bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Pyroptosis-Related Immune Signatures and Identification of Pyroptosis-Related LncRNA Prognostic Signature in Clear Cell Renal Cell Carcinoma
Authors: Zhong Ming , Wang Xiaohua , Zhu Enyi , Gong Lian , Fei Lingyan , Zhao Liang , Wu Keping , Tang Chun , Zhang Lizhen , Wang Zhongli , Zheng Zhihua
Published: June 2022

Clear cell renal cell carcinoma (ccRCC) is a common urinary system malignant tumor with a high incidence and recurrence rate. Pyroptosis is a kind of programmed cell death caused by inflammasomes. More and more evidence had confirmed that pyroptosis plays a very significant part in cancer, and it is controversial whether pyroptosis promotes or inhibits tumors. Consistently, its potential role in ccRCC treatment efficacy and prognosis remains unclear. In this study, we systematically investigated the role of pyroptosis in the ccRCC samples from The Cancer Genome Atlas (TCGA) database. Based on the differentially expressed pyroptosis-related genes (DEPRGs), we identified three pyroptosis subtypes with different clinical outcomes, immune signatures, and responses to immunotherapy. Gene set variation analysis (GSVA), Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that pyroptosis activation meant infiltration of more immune cells that is conducive to tumor progression. To further investigate the immunomodulatory effect of pyroptosis in ccRCC, we constructed a pyroptosis-score based on the common differential prognostic genes of the three pyroptosis subtypes. It was found that patients with high pyroptosis-score were in an unfavorable immune environment and the prognosis was worse. Gene set enrichment analysis suggested that immune-related biological processes were activated in the high pyroptosis-score group. Then, the least absolute shrinkage and selection operator (LASSO) Cox regression was implemented for constructing a prognostic model of eight pyroptosis-related long noncoding RNAs (PRlncRNAs) in the TCGA dataset, and the outcomes revealed that, compared with the low-risk group, the model-based high-risk group was intently associated with poor overall survival (OS). We further explored the relationship between high- and low-risk groups with tumor microenvironment (TME), immune infiltration, and drug therapy. Finally, we constructed and confirmed a robust and reliable PRlncRNA pairs prediction model of ccRCC, identified PRlncRNA, and verified it by experiments. Our findings suggested the potential role of pyroptosis in ccRCC, offering new insights into the prognosis of ccRCC and guiding effectual targeted therapy and immunotherapy.
Diabetes Mellitus Promotes the Development of Atherosclerosis: The Role of NLRP3
Authors: Ye Jingxue , Li Lanfang , Wang Min , Ma Qiuxiao , Tian Yu , Zhang Qiong , Liu Jiushi , Li Bin , Zhang Bengang , Liu Haitao , Sun Guibo
Published: June 2022

Atherosclerosis is one of the main complications of diabetes mellitus, involving a variety of pathogenic factors. Endothelial dysfunction, inflammation, and oxidative stress are hallmarks of diabetes mellitus and atherosclerosis. Although the ability of diabetes to promote atherosclerosis has been demonstrated, a deeper understanding of the underlying biological mechanisms is critical to identifying new targets. NLRP3 plays an important role in both diabetes and atherosclerosis. While the diversity of its activation modes is one of the underlying causes of complex effects in the progression of diabetes and atherosclerosis, it also provides many new insights for targeted interventions in metabolic diseases.
Human Milk Oligosaccharides Impact Cellular and Inflammatory Gene Expression and Immune Response
Authors: Rosa Fernanda , Sharma Ashok K. , Gurung Manoj , Casero David , Matazel Katelin , Bode Lars , Simecka Christy , Elolimy Ahmed A. , Tripp Patricia , Randolph Christopher , Hand Timothy W. , Williams Keith D. , LeRoith Tanya , Yeruva Laxmi
Published: June 2022

Human milk harbors complex carbohydrates, including human milk oligosaccharides (HMOs), the third most abundant component after lactose and lipids. HMOs have been shown to impact intestinal microbiota, modulate the intestinal immune response, and prevent pathogenic bacterial binding by serving as decoy receptors. However, the direct effect of HMOs on intestinal function and immunity remains to be elucidated. To address this knowledge gap, 21-day-old germ-free mice (C57BI/6) were orally gavaged with 15 mg/day of pooled HMOs for 7 or 14 days and euthanized at day 28 or 35. A set of mice was maintained until day 50 to determine the persistent effects of HMOs. Control groups were maintained in the isolators for 28, 35, or 50 days of age. At the respective endpoints, intestinal tissues were subjected to histomorphometric and transcriptomic analyses, while the spleen and mesenteric lymph nodes (MLNs) were subjected to flow cytometric analysis. The small intestine (SI) crypt was reduced after HMO treatment relative to control at days 28 and 35, while the SI villus height and large intestine (LI) gland depth were decreased in the HMO-treated mice relative to the control at day 35. We report significant HMO-induced and location-specific gene expression changes in host intestinal tissues. HMO treatment significantly upregulated genes involved in extracellular matrix, protein ubiquitination, nuclear transport, and mononuclear cell differentiation. CD4+ T cells were increased in both MLNs and the spleen, while CD8+ T cells were increased in the spleen at day 50 in the HMO group in comparison to controls. In MLNs, plasma cells were increased in HMO group at days 28 and 35, while in the spleen, only at day 28 relative to controls. Macrophages/monocytes and neutrophils were lower in the spleen of the HMO group at days 28, 35, and 50, while in MLNs, only neutrophils were lower at day 50 in the 14-day HMO group. In addition, diphtheria toxoid and tetanus toxoid antibody–secreting cells were higher in HMO-supplemented group compared to controls. Our data suggest that HMOs have a direct effect on gastrointestinal tract metabolism and the immune system even in the absence of host microbiota.
Candida albicans Sap6 Initiates Oral Mucosal Inflammation via the Protease Activated Receptor PAR2
Authors: Kumar Rohitashw , Rojas Isolde Gina , Edgerton Mira
Published: June 2022

