Defining the Activated Fibroblast Population in Lung Fibrosis Using Single-Cell Sequencing.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disorder driven by unrelenting extracellular matrix deposition. Fibroblasts are recognized as the central mediators of extracellular matrix production in IPF; however, the characteristics of the underlying fibroblast cell populations in IPF remain poorly understood. Here, we use an unbiased single-cell RNA sequencing analysis of a bleomycin-induced pulmonary fibrosis model to characterize molecular responses to fibrotic injury. Lung cells were isolated on Day 11 to capture emerging fibrosis and gene expression was analyzed by three complementary techniques, which, together, generated a 49-gene signature that defined an activated subpopulation of fibroblasts. However, none of the identified genes were specific to the activated cells or to the disease setting, implying that the activated fibroblasts are not uniquely defined, but exhibit a similar, yet amplified, gene expression pattern to control cells. Our findings have important implications for fibrosis research, including: 1) defining myofibroblasts with any single marker will fail to capture much of the underlying biology; 2) fibroblast activation is poorly correlated with expression of transforming growth factor-ß pathway genes; 3) single-cell analysis provides insight into the mechanism of action of effective therapies (nintedanib); 4) early events in lung fibrosis need not involve significant changes in fibroblast number; populations that do increase in number, such as macrophages, dendritic cells, and proliferating myeloid cells, may merit closer examination for their role in pathogenesis.

Inhomogeneous Oxygen Vacancy Distribution in Semiconductor Gas Sensors: Formation, Migration and Determination on Gas Sensing Characteristics.

The density of oxygen vacancies in semiconductor gas sensors was often assumed to be identical throughout the grain in the numerical discussion of the gas-sensing mechanism of the devices. In contrast, the actual devices had grains with inhomogeneous distribution of oxygen vacancy under non-ideal conditions. This conflict between reality and discussion drove us to study the formation and migration of the oxygen defects in semiconductor grains. A model of the gradient-distributed oxygen vacancy was proposed based on the effects of cooling rate and re-annealing on semiconductive thin films. The model established the diffusion equations of oxygen vacancy according to the defect kinetics of diffusion and exclusion. We described that the steady-state and transient-state oxygen vacancy distributions, which were used to calculate the gas-sensing characteristics of the sensor resistance and response to reducing gases under two different conditions. The gradient-distributed oxygen vacancy model had the applications in simulating the sensor performances, such as the power law, the grain size effect and the effect of depletion layer width.

Practice Patterns and Outcomes of Patients With Retained Gastric Food Content Encountered During Endoscopy.

INTRODUCTION: Retained gastric food content encountered during upper endoscopy may reduce diagnostic accuracy and increase the risk of aspiration. The aim of this study was to evaluate endoscopists' practice patterns and clinical outcomes in patients with retained gastric food content encountered during endoscopy. METHODS: Consecutive patients with retained gastric food content during first-time endoscopy at Loma Linda University Health (January 2016-March 2021) were identified. Primary endpoints were a complete examination (deep duodenal intubation) and 30-day postprocedural respiratory adverse events. RESULTS: Of 17,868 patients undergoing endoscopy, 629 (3.5%) (mean age 55 ± 17 years) met inclusion criteria. Moderate sedation was performed in 506 (80.4%), anesthesiologist-assisted sedation in 16 (2.5%), and general anesthesia in 107 (17.0%) patients. 534 (84.9%) patients received a complete examination, and endoscopist-specific completion rates varied by quintile among 26 endoscopists (range 70.3%-98.0%, P < 0.0001). Large food gastric content decreased (adjusted odds ratio [aOR] 0.3, 95% confidence interval [CI] 0.2-0.4) while obtaining mucosal biopsies increased (aOR 2.5, 95% CI 1.4-4.7) the likelihood of complete examination after adjusting for endoscopist-specific completion rates. Subsequently, 58 (9.2%) patients required repeat endoscopy within 30 days. During follow-up, 41 (6.5%) patients developed respiratory adverse events including 21 (3.3%) requiring ventilatory support. Hospitalized patients (aOR 37.8, 95% CI 4.9-289.0) compared with outpatients and large compared with small gastric food content (aOR 2.1, 95% CI 1.1-4.2) increased the likelihood of respiratory adverse events. DISCUSSION: Although deep duodenal intubation was achieved in most patients receiving endoscopy, the rate of complete examination varied among individual endoscopists and the extent of food burden. Respiratory adverse events occurred almost exclusively in hospitalized patients and were associated with high morbidity including half developing respiratory failure.

