as apremilast while conventional therapies included methotrexate, cyclosporine, or retinoids, phototherapy and others. The therapeutic guidelines are proposed with the aim to provide evidenced based approach to combine newer and conventional agents in day-to-day psoriasis management.

Findings: Combination of acitretin and narrow band ultraviolet B (NB-UVB)/Psoralen with ultraviolet A (PUVA) achieves faster clearance and allows reduction of dose of the latter. A variable outcome is reported of methotrexate with TNF-α inhibitors vs. TNF-α inhibitors alone, although addition of methotrexate appears to reduce immunogenicity of TNF-α inhibitors thereby preventing formation of anti-drug antibodies especially in case of infliximab. While combination of acitretin and PUVA is beneficial, combining TNF-α inhibitors and phototherapy too produces better and faster results but long term risks of Non Melanoma Skin Cancers (NMSCs) may preclude their use together. Combination of cyclosporine and phototherapy is not recommended due to greater chances of NMSCs. Adding phototherapy to Fumaric Acid Esters (FAEs) improves efficacy. Apremilast can be safely combined with available biologic agents in patients with plaque psoriasis or psoriatic arthritis not responding adequately to biologics alone. Hydroxyurea and acitretin may be used together increasing their efficacy and reducing doses of both and hence their adverse effects.

Conclusion: Selected clinical scenarios shall benefit from combinations therapies, improving efficacy of both conventional and newer agents and at the same time helping reduce toxicity of higher dosages when used individually.
Characterization of the Genitourinary Microbiome of 1,165 Middle-Aged and Elderly Healthy Individuals
Authors: Qin Junjie , Shi Xulian , Xu Junming , Yuan Simin , Zheng Bo , Zhang Enpu , Huang Guixiao , Li Guo , Jiang Ganggang , Gao Shan , Tian Cheng , Guo Ruochun , Fu Zhicong , Huang Qingru , Yang Rentao , Zhang Wenyong , Li Shenghui , Wu Song
Published: August 2021

Accumulated evidence shows that complex microbial communities resides in the healthy human urinary tract and can change in urological disorders. However, there lacks a comprehensive profiling of the genitourinary microbiota in healthy cohort. Here, we performed 16S rRNA gene sequencing of midstream urine specimens from 1,172 middle-aged and elderly healthy individuals. The core microbiota included 6 dominant genera (mean relative abundance >5%), including Prevotella, Streptococcus, Lactobacillus, Gardnerella, Escherichia-Shigella, and Veillonella, and 131 low-abundance genera (0.01–5%), displaying a distinct microbiome profiles to that of host-matched gut microbiota. The composition and diversity of genitourinary microbiome (GM) were distinct between genders and may fluctuate with ages. Several urotypes were identified by the stratification of microbiome profiles, which were mainly dominated by the six most predominant genera. The prevalence of urotypes was disparate between genders, and the male sample additionally harbored other urotypes dominated by Acinetobacter, Corynebacterium, Staphylococcus, or Sphingomonas. Peptoniphilus, Ezakiella, and Porphyromonas were co-occurred and co-abundant, and they may play crucial roles as keystone genera and be associated with increased microbial diversity. Our results delineated the microbial structure and diversity landscape of the GM in healthy middle-aged and elderly adults and provided insights into the influence of gender and age to it.
Antibiotic Breakdown by Susceptible Bacteria Enhances the Establishment of β-Lactam Resistant Mutants
Authors: Saebelfeld Manja , Das Suman G. , Brink Jorn , Hagenbeek Arno , Krug Joachim , de Visser J. Arjan G. M.
Published: August 2021