Candida albicans Sap6, a secreted aspartyl protease (Sap), contributes to fungal virulence in oral candidiasis. Beside its protease activity, Sap6 contains RGD (RGDRGD) motif required for its binding to host integrins. Sap6 activates immune cells to induce proinflammatory cytokines, although its ability to interact and activate human oral epithelial cells (OECs) remain unknown. Addition of purified recombinant Sap6 (rSap6) to OECs resulted in production of IL-1β and IL-8 cytokines similar to live hyphal C. albicans. OECs exposed to rSap6 showed phosphorylation of p38 and MKP1 and expression of c-Fos not found with C. albicans Δsap6, heat-inactivated Sap6, or rSap6ΔRGD. Heat inactivated rSap6 was able to induce IL-1β but not IL-8 in OECs, while rSap6ΔRGD induced IL-8 but not IL-1β suggesting parallel signaling pathways. C. albicans hyphae increased surface expression of Protease Activated Receptors PAR1, PAR2 and PAR3, while rSap6 increased PAR2 expression exclusively. Pretreatment of OECs with a PAR2 antagonist blocked rSap6-induced p38 MAPK signaling and IL-8 release, while rSap6ΔRGD had reduced MKP1 signaling and IL-1β release independent from PAR2. OECs exposed to rSap6 exhibited loss of barrier function as measured by TEER and reduction in levels of E-cadherin and occludin junctional proteins that was prevented by pretreating OECs with a PAR2 antagonist. OECs treated with PAR2 antagonist also showed reduced rSap6-mediated invasion by C. albicans cells. Thus, Sap6 may initiate OEC responses mediated both through protease activation of PAR2 and by its RGD domain. This novel role of PAR2 suggests new drug targets to block C. albicans oral infection.
The Non-Receptor Protein Tyrosine Phosphatase PTPN6 Mediates a Positive Regulatory Approach From the Interferon Regulatory Factor to the JAK/STAT Pathway in Litopenaeus vannamei
Authors: Luo Mengting , Xu Xiaopeng , Liu Xinxin , Shen Wenjie , Yang Linwei , Zhu Zhiming , Weng Shaoping , He Jianguo , Zuo Hongliang
Published: June 2022

SH2-domain-containing protein tyrosine phosphatases (PTPs), belonging to the class I PTP superfamily, are responsible for the dephosphorylation on the phosphorylated tyrosine residues in some proteins that are involved in multiple biological processes in eukaryotes. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway transduce signaling responding to interferons and initiate cellular antiviral responses. The activity of the JAK/STAT pathway is generally orchestrated by the de-/phosphorylation of the tyrosine and serine residues of JAKs and STATs, in which the dephosphorylation processes are mainly controlled by PTPs. In the present study, an SH2-domian-contianing PTP, temporally named as LvPTPN6, was identified inLitopenaeus vannamei. LvPTPN6 shares high similarity with PTPN6s from other organisms and was phylogenetically categorized into the clade of arthropods that differs from those of fishes and mammals. LvPTPN6 was constitutively expressed in all detected tissues, located mainly in the cytoplasm, and differentially induced in hemocyte and gill after the challenge of stimulants, indicating its complicated regulatory roles in shrimp immune responses. Intriguingly, the expression of LvPTPN6 was regulated by interferon regulatory factor (IRF), which could directly bind to the LvPTPN6 promoter. Surprisingly, unlike other PTPN6s, LvPTPN6 could promote the dimerization of STAT and facilitate its nuclear localization, which further elevated the expression of STAT-targeting immune effector genes and enhanced the antiviral immunity of shrimp. Therefore, this study suggests a PTPN6-mediated regulatory approach from IRF to the JAK/STAT signaling pathway in shrimp, which provides new insights into the regulatory roles of PTPs in the JAK/STAT signaling pathway and contributes to the further understanding of the mechanisms of antiviral immunity in invertebrates.
Heterogeneity of Group 2 Innate Lymphoid Cells Defines Their Pleiotropic Roles in Cancer, Obesity, and Cardiovascular Diseases
Authors: Ikutani Masashi , Nakae Susumu
Published: June 2022

Group 2 innate lymphoid cells (ILC2s) are typically known for their ability to respond rapidly to parasitic infections and play a pivotal role in the development of certain allergic disorders. ILC2s produce cytokines such as Interleukin (IL)-5 and IL-13 similar to the type 2 T helper (Th2) cells. Recent findings have highlighted that ILC2s, together with IL-33 and eosinophils, participate in a considerably broad range of physiological roles such as anti-tumor immunity, metabolic regulation, and vascular disorders. Therefore, the focus of the ILC2 study has been extended from conventional Th2 responses to these unexplored areas of research. However, disease outcomes accompanied by ILC2 activities are paradoxical mostly in tumor immunity requiring further investigations. Although various environmental factors that direct the development, activation, and localization of ILC2s have been studied, IL-33/ILC2/eosinophil axis is presumably central in a multitude of inflammatory conditions and has guided the research in ILC2 biology. With a particular focus on this axis, we discuss ILC2s across different diseases.
Management of Cardiovascular Disease in Patients With COVID-19 and Chronic Chagas Disease: Implications to Prevent a Scourge Still Larger
Authors: Bestetti Reinaldo Bulgarelli , Bocchi Edimar Alcides , Bestetti Renato , Issa Victor Sarli , Furlan-Daniel Rosemary Aparecida , Nakazone Marcelo Arruda
Published: June 2022

