ABSTRACT
The co-localization of the lysosomal protease cathepsin B (CTSB) and the digestive zymogen trypsinogen is a prerequisite for the initiation of acute pancreatitis. However, the exact molecular mechanisms of co-localization are not fully understood. In this study, we investigated the role of lysosomes in the onset of acute pancreatitis by using two different experimental approaches. Using an acinar cell-specific genetic deletion of the ras-related protein Rab7, important for intracellular vesicle trafficking and fusion, we analyzed the subcellular distribution of lysosomal enzymes and the severity of pancreatitis in vivo and ex vivo. Lysosomal permeabilization was performed by the lysosomotropic agent Glycyl-L-phenylalanine 2-naphthylamide (GPN). Acinar cell-specific deletion of Rab7 increased endogenous CTSB activity and despite the lack of re-distribution of CTSB from lysosomes to the secretory vesicles, the activation of CTSB localized in the zymogen compartment still took place leading to trypsinogen activation and pancreatic injury. Disease severity was comparable to controls during the early phase but more severe at later time points. Similarly, GPN did not prevent CTSB activation inside the secretory compartment upon caerulein stimulation, while lysosomal CTSB shifted to the cytosol. Intracellular trypsinogen activation was maintained leading to acute pancreatitis similar to controls. Our results indicate that initiation of acute pancreatitis seems to be independent of the presence of lysosomes and that fusion of lysosomes and zymogen granules is dispensable for the disease onset. Intact lysosomes rather appear to have protective effects at later disease stages.
Subject(s)
Cathepsin B , Lysosomes , Pancreatitis , Secretory Vesicles , rab GTP-Binding Proteins , rab7 GTP-Binding Proteins , Animals , Lysosomes/metabolism , Pancreatitis/metabolism , Pancreatitis/pathology , Pancreatitis/genetics , Cathepsin B/metabolism , Cathepsin B/genetics , Mice , Secretory Vesicles/metabolism , rab GTP-Binding Proteins/metabolism , rab GTP-Binding Proteins/genetics , rab7 GTP-Binding Proteins/metabolism , Acute Disease , Acinar Cells/metabolism , Acinar Cells/pathology , Trypsinogen/metabolism , Trypsinogen/genetics , Ceruletide , Enzyme Precursors/metabolism , Enzyme Precursors/genetics , Mice, Inbred C57BL , Mice, KnockoutABSTRACT
The aetiology of mechanical bowel obstruction exhibits significant variability based on geographical location and age. In high-income countries, postoperative adhesions and hernias are frequently cited as the primary causes, whereas in low- and middle-income countries (LMCIs), hernias take precedence. Speculation exists within the surgical community regarding whether this trend has evolved in LMCIs. To address this knowledge gap, our study aims to conduct a systematic review of existing literature, focusing on understanding the most prevalent causes of mechanical bowel obstruction in both pediatric and adult populations within LMCIs, providing valuable insights for surgical practice. This protocol was designed and written according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-analysis Protocol 2015 (PRISMA-P 2015) statement. However, the results of the systematic review will be reported following the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. We will consider studies published in English and French between 2002 and 2022 that reported on the aetiology of mechanical bowel obstruction in any age group in low- and middle-income countries. We will conduct a literature search using Ovid MEDLINE, Ovid Embase, CINAHL on EBSCO and Web of Science databases employing relevant subject headings, keywords and synonyms, which will be combined using Boolean operators to refine the search results. A hand search of references of retrieved literature will be conducted. The retrieved articles will be imported into Zotero for de-duplication. The resulting set of titles and abstracts will be uploaded to Rayyan (an AI-assisted online systematic review tool), where they will be double-checked to identify articles eligible for inclusion. Two independent reviewers will screen articles to be included and disagreement will be resolved by discussion or by a third reviewer as a tie-breaker. Also, data extraction will be done by one reviewer and confirmed by another. Critical appraisal to assess the quality of the included studies will be carried out by two independent reviewers using the Joanna Briggs Institute (JBI) tools. We anticipate that the eligible studies will be quite heterogeneous in terms of their design, outcomes of interest, populations and comorbidities. Therefore, resmay be synthesised descriptively without meta-analysis using charts, graphs and tables. Where possible, we will conduct a sub-analysis using conceptual frameworks based on age, WHO regions and continents.