For a better understanding of the evolution of antibiotic resistance, it is imperative to study the factors that determine the initial establishment of mutant resistance alleles. In addition to the antibiotic concentration, the establishment of resistance alleles may be affected by interactions with the surrounding susceptible cells from which they derive, for instance via the release of nutrients or removal of the antibiotic. Here, we investigate the effects of social interactions with surrounding susceptible cells on the establishment of Escherichia coli mutants with increasing β-lactamase activity (i.e., the capacity to hydrolyze β-lactam antibiotics) from single cells under the exposure of the antibiotic cefotaxime (CTX) on agar plates. We find that relatively susceptible cells, expressing a β-lactamase with very low antibiotic-hydrolyzing activity, increase the probability of mutant cells to survive and outgrow into colonies due to the active breakdown of the antibiotic. However, the rate of breakdown by the susceptible strain is much higher than expected based on its low enzymatic activity. A detailed theoretical model suggests that this observation may be explained by cell filamentation causing delayed lysis. While susceptible cells may hamper the spread of higher-resistant β-lactamase mutants at relatively high frequencies, our findings show that they promote their initial establishment.
Inflammatory Biomarkers Aid in Diagnosis of Dementia
Authors: Erhardt Erik B. , Adair John C. , Knoefel Janice E. , Caprihan Arvind , Prestopnik Jillian , Thompson Jeffrey , Hobson Sasha , Siegel David , Rosenberg Gary A.
Published: August 2021

Dual pathology of Alzheimer's disease (AD) and vascular cognitive impairment and dementia (VCID) commonly are found together at autopsy, but mixed dementia (MX) is difficult to diagnose during life. Biological criteria to diagnose AD have been defined, but are not available for vascular disease. We used the biological criteria for AD and white matter injury based on MRI to diagnose MX. Then we measured multiple biomarkers in CSF and blood with multiplex biomarker kits for proteases, angiogenic factors, and cytokines to explore pathophysiology in each group. Finally, we used machine learning with the Random forest algorithm to select the biomarkers of maximal importance; that analysis identified three proteases, matrix metalloproteinase-10 (MMP-10), MMP-3 and MMP-1; three angiogenic factors, VEGF-C, Tie-2 and PLGF, and three cytokines interleukin-2 (IL-2), IL-6, IL-13. To confirm the clinical importance of the variables, we showed that they correlated with results of neuropsychological testing.
The Role of the Ventromedial Prefrontal Cortex in Public Good and Public Bad Games: Evidence From a tDCS Study
Authors: Chen Yuyou , Lu Xinbo , Li Yuzhen , Zeng Lulu , Yu Ping , Luo Jun , Ye Hang , Zheng Wanjun
Published: August 2021

Although humans constitute an exceptionally cooperative species that is able to collaborate on large scales for common benefits, cooperation remains a longstanding puzzle in biological and social science. Moreover, cooperation is not always related to resource allocation and gains but is often related to losses. Revealing the neurological mechanisms and brain regions related to cooperation is important for reinforcing cooperation-related gains and losses. Recent neuroscience studies have found that the decision-making process of cooperation is involved in the function of the ventromedial prefrontal cortex (VMPFC). In the present study, we aimed to investigate the causal role of the VMPFC in cooperative behavior concerning gains and losses through the application of transcranial direct current stimulation (tDCS). We integrated cooperation-related gains and losses into a unified paradigm. Based on the paradigm, we researched cooperation behaviors regarding gains in standard public good games and introduced public bad games to investigate cooperative behavior regarding losses. Our study revealed that the VMPFC plays different roles concerning gains and losses in situations requiring cooperation. Anodal stimulation over the VMPFC decreased cooperative behavior in public bad games, whereas stimulation over the VMPFC did not change cooperative behavior in public good games. Moreover, participants’ beliefs about others’ cooperation were changed in public bad games but not in public good games. Finally, participants’ cooperative attitudes were not influenced in the public good or public bad games under the three stimulation conditions.
Acute Polyradiculomyelitis With Spinal Cord Gray Matter Lesions: A Report of Two Cases
Authors: Tsagkas Charidimos , Wendebourg Maria Janina , Mehling Matthias , Lorscheider Johannes , Lyrer Philippe , Décard Bernhard Friedrich
Published: August 2021

Objective: Inflammatory polyradiculomyelitis belongs to a rare group of immune-mediated diseases affecting both the central and peripheral nervous system. We aimed to describe an unusual presentation of acute polyradiculomyelitis with marked spinal cord lesions restricted to the gray matter.

Methods: Thorough examination of two case reports including clinical, MRI, serologic, electrophysiologic and CSF examinations as well as short-term follow-up.