Cardiovascular diseases (CVD) are the most important cause of morbidity and mortality in the general population. Because the high prevalence of COVID-19 and chronic Chagas disease (CCD) where the latter is endemic, all such diseases will likely be observed in the same patient. While COVID-19 can provoke generalized endotheliitis, which can lead to a cytokine storm and a hyper-coagulable state culminating into in-site and at a distance thrombosis. Therefore, small-vessel coronary artery disease (CAD), cerebrovascular disease, thromboembolism, and arrhythmias are prominent findings in COVID-19. In CCD, small-vessel CAD, cardioembolic stroke, pulmonary embolism, heart failure and arrhythmias are frequently observed as a result of a similar but less intense mechanism. Consequently, the association of CCD and COVID-19 will likely increase the incidence of CVD. Thus, doctors on the frontline should be on the alert for this diagnostic possibility so that the proper treatment can be given without any delay.
Evaluating the Antagonistic Potential of Actinomycete Strains Isolated From Sudan’s Soils Against Phytophthora infestans
Authors: Abdelrahman Ola , Yagi Sakina , El Siddig Marmar , El Hussein Adil , Germanier Fanny , De Vrieze Mout , L’Haridon Floriane , Weisskopf Laure
Published: June 2022

Soil microorganisms play crucial roles in soil fertility, e.g., through decomposing organic matter, cycling nutrients or through beneficial interactions with plants. Actinomycetes are a major component of soil inhabitants; they are prolific producers of specialized metabolites, among which many antibiotics. Here we report the isolation and characterization of 175 Actinomycetes from rhizosphere and bulk soil samples collected in 18 locations in Sudan. We evaluated the strains’ metabolic potential for plant protection by testing their ability to inhibit the mycelial growth of the oomycete Phytophthora infestans, which is one of the most devastating plant pathogens worldwide. Most strains significantly reduced the oomycete’s growth in direct confrontational in vitro assays. A significant proportion of the tested strains (15%) were able to inhibit P. infestans to more than 80%, 23% to 50%–80%, while the remaining 62% had inhibition percentages lesser than 50%. Different morphologies of P. infestans mycelial growth and sporangia formation were observed upon co-inoculation with some of the Actinomycetes isolates, such as the production of fewer, thinner hyphae without sporangia leading to a faint growth morphology, or on the contrary, of clusters of thick-walled hyphae leading to a bushy, or “frozen” morphology. These morphologies were caused by strains differing in activity levels but phylogenetically closely related with each other. To evaluate whether the isolated Actinomycetes could also inhibit the pathogen’s growth in planta, the most active strains were tested for their ability to restrict disease progress in leaf disc and full plant assays. Five of the active strains showed highly significant protection of potato leaves against the pathogen in leaf disc assays, as well as substantial reduction of disease progress in full plants assays. Using cell-free filtrates instead of the bacterial spores also led to full protection against disease on leaf discs, which highlights the strong crop protective potential of the secreted metabolites that could be applied as leaf spray. This study demonstrates the strong anti-oomycete activity of soil- and rhizosphere-borne Actinomycetes and highlights their significant potential for the development of sustainable solutions based on either cell suspensions or cell-free filtrates to safeguard potatoes from their most damaging pathogen.
Effects of a 5-Year Exercise Intervention on White Matter Microstructural Organization in Older Adults. A Generation 100 Substudy
Authors: Pani Jasmine , Eikenes Live , Reitlo Line S. , Stensvold Dorthe , Wisløff Ulrik , Håberg Asta Kristine
Published: June 2022

Aerobic fitness and exercise could preserve white matter (WM) integrity in older adults. This study investigated the effect on WM microstructural organization of 5 years of exercise intervention with either supervised moderate-intensity continuous training (MICT), high-intensity interval training (HIIT), or following the national physical activity guidelines. A total of 105 participants (70–77 years at baseline), participating in the randomized controlled trial Generation 100 Study, volunteered to take part in this longitudinal 3T magnetic resonance imaging (MRI) study. The HIIT group (n = 33) exercised for four intervals of 4 min at 90% of peak heart rate two times a week, the MICT group (n = 24) exercised continuously for 50 min at 70% peak heart rate two times a week, and the control group (n = 48) followed the national guidelines of ≥30 min of physical activity almost every day. At baseline and at 1-, 3-, and 5-year follow-ups, diffusion tensor imaging (DTI) scans were performed, cardiorespiratory fitness (CRF) was measured as peak oxygen uptake (VO2peak) with ergospirometry, and information on exercise habits was collected. There was no group*time or group effect on any of the DTI indices at any time point during the intervention. Across all groups, CRF was positively associated with fractional anisotropy (FA) and axial diffusivity (AxD) at the follow-ups, and the effect became smaller with time. Exercise intensity was associated with mean diffusivity (MD)/FA, with the greatest effect at 1-year and no effect at 5-year follow-up. There was an association between exercise duration and FA and radial diffusivity (RD) only after 1 year. Despite the lack of group*time interaction or group effect, both higher CRF and exercise intensity was associated with better WM microstructural organization throughout the intervention, but the effect became attenuated over time. Different aspects of exercising affected the WM metrics and WM tracts differently with the greatest and most overlapping effects in the corpus callosum. The current study indicates not only that high CRF and exercise intensity are associated with WM microstructural organization in aging but also that exercise’s positive effects on WM may decline with increasing age.
Scene Construction and Spatial Processing in Post-traumatic Stress Disorder
Authors: Marlatte Hannah , Beaton Derek , Adler-Luzon Sarah , Abo-Ahmad Lina , Gilboa Asaf
Published: June 2022

