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Nature Communications Jun 2024The growing scale and dimensionality of multiplexed imaging require reproducible and comprehensive yet user-friendly computational pipelines. TRACERx-PHLEX performs deep...
The growing scale and dimensionality of multiplexed imaging require reproducible and comprehensive yet user-friendly computational pipelines. TRACERx-PHLEX performs deep learning-based cell segmentation (deep-imcyto), automated cell-type annotation (TYPEx) and interpretable spatial analysis (Spatial-PHLEX) as three independent but interoperable modules. PHLEX generates single-cell identities, cell densities within tissue compartments, marker positivity calls and spatial metrics such as cellular barrier scores, along with summary graphs and spatial visualisations. PHLEX was developed using imaging mass cytometry (IMC) in the TRACERx study, validated using published Co-detection by indexing (CODEX), IMC and orthogonal data and benchmarked against state-of-the-art approaches. We evaluated its use on different tissue types, tissue fixation conditions, image sizes and antibody panels. As PHLEX is an automated and containerised Nextflow pipeline, manual assessment, programming skills or pathology expertise are not essential. PHLEX offers an end-to-end solution in a growing field of highly multiplexed data and provides clinically relevant insights.
Topics: Humans; Deep Learning; Image Processing, Computer-Assisted; Animals; Software; Spatial Analysis; Single-Cell Analysis; Phenotype; Mice; Image Cytometry
PubMed: 38879602
DOI: 10.1038/s41467-024-48870-5 -
Journal of Translational Medicine Jun 2024Gut microbiota (GM) have been implicated as important regulators of gastrointestinal symptom which is commonly occurred along with respiratory influenza A virus (IAV)...
BACKGROUND
Gut microbiota (GM) have been implicated as important regulators of gastrointestinal symptom which is commonly occurred along with respiratory influenza A virus (IAV) infection, suggesting the involvement of the gut-to-lung axis in a host's response to IAV. IAV primarily destroys airway epithelium tight junctions (TJs) and consequently causes acute respiratory disease syndrome. It is known that GM and their metabolism produce an anti-influenza effect, but their role in IAV-induced airway epithelial integrity remains unknown.
METHODS
A mouse model of IAV infection was established. GM were analyzed using 16S rRNA gene sequencing, and short-chain fatty acids (SCFAs) levels were measured. GM depletion and fecal microbiota transplantation (FMT) were conducted to validate the role of GM in IAV infection. A pair-feeding experiment was conducted to reveal whether IAV-induced GM dysbiosis is attributed to impaired food intake. Furthermore, human bronchial epithelial (HBE) cells were cocultured with IAV in the presence or absence of acetate. TJs function was analyzed by paracellular permeability and transepithelial electronic resistance (TEER). The mechanism of how acetate affects TJs integrity was evaluated in HBE cells transfected with G protein-coupled receptor 43 (GPR43) short hairpin RNA (shRNA).
RESULTS
IAV-infected mice exhibited lower relative abundance of acetate-producing bacteria (Bacteroides, Bifidobacterium, and Akkermansia) and decreased acetate levels in gut and serum. These changes were partly caused by a decrease in food consumption (due to anorexia). GM depletion exacerbated and FMT restored IAV-induced lung inflammatory injury. IAV infection suppressed expressions of TJs (occludin, ZO-1) leading to disrupted airway epithelial barrier function as evidenced by decreased TEER and increased permeability. Acetate pretreatment activated GPR43, partially restored IAV-induced airway epithelial barrier function, and reduced inflammatory cytokines levels (TNF-α, IL-6, and IL-1β). Such protective effects of acetate were absent in HBE cells transfected with GPR43 shRNA. Acetate and GPR43 improved TJs in an AMP-activated protein kinase (AMPK)-dependent manner.
CONCLUSION
Collectively, our results demonstrated that GM protected airway TJs by modulating GPR43-AMPK signaling in IAV-induced lung injury. Therefore, improving GM dysbiosis may be a potential therapeutic target for patients with IAV infection.