Results: We present two adult patients with acute polyradiculomyelitis and unusual spinal cord lesions restricted to the gray matter on MRI. The clinical presentation, serologic, electrophysiologic and CSF features of the two patients varied, whereas both patients demonstrated severe, asymmetrical, predominantly distal, motor deficits of the lower extremities as well as bladder and bowel dysfunction. Both patients only partially responded to anti-inflammatory treatment. Severe motor impairment and bladder dysfunction persisted even months after symptom onset.

Conclusions: To our best of knowledge, these are the first reports of acute polyradiculomyelitis with distinct involvement of the lower thoracic spinal cord gray matter. Currently, it remains unclear whether gray matter lesions reflect a separate pathophysiologic mechanism or an exceedingly rare presentation of spinal cord involvement in acute polyradiculomyelitis.
Continuous Myoelectric Prediction of Future Ankle Angle and Moment Across Ambulation Conditions and Their Transitions
Authors: Zabre-Gonzalez Erika V. , Riem Lara , Voglewede Philip A. , Silver-Thorn Barbara , Koehler-McNicholas Sara R. , Beardsley Scott A.
Published: August 2021

A hallmark of human locomotion is that it continuously adapts to changes in the environment and predictively adjusts to changes in the terrain, both of which are major challenges to lower limb amputees due to the limitations in prostheses and control algorithms. Here, the ability of a single-network nonlinear autoregressive model to continuously predict future ankle kinematics and kinetics simultaneously across ambulation conditions using lower limb surface electromyography (EMG) signals was examined. Ankle plantarflexor and dorsiflexor EMG from ten healthy young adults were mapped to normal ranges of ankle angle and ankle moment during level overground walking, stair ascent, and stair descent, including transitions between terrains (i.e., transitions to/from staircase). Prediction performance was characterized as a function of the time between current EMG/angle/moment inputs and future angle/moment model predictions (prediction interval), the number of past EMG/angle/moment input values over time (sampling window), and the number of units in the network hidden layer that minimized error between experimentally measured values (targets) and model predictions of ankle angle and moment. Ankle angle and moment predictions were robust across ambulation conditions with root mean squared errors less than 1° and 0.04 Nm/kg, respectively, and cross-correlations (R2) greater than 0.99 for prediction intervals of 58 ms. Model predictions at critical points of trip-related fall risk fell within the variability of the ankle angle and moment targets (Benjamini-Hochberg adjustedp> 0.065). EMG contribution to ankle angle and moment predictions occurred consistently across ambulation conditions and model outputs. EMG signals had the greatest impact on noncyclic regions of gait such as double limb support, transitions between terrains, and around plantarflexion and moment peaks. The use of natural muscle activation patterns to continuously predict variations in normal gait and the model’s predictive capabilities to counteract electromechanical inherent delays suggest that this approach could provide robust and intuitive user-driven real-time control of a wide variety of lower limb robotic devices, including active powered ankle-foot prostheses.
Antioxidant, Mineralogenic and Osteogenic Activities of Spartina alterniflora and Salicornia fragilis Extracts Rich in Polyphenols
Authors: Roberto Vânia P. , Surget Gwladys , Le Lann Klervi , Mira Sara , Tarasco Marco , Guérard Fabienne , Poupart Nathalie , Laizé Vincent , Stiger-Pouvreau Valérie , Cancela M. Leonor
Published: August 2021