Subject(s)
Developing Countries , Intestinal Obstruction , Systematic Reviews as Topic , Humans , Intestinal Obstruction/etiology , Intestinal Obstruction/epidemiologyABSTRACT
Head and Neck Squamous Cell Carcinoma (HNSCC) is a highly heterogeneous cancer that is characterized by distinct phenotypes based on anatomical site and etiological agents. Recently, the intratumor microbiome has been implicated in cancer pathogenesis and progression. Although it is well established that the gut microbiome varies with geographical location and is highly influenced by factors such as diet, environment, and genetics, the intratumor microbiome is not very well characterized. In this review, we aim to characterize the HNSCC intratumor microbiome by geographical location and anatomical site. We conducted a review of primary literature from PubMed and assessed studies based on relevancy and recency. To the best of our knowledge, we are the first to comprehensively examine the tumor microenvironment of HNSCC with respect to these two primary factors on a large scale. Our results suggest that there are unique bacterial and fungal biomarkers for HNSCC for each of the following geographical locations: North America, Asia, Europe, Australia, and Africa. We also identified a panel of microbial biomarkers that are unique to two primary HNSCC anatomic sites, as well as microbial biomarkers associated with various etiological agents of HNSCC. Future study of these microbes may improve HNSCC diagnostic and therapeutic modalities by accounting for differences based on geographic regions and anatomical sites.
Subject(s)
Head and Neck Neoplasms , Microbiota , Squamous Cell Carcinoma of Head and Neck , Humans , Squamous Cell Carcinoma of Head and Neck/microbiology , Squamous Cell Carcinoma of Head and Neck/pathology , Head and Neck Neoplasms/microbiology , Head and Neck Neoplasms/pathology , Tumor MicroenvironmentABSTRACT
PURPOSE: To investigate the prevalence, patterns, and predictors of SARS-CoV-2 RNA and culturable virus in tears of a case-ascertained household cohort. DESIGN: Prospective, longitudinal case-ascertained household cohort identified through convenience sampling. METHODS: This analysis was restricted to individuals who were non-hospitalized, symptomatic, and tested positive for SARS-CoV-2 by nasal RT-PCR. Tears and anterior nasal biospecimens were serially collected throughout the acute period. Tears specimens were collected by the study staff using Schirmer test strips, and nasal specimens were self-collected. For both, SARS-CoV-2 RNA was quantified using qRT-PCR, and culturable virus was detected using presence of cytopathic effect (CPE) in tissue culture; positive CPE was confirmed by a qRT-PCR step. A series of cross-sectional unadjusted analyses were performed investigating the relationship between different sociodemographic determinants and biological factors associated with tears RNA positivity. RESULTS: Among the 83 SARS-CoV-2 infected participants, 10 (12%) had at least one RNA-positive tears specimen. Amongst these 10, 5 (50%) had concurrent presence of culturable virus, at a median of 7 days postsymptom onset (IQR: 4-7 days) (absolute range: 4-8 days). CONCLUSIONS: In this longitudinal cohort, we found evidence of culturable virus in the tears of a small proportion of nonhospitalized SARS-CoV-2 infected individuals. Current public health infection precautions do not account for transmission via tears, so these findings may improve our understanding of potential sources of SARS-CoV-2 transmission and contribute to developing future guidelines.
Subject(s)
COVID-19 , RNA, Viral , SARS-CoV-2 , Tears , Humans , COVID-19/epidemiology , COVID-19/virology , COVID-19/diagnosis , SARS-CoV-2/genetics , Male , Female , RNA, Viral/genetics , RNA, Viral/analysis , Prospective Studies , Tears/virology , Prevalence , Adult , Middle Aged , Cross-Sectional Studies , COVID-19 Nucleic Acid Testing , Eye Infections, Viral/virology , Eye Infections, Viral/epidemiology , Eye Infections, Viral/diagnosis , Family Characteristics , Aged , Longitudinal StudiesABSTRACT
The thermodynamic favorability of an alkaline solution for the oxidation of water suggests the need for developing hydrogen evolution reaction (HER) catalysts that can function in basic aqueous solutions so that both of the half reactions in overall water splitting can occur in mutually compatible solutions. Although photocatalytic HERs have been reported mostly in acidic solutions and a few at basic pHs in mixed organic aqueous solutions, visible-light driven HER catalyzed by molecular metal complexes in purely alkaline aqueous solutions remains largely unexplored. Here, we report a new cobalt complex with a tetrapyridylamine ligand that catalyzes photolytic HER with turnover number up to 218 000 in purely aqueous solutions at pH 9.0. Density functional theory (DFT) calculations suggested a modified electron transfer (E)-proton transfer (C)-electron transfer (E)-proton transfer (C) (mod-ECEC) pathway for hydrogen production from the protonation of CoII-H species. The remarkable catalytic activity resulting from subtle structural changes of the ligand scaffold highlights the importance of studying structure-function relationships in molecular catalyst design. Our present work significantly advances the development of a molecular metal catalyst for visible-light driven HER in more challenging alkaline aqueous solutions that holds substantial promise in solar-driven water-splitting systems.