Topics: Animals; Tight Junctions; Gastrointestinal Microbiome; Acetates; Humans; Lung Injury; Orthomyxoviridae Infections; Mice, Inbred C57BL; Influenza A virus; Fecal Microbiota Transplantation; Receptors, G-Protein-Coupled; Mice; Epithelial Cells; Dysbiosis; Fatty Acids, Volatile
PubMed: 38879538
DOI: 10.1186/s12967-024-05376-4 -
Journal of Infection and Public Health May 2024The effectiveness of oral antiviral therapy including nirmatrelvir plus ritonavir and molnupiravir in managing COVID-19 among individuals with pre-existing lung cancer...
BACKGROUNDS
The effectiveness of oral antiviral therapy including nirmatrelvir plus ritonavir and molnupiravir in managing COVID-19 among individuals with pre-existing lung cancer was unclear. Therefore, this study was conducted to evaluate the usefulness of antiviral agents in the management of COVID-19 among patients with lung cancer.
METHODS
Utilizing data from the TriNetX - a global health research network, a retrospective cohort study was conducted involving 2484 patients diagnosed with both lung cancer and COVID-19. Propensity score matching (PSM) was employed to create well-balanced cohorts. The study assessed the primary outcome of all-cause hospitalization or mortality within a 30-day follow-up.
RESULTS
After PSM, the oral antiviral group exhibited a significantly lower risk of the primary composite outcome compared to the control group (6.1 % vs. 9.9 %; HR: 0.60; 95 % CI: 0.45-0.80). This association was consistent across various subgroups according to age, sex, vaccine status, type of oral antiviral agent, and lung cancer characteristics. Additionally, the oral antiviral group showed a lower risk of all-cause hospitalization (HR: 0.73; 95 % CI: 0.54-0.99) and a significantly lower risk of mortality (HR: 0.16; 95 % CI: 0.06-0.41).
CONCLUSION
The study suggests a favorable impact of oral antiviral therapy on the outcomes of COVID-19 in individuals with lung cancer and support the potential utility of oral antiviral agents in improving outcomes in this vulnerable population.
PubMed: 38878678
DOI: 10.1016/j.jiph.2024.05.053 -
Diagnostic Microbiology and Infectious... Jun 2024Due to the limitations of traditional laboratory methods (TMs), identification of causative pathogens of numerous pulmonary infections (PIs) remains difficult. This... (Review)
Review
Due to the limitations of traditional laboratory methods (TMs), identification of causative pathogens of numerous pulmonary infections (PIs) remains difficult. This study evaluated the value of metagenomic next generation sequencing (mNGS) in the identification of various respiratory pathogens. A total of 207 patients with TMs and mNGS data were collected for this retrospective study. TMs included sputum culture, blood, and bronchoalveolar lavage fluid (BALF) analysis, or polymerase chain reaction analysis of throat swabs. Otherwise, BALF was collected and analyzed using mNGS. For bacterial pathogens, sensitivities of mNGS as compared to TMs were 76.74 % and 58.14 % (P=0.012). For fungal pathogens, the detection rate of mNGS sensitivity was higher as compared to that of TMs (93.68 % vs 22.11 %; P<0.001). The positive predictive value and negative predictive value were also greater for mNGS. Use of mNGS for BALF analysis offers good specificity and thus facilitates to the clinical diagnosis of PIs.
PubMed: 38878340
DOI: 10.1016/j.diagmicrobio.2024.116402 -
Journal of Orthopaedic Surgery and... Jun 2024Postoperative pulmonary complications (PPCs) are among the most severe complications following total hip arthroplasty revision (THAR), imposing significant burdens on...
BACKGROUND
Postoperative pulmonary complications (PPCs) are among the most severe complications following total hip arthroplasty revision (THAR), imposing significant burdens on individuals and society. This study examined the prevalence and risk factors of PPCs following THAR using the NIS database, identifying specific pulmonary complications (SPCs) and their associated risks, including pneumonia, acute respiratory failure (ARF), and pulmonary embolism (PE).