Osteoporosis is an aging-related disease and a worldwide health issue. Current therapeutics have failed to reduce the prevalence of osteoporosis in the human population, thus the discovery of compounds with bone anabolic properties that could be the basis of next generation drugs is a priority. Marine plants contain a wide range of bioactive compounds and the presence of osteoactive phytochemicals was investigated in two halophytes collected in Brittany (France): the invasive Spartina alterniflora and the native Salicornia fragilis. Two semi-purified fractions, prepared through liquid-liquid extraction, were assessed for phenolic and flavonoid contents, and for the presence of antioxidant, mineralogenic and osteogenic bioactivities. Ethyl acetate fraction (EAF) was rich in phenolic compounds and exhibited the highest antioxidant activity. While S. fragilis EAF only triggered a weak proliferative effect in vitro, S. alterniflora EAF potently induced extracellular matrix mineralization (7-fold at 250 μg/mL). A strong osteogenic effect was also observed in vivo using zebrafish operculum assay (2.5-fold at 10 μg/mL in 9-dpf larvae). Results indicate that polyphenol rich EAF of S. alterniflora has both antioxidant and bone anabolic activities. As an invasive species, this marine plant may represent a sustainable source of molecules for therapeutic applications in bone disorders.
Development and Validation of Prognostic Nomogram for Primary Peritoneal Serous Carcinoma Compared With FIGO Staging System: A Population-Based Study
Authors: Chen Ming , Wen Zhenzhen , Qi Zhengwei , Gao Min
Published: August 2021

Background

Primary peritoneal serous carcinoma (PPSC) is a rare tumor that lacks a prognostic prediction model. Our study aims to develop a nomogram to predict overall survival (OS) of PPSC patients.

Methods

Patients confirmed to have PPSC between 2004 and 2012 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. LASSO and multivariate Cox regression analyses were used to screen for meaningful independent prognostic factors to construct a nomogram model for 3-, 5-, and 10-year OS among patients with PPSC. The nomogram compared the discrimination, calibration, and net benefits with the International Federation of Gynecology and Obstetrics (FIGO) staging system of PPSC patients.

Results

Eight variables were selected to establish the nomogram for PPSC. The established nomogram performed significantly better than the FIGO staging system (p < 0.05). The 3-, 5-, and 10-year OS of PPSC was 0.498, 0.306, and 0.152, respectively. Patients of old age, widowed marital status, grade high, FIGO IIIB, IIIC, or IV, lymph node metastasis, no lymphadenectomy, no surgery, and no chemotherapy got higher score which corresponds with higher risk and lower OS. In the multivariate Cox regression analysis, age, histological grade, FIGO staging, lymph node metastasis, and lymphadenectomy (four or more) were identified as independent prognostic factors for PPSC.

Conclusions

PPSC patients have distinct characteristics with respect to their presentation and survival outcomes. A prognostic nomogram constructed by various clinical indicators can provide better and more accurate predictions for patients with PPSC.
Deep Learning With Data Enhancement for the Differentiation of Solitary and Multiple Cerebral Glioblastoma, Lymphoma, and Tumefactive Demyelinating Lesion
Authors: Zhang Yu , Liang Kewei , He Jiaqi , Ma He , Chen Hongyan , Zheng Fei , Zhang Lingling , Wang Xinsheng , Ma Xibo , Chen Xuzhu
Published: August 2021

Objectives

To explore the MRI-based differential diagnosis of deep learning with data enhancement for cerebral glioblastoma (GBM), primary central nervous system lymphoma (PCNSL), and tumefactive demyelinating lesion (TDL).

Materials and Methods

This retrospective study analyzed the MRI data of 261 patients with pathologically diagnosed solitary and multiple cerebral GBM (n = 97), PCNSL (n = 92), and TDL (n = 72). The 3D segmentation model was trained to capture the lesion. Different enhancement data were generated by changing the pixel ratio of the lesion and non-lesion areas. The 3D classification network was trained by using the enhancement data. The accuracy, sensitivity, specificity, and area under the curve (AUC) were used to assess the value of different enhancement data on the discrimination performance. These results were then compared with the neuroradiologists’ diagnoses.

Results

The diagnostic performance fluctuated with the ratio of lesion to non-lesion area changed. The diagnostic performance was best when the ratio was 1.5. The AUCs of GBM, PCNSL, and TDL were 1.00 (95% confidence interval [CI]: 1.000–1.000), 0.96 (95% CI: 0.923–1.000), and 0.954 (95% CI: 0.904–1.000), respectively.

