bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Chronic and Acute Intranasal Oxytocin Treatments on Temporary Social Separation in Adult Titi Monkeys (Plecturocebus cupreus)
Authors: Arias del Razo Rocío , Velasco Vazquez Maria de Lourdes , Turcanu Petru , Legrand Mathieu , Lau Allison R. , Weinstein Tamara A. R. , Goetze Leana R. , Bales Karen L.
Published: June 2022

In socially monogamous titi monkeys, involuntary separation from a pair mate can produce behavioral distress and increased cortisol production. The neuropeptide oxytocin (OXT) is thought to play an important role in the separation response of pair-bonded species. Previous studies from our lab have shown that chronic intranasal oxytocin (IN OXT) during development can have long-term effects on adult social behavior. In the current study, we examined the chronic and acute effects of IN OXT or Saline (SAL) on the subjects’ response to a brief separation from their pair mates. Subjects with a history of chronic IN OXT or SAL treatment during development received a single dose of OXT or SAL as adults 30 min before being separated from their pair mate. Chronic treatment consisted of a daily dose of IN OXT (0.8 IU/kg) or SAL (control) from 12 to 18 months of age. Subjects (N = 29) were introduced to a pair mate at 30 months of age. After the pairs had cohabitated for 5 months, pairs underwent two “Brief Separation” (OXT and SAL) and two “Non-Separation” (OXT and SAL) test sessions. Vocalizations and locomotion were measured as behavioral indices of agitation or distress during the Brief Separation and Non-Separation periods (30 min each). We collected blood samples after the Brief Separation and Non-Separation periods to measure cortisol levels. Our results showed subjects treated with chronic OXT had a reduction in long call and peep vocalizations compared to subjects treated with chronic SAL. Subjects treated with chronic SAL and acute OXT produced more peeps and long calls compared to animals treated with acute SAL; however, patterns in this response depended on sex. Cortisol and locomotion were significantly higher during the Brief Separation period compared to the Non-Separation period; however, we did not find any treatment or sex effects. We conclude that chronic IN OXT given during development blunts the separation response, while acute OXT in chronic SAL subjects had sexually dimorphic effects, which could reflect increased partner seeking behaviors in males and increased anxiety in females.
The Potential Use of Carnosine in Diabetes and Other Afflictions Reported in Long COVID Patients
Authors: Diniz Fabiola Cardoso , Hipkiss Alan Roger , Ferreira Gustavo Costa
Published: June 2022

Carnosine is a dipeptide expressed in both the central nervous system and periphery. Several biological functions have been attributed to carnosine, including as an anti-inflammatory and antioxidant agent, and as a modulator of mitochondrial metabolism. Some of these mechanisms have been implicated in the pathophysiology of coronavirus disease-2019 (COVID-19). COVID-19 is caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The clinical manifestation and recovery time for COVID-19 are variable. Some patients are severely affected by SARS-CoV-2 infection and may experience respiratory failure, thromboembolic disease, neurological symptoms, kidney damage, acute pancreatitis, and even death. COVID-19 patients with comorbidities, including diabetes, are at higher risk of death. Mechanisms underlying the dysfunction of the afflicted organs in COVID-19 patients have been discussed, the most common being the so-called cytokine storm. Given the biological effects attributed to carnosine, adjuvant therapy with this dipeptide could be considered as supportive treatment in patients with either COVID-19 or long COVID.
Euglena gracilis Promotes Lactobacillus Growth and Antioxidants Accumulation as a Potential Next-Generation Prebiotic
Authors: Dai Junjie , He Jiayi , Chen Zixi , Qin Huan , Du Ming , Lei Anping , Zhao Liqing , Wang Jiangxin
Published: June 2022

Euglena gracilis, a single-celled microalga with various trophic growth styles under different cultivation conditions, contains nutrients, such as ß-1,3-glucans, essential amino acids, fatty acids, vitamins, and minerals. It has recently attracted attention as a new health food. Among them, ß-1,3-glucans, paramylon of Euglena, is an insoluble dietary fiber and is well known as an immune booster, attenuator of obesity and diabetes, reducer of acute liver injury, and suppressor of atopic dermatitis, and other chronic inflammatory disorders. Recently, evidence has appeared for the positive health effects of foods, food ingredients, or biochemical compounds derived from several other microalgae, such as Chlorella, Spirulina, Dunaliella, Phaeodactylum, and Pavlova. Until most recently, the prebiotic activity of Euglena and paramylon was reported. Emerging prospects of microalgae as prebiotics were well summarized, but the mechanisms behind the bacterial growth promotion by microalgae are not elucidated yet. Thus, we evaluated the prebiotic prospects of both autotrophic and heterotrophic Euglena on six different Lactobacillus. What’s more, the stimulated mechanism was revealed by bacterial culture medium metabolomic analysis. This study could widen the knowledge about the prebiotic activity of Euglena as a next-generation prebiotic and other microalgae-derived compounds as potential health foods.
The Clinicopathological Significance and Prognostic Value of Androgen Receptor in Endometrial Carcinoma: A Meta-Analysis
Authors: Wu Xirong , Zhong Xiuli , Huo Xiaoqing , Zhang Junrong , Yang Xiaoqing , Zhang Yuquan
Published: June 2022

Background

The role of androgen receptor (AR) in evaluating the prognosis of patients with endometrial cancer (EC) remains controversial. Here, we performed a meta-analysis to assess whether AR expression improves EC survival outcomes.