METHODS
The National Inpatient Sample (NIS) database was used for this cross-sectional study. The analysis included patients undergoing THAR based on NIS from 2010 to 2019. Available data include demographic data, diagnostic and procedure codes, total charges, length of stay (LOS), hospital information, insurance information, and discharges.
RESULTS
From the NIS database, a total of 112,735 THAR patients in total were extracted. After THAR surgery, there was a 2.62% overall incidence of PPCs. Patients with PPCs after THAR demonstrated increased LOS, total charges, usage of Medicare, and in-hospital mortality. The following variables have been determined as potential risk factors for PPCs: advanced age, pulmonary circulation disorders, fluid and electrolyte disorders, weight loss, congestive heart failure, metastatic cancer, other neurological disorders (encephalopathy, cerebral edema, multiple sclerosis etc.), coagulopathy, paralysis, chronic pulmonary disease, renal failure, acute heart failure, deep vein thrombosis, acute myocardial infarction, peripheral vascular disease, stroke, continuous trauma ventilation, cardiac arrest, blood transfusion, dislocation of joint, and hemorrhage.
CONCLUSIONS
Our study revealed a 2.62% incidence of PPCs, with pneumonia, ARF, and PE accounting for 1.24%, 1.31%, and 0.41%, respectively. A multitude of risk factors for PPCs were identified, underscoring the importance of preoperative optimization to mitigate PPCs and enhance postoperative outcomes.
Topics: Humans; Arthroplasty, Replacement, Hip; Risk Factors; Postoperative Complications; Male; Female; Retrospective Studies; Incidence; Aged; Middle Aged; Cross-Sectional Studies; Databases, Factual; Pulmonary Embolism; Reoperation; Length of Stay; Lung Diseases; United States; Pneumonia; Adult; Aged, 80 and over; Respiratory Insufficiency; Inpatients
PubMed: 38877587
DOI: 10.1186/s13018-024-04836-3 -
Infectious Diseases of Poverty Jun 2024Digenetic trematodes, including blood flukes, intestinal flukes, liver flukes, lung flukes, and pancreatic flukes, are highly diverse and distributed widely. They affect... (Review)
Review
BACKGROUND
Digenetic trematodes, including blood flukes, intestinal flukes, liver flukes, lung flukes, and pancreatic flukes, are highly diverse and distributed widely. They affect at least 200 million people worldwide, so better understanding of their global distribution and prevalence are crucial for controlling and preventing human trematodiosis. Hence, this scoping review aims to conduct a comprehensive investigation on the spatio-temporal distribution and epidemiology of some important zoonotic digenetic trematodes.
METHODS
We conducted a scoping review by searching PubMed, Web of Science, Google Scholar, China National Knowledge Infrastructure, and Wanfang databases for articles, reviews, and case reports of zoonotic digenetic trematodes, without any restrictions on the year of publication. We followed the inclusion and exclusion criteria to identify relevant studies. And relevant information of the identified studies were collected and summarized.
RESULTS
We identified a total of 470 articles that met the inclusion criteria and were included in the review finally. Our analysis revealed the prevalence and global distribution of species in Schistosoma, Echinostoma, Isthmiophora, Echinochasmus, Paragonimus, Opisthorchiidae, Fasciolidae, Heterophyidae, and Eurytrema. Although some flukes are distributed worldwide, developing countries in Asia and Africa are still the most prevalent areas. Furthermore, there were some overlaps between the distribution of zoonotic digenetic trematodes from the same genus, and the prevalence of some zoonotic digenetic trematodes was not entirely consistent with their global distribution. The temporal disparities in zoonotic digenetic trematodes may attribute to the environmental changes. The gaps in our knowledge of the epidemiology and control of zoonotic digenetic trematodes indicate the need for large cohort studies in most countries.
CONCLUSIONS
This review provides important insights into the prevalence and global distribution of some zoonotic digenetic trematodes, firstly reveals spatio-temporal disparities in these digenetic trematodes. Countries with higher prevalence rate could be potential sources of transmitting diseases to other areas and are threat for possible outbreaks in the future. Therefore, continued global efforts to control and prevent human trematodiosis, and more international collaborations are necessary in the future.
