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Abstract Background There is evidence from existing literature that ambient air pollutant exposure in early childhood likely plays an important role in asthma exacerbation and other respiratory symptoms, with greater effect among asthmatic children. However, there is inconclusive evidence on the role of ambient air pollutant exposures in relation to increasing asthma prevalence as well as asthma induction in children. At the population level, little is known about the potential synergistic effects between pollen allergens and air pollutants since this type of association poses challenges in uncontrolled real life settings. In particular, data from sub-Sahara Africa is scarce and virtually absent among populations residing in informal residential settlements. Methods/design A prospective cohort study of 600 school children residing in four informal settlement areas with varying potential ambient air pollutant exposure levels in the Western Cape in South Africa is carried-out. The study has two follow-up periods of at least six-months apart including an embedded panel study in summer and winter. The exposure assessment component models temporal and spatial variability of air quality in the four study areas over the study duration using land-use regression modelling (LUR). Additionally, daily pollen levels (mould spores, tree, grass and weed pollen) in the study areas are recorded. In the panel study asthma symptoms and serial peak flow measurements is recorded three times daily to determine short-term serial airway changes in relation to varying ambient air quality and pollen over 10-days during winter and summer. The health outcome component of the cohort study include; the presence of asthma using a standardised ISAAC questionnaire, spirometry, fractional exhaled nitric-oxide (FeNO) and the presence of atopy (Phadiatop). Discussion This research applies state of the art exposure assessment approaches to characterize the effects of ambient air pollutants on childhood respiratory health, with a specific focus on asthma and markers of airway inflammation (FeNO) in South African informal settlement areas by considering also pollen counts and meteorological factors. The study will generate crucial data on air pollution and asthma in low income settings in sub-Sahara Africa that is lacking in the international literature.

Breast conserving surgery (BCS) has become the preferred surgical option for the management of patients with nonmetastatic breast cancer in high-income countries. However, little is known about the distribution and determinants of BCS in low-and middle-income countries, especially those with high HIV prevalence.We compared demographic and clinical characteristics of female patients who received BCS and those who received total mastectomy (TM) for nonmetastatic invasive carcinoma of the breast in Soweto, South Africa, 2009-2011. We also developed a multivariable logistic regression model of predictors of type of surgery.Of 445 patients, 354 (80%) underwent TM and 91 (20%) BCS. Of 373 patients screened for HIV, 59 (15.8%) tested positive. Eighty-two of 294 patients with stage I/II disease (28%), but just 9 of 151 (6%) with stage III disease had BCS (p

Air pollution is an important risk factor for global burden of disease. There has been recent interest in its possible role in the etiology of diabetes mellitus. Experimental evidence is suggestive, but epidemiological evidence is limited and mixed. We therefore explored the association between air pollution and prevalent diabetes, in a population-based Swiss cohort.We did cross-sectional analyses of 6392 participants of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults [SAPALDIA], aged between 29 and 73 years. We used estimates of average individual home outdoor PM10 [particulate matter

Introduction: Lung cancer is one of the most prevalent malignancies worldwide. Substantial research has illuminated the intricate interplay between microorganisms and human health, revealing their role in disease regulation. Trichomonads is a flagellated protozoan in the human cavity and have been previously identified as a pathogen associated with pneumonia, contributing to tissue chronic inflammation and carcinogenesis. Methods: Nested polymerase chain reaction methods were employed to scrutinize the prevalence of trichomonads in the bronchovesicular fluid of patients diagnosed with lung cancer. Subsequently, the influence of Trichomonas tenax invasion on lung cancer cells was elucidated through proliferation assays, migration assays, and transcription analysis. Results: Bronchoalveolar fluid samples from lung cancer patients yielded positive nested PCR results for eight out of twenty-seven samples. Seven of these samples were identified as Trichomonas tenax, while one was identified as Tetratrichomonas spp. Our findings revealed a significant upregulation of pathways associated with carcinogenesis, including cellular proliferation, migration, and drug resistance, in response to T. tenax invasion. Conclusions: This study underscores the importance of recognizing the presence of trichomonads and the influence of T. tenax invasion on host responses to respiratory diseases. The identified pathways implicated in cancer development may pave the way for developing targeted treatment strategies for pulmonary diseases. These findings hold promise for informing and improving the precision of therapeutic interventions in the context of pulmonary ailments.