Methods

We searched related articles published before August 2021 in PubMed, EMBASE, and Web of Science. The association between AR expression and patient prognosis was estimated with hazard ratios (HRs) and odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs). The review is registered on PROSPERO, registration number: CRD42021268591.

Results

Ten studies including 1,485 patients were enrolled in the meta-analysis. The results showed that AR expression in EC tissues was associated with a better survival in crude analyses (HR = 1.63, 95% CI = 1.32–2.02, P < 0.001). However, no significant relation was found after the adjustment of the confounding factors (HR = 1.68, 95% CI = 0.75–3.75, P = 0.205). In subgroup analyses, grade 1–2 disease, stage I–II disease, negative lymph node status, and lack of the lymphovascular invasion were more common in AR-positive groups (OR = 0.47, 0.48, 0.37, and 0.57; 95% CI = 0.45–0.62, 0.35–0.65, 0.24–0.56, and 0.37–0.89). Furthermore, AR expression was more common in endometrioid cancers (OR = 2.39, 95% CI = 1.79–3.20).

Conclusions

AR expression is significantly associated favorable characteristics including low-grade disease, early-stage disease, negative lymph node status, and lack of the lymphovascular invasion and a specific histology—endometrioid cancer. However, AR is not an independent prognostic factor.
Monocarboxylate Transporter 4 in Cancer-Associated Fibroblasts Is a Driver of Aggressiveness in Aerodigestive Tract Cancers
Authors: Domingo-Vidal Marina , Whitaker-Menezes Diana , Mollaee Mehri , Lin Zhao , Tuluc Madalina , Philp Nancy , Johnson Jennifer M. , Zhan Tingting , Curry Joseph , Martinez-Outschoorn Ubaldo
Published: June 2022

The most common cancers of the aerodigestive tract (ADT) are non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC). The tumor stroma plays an important role in ADT cancer development and progression, and contributes to the metabolic heterogeneity of tumors. Cancer-associated fibroblasts (CAFs) are the most abundant cell type in the tumor stroma of ADT cancers and exert pro-tumorigenic functions. Metabolically, glycolytic CAFs support the energy needs of oxidative (OXPHOS) carcinoma cells. Upregulation of the monocarboxylate transporter 4 (MCT4) and downregulation of isocitrate dehydrogenase 3α (IDH3α) are markers of glycolysis in CAFs, and upregulation of the monocarboxylate transporter 1 (MCT1) and the translocase of the outer mitochondrial membrane 20 (TOMM20) are markers of OXPHOS in carcinoma cells. It is unknown if glycolytic metabolism in CAFs is a driver of ADT cancer aggressiveness. In this study, co-cultures in vitro and co-injections in mice of ADT carcinoma cells with fibroblasts were used as experimental models to study the effects of fibroblasts on metabolic compartmentalization, oxidative stress, carcinoma cell proliferation and apoptosis, and overall tumor growth. Glycolytic metabolism in fibroblasts was modulated using the HIF-1α inhibitor BAY 87-2243, the antioxidant N-acetyl cysteine, and genetic depletion of MCT4. We found that ADT human tumors express markers of metabolic compartmentalization and that co-culture models of ADT cancers recapitulate human metabolic compartmentalization, have high levels of oxidative stress, and promote carcinoma cell proliferation and survival. In these models, BAY 87-2243 rescues IDH3α expression and NAC reduces MCT4 expression in fibroblasts, and these treatments decrease ADT carcinoma cell proliferation and increase cell death. Genetic depletion of fibroblast MCT4 decreases proliferation and survival of ADT carcinoma cells in co-culture. Moreover, co-injection of ADT carcinoma cells with fibroblasts lacking MCT4 reduces tumor growth and decreases the expression of markers of metabolic compartmentalization in tumors. In conclusion, metabolic compartmentalization with high expression of MCT4 in CAFs drives aggressiveness in ADT cancers.
Targeting Tumour-Associated Fibroblasts in Cancers
Authors: Shah Kairav , Mallik Sanchari Basu , Gupta Praveer , Iyer Abishek
Published: June 2022

Tumours develop within complex tissue environments consisting of aberrant oncogenic cancer cells, diverse innate and adaptive immune cells, along with structural stromal cells, extracellular matrix and vascular networks, and many other cellular and non-cellular soluble constituents. Understanding the heterogeneity and the complex interplay between these cells remains a key barrier in treating tumours and cancers. The immune status of the pre-tumour and tumour milieu can dictate if the tumour microenvironment (TME) supports either a pro-malignancy or an anti-malignancy phenotype. Identification of the factors and cell types that regulate the dysfunction of the TME is crucial in order to understand and modulate the immune status of tumours. Among these cell types, tumour-associated fibroblasts are emerging as a major component of the TME that is often correlated with poor prognosis and therapy resistance, including immunotherapies. Thus, a deeper understanding of the complex roles of tumour-associated fibroblasts in regulating tumour immunity and cancer therapy could provide new insight into targeting the TME in various human cancers. In this review, we summarize recent studies investigating the role of immune and key stromal cells in regulating the immune status of the TME and discuss the therapeutic potential of targeting stromal cells, especially tumour-associated fibroblasts, within the TME as an adjuvant therapy to sensitize immunosuppressive tumours and prevent cancer progression, chemo-resistance and metastasis.
The Role of Tumor Microenvironment in Invasion and Metastasis of Esophageal Squamous Cell Carcinoma
Authors: Zheng Shuyue , Liu Beilei , Guan Xinyuan
Published: June 2022