Conclusions

Deep learning with data enhancement is useful for the accurate identification of GBM, PCNSL, and TDL, and its diagnostic performance is better than that of the neuroradiologists.
The Clinical Application of 3D-Printed Boluses in Superficial Tumor Radiotherapy
Authors: Wang Xiran , Wang Xuetao , Xiang Zhongzheng , Zeng Yuanyuan , Liu Fang , Shao Bianfei , He Tao , Ma Jiachun , Yu Siting , Liu Lei
Published: August 2021

During the procedure of radiotherapy for superficial tumors, the key to treatment is to ensure that the skin surface receives an adequate radiation dose. However, due to the presence of the built-up effect of high-energy rays, equivalent tissue compensators (boluses) with appropriate thickness should be placed on the skin surface to increase the target radiation dose. Traditional boluses do not usually fit the skin perfectly. Wet gauze is variable in thickness day to day which results in air gaps between the skin and the bolus. These unwanted but avoidable air gaps lead to a decrease of the radiation dose in the target area and can have a poor effect on the outcome. Three-dimensional (3D) printing, a new rising technology named “additive manufacturing” (AM), could create physical models with specific shapes from digital information by using special materials. It has been favored in many fields because of its advantages, including less waste, low-cost, and individualized design. It is not an exception in the field of radiotherapy, personalized boluses made through 3D printing technology also make up for a number of shortcomings of the traditional commercial bolus. Therefore, an increasing number of researchers have tried to use 3D-printed boluses for clinical applications rather than commercial boluses. Here, we review the 3D-printed bolus’s material selection and production process, its clinical applications, and potential radioactive dermatitis. Finally, we discuss some of the challenges that still need to be addressed with the 3D-printed boluses.
A 14-Marker Multiplexed Imaging Panel for Prognostic Biomarkers and Tumor Heterogeneity in Head and Neck Squamous Cell Carcinoma
Authors: Mitsuda Junichi , Tsujikawa Takahiro , Yoshimura Kanako , Saburi Sumiyo , Suetsugu Masaho , Kitamoto Kayo , Takenaka Mari , Ohmura Gaku , Arai Akihito , Ogi Hiroshi , Itoh Kyoko , Hirano Shigeru
Published: August 2021

Recent advances made in treatment for head and neck squamous cell carcinoma (HNSCC) highlight the need for new prediction tools to guide therapeutic strategies. In this study, we aimed to develop a HNSCC-targeting multiplex immunohistochemical (IHC) panel that can evaluate prognostic factors and the intratumor heterogeneity of HNSCC. To identify IHC-based tissue biomarkers that constitute new multiplex IHC panel, a systematic review and meta-analysis were performed to analyze reported IHC biomarkers in laryngeal and pharyngeal SCC in the period of 2008–2018. The Cancer Genome Atlas (TCGA) and Reactome pathway databases were used to validate the prognostic and functional significance of the identified biomarkers. A 14-marker chromogenic multiplex IHC panel including identified biomarkers was used to analyze untreated HNSCC tissue. Forty-five high-quality studies and thirty-one candidate tissue biomarkers were identified (N = 7062). Prognostic validation in TCGA laryngeal and pharyngeal SCC cohort (N = 205) showed that β-catenin, DKK1, PINCH1, ADAM10, and TIMP1 were significantly associated with poor prognosis, which were related to functional categories such as immune system, cellular response, cell cycle, and developmental systems. Selected biomarkers were assembled to build a 14-marker panel, evaluating heterogeneity and polarized expression of tumor biomarkers in the tissue structures, which was particularly related to activation of Wnt/β-catenin pathway. Integrated IHC analysis based on a systemic review and meta-analysis provides an in situ proteomics tool to assess the aggressiveness and intratumor heterogeneity of HNSCC.
Identification of Hub Genes Related to Liver Metastasis of Colorectal Cancer by Integrative Analysis
Authors: Liu Sicheng , Zhang Yaguang , Zhang Su , Qiu Lei , Zhang Bo , Han Junhong
Published: August 2021