Gastric inflammation-related disorders are commonly observed digestive system illnesses characterized by the activation of proinflammatory cytokines, particularly tumor necrosis factor-α (TNF-α). This results in the induction of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PEG2) and matrix metallopeptidase-9 (MMP-9). These factors contribute to the pathogenesis of gastric inflammation disorders. We examined the preventive effects of Lonicera japonica Thunb. ethanol extract (Lj-EtOH) on gastric inflammation induced by TNF-α in normal human gastric mucosa epithelial cells (GES-1). The GES-1 cell line was used to establish a model that simulated the overexpression of COX-2/PGE2 and MMP-9 proteins induced by TNF-α to examine the anti-inflammatory properties of Lj extracts. The results indicated that Lj-EtOH exhibits significant inhibitory effects on COX-2/PEG2 and MMP-9 activity, attenuates cell migration, and provides protection against TNF-α-induced gastric inflammation. The protective effects of Lj-EtOH are associated with the modulation of COX-2/PEG2 and MMP-9 through the activation of TNFR–ERK 1/2 signaling pathways as well as the involvement of c-Fos and nuclear factor kappa B (NF-κB) signaling pathways. Based on our findings, Lj-EtOH exhibits a preventive effect on human gastric epithelial cells. Consequently, it may represent a novel treatment for the management of gastric inflammation.

Background: Central venous catheterization (CVC) is a critical clinical procedure. To avoid complications, possessing good knowledge regarding the CVC care bundle and skills for the proper insertion and maintenance of CVC are important. Objectives: To evaluate the effectiveness of an educational intervention and the use of an interactive response system in enhancing the CVC bundle care and insertion skills of medical students undergoing critical care medicine training. Materials and Methods: Sixth-year medical students (equivalent to fourth-year students in the United States) engaged in didactic lessons, interactive demonstrations, and simulator training facilitated by a CVC team comprising three thoracic and two vascular surgeons (all with a minimum 5 years of experience in central venous access) during their intensive care unit (ICU) rotation. Self-reported knowledge and confidence levels were assessed using pre-and posttests administered through the Zuvio App, an interactive response system. Results: A total of 60 students underwent the educational intervention, of which 54 completed the pretest and 40 completed the posttest. In the posttest, significant improvement was found in the CVC bundle care competency and understanding (P = 0.002), preprocedural preparation (P = 0.002), insertion procedures (P = 0.004), complications (P = 0.003), and insertion depth decisions (P = 0.001). Staff and students reported that assessment and interaction via the Zuvio App were valuable, practical, and feasible in a clinical setting, providing trainees with an individual competency portfolio of receiving precise medical education. Conclusions: Integrating the training provided by a specialized team with an interactive response system enhanced the knowledge and competency level in CVC insertion among medical students in this study.

Background: Microbiota manipulation through preoperative probiotic supplementation to reduce surgical site infection has shown promising results in recent years. However, the changes in gut microbiota resulting from this manipulation remain unclear. In eastern Asia, Clostridium butyricum (CBM588) has been demonstrated to have antimicrobial ability. This study aimed to explore postoperative outcomes associated with microbiota changes in a murine colonic anastomosis model. Materials and Methods: C57BL/6 mice were divided into four groups. All mice, including group A as the control, received standard oral neomycin and metronidazole before surgery. Group B received CBM588 before surgery. Group C received the antibiotic cocktail therapy before surgery. Group D received the antibiotic cocktail therapy followed by CBM588 supplementation before surgery. A 16S rRNA amplicon with SMS was used to show the impact of different treatments on the murine gut microbiota. Results: The implementation of the antibiotic cocktail therapy resulted in improved postoperative performance, significantly better anastomotic healing scores, and reduced areas of anastomotic necrosis in both group C and D, but particularly prominently in group D. Metagenomic analysis revealed that group D was enriched with the order Clostridiales, the family Clostridiaceae, and the genus Clostridium, with low bacterial diversity and distinct bacterial composition. Conclusions: A preoperative antibiotic cocktail therapy followed by CBM588 supplementation modulates bacterial diversity and composition, resulting in an increased percentage of Clostridiaceae in a murine colonic anastomosis model. The associated outcomes include lower intra-abdominal adhesion scores, improved postoperative performance, improved anastomotic healing scores, and reduced areas of anastomotic necrosis.