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in the world, with a high rate of morbidity. The invasion and metastasis of ESCC is the main reason for high mortality. More and more evidence suggests that metastasized cancer cells require cellular elements that contribute to ESCC tumor microenvironment (TME) formation. TME contains many immune cells and stromal components, which are critical to epithelial–mesenchymal transition, immune escape, angiogenesis/lymphangiogenesis, metastasis niche formation, and invasion/metastasis. In this review, we will focus on the mechanism of different microenvironment cellular elements in ESCC invasion and metastasis and discuss recent therapeutic attempts to restore the tumor-suppressing function of cells within the TME. It will represent the whole picture of TME in the metastasis and invasion process of ESCC.
Molecular Characterization and Clinical Relevance of N6-Methyladenosine Regulators in Metastatic Prostate Cancer
Authors: Liu Qiwei , Li Zhen , He Lizhao , Li Ke , Hu Chen , Chen Jialiang , Zhou Fangjian , Wang Jun , Li Yonghong , Xiao Hengjun
Published: June 2022

Prostate cancer is a leading malignancy in the male population globally. N6-methylation of adenosine (m6A) is the most prevalent mRNA modification and plays an essential role in various biological processes in vivo. However, the potential roles of m6A in metastatic prostate cancer are largely unknown. In this study, we evaluated and identified two m6A modification patterns based on 21 m6A regulators in four public metastatic prostate cancer datasets. Different modification patterns correlated with distinct molecular characteristics. According to m6A-associated genes, we constructed a prognostic model, called m6Ascore, to predict the outcomes of patients with metastatic prostate cancer. We found that high m6A score level was related to dismal prognosis and characterized by higher cell cycle, DNA repair and mismatch repair pathway score. In vitro experiments confirmed that upregulation of METTL14, an m6A writer, enhanced the invasion, metastasis, and sensitivity of prostate cancer cells to poly (ADP-ribose) polymerase inhibitor. Conversely, down-regulation of potential target genes of m6A had the opposite effect. Finally, we validated that a higher m6A score was associated with a worse prognosis and a higher Gleason score in The Cancer Genome Atlas Program (TCGA) cohort. This work illustrated the nonnegligible role of m6A modification in multiple biological processes of metastatic prostate cancer. Evaluating the m6A risk scores of individual tumours will guide more effective judgement of prognosis as well as treatments for metastatic prostate cancer in clinical practice.
Neurological Symptom Improvement After Re-Irradiation in Patients With Diffuse Intrinsic Pontine Glioma: A Retrospective Analysis of the SIOP-E-HGG/DIPG Project
Authors: Chavaz Lara , Janssens Geert O. , Bolle Stephanie , Mandeville Henry , Ramos-Albiac Monica , Van Beek Karen , Benghiat Helen , Hoeben Bianca , Morales La Madrid Andres , Seidel Clemens , Kortmann Rolf-Dieter , Hargrave Darren , Gandola Lorenza , Pecori Emilia , van Vuurden Dannis G. , Biassoni Veronica , Massimino Maura , Kramm Christof M. , von Bueren Andre O.
Published: June 2022

Purpose

The aim of this study is to investigate the spectrum of neurological triad improvement in patients with diffuse intrinsic pontine glioma (DIPG) treated by re-irradiation (re-RT) at first progression.

Methods

We carried out a re-analysis of the SIOP-E retrospective DIPG cohort by investigating the clinical benefits after re-RT with a focus on the neurological triad (cranial nerve deficits, ataxia, and long tract signs). Patients were categorized as “responding” or “non-responding” to re-RT. To assess the interdependence between patients’ characteristics and clinical benefits, we used a chi-square or Fisher’s exact test. Survival according to clinical response to re-RT was calculated by the Kaplan–Meier method.

Results

As earlier reported, 77% (n = 24/31) of patients had any clinical benefit after re-RT. Among 25/31 well-documented patients, 44% (n = 11/25) had improvement in cranial nerve palsies, 40% (n = 10/25) had improvement in long-tract signs, and 44% (11/25) had improvement in cerebellar signs. Clinical benefits were observed in at least 1, 2, or 3 out of 3 symptoms of the DIPG triad, in 64%, 40%, and 24%, respectively. Patients irradiated with a dose ≥20 Gy versus <20 Gy may improve slightly better with regard to ataxia (67% versus 23%; p-value = 0.028). The survival from the start of re-RT to death was not different between responding and non-responding DIPG patients (p-value = 0.871).