ABSTRACT
There are a total of 82,290 new cases and 16,710 deaths estimated for bladder cancer in the United States in 2023. Currently, urine cytology tests are widely used for bladder cancer diagnosis, though they suffer from variable sensitivity, ranging from 45 to 97%. More recently, the microbiome has become increasingly recognized for its role in human diseases, including cancers. This study attempts to characterize urinary microbiome bladder cancer-specific dysbiosis to explore its diagnostic potential. RNA-sequencing data of urine samples from patients with bladder cancer (n = 18) and matched controls (n = 12) were mapped to bacterial sequences to yield species-level abundance approximations. Urine samples were analyzed at both the population and species level to reveal dysbiosis associated with bladder cancer. A panel of 35 differentially abundant species was discovered, which may be useful as urinary biomarkers for this disease. We further assessed whether these species were of similar significance in a validation dataset (n = 81), revealing that the genera Escherichia, Acinetobacter, and Enterobacter were consistently differentially abundant. We discovered distinct patterns of microbial-associated immune modulation in these samples. Several immune pathways were found to be significantly enriched with respect to the abundance of these species, including antigen processing and presentation, cytosolic DNA sensing, and leukocyte transendothelial migration. Differential cytokine activity was similarly observed, suggesting the urinary microbiome's correlation to immune modulation. The adherens junction and WNT signaling pathways, both implicated in the development and progression of bladder cancer, were also enriched with these species. Our findings indicate that the urinary microbiome may reflect both microbial and immune dysregulations of the tumor microenvironment in bladder cancer. Given the potential biomarker species identified, the urinary microbiome may provide a non-invasive, more sensitive, and more specific diagnostic tool, allowing for the earlier diagnosis of patients with bladder cancer.
ABSTRACT
Diplopia is a relatively common chief complaint encountered in an outpatient neurology clinic and carries a broad differential diagnosis. In this case, a 67-year-old woman presented with new horizontal, binocular diplopia and ptosis of 8-month duration, which persisted without significant progression. This case highlights the need for a comprehensive list of differential diagnoses for patients with acquired ophthalmoplegia and ptosis. Key learning points include an illustration of the stepwise diagnostic approach to evaluate for common etiologies, the importance of interpreting test results in the appropriate clinical setting, and the significance of recognizing specific signs and symptoms in achieving the correct diagnosis.
Subject(s)
Blepharoptosis , Ophthalmoplegia , Female , Humans , Aged , Diplopia/etiology , Diplopia/complications , Blepharoptosis/diagnosis , Blepharoptosis/etiology , Ophthalmoplegia/complications , Ophthalmoplegia/diagnosis , Diagnosis, Differential , Clinical ReasoningABSTRACT
The purpose of this study is to further validate the utility of our previously developed CNN in an alternative small animal model of BM through transfer learning. Unlike the glioma model, the BM mouse model develops multifocal intracranial metastases, including both contrast enhancing and non-enhancing lesions on DCE MRI, thus serving as an excellent brain tumor model to study tumor vascular permeability. Here, we conducted transfer learning by transferring the previously trained GBM CNN to DCE MRI datasets of BM mice. The CNN was re-trained to learn about the relationship between BM DCE images and target permeability maps extracted from the Extended Tofts Model (ETM). The transferred network was found to accurately predict BM permeability and presented with excellent spatial correlation with the target ETM PK maps. The CNN model was further tested in another cohort of BM mice treated with WBRT to assess vascular permeability changes induced via radiotherapy. The CNN detected significantly increased permeability parameter Ktrans in WBRT-treated tumors (p < 0.01), which was in good agreement with the target ETM PK maps. In conclusion, the proposed CNN can serve as an efficient and accurate tool for characterizing vascular permeability and treatment responses in small animal brain tumor models.