Topics: Animals; Zoonoses; Trematode Infections; Humans; Trematoda; Prevalence; Global Health
PubMed: 38877531
DOI: 10.1186/s40249-024-01208-1 -
BMC Anesthesiology Jun 2024Patients with sepsis with low albumin levels and high red blood cell distribution width levels have poor prognoses. Red blood cell distribution width to albumin ratio... (Observational Study)
Observational Study
BACKGROUND
Patients with sepsis with low albumin levels and high red blood cell distribution width levels have poor prognoses. Red blood cell distribution width to albumin ratio (RAR) has recently attracted attention as an innovative inflammation biomarker. We aimed to explore the association between RAR and the prognosis of patients with sepsis.
METHODS
This retrospective observational study included 402 patients meeting the sepsis-3 standards admitted to Yantai Yuhuangding Hospital's intensive care units (ICUs) between January 2020 and December 2022. The relationship between RAR and mortality in patients with sepsis was examined using regression analysis, Kaplan-Meier analyses, and a receiver operating characteristic curve. Subgroup and sensitivity analyses were conducted to assess the results' robustness.
RESULTS
RAR, when considered as a continuous variable, was a significant independent in-hospital mortality risk factor (adjusted odds ratio [OR]: 1.383; 95% confidence interval [CI]: 1.164-1.645; P < 0.001). When considering RAR as a categorical variable, the ORs (95% CIs) of hospital mortality for quartile 2 (Q2), Q3, and Q4 compared with Q1 were 1.027 (0.413-2.551), 3.632 (1.579-8.354), and 4.175 (1.625-10.729), respectively, P < 0.001. Similar outcomes were observed for 28- and 90-day mortalities.
CONCLUSIONS
RAR may indicate clinical prognosis for patients with sepsis in the ICU, potentially providing a low-cost, easily repeatable, and accessible biomarker for risk categorization for these patients.
Topics: Humans; Sepsis; Male; Female; Retrospective Studies; Intensive Care Units; Middle Aged; Prognosis; Hospital Mortality; Aged; Erythrocyte Indices; Serum Albumin; Biomarkers; Predictive Value of Tests; Adult
PubMed: 38877408
DOI: 10.1186/s12871-024-02585-8 -
Scientific Reports Jun 2024Adjuvants enhance, prolong, and modulate immune responses by vaccine antigens to maximize protective immunity and enable more effective immunization in the young and...
Adjuvants enhance, prolong, and modulate immune responses by vaccine antigens to maximize protective immunity and enable more effective immunization in the young and elderly. Most adjuvants are formulated with injectable vaccines. However, an intranasal route of vaccination may induce mucosal and systemic immune responses for enhancing protective immunity in individuals and be easier to administer compared to injectable vaccines. In this study, a next generation of broadly-reactive influenza hemagglutinin (HA) vaccines were developed using the Computationally Optimized Broadly Reactive Antigen (COBRA) methodology. These HA vaccines were formulated with Mastoparan 7 (M7-NH) mast cell degranulating peptide adjuvant and administered intranasally to determine vaccine-induced seroconversion of antibodies against a panel of influenza viruses and protection following infection with H1N1 and H3N2 viruses in mice. Mice vaccinated intranasally with M7-NH-adjuvanted COBRA HA vaccines had high HAIs against a panel of H1N1 and H3N2 influenza viruses and were protected against both morbidity and mortality, with reduced viral lung titers, following challenge with an H1N1 influenza virus. Additionally, M7-NH adjuvanted COBRA HA vaccines induced Th2 skewed immune responses with robust IgG and isotype antibodies in the serum and mucosal lung lavages. Overall, this intranasally delivered M7-NH -adjuvanted COBRA HA vaccine provides effective protection against drifted H1N1 and H3N2 viruses.