Background: Advanced non-small-cell lung cancer (NSCLC) can be treated with novel targeted therapies that are tailored to the genetic characteristics of malignancy. While tissue-based genomic testing is considered the gold standard for the detection of oncogenic driver mutations, several challenges like inadequate tissue availability, the invasiveness of procuring tumors, and prolonged turnaround time of analysis are encountered. Considering these limitations, guidelines have recognized liquid biopsies using circulating cell-free DNA (cfDNA) as a useful tool to complement conventional tissue testing. Even though cfDNA next-generation sequencing (NGS) can have high sensitivity and specificity, optimal patient benefit requires the interpretation of the molecular profiling results in the context of clinical and diagnostic features to achieve the best outcomes. Case Descriptions: In this case series, we present six patients with advanced NSCLC whose plasma or tissue biopsy samples were analyzed with commercially available comprehensive NGS assays that elucidate the role of testing at various time points in the treatment journey. In all six cases, comprehensive genomic profiling (CGP) provided clinically useful information to guide treatment decisions. Conclusion: Adding to the existing real-world evidence, this case series reinforces that CGP-driven treatment strategies in advanced NSCLC, coupled with other available clinical information, can optimize treatment decisions.

This study introduces a novel approach for analyzing thin film interference spectra by employing a micro-spectrometer equipped with a spectral chip. Focusing on zinc oxide (ZnO) thin films prepared via the sol–gel method, this research aims to explore the films’ physical properties through spectral analysis. After obtaining the interference spectrum of the ZnO thin films, the peak positions within the spectrum were cataloged. Mathematical simulation was used to adjust the refractive index and thickness of the films to match the simulated interference peak positions with the observed peak positions. The thickness of the prepared ZnO film was estimated to be 4.9 μm and its refractive index at 80 °C was estimated to be 1.96. In addition, the measurement system was used to detect environmental changes, including temperature changes and gas exposure. It was observed that the optical characteristics of ZnO films exhibit marked variations with temperature shifts, enabling the establishment of a temperature calibration curve based on spectral feature displacement. In addition, experiments using a variety of gases showed that NO2 and gaseous isopropanol significantly affect the interference spectrum of ZnO, with the peak of the interference spectrum shifted by 2.3 nm and 5.2 nm, respectively, after injection of the two gases. This indicates that interferometric spectroscopy can serve as an effective tool for ZnO monitoring, capable of selectively detecting specific gases.

Background: Diagnosing peripheral pulmonary lesions using a traditional bronchoscope is difficult. Reports on the learning experience for Veran's SPiN electromagnetic navigation bronchoscopy (ENB) for the diagnosis of pulmonary lesions are limited. Aim: We aimed to evaluate the skills developed by trainees who underwent Veran ENB learning in a clinical setting. Methods: We retrospectively examined the data of patients who had undergone Veran ENB to guide instruments through the airways to a target lesion for biopsy or localization from November 2019 to March 2022. Results: In total, 23 patients, including 16 with solid lesions (69.6%), 4 with pure ground-glass opacity (17.4%), and 3 with mixed (13.0%) were included. The median largest diameter of the pulmonary lesions was 2.7 ± 1.8 cm, whereas the median distance from the pleural surface to the edge of the pulmonary lesion in its shortest path was 1.9 ± 1.6 cm. Most lesions in this cohort had a positive air bronchus sign (69.6%). The mean procedure time for a young thoracic surgeon was longer after 10 cases of operation (45.6 ± 13.4 vs. 33.8 ± 9.2 min, P = 0.027). There were no complications reported related to the procedure. Conclusion: ENB is a safe and less invasive method for tissue diagnosis or preoperative localization for patients with pulmonary lesions. However, a young thoracic surgeon in the learning process requires more time to perform ENB. This study provides basic information about the learning experience of trainees while performing the ENB procedure.