Introduction

Post-traumatic stress disorder (PTSD) is associated with hippocampal system structural and functional impairments. Neurobiological models of PTSD posit that contextual memory for traumatic events is impaired due to hippocampal system dysfunction whilst memory of sensory details is enhanced due to amygdalar impact on sensory cortices. If hippocampal system dysfunction is a core feature of PTSD, then non-traumatic hippocampal-dependent cognitive functions such as scene construction, spatial processing, and memory should also be impaired in individuals with PTSD.

Methods

Forty-six trauma survivors, half diagnosed with PTSD, performed two tasks that involved spatial processing. The first was a scene construction task which requires conjuring-up spatially coherent multimodal scenarios, completed by all participants. Twenty-six participants (PTSD: n = 13) also completed a navigation task in a virtual environment, and underwent structural T1, T2 and diffusion-tensor MRI to quantify gray and white matter integrity. We examined the relationship between spatial processing, neural integrity, and symptom severity in a multiple factor analysis.

Results

Overall, patients with PTSD showed impaired performance in both tasks compared to controls. Scenes imagined by patients were less vivid, less detailed, and generated less sense of presence; importantly they had disproportionally reduced spatial coherence between details. Patients also made more errors during virtual navigation. Two components of the multiple factor analysis captured group differences. The first component explained 25% of the shared variance: participants that constructed less spatially coherent scenes also made more navigation errors and had reduced white matter integrity to long association tracts and tracts connecting the hippocampus, thalamus, and cingulate. The second component explained 20% of the variance: participants who generated fewer scene details, with less spatial coherence between them, had smaller hippocampal, parahippocampal and isthmus cingulate volumes. These participants also had increased white matter integrity to the right hippocampal cingulum bundle.

Conclusion

Our results suggest that patients with PTSD are impaired at imagining even neutral spatially coherent scenes and navigating through a complex spatial environment. Patients that showed reduced spatial processing more broadly had reduced hippocampal systems volumes and abnormal white matter integrity to tracts implicated in multisensory integration.
Quantification of Silent Cerebral Infarction on High-Resolution FLAIR and Cognition in Sickle Cell Anemia
Authors: Stotesbury Hanne , Kawadler Jamie M. , Clayden Jonathan D. , Saunders Dawn E. , Hood Anna M. , Koelbel Melanie , Sahota Sati , Rees David C. , Wilkey Olu , Layton Mark , Pelidis Maria , Inusa Baba P. D. , Howard Jo , Chakravorty Subarna , Clark Chris A. , Kirkham Fenella J.
Published: June 2022

Research in sickle cell anemia (SCA) has used, with limited race-matched control data, binary categorization of patients according to the presence or absence of silent cerebral infarction (SCI). SCI have primarily been identified using low-resolution MRI, with radiological definitions varying in lesion length and the requirement for abnormality on both fluid attenuated inversion recovery (FLAIR) and T1-weighted images. We aimed to assess the effect of published SCI definitions on global, regional, and lobar lesion metrics and their value in predicting cognition. One hundred and six patients with SCA and 48 controls aged 8–30 years underwent 3T MRI with a high-resolution FLAIR sequence and Wechsler cognitive assessment. Prevalence, number, and volume of lesions were calculated using a semi-automated pipeline for SCI defined as: (1) Liberal: any length (L-SCI); (2) Traditional: >3 mm in greatest dimension (T-SCI); (3) Restrictive; >3 mm in greatest dimension with a corresponding T1-weighted hypo-intensity (R-SCI). Globally, as hypothesized, there were large effects of SCI definition on lesion metrics in patients and controls, with prevalence varying from 24–42% in patients, and 4–23% in controls. However, contrary to hypotheses, there was no effect of any global metric on cognition. Regionally, there was a consistent distribution of SCI in frontal and parietal deep and juxta-cortical regions across definitions and metrics in patients, but no consistent distribution in controls. Effects of regional SCI metrics on cognitive performance were of small magnitude; some were paradoxical. These findings expose the challenges associated with the widespread use of SCI presence as a biomarker of white-matter injury and cognitive dysfunction in cross-sectional high-resolution MRI studies in patients with SCA. The findings indicate that with high-resolution MRI: (1) radiological definitions have a large effect on resulting lesion groups, numbers, and volumes; (2) there is a non-negligible prevalence of lesions in young healthy controls; and (3) at the group-level, there is no cross-sectional association between global lesion metrics and general cognitive impairment irrespective of lesion definition and metric. With high-resolution multi-modal MRI, the dichotomy of presence or absence of SCI does not appear to be a sensitive biomarker for the detection of functionally significant pathology; the search for appropriate endpoints for clinical treatment trials should continue.
A Spherical Phase Space Partitioning Based Symbolic Time Series Analysis (SPSP—STSA) for Emotion Recognition Using EEG Signals
Authors: Tavakkoli Hoda , Motie Nasrabadi Ali
Published: June 2022