ABSTRACT
In this paper, we provide guidance for the organization and implementation of EEG studies. This work was inspired by our experience conducting a large-scale, multi-site study, but many elements could be applied to any EEG project. Section 1 focuses on study activities that take place before data collection begins. Topics covered include: establishing and training study teams, considerations for task design and piloting, setting up equipment and software, development of formal protocol documents, and planning communication strategy with all study team members. Section 2 focuses on what to do once data collection has already begun. Topics covered include: (1) how to effectively monitor and maintain EEG data quality, (2) how to ensure consistent implementation of experimental protocols, and (3) how to develop rigorous preprocessing procedures that are feasible for use in a large-scale study. Links to resources are also provided, including sample protocols, sample equipment and software tracking forms, sample code, and tutorial videos (to access resources, please visit: https://osf.io/wdrj3/).
ABSTRACT
BACKGROUND: To evaluate the degree to which clinical comorbidities or combinations of comorbidities are associated with SARS-CoV-2 breakthrough infection. MATERIALS AND METHODS: A breakthrough infection was defined as a positive test at least 14 days after a full vaccination regimen. Logistic regression was used to calculate aORs, which were adjusted for age, sex, and race information. RESULTS: A total of 110,380 patients from the UC CORDS database were included. After adjustment, stage 5 CKD due to hypertension (aOR: 7.33; 95% CI: 4.86-10.69; p<.001; power=1) displayed higher odds of infection than any other comorbidity. Lung transplantation history (aOR: 4.79; 95% CI: 3.25-6.82; p<.001; power= 1), coronary atherosclerosis (aOR: 2.12; 95% CI: 1.77-2.52; p<.001; power=1), and vitamin D deficiency (aOR: 1.87; 95% CI: 1.69-2.06; p<.001; power=1) were significantly correlated to breakthrough infection. Patients with obesity in addition to essential hypertension (aOR: 1.74; 95% CI: 1.51-2.01; p<.001; power=1) and anemia (aOR: 1.80; 95% CI: 1.47-2.19; p<.001; power=1) were at additional risk of breakthrough infection compared to those with essential hypertension and anemia alone. CONCLUSIONS: Further measures should be taken to prevent breakthrough infection for individuals with these conditions, such as acquiring additional doses of the SARS-CoV-2 vaccine to boost immunity.
Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , COVID-19/epidemiology , SARS-CoV-2 , Breakthrough Infections , Comorbidity , Essential HypertensionABSTRACT
Lung squamous cell carcinoma (LUSC) is a highly heterogeneous cancer that is influenced by etiological agents such as tobacco smoke. Accordingly, transfer RNA-derived fragments (tRFs) are implicated in both cancer onset and development and demonstrate the potential to act as targets for cancer treatments and therapies. Therefore, we aimed to characterize tRF expression with respect to LUSC pathogenesis and clinical outcomes. Specifically, we analyzed the effect of tobacco smoke on tRF expression. In order to do so, we extracted tRF read counts from MINTbase v2.0 for 425 primary tumor samples and 36 adjacent normal samples. We analyzed the data in three primary cohorts: (1) all primary tumor samples (425 samples), (2) smoking-induced LUSC primary tumor samples (134 samples), and (3) non-smoking-induced LUSC primary tumor samples (18 samples). Differential expression analysis was performed to examine tRF expression in each of the three cohorts. tRF expression was correlated to clinical variables and patient survival outcomes. We identified unique tRFs in primary tumor samples, smoking-induced LUSC primary tumor samples, and non-smoking-induced LUSC primary tumor samples. In addition, many of these tRFs demonstrated correlations to worse patient survival outcomes. Notably, tRFs in the smoking-induced LUSC and non-smoking-induced LUSC primary tumor cohorts were significantly correlated to clinical variables pertaining to cancer stage and treatment efficacy. We hope that our results will be used to better inform future LUSC diagnostic and therapeutic modalities.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Carcinoma, Squamous Cell , Lung Neoplasms , Tobacco Smoke Pollution , Humans , RNA, Transfer/genetics , Carcinoma, Squamous Cell/genetics , Lung Neoplasms/genetics , LungABSTRACT
The use of flow cytometry to enumerate microorganisms is gaining traction over the traditional plate count technique on the basis of superior accuracy, precision and time-to-result. Here, we assessed the suitability of live/dead flow cytometry for the enumeration of mixed populations of probiotic bacteria (L. acidophilus, L. paracasei, L. plantarum, L. salivarius, B. lactis and B. bifidum) whilst comparing outcomes with plate counting. Using a novel gating strategy designed specifically for the enumeration of mixed populations, the application of flow cytometry resulted in the detection of higher numbers of viable bacteria with a greater level of repeatability than plate counting (RSD of 6.82 and 13.14% respectively). Across all multi-species blends tested, viable cell input was more accurately recovered by flow cytometry (101.8 ± 6.95%) than plate counts (81.37 ± 16.03%). However, when certain probiotic mixtures contained preparations with high numbers of non-viable cells in their total population, flow cytometry had the potential for overestimation of the viable population. Nevertheless, the comparative plate counts of these mixtures were low and variable, thus supporting the use of flow cytometry for the enumeration of viable bacteria in mixed populations.
