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BioMed Research International 2024The zoonotic viruses pose significant threats to public health. Nipah virus (NiV) is an emerging virus transmitted from bats to humans. The NiV causes severe...
The zoonotic viruses pose significant threats to public health. Nipah virus (NiV) is an emerging virus transmitted from bats to humans. The NiV causes severe encephalitis and acute respiratory distress syndrome, leading to high mortality rates, with fatality rates ranging from 40% to 75%. The first emergence of the disease was found in Malaysia in 1998-1999 and later in Bangladesh, Cambodia, Timor-Leste, Indonesia, Singapore, Papua New Guinea, Vietnam, Thailand, India, and other South and Southeast Asian nations. Currently, no specific vaccines or antiviral drugs are available. The potential advantages of epitope-based vaccines include their ability to elicit specific immune responses while minimizing potential side effects. The epitopes have been identified from the conserved region of viral proteins obtained from the UniProt database. The selection of conserved epitopes involves analyzing the genetic sequences of various viral strains. The present study identified two B cell epitopes, seven cytotoxic T lymphocyte (CTL) epitopes, and seven helper T lymphocyte (HTL) epitope interactions from the NiV proteomic inventory. The antigenic and physiological properties of retrieved protein were analyzed using online servers ToxinPred, VaxiJen v2.0, and AllerTOP. The final vaccine candidate has a total combined coverage range of 80.53%. The tertiary structure of the constructed vaccine was optimized, and its stability was confirmed with the help of molecular simulation. Molecular docking was performed to check the binding affinity and binding energy of the constructed vaccine with TLR-3 and TLR-5. Codon optimization was performed in the constructed vaccine within the K12 strain, to eliminate the danger of codon bias. However, these findings must require further validation to assess their effectiveness and safety. The development of vaccines and therapeutic approaches for virus infection is an ongoing area of research, and it may take time before effective interventions are available for clinical use.
Topics: Nipah Virus; Humans; Computer Simulation; Henipavirus Infections; Viral Vaccines; Epitopes, B-Lymphocyte; Computational Biology; Epitopes, T-Lymphocyte; Vaccination; Molecular Docking Simulation; Viral Proteins; Animals
PubMed: 38962403
DOI: 10.1155/2024/4066641 -
Respirology Case Reports Jul 2024Allergic bronchopulmonary aspergillosis (ABPA) is an inflammatory disease induced by exaggerated immune responses to species. Although ABPA has a high recurrence (48%),...
Allergic bronchopulmonary aspergillosis (ABPA) is an inflammatory disease induced by exaggerated immune responses to species. Although ABPA has a high recurrence (48%), its instances with sequential isolation of distinct species are sporadic. Only one case report has documented the metachronous isolation of and . However, no reported cases of metachronous isolation involving three distinct species exist. Herein, we report a novel case of a 47-year-old Japanese man with sequential metachronous isolation of , , and . Initially presenting with symptoms of productive cough and pulmonary infiltration, the patient experienced two relapses following treatment with oral prednisolone. Adjustments in therapy, including voriconazole and a tailored corticosteroid regimen, resulted in significant improvement without relapse for over 6 months. This case report highlights the challenges and successful management of ABPA involving multiple species.
PubMed: 38962400
DOI: 10.1002/rcr2.1423 -
Neurology. Clinical Practice Oct 2024Cognitive impairment is experienced by up to 80% of people with Parkinson disease (PD). Little is known regarding the subjective experience and frequency of bothersome...
BACKGROUND AND OBJECTIVES
Cognitive impairment is experienced by up to 80% of people with Parkinson disease (PD). Little is known regarding the subjective experience and frequency of bothersome cognitive problems across the range of disease duration as expressed directly in patients' own words. We describe the types and frequency of bothersome cognitive symptoms reported verbatim by patients with PD.
METHODS
Through the online Fox Insight study and the Parkinson Disease Patient Report of Problems, we asked patients with PD to self-report by keyboard entry up to five most bothersome problems and how these problems affect their functioning. Human-in-the-loop curation, natural language processing, and machine learning were used to categorize responses into 8 cognitive symptoms: memory, concentration/attention, cognitive slowing, language/word finding, mental alertness/awareness, visuospatial abilities, executive abilities/working memory, and cognitive impairment not otherwise specified. Associations between cognitive symptoms and demographic and disease-related variables were examined in our cross-sectional cohort using multivariate logistic regression.