Emotion recognition systems have been of interest to researchers for a long time. Improvement of brain-computer interface systems currently makes EEG-based emotion recognition more attractive. These systems try to develop strategies that are capable of recognizing emotions automatically. There are many approaches due to different features extractions methods for analyzing the EEG signals. Still, Since the brain is supposed to be a nonlinear dynamic system, it seems a nonlinear dynamic analysis tool may yield more convenient results. A novel approach in Symbolic Time Series Analysis (STSA) for signal phase space partitioning and symbol sequence generating is introduced in this study. Symbolic sequences have been produced by means of spherical partitioning of phase space; then, they have been compared and classified based on the maximum value of a similarity index. Obtaining the automatic independent emotion recognition EEG-based system has always been discussed because of the subject-dependent content of emotion. Here we introduce a subject-independent protocol to solve the generalization problem. To prove our method’s effectiveness, we used the DEAP dataset, and we reached an accuracy of 98.44% for classifying happiness from sadness (two- emotion groups). It was 93.75% for three (happiness, sadness, and joy), 89.06% for four (happiness, sadness, joy, and terrible), and 85% for five emotional groups (happiness, sadness, joy, terrible and mellow). According to these results, it is evident that our subject-independent method is more accurate rather than many other methods in different studies. In addition, a subject-independent method has been proposed in this study, which is not considered in most of the studies in this field.
Neurovascular Dysfunction in Diverse Communities With Health Disparities—Contributions to Dementia and Alzheimer’s Disease
Authors: Saiyasit Napatsorn , Butlig Evan-Angelo R. , Chaney Samantha D. , Traylor Miranda K. , Hawley Nanako A. , Randall Ryleigh B. , Bobinger Hanna V. , Frizell Carl A. , Trimm Franklin , Crook Errol D. , Lin Mike , Hill Benjamin D. , Keller Joshua L. , Nelson Amy R.
Published: June 2022

Alzheimer’s disease and related dementias (ADRD) are an expanding worldwide crisis. In the absence of scientific breakthroughs, the global prevalence of ADRD will continue to increase as more people are living longer. Racial or ethnic minority groups have an increased risk and incidence of ADRD and have often been neglected by the scientific research community. There is mounting evidence that vascular insults in the brain can initiate a series of biological events leading to neurodegeneration, cognitive impairment, and ADRD. We are a group of researchers interested in developing and expanding ADRD research, with an emphasis on vascular contributions to dementia, to serve our local diverse community. Toward this goal, the primary objective of this review was to investigate and better understand health disparities in Alabama and the contributions of the social determinants of health to those disparities, particularly in the context of vascular dysfunction in ADRD. Here, we explain the neurovascular dysfunction associated with Alzheimer’s disease (AD) as well as the intrinsic and extrinsic risk factors contributing to dysfunction of the neurovascular unit (NVU). Next, we ascertain ethnoregional health disparities of individuals living in Alabama, as well as relevant vascular risk factors linked to AD. We also discuss current pharmaceutical and non-pharmaceutical treatment options for neurovascular dysfunction, mild cognitive impairment (MCI) and AD, including relevant studies and ongoing clinical trials. Overall, individuals in Alabama are adversely affected by social and structural determinants of health leading to health disparities, driven by rurality, ethnic minority status, and lower socioeconomic status (SES). In general, these communities have limited access to healthcare and healthy food and other amenities resulting in decreased opportunities for early diagnosis of and pharmaceutical treatments for ADRD. Although this review is focused on the current state of health disparities of ADRD patients in Alabama, future studies must include diversity of race, ethnicity, and region to best be able to treat all individuals affected by ADRD.
Effect of Enteral Immunonutrition in Patients Undergoing Surgery for Gastrointestinal Cancer: An Updated Systematic Review and Meta-Analysis
Authors: Shen Jingyi , Dai Senjie , Li Zongze , Dai Wei , Hong Jiaze , Huang Jin , Chen Jingjie
Published: June 2022

Background

The efficacy of enteral immunonutrition (EIN) in patients undergoing gastrointestinal cancer surgery remains debatable. This meta-analysis aimed to investigate the effectiveness of EIN administration in patients undergoing surgery for gastrointestinal cancer.

Methods

From January 2000 to January 2022, PubMed, EMBASE, Cochrane Library, and Web of Science were thoroughly searched for randomized controlled trials (RCTs) with EIN versus standard diet or no supplement in patients undergoing surgery for gastrointestinal cancer. Overall complications and infectious complications were the primary outcomes. The secondary results were non-infectious complications, mortality, length of hospital stay, and enteral nutrition-related complications.

Results

Thirty-five studies reporting 3,692 patients undergoing surgery for gastrointestinal cancer (including gastric cancer, colorectal cancer, esophageal cancer, periampullary cancer, or pancreatic cancer) were included. Compared with the control group, EIN group had a significantly decreased incidence of overall complications (RR = 0.79, p < 0.001). Infectious complications in patients who received EIN were considerably lower than in the control group (RR = 0.66, p < 0.001). Compared to the control group, the incidence of surgical site infection, abdominal abscess, anastomotic leakage, bacteremia, duration of systemic inflammatory response syndrome (SIRS), and duration of antibiotic therapy was significantly lower in the specific infectious complications treated with EIN. Still, there was no significant difference between the two groups with other infectious complications. Moreover, a substantial shortening in the length of hospital stay was shown in EIN group compared with the control group. Still, no significant effect of EIN was demonstrated in non-infectious complicatios and mortality. The enteral nutrition-related complications had no significant difference between two groups.