Subject(s)
Bifidobacterium bifidum , Probiotics , Flow Cytometry , Lactobacillus acidophilusABSTRACT
Papillary Thyroid Carcinoma (PTC) is characterized by unique tumor morphology, treatment response, and patient outcomes according to subtype and gender. While previous studies have implicated the intratumor bacterial microbiome in the incidence and progression of PTC, few studies have investigated the potential role of fungal and archaeal species in oncogenesis. In this study, we aimed to characterize the intratumor mycobiome and archaeometry in PTC with respect to its three primary subtypes: Classical (CPTC), Follicular Variant (FVPTC), and Tall Cell (TCPTC), and also with respect to gender. RNA-sequencing data were downloaded from The Cancer Genome Atlas (TCGA), including 453 primary tumor tissue samples and 54 adjacent solid tissue normal samples. The PathoScope 2.0 framework was used to extract fungal and archaeal microbial read counts from raw RNA-sequencing data. Overall, we found that the intratumor mycobiome and archaeometry share significant similarities in CPTC, FVPTC, and TCPTC, although most dysregulated species in CPTC are underabundant compared to normal. Furthermore, differences between the mycobiome and archaeometry were more significant between males and females, with a disproportionate number of fungal species overabundant in female tumor samples. Additionally, the expression of oncogenic PTC pathways was distinct across CPTC, FVPTC, and TCPTC, indicating that these microbes may uniquely contribute to PTC pathogenesis in each subtype. Furthermore, differences in the expression of these pathways were observed between males and females. Finally, we found a specific panel of fungi to be dysregulated in BRAF V600E-positive tumors. This study demonstrates the potential importance of microbial species to PTC incidence and oncogenesis.
Subject(s)
Carcinoma, Papillary , Mycobiome , Thyroid Neoplasms , Male , Humans , Female , Thyroid Cancer, Papillary , Thyroid Neoplasms/pathology , Carcinoma, Papillary/pathology , Transcriptome , RNA , Carcinogenesis , Proto-Oncogene Proteins B-raf/geneticsABSTRACT
Improving access to grant funding is a critical aspect of strengthening research capacity outside of higher income settings, particularly in HIV/AIDS where randomized control trials (RCTs) that require substantial resources are common. In this article, we assessed recent RCTs to examine variation in how studies were funded, depending on study location and the countries where publication authors were based. We conducted a PubMed literature review to identify RCTs with HIV status or viral load endpoints published in 2019 and 2020, then analyzed cross-tabulations of funding sources by study characteristics. One hundred sixteen publications met the inclusion criteria. Research in higher income countries was most likely to be funded by biotech/pharmaceutical companies, whereas research in lower- and middle-income countries was most likely to be funded by U.S. government sources. Overall, we found the distribution of funding sources differed significantly by study and author location (χ2 = 23, p < .001). Published RCTs with HIV status or viral load endpoints are financed differently based on where studies take place and where the authors are based. As part of future research, understanding why this variation exists is critical for assessing how funding contributes to global imbalances in scientific resources.