Conclusion

A median re-irradiation dose of 20 Gy provides a neurological benefit in two-thirds of patients with an improvement of at least one symptom of the triad. DIPG patients receiving ≥20 Gy appear to improve slightly better with regard to ataxia; however, we need more data to determine whether dose escalation up to 30 Gy provides additional benefits.
Automated Oxygen Delivery in Neonatal Intensive Care
Authors: Nair Vrinda , Loganathan Prakash , Lal Mithilesh Kumar , Bachman Thomas
Published: June 2022

Oxygen is the most common drug used in the neonatal intensive care. It has a narrow therapeutic range in preterm infants. Too high (hyperoxemia) or low oxygen (hypoxemia) is associated with adverse neonatal outcomes. It is not only prudent to maintain oxygen saturations in the target range, but also to avoid extremes of oxygen saturations. In routine practice when done manually by the staff, it is challenging to maintain oxygen saturations within the target range. Automatic control of oxygen delivery is now feasible and has shown to improve the time spent with in the target range of oxygen saturations. In addition, it also helps to avoid extremes of oxygen saturation. However, there are no studies that evaluated the clinical outcomes with automatic control of oxygen delivery. In this narrative review article, we aim to present the current evidence on automatic oxygen control and the future directions.
Profiling Differential Effects of 5 Selective Serotonin Reuptake Inhibitors on TLRs-Dependent and -Independent IL-6 Production in Immune Cells Identifies Fluoxetine as Preferred Anti-Inflammatory Drug Candidate
Authors: Takenaka Yohei , Tanaka Ryu , Kitabatake Kazuki , Kuramochi Kouji , Aoki Shin , Tsukimoto Mitsutoshi
Published: June 2022

Excessive proinflammatory cytokine production induced by abnormal activation of Toll-like receptor (TLR) signaling, for example, by SARS-CoV-2 infection, can cause a fatal cytokine storm. The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and fluvoxamine, used to treat depression, were recently reported to reduce the risk of severe disease in patients with coronavirus disease 2019 (COVID-19), but the mechanisms of the anti-inflammatory effects of SSRIs, and which SSRI would be most suitable as an anti-inflammatory drug, remain unclear. Here, we examined the inhibitory effects of 5 FDA-approved SSRIs, paroxetine, fluoxetine, fluvoxamine, sertraline and escitalopram, on the production of interleukin-6 (IL-6) induced by stimulation with multiple TLR agonists in murine macrophages and dendritic cells, and on the production of cytokines induced by concanavalin A in murine lymphocytes. In J774.1 murine macrophage cells, pretreatment with SSRIs significantly suppressed IL-6 release induced by TLR3 agonist poly(I:C), TLR4 agonist LPS or TLR9 agonist CpG ODN, but did not affect IL-6 release induced by TLR7 agonists imiquimod or resiquimod. In accordance with the results obtained in J774.1 cells, pretreatment with SSRIs also suppressed IL-6 release induced by a TLR3, TLR4 or TLR9 agonist in bone marrow-derived dendritic cells and peritoneal cells of C57BL/6 mice. On the other hand, interestingly, sertraline alone among the SSRIs amplified IL-6 production induced by TLR7 agonists in murine dendritic cells, though not in macrophages. Concanavalin A-induced production of IL-6 or IL-2 in murine lymphocytes was suppressed by SSRIs, suggesting that SSRIs also inhibit TLRs-independent IL-6 production. Since SSRIs suppressed both IL-6 production induced by multiple TLR agonists in macrophages or dendritic cells and TLR-independent IL-6 production in lymphocytes, they are promising candidates for treatment of patients with cytokine storm, which is mediated by overactivation of multiple TLRs in a complex manner, leading to the so-called IL-6 amplifier, an IL-6 overproduction loop. However, the 5 SSRIs examined here all showed different effects. Overall, our results suggest that fluoxetine may be the most promising candidate as an anti-inflammatory drug. An examination of the structural requirements indicated that the N-methyl group of fluoxetine has a critical role in the inhibition of IL-6 production.
Combination of Panax ginseng C. A. Mey and Febuxostat Boasted Cardioprotective Effects Against Doxorubicin-Induced Acute Cardiotoxicity in Rats
Authors: Al-Kuraishy Hayder M. , Al-Hussaniy Hany A. , Al-Gareeb Ali I. , Negm Walaa A. , El-Kadem Aya H. , Batiha Gaber El-Saber , N. Welson Nermeen , Mostafa-Hedeab Gomaa , Qasem Ahmed H , Conte-Junior Carlos Adam
Published: June 2022

Doxorubicin (DOX) is an anticancer agent for treating solid and soft tissue malignancies. However, the clinical use of DOX is restricted by cumulative, dose-dependent cardiotoxicity. Therefore, the present study aimed to assess the cardioprotective effects of P. ginseng C. A. Mey, febuxostat, and their combination against DOX-induced cardiotoxicity. Thirty-five Sprague Dawley male rats were used in this study. The animals were randomly divided into five groups, with seven rats per group. The control group received normal saline, the induced group received DOX only, and the treated group received P. ginseng, febuxostat, and their combination before DOX treatment. Biomarkers of acute cardiac toxicity were assessed in each group. Results showed that treatment with the combination of febuxostat and P. ginseng before DOX led to a significant improvement in the biomarkers of acute DOX-induced cardiotoxicity. In conclusion, the combination of P. ginseng and febuxostat produced more significant cardioprotective effects against DOX-induced cardiotoxicity when compared to either P. ginseng or febuxostat when used alone. The potential mechanism of this combination was mainly mediated by the anti-inflammatory and antioxidant effects of P. ginseng and febuxostat.
Investigating Fake and Reliable News Sources Using Complex Networks Analysis
Authors: Mazzeo Valeria , Rapisarda Andrea
Published: June 2022