Conclusions

EIN is safe and effective in reducing overall complications, infectious complications, and hospital stay in patients undergoing gastrointestinal cancer surgery (including gastric cancer, colorectal cancer, esophageal cancer, periampullary cancer, or pancreatic cancer).
Novel Plasma Proteomic Biomarkers for Early Identification of Induction Chemotherapy Beneficiaries in Locoregionally Advanced Nasopharyngeal Carcinoma
Authors: Zhang Shan-Qiang , Pan Su-Ming , Lai Shu-Zhen , Situ Hui-Jing , Liu Jun , Dai Wen-Jie , Liang Si-Xian , Zhou Li-Qing , Lu Qi-Qi , Ke Pei-Feng , Zhang Fan , Chen Hai-Bin , Li Ji-Cheng
Published: June 2022

Background

Induction chemotherapy (IC) can alleviate locoregionally advanced nasopharyngeal carcinoma (LA-NPC), but effectiveness differs between patients, toxicity is problematic, and effective blood-based IC efficacy predictors are lacking. Here, we aimed to identify biomarkers for early identification of IC beneficiaries.

Methods

Sixty-four pairs of matched plasma samples collected before and after IC from LA-NPC patients including 34 responders and 30 non-responders, as well as 50 plasma samples of healthy individuals, were tested using data-independent acquisition mass spectrometry. The proteins associated with clinical traits or IC benefits were investigated by weighted gene co-expression network analysis (WGCNA) and soft cluster analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional annotations were performed to determine the potential function of the identified proteins. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of candidate biomarkers in predicting IC beneficiaries.

Results

Compared with healthy individuals, 1027 differentially expressed proteins (DEPs) were found in the plasma of LA-NPC patients. Based on feedback from IC outcomes, 463 DEPs were identified in the pre-IC plasma between responders and non-responders. A total of 1212 DEPs represented the proteomic changes before and after IC in responders, while 276 DEPs were identified in post-IC plasma between responders and non-responders. WGCNA identified nine protein co-expression modules correlated with clinical traits. Soft cluster analysis identified four IC benefits-related protein clusters. Functional enrichment analysis showed that these proteins may play a role in IC via immunity, complement, coagulation, glycosaminoglycan and serine. Four proteins differentially expressed in all group comparisons, paraoxonase/arylesterase 1 (PON1), insulin-like growth factor-binding protein 3 (IGFBP-3), rheumatoid factor D5 light chain (v-kappa-3) and RNA helicase (DDX55), were associated with clinical traits or IC benefits. A four-protein model accurately identified potential IC beneficiaries (AUC=0.95) while diagnosing LA-NPC (AUC=0.92), and the prediction performance was verified using the models to confirm the effective IC (AUC=0.97) and evaluate IC outcome (AUC=0.94).

Conclusion

The plasma protein profiles among IC responders and non-responders were different. PON1, IGFBP3, v-kappa-3 and DDX55 could serve as potential biomarkers for early identification of IC beneficiaries for individualised treatment of LA-NPC.
Bing-Neel Syndrome: Real-Life Experience in Personalized Diagnostic Approach and Treatment
Authors: Kotsos Dimitrios , Chatzileontiadou Sofia , Apsemidou Athanasia , Xanthopoulou Anna , Rapi Aikaterini , Frouzaki Christina , Hatjiharissi Evdoxia
Published: June 2022

The involvement of the central nervous system (CNS) in Waldenström’s Macroglobulinemia (WM) is a rare extramedullary manifestation of the disease known as Bing-Neel syndrome (BNS). To expand our understanding of this disease manifestation, we conducted a retrospective analysis of the incidence of BNS in 86 consecutive patients with WM [70% male, median age 65 years (range 33-86)] seen in our center during a 30-year period. Six patients (7%) from this group were diagnosed with BNS. The median period of time between WM diagnosis and BNS diagnosis was 6.8 years (range 2.3-15). They demonstrated a range of neurological deficits, including transient expressive aphasia, impaired vision, resting hand tremor, foot drop, and headache. Between the onset of symptoms and the diagnosis of BNS, the median time interval was 12.5 months (range 1-30). The diagnosis was made not on the basis of neurological symptoms or radiological evidence, but on the basis of the presence of WM cells in cerebrospinal fluid (CSF). Intrathecal chemotherapy with methotrexate, cytarabine, and dexamethasone (IT MTX, ARA-C, DEX) was used as front-line treatment, followed by intensive immunochemotherapy with rituximab, high-dose MTX, and ARA-C (R-Hi MTX/ARA-C) in three patients who were fit enough to receive this type of cytotoxic regimen, and rituximab plus bendamustine (R-Benda) in two patients who simultaneously required treatment for WM. Ibrutinib was administered to five patients (three as consolidation and two for initial treatment). All patients responded to front-line treatment, with four (67%) achieving partial response (PR) and two (33%) achieving complete response (CR). This study provides insight into the clinical presentation, diagnostic and treatment options, as well as the outcome of patients who have BNS.
Acute Myeloid Leukaemia Drives Metabolic Changes in the Bone Marrow Niche
Authors: Maynard Rebecca S. , Hellmich Charlotte , Bowles Kristian M. , Rushworth Stuart A.
Published: June 2022