Subject(s)
Acquired Immunodeficiency Syndrome , HIV Infections , Humans , Government , Financing, Organized , Randomized Controlled Trials as Topic , Global HealthABSTRACT
Human Papilloma Virus (HPV) is highly prevalent within the U.S., with studies estimating that over 80% of individuals will contract the virus in their lifetime. HPV is considered a primary risk factor for the development and progression of oropharyngeal cancers. The impact of the HPV virus's E6 and E7 oncoproteins on cellular signaling pathways and genomic integration has been extensively characterized. Indirect genomic effects; however, remain relatively unidentified. In this study, we analyzed 83 HPV+ Head and Neck Squamous Cell Carcinoma (HNSCC) patients of varying HPV types. Expression counts of the HPV E6 and E7 oncogenes were estimated across samples and correlated with genomic mutational classes. High expression of E6 and E7 oncoproteins was associated with a greater number of total point mutations, especially on chromosomes 1, 11, and 17, which have been implicated in HPV-mediated cancers in previous studies. Samples with high E6 and E7 expression also exhibited more frequent non-clustered structural variation and a lack of clustered variation altogether. Copy number segments were present with fewer number of repeats in high E6 and E7 expression samples, which is known to correlate with decreased expression of affected genes. E6 and E7 expression was associated with increased activity of several cellular pathways associated in oncogenesis and telomere maintenance. In comprehensively characterizing the effects of the HPV oncoproteins on the human genome, potential mechanisms of HNSCC pathogenesis may be further elucidated.
ABSTRACT
Objective: Coronavirus disease 2019 (COVID-19) is a systemic disease induced by SARS-CoV-2 causing myocardial injury. To date, there are few data on the correlation between mid-regional proAdrenomedullin (MR-proADM) and myocardial injury. The aim of this study was to evaluate whether the association of myocardial injury and elevated mid-regional proAdrenomedullin values could predict mortality of SARS-CoV-2 patients, to offer the best management to COVID-19 patients. Materials and methods: All patients hospitalized for SARS-CoV-2 infection at the COVID-19 Center of the Campus Bio-Medico of Rome University were included between October 2020 and March 2021 and were retrospectively analyzed. Myocardial injury was defined as rising and/or fall of cardiac hs Troponin I values with at least one value above the 99th percentile of the upper reference limit (≥15.6 ng/L in women and ≥34.2 ng/L in men). The primary outcome was 30-day mortality. Secondary outcomes were the comparison of MR-proADM, CRP, ferritin, and PCT as diagnostic and prognostic biomarkers of myocardial injury. Additionally, we analyzed the development of ARDS, the need for ICU transfer, and length of stay (LOS). Results: A total of 161 patients were included in this study. Of these, 58 (36.0%) presented myocardial injury at admission. An MR-proADM value ≥ 1.19 nmol/L was defined as the optimal cut-off to identify patients with myocardial injury (sensitivity 81.0% and specificity 73.5%). A total of 121 patients (75.2%) developed ARDS, which was significantly more frequent among patients with myocardial injury (86.2 vs. 68.9%, p = 0.015). The overall 30-day mortality was 21%. Patients with myocardial injury presented significantly higher mortality compared to those without the same (46.6 vs. 6.8%, p < 0.001). When dividing the entire study population into four groups, based on the presence of myocardial injury and MR-proADM values, those patients with both myocardial injury and MR-proADM ≥ 1.19 nmol/L presented the highest mortality (53.2%, p < 0.001). The combination of myocardial injury and MR-proADM values ≥ 1.19 nmol/L was an independent predictor of death (OR = 7.82, 95% CI = 2.87-21.30; p < 0.001). Conclusion: The study is focused on the correlation between myocardial injury and MR-proADM. Myocardial injury induced by SARS-CoV-2 is strongly associated with high MR-proADM values and mortality.
ABSTRACT
Head and neck squamous cell carcinoma (HNSCC) tumor phenotypes and clinical outcomes are significantly influenced by etiological agents, such as HPV infection, smoking, and alcohol consumption. Accordingly, the intratumor microbiome has been increasingly implicated in cancer progression and metastasis. However, few studies characterize the intratumor microbial landscape of HNSCC with respect to these etiological agents. In this study, we aimed to investigate the bacterial and fungal landscape of HNSCC in association with HPV infection, smoking, and alcohol consumption. RNA-sequencing data were extracted from The Cancer Genome Atlas (TCGA) regarding 449 tissue samples and 44 normal samples. Pathoscope 2.0 was used to extract the microbial reads. Microbe abundance was compared to clinical variables, oncogenic signatures, and immune-associated pathways. Our results demonstrated that a similar number of dysregulated microbes was overabundant in smokers and nonsmokers, while heavy drinkers were characterized by an underabundance of dysregulated microbes. Conversely, the majority of dysregulated microbes were overabundant in HPV+ tumor samples when compared to HPV- tumor samples. Moreover, we observed that many dysregulated microbes were associated with oncogenic and metastatic pathways, suggesting their roles in influencing carcinogenesis. These microbes provide insights regarding potential mechanisms for tumor pathogenesis and progression with respect to the three etiological agents.