The rise of disinformation in the last years has shed light on the presence of bad actors that produce and spread misleading content every day. Therefore, looking at the characteristics of these actors has become crucial for gaining better knowledge of the phenomenon of disinformation to fight it. This study seeks to understand how these actors, meant here as unreliable news websites, differ from reliable ones. With this aim, we investigated some well-known fake and reliable news sources and their relationships, using a network growth model based on the overlap of their audience. Then, we peered into the news sites’ sub-networks and their structure, finding that unreliable news sources’ sub-networks are overall disassortative and have a low–medium clustering coefficient, indicative of a higher fragmentation. The k-core decomposition allowed us to find the coreness value for each node in the network, identifying the most connectedness site communities and revealing the structural organization of the network, where the unreliable websites tend to populate the inner shells. By analyzing WHOIS information, it also emerged that unreliable websites generally have a newer registration date and shorter-term registrations compared to reliable websites. The results on the political leaning of the news sources show extremist news sources of any political leaning are generally mostly responsible for producing and spreading disinformation.
Quantifying Award Network and Career Development in the Movie Industry
Authors: Liu Yixuan , Ma Yifang
Published: June 2022

In show business, awards are conferred to persons and films to provide incentives to performers’ future career development through periodic film festivals and events. In this work, we focused on exploring the growth and dynamics of the film award system, the structure of the award network, and the relationships between historical performance, collaborations, and future career success of performers in the movie industry. We collected data from IMDb, which covers more than 3.5K movie events for 520K individuals with their award-winning and career records for over 90 years. By using network analysis and regression models, we find several novel results. At first, we found the exponential proliferation of awards across all genres of films and all professions of individuals and the uneven distribution of the number of awards in careers across time. More than 30% of the performers have won multiple awards. Second, we built an award network to reveal the interlocks between awards based on multiple award-winning phenomena. We found that for prestigious awards, 47% of the linkages were over-representative than the expectations from the null model. Furthermore, the performers’ collaboration network was highly clustered, exhibiting a high propensity of linkages between awarded performers. Lastly, our regression models revealed that multiple factors were related to performers’ early career success and award winning. Specifically, we showed that along with the performers’ historical achievements, their collaborators serve an important role in award winning after being nominated, with the scope and depth of the impact differing in the awards’ prestige. This work has strong implications for the harmonious dynamics of the movie industry and the career development of performers.
Cardiac Macrophages and Their Effects on Arrhythmogenesis
Authors: Xia Ruibing , Tomsits Philipp , Loy Simone , Zhang Zhihao , Pauly Valerie , Schüttler Dominik , Clauss Sebastian
Published: June 2022

Cardiac electrophysiology is a complex system established by a plethora of inward and outward ion currents in cardiomyocytes generating and conducting electrical signals in the heart. However, not only cardiomyocytes but also other cell types can modulate the heart rhythm. Recently, cardiac macrophages were demonstrated as important players in both electrophysiology and arrhythmogenesis. Cardiac macrophages are a heterogeneous group of immune cells including resident macrophages derived from embryonic and fetal precursors and recruited macrophages derived from circulating monocytes from the bone marrow. Recent studies suggest antiarrhythmic as well as proarrhythmic effects of cardiac macrophages. The proposed mechanisms of how cardiac macrophages affect electrophysiology vary and include both direct and indirect interactions with other cardiac cells. In this review, we provide an overview of the different subsets of macrophages in the heart and their possible interactions with cardiomyocytes under both physiologic conditions and heart disease. Furthermore, we elucidate similarities and differences between human, murine and porcine cardiac macrophages, thus providing detailed information for researchers investigating cardiac macrophages in important animal species for electrophysiologic research. Finally, we discuss the pros and cons of mice and pigs to investigate the role of cardiac macrophages in arrhythmogenesis from a translational perspective.
eNAMPT Neutralization Preserves Lung Fluid Balance and Reduces Acute Renal Injury in Porcine Sepsis/VILI-Induced Inflammatory Lung Injury
Authors: Sammani Saad , Bermudez Tadeo , Kempf Carrie L. , Song Jin H. , Fleming Justin C , Reyes Hernon Vivian , Hufford Matthew , Tang Lin , Cai Hua , Camp Sara M. , Natarajan Viswanathan , Jacobson Jeffrey R. , Dudek Steven M. , Martin Diego R. , Karmonik Christof , Sun Xiaoguang , Sun Belinda , Casanova Nancy G. , Bime Christian , Garcia Joe G. N.
Published: June 2022

Background: Numerous potential ARDS therapeutics, based upon preclinical successful rodent studies that utilized LPS challenge without mechanical ventilation, have failed in Phase 2/3 clinical trials. Recently, ALT-100 mAb, a novel biologic that neutralizes the TLR4 ligand and DAMP, eNAMPT (extracellular nicotinamide phosphoribosyltransferase), was shown to reduce septic shock/VILI-induced porcine lung injury when delivered 2 h after injury onset. We now examine the ALT-100 mAb efficacy on acute kidney injury (AKI) and lung fluid balance in a porcine ARDS/VILI model when delivered 6 h post injury.

Methods/Results: Compared to control PBS-treated pigs, exposure of ALT-100 mAb-treated pigs (0.4 mg/kg, 2 h or 6 h after injury initiation) to LPS-induced pneumonia/septic shock and VILI (12 h), demonstrated significantly diminished lung injury severity (histology, BAL PMNs, plasma cytokines), biochemical/genomic evidence of NF-kB/MAP kinase/cytokine receptor signaling, and AKI (histology, plasma lipocalin). ALT-100 mAb treatment effectively preserved lung fluid balance reflected by reduced BAL protein/tissue albumin levels, lung wet/dry tissue ratios, ultrasound-derived B lines, and chest radiograph opacities. Delayed ALT-100 mAb at 2 h was significantly more protective than 6 h delivery only for plasma eNAMPT while trending toward greater protection for remaining inflammatory indices. Delayed ALT-100 treatment also decreased lung/renal injury indices in LPS/VILI-exposed rats when delivered up to 12 h after LPS.