Acute myeloid leukaemia (AML) is a highly proliferative cancer characterised by infiltration of immature haematopoietic cells in the bone marrow (BM). AML predominantly affects older people and outcomes, particularly in this difficult to treat population remain poor, in part due to inadequate response to therapy, and treatment toxicity. Normal haematopoiesis is supported by numerous support cells within the BM microenvironment or niche, including adipocytes, stromal cells and endothelial cells. In steady state haematopoiesis, haematopoietic stem cells (HSCs) primarily acquire ATP through glycolysis. However, during stress-responses HSCs rapidly transition to oxidative phosphorylation, enabled by mitochondrial plasticity. Historically it was thought that cancer cells preferentially used glycolysis for ATP production, however recently it has become evident that many cancers, including AML primarily use the TCA cycle and oxidative phosphorylation for rapid proliferation. AML cells hijack the stress-response pathways of their non-malignant counterparts, utilising mitochondrial changes to drive expansion. In addition, amino acids are also utilised by leukaemic stem cells to aid their metabolic output. Together, these processes allow AML cells to maximise their ATP production, using multiple metabolites and fuelling rapid cell turnover which is a hallmark of the disease. This review of AML derived changes in the BM niche, which enable enhanced metabolism, will consider the important pathways and discuss future challenges with a view to understanding how AML cells are able to hijack metabolic pathways and how we may elucidate new targets for potential therapies.
The Application of Pulmonary Ultrasound in Neonatal Ventilator-Associated Pneumonia
Authors: Jiang Peng , Wei Jing
Published: June 2022

This study explored the application value of lung ultrasound (LUS) in neonatal ventilator-associated pneumonia (NVAP). In this study, 122 newborns suspected of NVAP were treated in the NICU of Liaocheng People’s Hospital between July 1, 2020, and July 1, 2021. Of these, 115 were clinically diagnosed with NVAP. The diagnostic value of LUS for NVAP was determined by comparing the different signs of LUS and chest X-ray (CXR). The confirmed cases were divided into the failure and success groups according to the first ventilator weaning test results. The consistency between the results of LUS and CXR and the actual test results was compared between the two groups. Before treatment, the LUS findings of the confirmed cases showed a lung consolidation with air bronchogram sign (111/115), alveolar-interstitial syndrome (113/115), pleural effusion (12/115), pleural line abnormalities (114/115), and lung pulse (15/115). CXR showed 109 cases of pneumonia. Taking the clinical diagnosis of VAP as the gold standard, the lung consolidation with air bronchogram sign on LUS had a higher sensitivity, specificity, and accuracy for the diagnosis of NVAP than those of other LUS and CXR findings and showed better consistency with the clinical diagnosis (AUC = 0.983, kappa value = 0.761, p < 0.05). After treatment, the 115 cases were divided into two groups according to the results of the first weaning from ventilation: the failed group (19 cases) and the successful group (96 cases). The lung consolidation with air bronchogram sign was used as the positive diagnostic standard of ultrasound. The sensitivity and specificity of LUS (94.7 and 89.6%, respectively) in evaluating the outcome of weaning from the ventilator of pneumonia were higher than those of CXR (73.7 and 84.4%, respectively). Additionally, the consistency of the LUS findings with the weaning results was higher than that of CXR (AUC = 0.922, kappa value = 0.709, p < 0.05). Therefore, compared with CXR, LUS has a higher value in diagnosing NVAP and can better predict the results of the ventilator off-line test. LUS can replace CXR as the first imaging examination for NVAP.
The Roles of TNF Signaling Pathways in Metabolism of Bone Tumors
Authors: Zhou Haiying , Dong Yanzhao , Alhaskawi Ahmad , Lai Jingtian , Wang Zewei , Ezzi Sohaib Hasan Abdullah , Kota Vishnu Goutham , Abdulla Mohamed Hasan Abdulla Hasan , Sun Zhenyu , Lu Hui
Published: June 2022

The metabolism of bone tumors is extraordinarily complex and involves many signaling pathways and processes, including the tumor necrosis factor (TNF) signaling pathway, which consists of TNF factors and the TNF receptors that belong to the TNF receptor superfamily (TNFRSF). It is appreciated that signaling events and pathways involving TNFRSF components are essential in coordinating the functions of multiple cell types that act as a host defense network against pathogens and malignant cells, the implications of TNFRSF-related signaling pathways on bone tumor metabolism remain to be summarized, which is one of the significant obstacles to the application of TNF-related treatment modalities in the domain of bone oncology. This review will discuss and summarize the anti-tumor properties of important TNFRSF components concerning osteosarcoma, chondrosarcoma, and Ewing sarcoma.
Integrative Analysis of Genes Involved in the Global Response to Potato Wart Formation
Authors: Yan Lang , Li Yan , Qing Yuan , Tao Xiang , Wang Haiyan , Lai Xianjun , Zhang Yizheng
Published: June 2022

Synchytrium endobioticum, the causal agent of potato wart disease, poses a major threat to commercial potato production. Understanding the roles of transcriptionally regulated genes following pathogen infection is necessary for understanding the system-level host response to pathogen. Although some understanding of defense mechanisms against S. endobioticum infection has been gained for incompatible interactions, the genes and signaling pathways involved in the compatible interaction remain unclear. Based on the collection of wart diseased tubers of a susceptible cultivar, we performed phenotypic and dual RNA-Seq analyses of wart lesions in seven stages of disease progression. We totally detected 5,052 differentially expressed genes (DEGs) by comparing the different stages of infection to uninfected controls. The tendency toward differential gene expression was active rather than suppressed under attack by the pathogen. The number of DEGs step-up along with the development of the disease and the first, third and seventh of the disease stages showed substantially increase of DEGs in comparison of the previous stage. The important functional groups identified via Gene ontology (GO) and KEGG enrichment were those responsible for plant-pathogen interaction, fatty acid elongation and phenylpropanoid biosynthesis. Gene coexpression networks, composed of 17 distinct gene modules that contained between 25 and 813 genes, revealed high interconnectivity of the induced response and led to the identification of a number of hub genes enriched at different stages of infection. These results provide a comprehensive perspective on the global response of potato to S. endobioticum infection and identify a potential transcriptional regulatory network underlying this susceptible response, which contribute to a better understanding of the potato–S. endobioticum pathosystem.
Adaptation of the Invasive Plant (Sphagneticola trilobata L. Pruski) to a High Cadmium Environment by Hybridizing With Native Relatives
Authors: Gao Lei , Cai Minling , Zeng Lingda , Zhang Qilei , Zhu Haoqiang , Gu Xiaoqian , Peng Changlian
Published: June 2022