Topics: Influenza Vaccines; Animals; Mice; Hemagglutinin Glycoproteins, Influenza Virus; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Adjuvants, Immunologic; Antibodies, Viral; Orthomyxoviridae Infections; Administration, Intranasal; Female; Mice, Inbred BALB C; Intercellular Signaling Peptides and Proteins; Adjuvants, Vaccine
PubMed: 38877101
DOI: 10.1038/s41598-024-64351-7 -
The Lancet. Global Health Jul 2024Better access to tuberculosis testing is a key priority for fighting tuberculosis, the leading cause of infectious disease deaths in people. Despite the roll-out of... (Review)
Review
Better access to tuberculosis testing is a key priority for fighting tuberculosis, the leading cause of infectious disease deaths in people. Despite the roll-out of molecular WHO-recommended rapid diagnostics to replace sputum smear microscopy over the past decade, a large diagnostic gap remains. Of the estimated 10·6 million people who developed tuberculosis globally in 2022, more than 3·1 million were not diagnosed. An exclusive focus on improving tuberculosis test accuracy alone will not be sufficient to close the diagnostic gap for tuberculosis. Diagnostic yield, which we define as the proportion of people in whom a diagnostic test identifies tuberculosis among all people we attempt to test for tuberculosis, is an important metric not adequately explored. Diagnostic yield is particularly relevant for subpopulations unable to produce sputum such as young children, people living with HIV, and people with subclinical tuberculosis. As more accessible non-sputum specimens (eg, urine, oral swabs, saliva, capillary blood, and breath) are being explored for point-of-care tuberculosis testing, the concept of yield will be of growing importance. Using the example of urine lipoarabinomannan testing, we illustrate how even tests with limited sensitivity can diagnose more people with tuberculosis if they enable increased diagnostic yield. Using tongue swab-based molecular tuberculosis testing as another example, we provide definitions and guidance for the design and conduct of pragmatic studies that assess diagnostic yield. Lastly, we show how diagnostic yield and other important test characteristics, such as cost and implementation feasibility, are essential for increased effective population coverage, which is required for optimal clinical care and transmission impact. We are calling for diagnostic yield to be incorporated into tuberculosis test evaluation processes, including the WHO Grading of Recommendations, Assessment, Development, and Evaluations process, providing a crucial real-life implementation metric that complements traditional accuracy measures.
Topics: Humans; Tuberculosis; Diagnostic Tests, Routine; Sputum
PubMed: 38876764
DOI: 10.1016/S2214-109X(24)00148-7 -
Journal of Infection and Chemotherapy :... Jun 2024A 45-year-old man visited our hospital with a chronic cough and breathing difficulties. Chest computed tomography revealed diffuse granular shadows. Mycobacterium avium...
A 45-year-old man visited our hospital with a chronic cough and breathing difficulties. Chest computed tomography revealed diffuse granular shadows. Mycobacterium avium (M. avium) was cultured from bronchoalveolar lavage fluid (BALF). Surgical lung biopsy revealed non-necrotizing granulomas, and M. avium-specific PCR was positive in the tissue. M. avium was also cultured in a sample from the inlet of the patient's bathtub. Mycobacterium avium tandem repeat variable-number tandem-repeat loci (MATR-VNTR) analysis confirmed that the M. avium cultured from BALF and the bathtub inlet had identical allele profiles. The patient's symptoms and oxygenation improved while the patient was in hospital, presumably because of lack of ongoing exposure to M. avium. He was diagnosed with hot tub lung. We advised the patient to avoid bathing to avoid re-exposure. However, the patient was unwilling to follow this advice. Therefore, his bathtub and pipework were disinfected by heating them to over 70 °C. We confirmed that the disinfection has been successful by repeated culture of environmental samples. Three months after resuming bathtub use, the patient's symptoms resolved, and the pulmonary shadows seen on the initial radiography did not recur. For the treatment of hot tub lung, disinfection of M. avium complex in the environment should be considered and the environment should be monitored to confirm eradication.
PubMed: 38876204
DOI: 10.1016/j.jiac.2024.06.005