Conclusions: These studies indicate the delayed delivery of the eNAMPT-neutralizing ALT-100 mAb reduces inflammatory lung injury, preserves lung fluid balance, and reduces multi-organ dysfunction, and may potentially address the unmet need for novel therapeutics that reduce ARDS/VILI mortality.
A Photosynthetic Light Acclimation Model Accounting for the Effects of Leaf Age, Chlorophyll Content, and Intra-Leaf Radiation Transfer
Authors: Graefe Jan , Yu Wenjuan , Körner Oliver
Published: June 2022

Mechanistic models of canopy photosynthesis usually upscale leaf photosynthesis to crop level. A detailed prediction of canopy microclimate with accurate leaf morphological and physiological model parameters is the pre-requisite for accurate predictions. It is well established that certain leaf model parameters (Vcmax, Jmax) of the frequently adopted Farquhar and Caemmerer photosynthesis model change with leaf age and light interception history. Previous approaches to predict Vcmax and Jmax focused primarily on light interception, either by cumulative intercepted photosynthetic photon flux density (PPFD) or by closely related proxy variables such as leaf nitrogen content per leaf area. However, for plants with monopodial growth, such as vertically grown tomatoes or cucumber crops, in greenhouse production, there is a strong relationship between leaf age and light interception, complicating the experimental and mathematical separation of both effects. We propose a modeling framework that separates age and light intensity-related acclimation effects in a crop stand: Improved approximation of intra-leaf light absorption profiles with cumulative chlorophyll content (Chl) is the basis, while parameters are estimated via Gaussian process regression from total Chl, carotenoid content (Car), and leaf mass per area (LMA). The model approximates light absorption profiles within a leaf and links them to leaf capacity profiles of photosynthetic electron transport. Published datasets for Spinacia oleracea and Eucalyptus pauciflora were used to parameterize the relationship between light and capacity profiles and to set the curvature parameter of electron transport rate described by a non-rectangular hyperbola on Cucumis sativus. Using the modified capacity and light absorption profile functions, the new model was then able to predict light acclimation in a 2-month period of a fully grown tomato crop. An age-dependent lower limit of the electron transport capacity per unit Chl was essential in order to capture the decline of Vcmax and Jmax over time and space of the investigated tomato crop. We detected that current leaf photosynthetic capacity in tomato is highly affected by intercepted light-sum of 3–5 previous days.
Identification of Candidate Genes Responsible for Flower Colour Intensity in Gentiana triflora
Authors: Tasaki Keisuke , Watanabe Aiko , Nemoto Keiichirou , Takahashi Shigekazu , Goto Fumina , Sasaki Nobuhiro , Hikage Takashi , Nishihara Masahiro
Published: June 2022

Gentians cultivated in Japan (Gentiana trifloraandGentiana scabraand hybrids) have blue flowers, but flower colour intensity differs among cultivars. The molecular mechanism underlying the variation in flower colour intensity is unclear. Here, we produced F2progeny derived from an F1cross of intense- and faint-blue lines and attempted to identify the genes responsible for flower colour intensity using RNA-sequencing analyses. Comparative analysis of flower colour intensity and transcriptome data revealed differentially expressed genes (DEGs), although known flavonoid biosynthesis-related genes showed similar expression patterns. From quantitative RT-PCR (qRT-PCR) analysis, we identified two and four genes with significantly different expression levels in the intense- and faint-blue flower lines, respectively. We conducted further analyses on one of the DEGs, termedGtMIF1, which encodes a putative mini zinc-finger protein homolog, which was most differently expressed in faint-blue individuals. Functional analysis ofGtMIF1was performed by producing stable tobacco transformants.GtMIF1-overexpressing tobacco plants showed reduced flower colour intensity compared with untransformed control plants. DNA-marker analysis also confirmed that theGtMIF1allele of the faint-blue flower line correlated well with faint flower colour in F2progeny. These results suggest thatGtMIF1is one of the key genes involved in determining the flower colour intensity of gentian.
Genome-Wide Screening of Broad-Spectrum Resistance to Leaf Rust (Puccinia triticina Eriks) in Spring Wheat (Triticum aestivum L.)
Authors: Mourad Amira M. I. , Draz Ibrahim S. , Omar Ghady E. , Börner Andreas , Esmail Samar M.
Published: June 2022

Wheat leaf rust (LR) causes significant yield losses worldwide. In Egypt, resistant cultivars began to lose their efficiency in leaf rust resistance. Therefore, a diverse spring wheat panel was evaluated at the seedling stage to identify new sources of broad-spectrum seedling resistance against the Egyptian Puccinia triticina (Pt) races. In three different experiments, seedling evaluation was done using Pt spores collected from different fields and growing seasons. Highly significant differences were found among experiments confirming the presence of different races population in each experiment. Highly significant differences were found among the tested genotypes confirming the ability to select superior genotypes. Genome-wide association study (GWAS) was conducted for each experiment and a set of 87 markers located within 48 gene models were identified. The identified gene models were associated with disease resistance in wheat. Five gene models were identified to resist all Pt races in at least two experiments and could be identified as stable genes under Egyptian conditions. Ten genotypes from five different countries were stable against all the tested Pt races but showed different degrees of resistance.
The Indole-3-Acetamide-Induced Arabidopsis Transcription Factor MYB74 Decreases Plant Growth and Contributes to the Control of Osmotic Stress Responses
Authors: Ortiz-García Paloma , Pérez-Alonso Marta-Marina , González Ortega-Villaizán Adrián , Sánchez-Parra Beatriz , Ludwig-Müller Jutta , Wilkinson Mark D. , Pollmann Stephan
Published: June 2022