RESULTS
Among 25,192 participants (55% men) of median age 67 years and 3 years since diagnosis (YSD), 8,001 (32%) reported a cognitive symptom at baseline. The 3 most frequently reported symptoms were memory (13%), language/word finding (12%), and concentration/attention (9%). Depression was significantly associated with bothersome cognitive problems in all domains except visuospatial abilities. Predictors of reporting any cognitive symptom in PD were depression (adjusted OR 1.5), increasing MDS-UPDRS Part II score (OR 1.4 per 10-point increment), higher education (OR 1.2 per year), and YSD 1, 2, 6-7, and 8-9 vs 0 YSD. Among individuals with at least one cognitive symptom, posterior cortical-related cognitive symptoms (i.e., visuospatial, memory, and language) were reported by 17% (n = 4325), frontostriatal-related symptoms (i.e., executive abilities, concentration/attention) by 7% (n = 1,827), and both by 14.2% (n = 1,020). Odds of reporting posterior cortical symptoms vs frontostriatal symptoms increased with age and MDS-UPDRS part II score, but not depression.
DISCUSSION
Nearly one-third of participants with PD, even early in the disease course, report cognitive symptoms as among their most bothersome problems. Online verbatim reporting analyzed by human-in-the-loop curation, natural language processing, and machine learning is feasible on a large scale and allows a detailed examination of the nature and distribution of cognitive symptoms in PD.
PubMed: 38962394
DOI: 10.1212/CPJ.0000000000200334 -
Frontiers in Pharmacology 2024This study compares the cardiovascular risk in anemic chronic kidney disease patients treated with Roxadustat versus erythropoietin stimulating agents (ESAs). It also...
OBJECTIVE
This study compares the cardiovascular risk in anemic chronic kidney disease patients treated with Roxadustat versus erythropoietin stimulating agents (ESAs). It also explores the cardiovascular impact of Roxadustat.
METHODS
We searched PubMed, EMBASE, Cochrane, Scopus, and Web of Science databases up to 13 August 2023, using terms such as "ESA," "Roxadustat," "MACE," "stroke," "death," "myocardial infarction," and "heart failure." Two researchers independently selected and extracted data based on predefined criteria. We assessed the risk of bias with the Cochrane tool and analyzed statistical heterogeneity using the Q and I2 tests. We conducted subgroup analyses by geographical region and performed data analysis with Stata 14.0 and RevMan 5.4 software. Data were sourced from the NCBI database by filtering for "Roxadustat" and "human," and differentially expressed genes were identified using R software, setting the significance at < 0.01 and a 2-fold logFC, followed by GO enrichment analysis, KEGG pathway analysis, and protein interaction network analysis.
RESULTS
A total of 15 articles encompassing 1,43,065 patients were analyzed, including 1,38,739 patients treated with ESA and 4,326 patients treated with Roxadustat. In the overall population meta-analysis, the incidences of Major Adverse Cardiovascular Events (MACE), death, and heart failure (HF) were 13%, 8%, and 4% in the Roxadustat group, compared to 17%, 12%, and 6% in the ESA group, respectively, with -values greater than 0.05. In the subgroup analysis, the incidences were 13%, 11%, and 4% for the Roxadustat group versus 17%, 15%, and 5% for the ESA group, also with -values greater than 0.05. Bioinformatics analysis identified 59 differentially expressed genes, mainly involved in the inflammatory response. GO enrichment analysis revealed that these genes are primarily related to integrin binding. The main pathways identified were the TNF signaling pathway, NF-κB signaling pathway, and lipid metabolism related to atherosclerosis. The protein interaction network highlighted IL1B, CXCL8, ICAM1, CCL2, and CCL5 as the top five significantly different genes, all involved in the inflammatory response and downregulated by Roxadustat, suggesting a potential role in reducing inflammation.