Invasive species can evolve rapidly in the invasion areas to adapt to new habitats. Sphagneticola trilobata L. Pruski, an invasive species, was studied for its tolerance to cadmium (Cd) in the soil and compared with its natural hybrid. From the perspective of photosynthetic physiology, antioxidant characteristics, and leaf hormone levels, the differences between the leaves of the two species before and after Cd treatment were compared. The results showed that the hybrid had stronger tolerance to Cd stress than invasive species. After Cd stress, the indexes of gas-exchange [net photosynthetic rate (Pn), intercellular CO2 concentration (Ci), stomatal conductance (Gs), and transpiration rate (Tr)] of the hybrid was higher than invasive species, while the content of non-enzymatic antioxidants (flavonoids and total phenols) and antioxidant enzyme activities [peroxidase (POD) and superoxide dismutase (SOD)] was lower in hybrid than in invasive species. The changes in the content of plant hormones [auxin (IAA) and abscisic acid (ABA)] under Cd stress showed that hybrid can still maintain growth and prevent leaf senescence. Furthermore, the differences in gene expression between hybrid and invasive species in photosynthetic physiology, the antioxidant capacity of leaves, and endogenous hormone (IAA and ABA) synthesis pathway also showed that hybrid has stronger Cd tolerance than invasive species. This suggests that invasive species will realize the invasion through hybridization with the native relatives to overcome the stress from environmental factors. The study implied that hybridization between invasive species and native relatives is an important way for invasive species to spread in a wider and new environment that invasive species have not experienced in the area of origin.
Molecular Advancements Establishing Chlamydomonas as a Host for Biotechnological Exploitation
Authors: Schroda Michael , Remacle Claire
Published: June 2022

Chlamydomonas reinhardtii is emerging as a production platform for biotechnological purposes thanks to recent achievements, which we briefly summarize in this review. Firstly, robust nuclear transgene expression is now possible because several impressive improvements have been made in recent years. Strains allowing efficient and stable nuclear transgene expression are available and were recently made more amenable to rational biotechnological approaches by enabling genetic crosses and identifying their causative mutation. The MoClo synthetic biology strategy, based on Golden Gate cloning, was developed for Chlamydomonas and includes a growing toolkit of more than 100 genetic parts that can be robustly and rapidly assembled in a predefined order. This allows for rapid iterative cycles of transgene design, building, testing, and learning. Another major advancement came from various findings improving transgene design and expression such as the systematic addition of introns into codon-optimized coding sequences. Lastly, the CRISPR/Cas9 technology for genome editing has undergone several improvements since its first successful report in 2016, which opens the possibility of optimizing biosynthetic pathways by switching off competing ones. We provide a few examples demonstrating that all these recent developments firmly establish Chlamydomonas as a chassis for synthetic biology and allow the rewiring of its metabolism to new capabilities.
The Physical Location of Stripe Rust Resistance Genes on Chromosome 6 of Rye (Secale cereale L.) AR106BONE
Authors: Duan Yanling , Luo Jie , Yang Zujun , Li Guangrong , Tang Zongxiang , Fu Shulan
Published: June 2022

It was reported that the chromosome 6R of rye (Secale cereale L.) carries stripe rust resistance gene Yr83, and the region with the candidate resistance gene(s) still needs to be narrowed down. This study confirmed that the chromosome 6RLAr derived from rye AR106BONE contains stripe rust resistance gene(s). A wheat-rye T6BS.6RLAr translocation chromosome, a wheat-rye small-segment translocation T6RLAr-6AS.6AL, and three kinds of deleted T6BS.6RLAr translocations, T6BS.6RLAr-1, T6BS.6RLAr-2, and T6BS.6RLAr-3, were identified. Translocations T6BS.6RLAr, T6BS.6RLAr-2, and T6RLAr-6AS.6AL were highly resistant to stripe rust and T6BS.6RLAr-1 and T6BS.6RLAr-3 were highly susceptible. The molecular markers specific to 6RL determined that the three regions of the 6RLAr arm from 732,999,830 bp to the telomere, from 735,010,030 to 848,010,414 bp, and from 848,011,262 bp to the telomere were deleted from T6BS.6RLAr-1, T6BS.6RLAr-2, and T6BS.6RLAr-3, respectively. T6BS.6RLAr-2 and T6RLAr-6AS.6AL contained the segment that was deleted in T6BS.6RLAr-3. Therefore, it can be concluded that about 37 Mb segment from 848,011,262 bp to the telomere carried stripe rust resistance gene(s), and it was smaller than that with the Yr83 gene. Gene annotation indicated that about 37 Mb region contains 43 potential resistance genes, and 42 of them are nucleotide-binding site and leucine-rich repeat (NBS-LRR)-like resistance protein genes. The results in this study narrowed down the size of the region with candidate stripe rust resistance gene(s) on the 6RL arm, and the T6RLAr-6AS.6AL is a promising small-segment translocation for improvement of wheat cultivars.