Subject(s)
Head and Neck Neoplasms , Mycobiome , Papillomavirus Infections , Humans , Squamous Cell Carcinoma of Head and Neck/complications , Papillomaviridae/genetics , Head and Neck Neoplasms/complications , Smoking/adverse effects , Alcohol Drinking/adverse effectsABSTRACT
Sicyopterus garra Hora, 1925 from the insular streams of South Andaman Islands was synonymized with Sicyopterus microcephalus described from Java, South East Asia and has retained this taxonomic status since then. Recent collections of Sicyopterus from the type locality of S. garra and the examination of syntypes of this species revealed significant morphological and genetic differences from S. microcephalus and the other Sicyopterus species with papillae on upper lip. S. garra is thus a valid species and not a synonym of S. microcephalus. S. garra differs from S. microcephalus in having fewer lateral scales 53-59 vs. 57-68, fewer zigzag series (12-14 vs. 13-16), a longer caudal peduncle length (16-21 vs. 13-17), and by having a high percentage of divergence in COI gene (5.5%-5.8%).
Subject(s)
Cyprinidae , Perciformes , Animals , Cyprinidae/anatomy & histology , Perciformes/anatomy & histology , India , IslandsABSTRACT
Brain degenerative disorders such as Alzheimer's disease (AD) can be exacerbated by aberrant metabolism. Supplementation with probiotic bacteria is emerging as a promising preventative strategy for both neurodegeneration and metabolic syndrome. In this study, we assess the impact of the Lab4b probiotic consortium on (i) cognitive and pathological markers of AD progression and (ii) metabolic status in 3xTg-AD mice subjected to metabolic challenge with a high fat diet. The group receiving the probiotic performed better in the novel object recognition test and displayed higher hippocampal neuronal spine density than the control group at the end of the 12 weeks intervention period. These changes were accompanied by differences in localised (brain) and systemic anti-inflammatory responses that favoured the Probiotic group together with the prevention of diet induced weight gain and hypercholesterolaemia and the modulation of liver function. Compositional differences between the faecal microbiotas of the study groups included a lower Firmicutes:Bacteroidetes ratio and less numbers of viable yeast in the Probiotic group compared to the Control. The results illustrate the potential of the Lab4b probiotic as a neuroprotective agent and encourage further studies with human participants.
ABSTRACT
The freeform generation of active electronics can impart advanced optical, computational, or sensing capabilities to an otherwise passive construct by overcoming the geometrical and mechanical dichotomies between conventional electronics manufacturing technologies and a broad range of three-dimensional (3D) systems. Previous work has demonstrated the capability to entirely 3D print active electronics such as photodetectors and light-emitting diodes by leveraging an evaporation-driven multi-scale 3D printing approach. However, the evaporative patterning process is highly sensitive to print parameters such as concentration and ink composition. The assembly process is governed by the multiphase interactions between solutes, solvents, and the microenvironment. The process is susceptible to environmental perturbations and instability, which can cause unexpected deviation from targeted print patterns. The ability to print consistently is particularly important for the printing of active electronics, which require the integration of multiple functional layers. Here we demonstrate a synergistic integration of a microfluidics-driven multi-scale 3D printer with a machine learning algorithm that can precisely tune colloidal ink composition and classify complex internal features. Specifically, the microfluidic-driven 3D printer can rapidly modulate ink composition, such as concentration and solvent-to-cosolvent ratio, to explore multi-dimensional parameter space. The integration of the printer with an image-processing algorithm and a support vector machine-guided classification model enables automated, in-situ pattern classification. We envision that such integration will provide valuable insights in understanding the complex evaporative-driven assembly process and ultimately enable an autonomous optimisation of printing parameters that can robustly adapt to unexpected perturbations.