CONCLUSION
The meta-analysis suggests that the use of Roxadustat and ESA in treating anemia associated with chronic kidney disease does not significantly alter the likelihood of cardiovascular events in the overall and American populations. However, Roxadustat exhibited a safer profile with respect to MACE, death, and heart failure. The bioinformatics findings suggest that Roxadustat may influence integrin adhesion and affect the TNF and NF-κB signaling pathways, along with lipid and atherosclerosis pathways, potentially reducing inflammation.
PubMed: 38962312
DOI: 10.3389/fphar.2024.1380326 -
Frontiers in Oncology 2024The management of soft tissue sarcomas presents considerable therapeutic challenges. This study was designed to assess the efficacy of neoadjuvant sequential...
Preoperative sequential chemotherapy and hypofractionated radiotherapy combined with comprehensive surgical resection for high-risk soft tissue sarcomas: a retrospective study.
INTRODUCTION
The management of soft tissue sarcomas presents considerable therapeutic challenges. This study was designed to assess the efficacy of neoadjuvant sequential chemotherapy and hypofractionated radiotherapy in conjunction with extensive surgical resection for the treatment of high-risk soft tissue sarcomas.
MATERIALS AND METHODS
We performed a retrospective review of 31 high-risk soft tissue sarcoma patients treated at our institution from June 2021 to June 2023. The cohort consisted of 21 males and 10 females with a mean age of 55.7 years and included both initial and recurrent disease presentations. Our treatment regimen comprised two to three cycles of neoadjuvant chemotherapy coupled with hypofractionated radiotherapy, delivered at 5 Gy per fraction to a total dose of 25-35 Gy across 5-7 days, prior to surgical resection aimed at achieving wide margins. Data collection was systematic, covering surgical outcomes, chemoradiotherapy-related complications, and prognostic factors.
RESULTS
All patients completed the prescribed course of neoadjuvant chemoradiotherapy. 29% patients experienced grade 3+ chemotherapy toxicity, necessitating a reduction or interruption in their chemotherapy regimen. Limb preservation was accomplished in 30 patients finally. Response evaluation using RECIST 1.1 criteria post-neoadjuvant therapy revealed 9.7% with PD, 58.1% with SD, 29% with a PR, and 3.2% with a CR, culminating in an ORR of 32.2%. Postoperative complications included superficial wound infections in four patients and deep incisional infections in another four. 6 patients had developed metastasis, and 3 patients were still alive. Two experienced local recurrence. One-year DFS was 79.3%, with a one-year OS rate of 89.6%.
CONCLUSION
Neoadjuvant sequential chemotherapy and hypofractionated radiotherapy followed by extensive surgical resection represents an effective treatment paradigm for high-risk soft tissue sarcomas. This multimodal approach not only facilitates tumor reduction but also significantly reduces the risks of local recurrence and distant metastasis.
PubMed: 38962275
DOI: 10.3389/fonc.2024.1423151 -
Frontiers in Oncology 2024We present a case of follicular dendritic cell sarcoma in the axillary lymph node, which unexpectedly showed favorable outcomes after the application of apatinib....
We present a case of follicular dendritic cell sarcoma in the axillary lymph node, which unexpectedly showed favorable outcomes after the application of apatinib. Follicular Dendritic Cell Sarcoma (FDCS) exhibits a rare incidence and an unclear pathogenic mechanism, contributing to the limited breakthroughs in its treatment to date within the medical field. The current mainstream therapeutic approaches include surgery, CHOP(cyclophosphamide, doxorubicin, vincristine, prednisone), ICE(ifosfamide, carboplatin, etoposide), ABVD(doxorubicin, bleomycin, vinblastine, dacarbazine), and immune checkpoint inhibitors. A 38-year-old male patient was admitted to the hospital due to a lump in the right axilla and underwent surgical treatment. Postoperative pathology confirmed the diagnosis of follicular dendritic cell sarcoma. Two months post-surgery, he faced a recurrence, prompting a subsequent surgical intervention complemented by tumor radiofrequency ablation. Despite these interventions, the treatment response was suboptimal. Subsequently, the patient was treated with the CHOP regimen, but after two cycles, he developed bone metastasis. Due to the patient's limited financial resources and refusal of immunotherapy, we switched to a regimen of gemcitabine and docetaxel, but the disease progressed again after two cycles. A one-cycle trial of albumin-bound paclitaxel yielded unsatisfactory results. Ultimately, the patient was treated with Apatinib, achieving a 10-month progression-free survival. Due to the patient's limited financial circumstances, we, in the absence of guideline recommendations and evidence from evidence-based medicine, achieved a 10-month progression-free survival (PFS) solely based on experiential use of the anti-angiogenic drug, Apatinib. The purpose of this case report is to provide additional therapeutic options for FDCS treatment and to pave the way for exploring the mechanism of action of Apatinib in FDCS.