Abstract Serious blunt chest trauma usually induces hemothorax, pneumothorax, and rib fractures. More studies have claimed that early video-assisted thoracoscopic surgery with surgical stabilization of rib fractures (SSRF) results in a good prognosis in patients with major trauma. This study aimed to verify the outcomes in patients with chest trauma whether SSRF was performed. Consecutive patients who were treated in a medical center in Taiwan, for traumatic events between January 2015 and June 2020, were retrospectively reviewed. This study focused on patients with major trauma and thoracic injuries, and they were divided into groups based on whether they received SSRF. We used electrical impedance tomography (EIT) to evaluate the change of ventilation conditions. Different scores used for the evaluation of trauma severity were also compared in this study. Among the 8396 patients who were included, 1529 (18.21%) had major trauma with injury severity score > 16 and were admitted to the intensive care unit initially. A total of 596 patients with chest trauma were admitted, of whom 519 (87%) survived. Younger age and a lower trauma score (including injury severity scale, new injury severity score, trauma and injury severity score, and revised trauma score) account for better survival rates. Moreover, 74 patients received SSRF. They had a shorter intensive care unit (ICU) stay (5.24, p = 0.045) and better performance in electrical impedance tomography (23.46, p

Abstract Acne is a dermatologic disease with a strong pathologic association with human commensal Cutibacterium acnes. Conspicuously, certain C. acnes phylotypes are associated with acne, whereas others are associated with healthy skin. Here we investigate if the evolution of a C. acnes enzyme contributes to health or acne. Two hyaluronidase variants exclusively expressed by C. acnes strains, HylA and HylB, demonstrate remarkable clinical correlation with acne or health. We show that HylA is strongly pro-inflammatory, and HylB is modestly anti-inflammatory in a murine (female) acne model. Structural and phylogenic studies suggest that the enzymes evolved from a common hyaluronidase that acquired distinct enzymatic activity. Health-associated HylB degrades hyaluronic acid (HA) exclusively to HA disaccharides leading to reduced inflammation, whereas HylA generates large-sized HA fragments that drive robust TLR2-dependent pathology. Replacing an amino acid, Serine to Glycine near the HylA catalytic site enhances the enzymatic activity of HylA and produces an HA degradation pattern intermediate to HylA and HylB. Selective targeting of HylA using peptide vaccine or inhibitors alleviates acne pathology. We suggest that the functional divergence of HylA and HylB is a major driving force behind C. acnes health- and acne- phenotype and propose targeting of HylA as an approach for acne therapy.

Information sharing on social media has become a common practice for people around the world. Since it is difficult to check user-generated content on social media, huge amounts of rumors and misinformation are being spread with authentic information. On the one hand, most of the social platforms identify rumors through manual fact-checking, which is very inefficient. On the other hand, with an emerging form of misinformation that contains inconsistent image–text pairs, it would be beneficial if we could compare the meaning of multimodal content within the same post for detecting image–text inconsistency. In this paper, we propose a novel approach to misinformation detection by multimodal feature fusion with transformers and credibility assessment with self-attention-based Bi-RNN networks. Firstly, captions are derived from images using an image captioning module to obtain their semantic descriptions. These are compared with surrounding text by fine-tuning transformers for consistency check in semantics. Then, to further aggregate sentiment features into text representation, we fine-tune a separate transformer for text sentiment classification, where the output is concatenated to augment text embeddings. Finally, Multi-Cell Bi-GRUs with self-attention are used to train the credibility assessment model for misinformation detection. From the experimental results on tweets, the best performance with an accuracy of 0.904 and an F1-score of 0.921 can be obtained when applying feature fusion of augmented embeddings with sentiment classification results. This shows the potential of the innovative way of applying transformers in our proposed approach to misinformation detection. Further investigation is needed to validate the performance on various types of multimodal discrepancies.