Anesthesia care provider sedation versus conscious sedation for endoscopic ultrasound-guided tissue acquisition: a retrospective cohort study.

BACKGROUND/AIMS: We aimed to study the effects of sedation on endoscopic ultrasound-guided tissue acquisition. METHODS: We conducted a retrospective study evaluating the role of sedation in endoscopic ultrasound-guided tissue acquisition by comparing two groups: anesthesia care provider (ACP) sedation and endoscopist-directed conscious sedation (CS). RESULTS: Technical success was achieved in 219/233 (94.0%) in the ACP group and 114/136 (83.8%) in the CS group (p=0.0086). In multivariate analysis, the difference in technical success between the two groups was not significant (adjusted odds ratio [aOR], 0.5; 95% confidence interval [CI], 0.234-1.069; p=0.0738). A successful diagnostic yield was present in 146/196 (74.5%) in the ACP group and 66/106 (62.3%) in the CS group, respectively (p=0.0274). In multivariate analysis, the difference in diagnostic yield between the two groups was not significant (aOR, 0.643; 95% CI, 0.356-1.159; p=0.142). A total of 33 adverse events (AEs) were observed. The incidence of AEs was significantly lower in the CS group (5/33 CS vs. 28/33 ACP; OR, 0.281; 95% CI, 0.095-0.833; p=0.022). CONCLUSION: CS provided equivalent technical success and diagnostic yield for malignancy in endoscopic ultrasound-guided tissue acquisition. Increased AEs were associated with anesthesia for the endoscopic ultrasound-guided tissue acquisition.

Outcomes and Resource Utilization in Liver Transplant Recipients Who Underwent Expedited Transplant Evaluation.

BACKGROUND: Expedited liver transplant evaluations of critically ill patients can be challenging due to limited time for data gathering and psychosocial evaluation. AIMS: To compare clinical outcomes between expedited and traditional transplant evaluation patients and assess for differences in outpatient resource utilization and staff burden between groups. DESIGN: Adult liver transplant recipients who underwent transplant from 2015 to 2019 were included. Expedited evaluation was defined as time from initiating transplant evaluation to transplant listing <2 weeks. Primary outcomes included rates of graft rejection, graft failure, and death within 1-year posttransplant. Secondary outcomes included number of acute care visits, office visits, and medical record documentation made by transplant staff within 1-year posttransplant. Outcomes were compared using Cox regression models. RESULTS: Of the 335 patients included, 92 (27.5%) were expedited and 243 (72.5%) were traditional. Expedited patients were significantly younger, had greater MELD scores, and required more inpatient care and life support at time of transplant. There was no significant difference in risk of graft rejection (HR 1.3, P = .4), graft failure (HR 1.3, P = .6), or mortality (HR 1.0, P = .9) between groups. Expedited transplant was not associated with increased healthcare or staff utilization: acute care visits (rate ratio 0.9, P = .7), office visits (ß = -1.05, P = .2), and medical record documentation (ß = 3.4, P = 0.4). CONCLUSIONS: Despite being more critically ill, patients requiring expedited transplant evaluation have favorable outcomes after transplant and do not require more intensive staff time and resources compared to traditional candidates.

Relationship between cervical disease and infection with human papillomavirus types 16 and 18, and herpes simplex virus 1 and 2.

Persistent infection with high-risk HPV, particularly Type HPV 16 and 18, is necessary in the development of cervical cancer, but apart from HPV infection, other causative factors of most cervical cancers remain unknown. The aim of this study was to determine the prevalence of HPV 16 and HPV 18 and HSV 1 and HSV 2 in cervical samples, and to assess the role of HSVs in cervical carcinogenesis. Two hundred thirty-three healthy controls and 567 cases (333 of cervicitis, 210 of cervical intraepithelial neoplasia, and 24 of squamous cell carcinoma) in cervical exfoliative cells were tested for HPV 16, HPV 18, HSV 1, and HSV 2 DNA using the triplex real-time polymerase chain reaction method. In contrast to healthy women, positive rate of HPV is related significantly to cervical lesions (odds ratios (ORs) = 4.1, P < 0.01 for cervical intraepithelial neoplasia; ORs = 24.9, P < 0.01 for squamous cell carcinoma), but not cervicitis (ORs = 2.3, P > 0.05). HSV 2 prevalence in cervical intraepithelial neoplasia and squamous cell carcinoma was higher than in healthy women (ORs = 4.9, P < 0.05 for cervical intraepithelial neoplasia; ORs = 4.7, P < 0.05 for squamous cell carcinoma). HSV 2 coinfection with HPV in cervical intraepithelial neoplasia and squamous cell carcinoma was strongly higher than in healthy women (ORs = 34.2, P < 0.01 for cervical intraepithelial neoplasia; ORs = 61.1, P < 0.01 for squamous cell carcinoma). The obtained results indicated that the presence of HPV is associated closely with cervical cancer, and that HSV 2 infection or co-infection with HPV might be involved in cervical cancer development, while HSV 1 might not be involved.