The accumulation of the auxin precursor indole-3-acetamide (IAM) in the ami1 mutant has recently been reported to reduce plant growth and to trigger abiotic stress responses in Arabidopsis thaliana. The observed response includes the induction of abscisic acid (ABA) biosynthesis through the promotion of NCED3 expression. The mechanism by which plant growth is limited, however, remained largely unclear. Here, we investigated the transcriptional responses evoked by the exogenous application of IAM using comprehensive RNA-sequencing (RNA-seq) and reverse genetics approaches. The RNA-seq results highlighted the induction of a small number of genes, including the R2R3 MYB transcription factor genes MYB74 and MYB102. The two MYB factors are known to respond to various stress cues and to ABA. Consistent with a role as negative plant growth regulator, conditional MYB74 overexpressor lines showed a considerable growth reduction. RNA-seq analysis of MYB74 mutants indicated an association of MYB74 with responses to osmotic stress, water deprivation, and seed development, which further linked MYB74 with the observed ami1 osmotic stress and seed phenotype. Collectively, our findings point toward a role for MYB74 in plant growth control and in responses to abiotic stress stimuli.
Personal Memories and Bodily-Cues Influence Our Sense of Self
Authors: Bréchet Lucie
Published: June 2022

How do our bodies influence who we are? Recent research in cognitive neuroscience has examined consciousness associated with the self and related multisensory processing of bodily signals, the so-called bodily self-consciousness. A parallel line of research has highlighted the concept of the autobiographical self and the associated autonoetic consciousness, which enables us to mentally travel in time. The subjective re-experiencing of past episodes is described as re-living them from within or outside one’s body. In this brief perspective, I aim to explore the underlying characteristics of self-consciousness and its relation to bodily signals and episodic memory. I will outline some recent behavioral and neuroimaging evidence indicating that bodily cues play a fundamental role in autobiographical memory. Finally, I will discuss these emerging concepts regarding the current understanding of bodily-self, autobiographical-self, their links to self-consciousness, and suggest directions for future research.
Oral Sensory Sensitivity Influences Attentional Bias to Food Logo Images in Children: A Preliminary Investigation
Authors: Wallisch Anna , Little Lauren M. , Bruce Amanda S. , Salley Brenda
Published: June 2022

Background

Children’s sensory processing patterns are linked with their eating habits; children with increased sensory sensitivity are often picky eaters. Research suggests that children’s eating habits are also partially influenced by attention to food and beverage advertising. However, the extent to which sensory processing influences children’s attention to food cues remains unknown. Therefore, we examined the attentional bias patterns to food vs. non-food logos among children 4–12 years with and without increased oral sensory sensitivity.

Design

Children were categorized into high (n = 8) vs. typical (n = 36) oral sensory sensitivity by the Sensory Profile-2. We used eye-tracking to examine orientation and attentional bias to food vs. non-food logos among children with high vs. typical oral sensory sensitivity. We used a mixed model regression to test the influence of oral sensory sensitivity to attentional biases to food vs. non-food logos among children.

Results

Results showed that children with high oral sensory sensitivity showed attentional biases toward non-food logos; specifically, children with high oral sensory sensitivity oriented more quickly to non-food logos as compared to food logos (p < 0.05), as well as spent more time looking at non-food logos as compared to food logos (p < 0.05). Findings were in the opposite direction for children with typical oral sensory sensitivity.

Conclusion

Sensory sensitivity may be an individual characteristic that serves as a protective mechanism against susceptibility to food and beverage advertising in young children.
Mediating Role of Psychological Capital in the Relationship Between Social Support and Self-Neglect Among Chinese Community-Dwelling Older Adults
Authors: Zhao Binyu , Wang Hangsai , Xie Chunqi , Huang Xianhong , Cao Meijuan
Published: June 2022

Objectives

Self-neglect in older adults has become an important public health issue and is associated with negative health outcomes and increased morbidity and mortality. Social support has been recognized as a prominent predictor of self-neglect, but the underlying mechanism is unclear. This study aims to investigate and illustrate the associations among social support, psychological capital, and self-neglect.

Methods

This study used a cross-sectional convenience sampling design. A total of 511 older adults were recruited in Chinese communities. Spearman’s correlation coefficient and hierarchical multiple regression analysis were performed to assess the influencing factors of self-neglect. A structural equation model was applied to test the hypothesized mediation model.

Results

Social support and psychological capital were found to be negatively related to self-neglect. Social support and psychological capital explained 5.1 and 11.9% of the incremental variances of older adults’ self-neglect, respectively. Psychological capital acts as a mediator between social support and self-neglect.