Abstract Introduction The complexity of the human papilloma virus (HPV)-host interaction, along with dense cervical cancer screening guidelines, hampers students' easy learning of the subject. This online learning module intends to provide a comprehensive overview of HPV infection to help students better understand the rationale behind the screening protocol. The content of this module summarizes key concepts such as viral structure and replication, human immune-defense, immunization strategy, pathogenesis of cervical pre-cancer and cancer, and finally, prevention and management strategy of HPV infection in gynecologic patients. The target audience will be primarily third-year medical students rotating through their OB-GYN clerkship. Methods The module takes advantage of the audio-visual effects to maximize student learning. It is organized in sessions of subtopics with core text, embedded images, illustrations, and recorded voice-over script. In addition, there is a video at the end of the module which simulates a patient encounter in a doctor's office to discuss cervical cancer screening and management. Pre- and posttest questions help the viewer keep track of their progress upon completion. Results Since making the online module active in November 2009, we have collected 19 evaluations from third-year OB-GYN clerkship medical students who have completed the module. The evaluation measures the module's effectiveness to the participant's learning. Of the 19 evaluations, 61% said the module matched very well or well to their learning needs, 24% said that it matched satisfactorily to their needs, and 15% said that the module didn't match at all to their learning needs. Of the 19 evaluations, 78% said the module was extremely clear, 10% said it was not at all clear, 42% said the module was an extremely effective way to teach the subject, and 10% said it was not at all an effective way. Discussion Based on the comments, this probably is a reflection of well-taught concepts on viral structure and immunology during the first and second year of the students' curriculum. However, it was not our intention to present an in-depth review of immunology but rather to present a brief introduction to help students better understand the clinical implication of HPV infection.

Abstract Objectives Tyrosine kinase inhibitors (TKIs) are the primary therapeutic option for patients with advanced-stage epidermal growth factor receptor-mutant (EGFR-m) lung adenocarcinoma. However, the role of EGFR-TKIs in advanced-stage lung cancer is uncertain regardless of therapeutic methods. This study investigated the outcome of the impact of epidermal growth factor receptor (EGFR)-TKI in patients with advanced lung adenocarcinoma treated with various therapeutic strategies. Methods This retrospective analysis used cancer registry data from 1159 patients with lung cancer treated between January 2015 and December 2017 at Tri-Service General Hospital. Only patients with lung adenocarcinoma stages 3B and four were selected for the study. All lung adenocarcinoma patients with ever TKI treatment had an EGFR mutation. Results Three-hundred sixty-two patients with advanced lung adenocarcinoma with complete medical records were enrolled. According to personalized therapeutic processes, they were divided into nine groups: only TKI treatment, only chemotherapy (CT), TKI with lung cancer salvage surgery, TKI with CT, TKI with radiotherapy (RT), CT with lung cancer salvage surgery, CT with RT, TKI with CT, and lung cancer salvage surgery. A multivariate Cox regression analysis showed TKI with lung cancer salvage surgery (HR: 4.675, p = 0.005) is the only good prognostic treatment. The poor predictors for overall survival were only CT (HR: 0.336, p = 0.048) and TKI with CT (HR: 0.359, p = 0.023). Kaplan–Meier survival analysis showed a statistical significance in an average overall survival (OS) of ever TKI treatment and never TKI treatment (33.24 vs. 17.64 months, p

Details of the design and operational status of the silicon-nitride-based entrance slit installed in the Taiwan Photon Source (TPS) 45A beamline are given. The slit is a diamond blade edge etched onto a copper slit part, which is in thermal contact with the silicon nitride base. A stable slit opening smaller than 4 µm is achieved in TPS 45A. The beam size at the slit has a full width at half-maximum of 3 µm in the vertical direction with a power of 20 W. Additionally, a hard stop made of invar is incorporated to control the thermal expansion displacement. The slit reduces the size and increases the stability of the source of the monochromator. Consequently, a higher energy resolution and excellent beamline stability are achieved.

Background/Purpose: No studies have compared between uniportal and multiportal nonintubated thoracoscopic anatomical resection for non-small cell lung cancer (NSCLC). We aimed to compare short- and long-term postoperative outcomes concerning these two methods. Methods: Our retrospective dataset comprised patients with NSCLC who underwent uniportal or multiportal nonintubated thoracoscopic anatomical resection between January 2011 and December 2019. The primary outcome was recurrence-free survival. Propensity scores were matched according to age, sex, body mass index, pulmonary function, tumor size, cancer stage, and surgical method. Results: In total, 1130 such patients underwent nonintubated video-assisted thoracoscopic surgery (VATS), and 490 consecutive patients with stage I–III NSCLC underwent nonintubated anatomical resection, including lobectomy and segmentectomy (uniportal, n = 158 [32.3%]; multiportal, n = 331 [67.7%]). The uniportal group had fewer dissected lymph nodes and lymph node stations. In paired group analysis, the uniportal group had shorter operation durations (99.8 vs. 138.2 min; P