A novel multiplex real-time PCR assay for the detection and quantification of HPV16/18 and HSV1/2 in cervical cancer screening.

Infection with human papillomavirus (HPV), particularly HPV16 and HPV18, is the main cause of invasive cervical cancer, although other factors such as herpes simplex virus (HSV) may act in conjunction with HPV in this context. To explore the possibility of developing a system for rapid diagnosis and clinical screening of cervical cancer, we developed a multiplex real-time PCR assay that can simultaneously detect and quantify HPV16/18 and HSV1/2. To evaluate its possibilities and practical uses, 177 samples collected from patients with suspected HPV and HSV infection in exfoliated cervical cells, genital herpes or labial herpes were tested by multiplex real-time PCR and compared with results obtained by DNA sequencing. Each virus was detected over a range from 1.0 × 10(1) to 1.0 × 10(7) copies/reaction. The clinical sensitivity was 100% for HPV16/18 and HSV1/2. The clinical specificity was 97.1% for HPV16, 98.1% for HPV18, 97.0% for HSV1 and 96.0% for HSV2. The kappa value was 0.96 for HPV16, 0.92 for HPV18, 0.94 for HSV1 and 0.93 for HSV2, when DNA sequencing was used as the reference standard. In summary, this novel multiplex real-time PCR allows the rapid and specific detection of HPV16/18 and HSV1/2, as well as coinfection with HPV and HSV, in clinical samples. In the future, this multiplex real-time PCR assay will assist in cervical cancer screening, viral treatment evaluation and epidemiological studies in which high throughput analysis is required.

Recurrent Aphthous Stomatitis Improved after Eradication Therapy for Helicobacter pylori.

Helicobacterpylori (H. pylori) is a Gram-negative bacterium that colonizes gastric mucosa and is often transmitted through direct contact with saliva, contaminated food or water, and vomit. The majority of the infected individuals remain asymptomatic for a long period. Infection with H. Pylori often presents with dyspepsia, nausea, frequent belching, bloating, abdominal discomfort, burning abdominal pain, and peptic ulcer. A potential association between H. Pylori and recurrent aphthous stomatitis was previously reported; however, the presence of causative relationship between the two remained controversial. We are presenting a case of recurrent aphthous stomatitis of twenty-four-year history resolved after H. pylori treatment.

Controlled release properties of Chitosan encapsulated volatile Citronella Oil microcapsules by thermal treatments.

This research uses modified orifice method to prepare the O/W type Chitosan encapsulated volatile Citronella Oil microcapsules. In this article, we investigated the forming condition of microcapsules and the influence to sustained release effect of volatile Citronella Oil by applying thermal pretreatment to microcapsules. The results suggest that the forming of microcapsules should be processed under the fundamental conditions of: (1) the concentration of Chitosan is at least 0.2wt%, (2) NaOH is greater than 0.1wt%, and (3) with the additive of coconut oil as natural surfactant, so that we could obtain final product of microcapsules with better formation and dispersion. The changes in concentration of Chitosan will affect the encapsulation efficiency of the volatile Citronella Oil. When the concentrations of Chitosan are 0.5%, 1.0% and 1.5%, the encapsulation efficiencies are 98.2%, 95.8% and 94.7%, respectively. The particle size of Chitosan microcapsules would decrease as the emulsification stirring speed increases. When the stirring speeds are 400 rpm, 800 rpm, and 1500 rpm, the average particle sizes of microcapsules produced are 225+/-24 microm, 131+/-20 microm, and 11+/-3 microm, respectively. If the microcapsules were thermal pretreated at 80 degrees C, the structure of Chitosan wall membrane would shrink and thus achieve the effect of sustained release. The sustaining effect would increase along with treatment time increases.