Liver metastasis of colorectal cancer (LMCRC) severely damages patient health, causing poor prognosis and tumor relapse. Marker genes associated with LMCRC identified by previous study did not meet therapeutic demand. Therefore, it is necessary to identify new biomarkers regulating the metastasis network and screen potential drugs for future treatment. Here, we identified that cell adhesion molecules and peroxisome proliferator-activated receptor (PPAR) signaling pathway were significantly enriched by analyzing the integrated-multiple expression profiles. Moreover, analysis with robust rank aggregation approach revealed a total of 138 differentially expressed genes (DEGs), including 108 upexpressed and 30 downexpressed genes. With establishing protein–protein interaction network, we also identified the subnetwork significantly enriching the metastasis-associated hub genes including ALB, APOE, CDH2, and ORM1. ESR2, FOXO3, and SRY were determined as key transcription factors regulating hub genes. In addition, ADH-1, epigallocatechin, CHEMBL1945287, and cochinchinenin C were predicted as potential therapeutic drugs. Moreover, the antimigration capacity of ADH-1 and epigallocatechin were confirmed in CRC cell lines. In conclusion, our findings not only offer opportunities to understand metastasis mechanism but also identify potential therapeutic targets for CRC.
SARS-CoV-2 Viral Load Is Correlated With the Disease Severity and Mortality in Patients With Cancer
Authors: Al-Mozaini Maha , Noman Abu Shadat M. , Alotaibi Jawaher , Karim Mohammed Rezaul , Zahed A. S. M. , Karim A. T. M. Rezaul , Alromiah Khaldoun , Islam Syed S.
Published: August 2021

The correlation between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral load and risk of disease severity in cancer patients is poorly understood. Given the fact that cancer patients are at increased risk of severe coronavirus disease 2019 (COVID-19), analysis of viral load and disease outcome in COVID-19-infected cancer patients is needed. Here, we measured the SARS-CoV-2 viral load using qPCR cycle threshold (Ct) values collected from 120 noncancer and 64 cancer patients’ nasopharyngeal swab samples who are admitted to hospitals. Our results showed that the in-hospital mortality for high viral load cancer patients was 41.38%, 23.81% for medium viral load and 14.29% for low viral load patients (p < −0.01). On the other hand, the mortality rate for noncancer patients was lower: 22.22% among patients with high viral load, 5.13% among patients with medium viral load, and 1.85% among patients with low viral load (p < 0.05). In addition, patients with lung and hematologic cancer showed higher possibilities of severe events in proportion to high viral load. Higher attributable mortality and severity were directly proportional to high viral load particularly in patients who are receiving anticancer treatment. Importantly, we found that the incubation period and serial interval time is shorter in cancer patients compared with noncancer cases. Our report suggests that high SARS-CoV-2 viral loads may play a significant role in the overall mortality and severity of COVID-19-positive cancer patients, and this warrants further study to explore the disease pathogenesis and their use as prognostic tools.
Rumination Syndrome in Children and Adolescents: A Mini Review
Authors: Martinez Marc , Rathod Sandeep , Friesen Hunter J. , Rosen John M. , Friesen Craig A. , Schurman Jennifer V.
Published: August 2021

Introduction: Rumination syndrome involves recurrent regurgitation of food and is believed to be underdiagnosed with patients experiencing long delays in diagnosis. It can be associated with significant social consequences, high rates of school absenteeism, and medical complications such as weight loss. The primary aims of the current review are to assess the literature regarding prevalence, pathophysiology, and treatment outcomes with a focus on neurotypical children and adolescents.

Results: Population studies in children/adolescents, 5 years of age or older, range from 0 to 5.1%. There are fewer studies in clinical settings, but the prevalence appears to be higher in patients with other gastrointestinal symptoms, particularly chronic vomiting. While physiologic changes that occur during a rumination episode are well-described, the underlying cause is less well-defined. In general, rumination appears to have similarities to other functional gastrointestinal disorders including dysmotility, possibly inflammation, and an interaction with psychologic function. While diaphragmatic breathing is considered the mainstay of treatment, pediatric data demonstrating efficacy is lacking, especially as an isolated treatment.

Conclusion: Pediatric rumination syndrome remains greatly understudied, particularly regarding treatment. There is a need to better define prevalence in both the primary care and subspecialty clinical settings, especially in patients presenting with vomiting or apparent gastroesophageal reflux. There is a need to determine whether treatment of co-morbid conditions results in improvement of rumination. Diaphragmatic breathing needs to be studied and compared to other competing responses.