PubMed: 38962273
DOI: 10.3389/fonc.2024.1388982 -
Oxidative Medicine and Cellular... 2024Approximately 70% of all strokes occur in patients over 65 years old, and stroke increases the risk of developing dementia. The circle of Willis (CoW), the ring of...
Approximately 70% of all strokes occur in patients over 65 years old, and stroke increases the risk of developing dementia. The circle of Willis (CoW), the ring of arteries at the base of the brain, links the intracerebral arteries to one another to maintain adequate cerebral perfusion. The CoW proteome is affected in cerebrovascular and neurodegenerative diseases, but changes related to aging have not been described. Here, we report on a quantitative proteomics analysis comparing the CoW from five young (2-3-month-old) and five aged male (18-20-month-old) mice using gene ontology (GO) enrichment, ingenuity pathway analysis (IPA), and iPathwayGuide tools. This revealed 242 proteins that were significantly dysregulated with aging, among which 189 were upregulated and 53 downregulated. GO enrichment-based analysis identified blood coagulation as the top biological function that changed with age and integrin binding and extracellular matrix constituents as the top molecular functions. Consistent with these findings, iPathwayGuide-based impact analysis revealed associations between aging and the complement and coagulation, platelet activation, ECM-receptor interaction, and metabolic process pathways. Furthermore, IPA analysis revealed the enrichment of 97 canonical pathways that contribute to inflammatory responses, as well as 59 inflammation-associated upstream regulators including 39 transcription factors and 20 cytokines. Thus, aging-associated changes in the CoW proteome in male mice demonstrate increases in metabolic, thrombotic, and inflammatory processes.
Topics: Animals; Circle of Willis; Aging; Male; Proteome; Mice; Vascular Diseases; Mice, Inbred C57BL; Proteomics
PubMed: 38962180
DOI: 10.1155/2024/4887877 -
Frontiers in Neuroscience 2024Unmatched by other non-invasive brain stimulation techniques, transcranial ultrasound (TUS) offers highly focal stimulation not only on the cortical surface but also in... (Review)
Review
Unmatched by other non-invasive brain stimulation techniques, transcranial ultrasound (TUS) offers highly focal stimulation not only on the cortical surface but also in deep brain structures. These unique attributes are invaluable in both basic and clinical research and might open new avenues for treating neurological and psychiatric diseases. Here, we provide a concise overview of the expanding volume of clinical investigations in recent years and upcoming research initiatives concerning focused ultrasound neuromodulation. Currently, clinical TUS research addresses a variety of neuropsychiatric conditions, such as pain, dementia, movement disorders, psychiatric conditions, epilepsy, disorders of consciousness, and developmental disorders. As demonstrated in sham-controlled randomized studies, TUS neuromodulation improved cognitive functions and mood, and alleviated symptoms in schizophrenia and autism. Further, preliminary uncontrolled evidence suggests relieved anxiety, enhanced motor functions in movement disorders, reduced epileptic seizure frequency, improved responsiveness in patients with minimally conscious state, as well as pain reduction after neuromodulatory TUS. While constrained by the relatively modest number of investigations, primarily consisting of uncontrolled feasibility trials with small sample sizes, TUS holds encouraging prospects for treating neuropsychiatric disorders. Larger sham-controlled randomized trials, alongside further basic research into the mechanisms of action and optimal sonication parameters, are inevitably needed to unfold the full potential of TUS neuromodulation.
PubMed: 38962179
DOI: 10.3389/fnins.2024.1420255 -
Journal of Clinical and Experimental... 2024Spontaneous bacterial peritonitis (SBP) is a common and serious complication in patients with decompensated cirrhosis. Precise quantification of bacterial DNA (bactDNA)...