Conclusion

Self-neglect among older adults is a rising problem in China. Social support and higher psychological capital could decrease the risk of self-neglect in older adults. It is crucial to improve social networks and facilitate psychological interventions to reduce such self-neglect.
Refugee Children and English Language: Challenges From English Language Teachers’ Perspectives
Authors: Alrawashdeh Haneen Abdaljaleel , Kunt Naciye
Published: June 2022

This study aimed to investigate the challenges refugee children face in learning the English language from teachers’ perspectives and the challenges of refugees’ English language teachers in Jordan. To achieve this aim, a quantitative approach was implemented using a questionnaire. The findings from this study suggest that refugee teachers’ acknowledge that they face challenges teaching refugees in terms of cultural competency, preparation, self-efficacy, and practices they implement, and refugee children face linguistic and psychological challenges in learning English. This study attempted to find out the relationship between teachers’ preparation and their cultural competency, self-efficacy, and practices they implement and then the relationship between refugees’ psychological needs and linguistic challenges, respectively, and teachers’ self-efficacy, cultural competency, and practices. Results revealed several significant relationships between challenges and presented them in a model.
The Perception of Teaching, Learning Styles and Commitment to Learning and Their Influence on the Practice of Physical Activity and Eating Habits Related to the Mediterranean Diet in Physical Education Students
Authors: Fernandez-Ortega Carmen , González-Bernal Jeronimo , Gonzalez-Bernal Sergio , Trigueros Ruben , Aguilar-Parra José M. , Minguez-Minguez Luis A. , Obregon Ana I. , De La Fuente Anuncibay Raquel
Published: June 2022

Childhood obesity, linked to a sedentary lifestyle and an unbalanced diet, is one of the main problems in today’s Western societies. In this sense, the aim of the study was to analyze students’ perceived satisfaction in physical education classes with learning strategies and engagement in learning and critical thinking as determinants of healthy lifestyle habits. The study involved 2,439 high school students aged 12–18 years (M= 14.66,SD= 1.78). Structural equation modeling was conducted to analyze the predictive relationships between the study variables. The results showed that teaching, teaching mastery, and cognitive development are precursors to deep thinking on the part of students, indicators of the adoption of healthy lifestyle habits. These results reflect the importance of the methodology adopted by the teacher in order to positively influence the students’ habits.
Combining S100B and Cytokines as Neuro-Inflammatory Biomarkers for Diagnosing Generalized Anxiety Disorder: A Proof-of-Concept Study Based on Machine Learning
Authors: Shen Zhongxia , Cui Lijun , Mou Shaoqi , Ren Lie , Yuan Yonggui , Shen Xinhua , Li Gang
Published: June 2022

Introduction

S100 calcium-binding protein B (S100B) is a neurotrophic factor that regulates neuronal growth and plasticity by activating astrocytes and microglia through the production of cytokines involved in Generalized Anxiety Disorder (GAD). However, few studies have combined S100B and cytokines to explore their role as neuro-inflammatory biomarkers in GAD.

Methods

Serum S100B and cytokines (IL-1β, IL-2, IL-4, and IL-10) of 108 untreated GAD cases and 123 healthy controls (HC) were determined by enzyme-linked immunosorbent assay (ELISA), while Hamilton Anxiety Rating Scale (HAMA) scores and Hamilton Depression Rating Scale (HAMD) scores were measured to evaluate anxiety and depression severity. This was used to help physicians identify persons having GAD. Machine learning techniques were applied for feature ordering of cytokines and S100B and the classification of persons with GAD and HC.

Results

The serum S100B, IL-1β, and IL-2 levels of GAD cases were significantly lower than HC (P < 0.001), and the IL-4 level in persons with GAD was significantly higher than HC (P < 0.001). At the same time, IL-10 had no significant difference between the two groups (P = 0.215). The feature ranking distinguishing GAD from HC using machine learning ranked the features in the following order: IL-2, IL-1β, IL-4, S100B, and IL-10. The accuracy of S100B combined with IL-1β, IL-2, IL-4, and IL-10 in distinguishing persons with GAD from HC was 94.47 ± 2.06% using an integrated back propagation neural network based on a bagging algorithm (BPNN-Bagging).

Conclusion

The serum S-100B, IL-1β, and IL-2 levels in persons with GAD were down-regulated while IL-4 was up-regulated. The combination of S100B and cytokines had a good diagnosis value in determining GAD with an accuracy of 94.47%. Machine learning was a very effective method to study neuro-inflammatory biomarkers interacting with each other and mediated by plenty of factors.
Event-Related Brain Potential Correlates of Event-Based Prospective Memory in Children With Learning Disability
Authors: Ji Lili , Zhao Qi , Zhang Yafei , Wan Jiaojiao , Yu Yifan , Zhao Junfeng , Li Xiaoming
Published: June 2022

Prospective memory (PM) has been reported to be impaired in children with learning disabilities (LD), but few studies have examined the underlying neural mechanism of this impairment. To address this issue, the present study applied ERP technique to explore the difference of event-based prospective memory (EBPM) in 21 children with LD and 20 non-LD children with double task paradigm. Results from behavioral data showed that LD children exhibited lower accuracy than non-LD children. The ERP results showed that the two groups displayed significant difference in the ERP components, with longer N300 latency in LD group, but there was no obvious difference found in the prospective positivity component. The present findings seem to indicate that the poor performance of LD children on PM task might be result from deficits in PM cues detection. These results provided evidence for the existence of altered PM processing in LD children, which was characterized by a selective deficit in cues detection of PM. Therefore, these findings shed new light on the neurophysiological processes underlying PM in children with LD.