BACKGROUND AND AIMS
Spontaneous bacterial peritonitis (SBP) is a common and serious complication in patients with decompensated cirrhosis. Precise quantification of bacterial DNA (bactDNA) and the related inflammatory response might add further information on the course of disease. The aim of the study was to evaluate the association between bactDNA, cytokine levels and clinical outcome.
METHODS
Ascites and serum samples of 98 patients with decompensated liver cirrhosis (42 with SBP and 56 without SBP) as well as serum samples of 21 healthy controls were collected. BactDNA in ascites and serum was detected and quantified by 16S rRNA PCR. Concentrations of IL-1β, TNF-α, IL-6, IL-8 and IL-10 were measured by a LEGENDplexTM multi-analyte flow assay. Clinical data were collected and analyzed retrospectively.
RESULTS
BactDNA was detected more frequently in ascites of patients with SBP ( = 24/42; 57.1%) than in ascites of patients without SBP ( = 5/56; 8.9%; < 0.001). Additionally, IL-6 levels in both ascites and serum were significantly higher in patients with SBP (ascites < 0.001, serum = 0.036). The quantity of bactDNA in ascites was strongly correlated with polymorphonuclear neutrophil count in ascites (r = 0.755; < 0.001) as well as ascites IL-6 levels (r = 0.399; < 0.001). Receiver operating characteristic (ROC) curve analysis to diagnose SBP provided an AUC of 0.764 (95% CI: 0.661-0.867) for serum IL-6 levels, an AUC of 0.810 (95% CI: 0.714-0.905) for ascites IL-6 levels, and an AUC of 0.755 (95% CI: 0.651-0.858) for bactDNA levels in ascites.
CONCLUSIONS
The correlation between the amount of bactDNA and IL-6 confirms the pathophysiological relevance of bactDNA and IL-6 as potential biomarkers for the diagnosis of SBP.
PubMed: 38962151
DOI: 10.1016/j.jceh.2024.101434 -
Frontiers in Microbiology 2024Marine bacterioplankton play a crucial role in the cycling of carbon, nitrogen, and phosphorus in coastal waters. And the impact of environmental factors on bacterial...
Marine bacterioplankton play a crucial role in the cycling of carbon, nitrogen, and phosphorus in coastal waters. And the impact of environmental factors on bacterial community structure and ecological functions is a dynamic ongoing process. To systematically assess the relationship between environmental changes and bacterioplankton communities, this study delved into the spatiotemporal distribution and predicted metabolic characteristics of bacterioplankton communities at two estuarine beaches in Northern China. Coastal water samples were collected regularly in spring, summer, and autumn, and were analyzed in combination with environmental parameters and bacterioplankton community. Results indicated significant seasonal variations in bacterioplankton communities as Bacteroidetes and Actinobacteria were enriched in spring, Cyanobacteria proliferated in summer. While Pseudomonadota and microorganisms associated with organic matter decomposition prevailed in autumn, closely linked to seasonal variation of temperature, light and nutrients such as nitrogen and phosphorus. Particularly in summer, increased tourism activities and riverine inputs significantly raised nutrient levels, promoting the proliferation of specific photosynthetic microorganisms, potentially linked to the occurrence of phytoplankton blooms. Spearman correlation analysis further revealed significant correlations between bacterioplankton communities and environmental factors such as salinity, chlorophyll , and total dissolved phosphorus (TDP). Additionally, the metabolic features of the spring bacterioplankton community were primarily characterized by enhanced activities in the prokaryotic carbon fixation pathways, reflecting rapid adaptation to increased light and temperature, as well as significant contributions to primary productivity. In summer, the bacterial communities were involved in enhanced glycolysis and biosynthetic pathways, reflecting high energy metabolism and responses to increased light and biomass. In autumn, microorganisms adapted to the accelerated decomposition of organic matter and the seasonal changes in environmental conditions through enhanced amino acid metabolism and material cycling pathways. These findings demonstrate that seasonal changes and human activities significantly influence the structure and function of bacterioplankton communities by altering nutrient dynamics and physical environmental conditions. This study provides important scientific insights into the marine biological responses under global change.
PubMed: 38962120
DOI: 10.3389/fmicb.2024.1431548