Acute respiratory distress syndrome (ARDS) is a critical illness in critically unwell patients, characterized by refractory hypoxemia and shock. This study evaluates an early detection tool and investigates the relationship between hypoxia and circulatory shock in ARDS, to improve diagnostic precision and therapy customization. We used a porcine model, inducing ARDS with mechanical ventilation and intratracheal plus intravenous lipopolysaccharide (LPS) injection. Hemodynamic changes were monitored using an Acumen IQ sensor and a ForeSight Elite sensor connected to the HemoSphere platform. We evaluated tissue damage, inflammatory response, and hypoxia-inducible factor (HIF) alterations using enzyme-linked immunosorbent assay and immunohistochemistry. The results showed severe hypotension and increased heart rates post-LPS exposure, with a notable rise in the hypotension prediction index (HPI) during acute lung injury (p = 0.024). Tissue oxygen saturation dropped considerably in the right brain region. Interestingly, post-injury HIF-2α levels were lower at the end of the experiment. Our findings imply that the HPI can effectively predict ARDS-related hypotension. HIF expression levels may serve as possible markers of rapid ARDS progression. Further research should be conducted on the clinical value of this novel approach in critical care, as well as the relationship between the HIF pathway and ARDS-associated hypotension.

Background: This study investigated the mechanism by which tazarotene-induced gene 1 (TIG1) inhibits melanoma cell growth. The main focus was to analyze downstream genes regulated by TIG1 in melanoma cells and its impact on cell growth. Methods: The effects of TIG1 expression on cell viability and death were assessed using water-soluble tetrazolium 1 (WST-1) mitochondrial staining and lactate dehydrogenase release assays. RNA sequencing and Western blot analysis were employed to investigate the genes regulated by TIG1 in melanoma cells. Additionally, the correlation between TIG1 expression and its downstream genes was analyzed in a melanoma tissue array. Results: TIG1 expression in melanoma cells was associated with decreased cell viability and increased cell death. RNA-sequencing (RNA-seq), quantitative reverse transcription PCR (reverse RT-QPCR), and immunoblots revealed that TIG1 expression induced the expression of Endoplasmic Reticulum (ER) stress response-related genes such as Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 (HERPUD1), Binding immunoglobulin protein (BIP), and DNA damage-inducible transcript 3 (DDIT3). Furthermore, analysis of the melanoma tissue array revealed a positive correlation between TIG1 expression and the expression of HERPUD1, BIP, and DDIT3. Additionally, attenuation of the ER stress response in melanoma cells weakened the impact of TIG1 on cell growth. Conclusions: TIG1 expression effectively hinders the growth of melanoma cells. TIG1 induces the upregulation of ER stress response-related genes, leading to an increase in caspase-3 activity and subsequent cell death. These findings suggest that the ability of retinoic acid to prevent melanoma formation may be associated with the anticancer effect of TIG1.

Abstract Background Acanthamoeba castellanii is a free-living protist that feeds on diverse bacteria. A. castellanii has frequently been utilized in studies on microbial interactions. Grazing bacteria also exhibit diverse effects on the physiological characteristics of amoebae, such as their growth, encystation, and cytotoxicity. Since the composition of amoebae amino acids is closely related to cellular activities, it can indicate the overall responses of A. castellanii to various stimuli. Method A. castellanii was exposed to different culture conditions in low-nutrient medium with heat-killed DH5α to clarify their effects. A targeted metabolomic technique was utilized to evaluate the concentration of cellular amino acids. The amino acid composition and pathways were analyzed by two web-based tools: MetaboAnalyst and Pathview. Then, long-term exposure to A. castellanii was investigated through in silico and in vitro methods to elucidate the homeostasis of amino acids and the growth of A. castellanii. Results Under short-term exposure, all kinds of amino acids were enriched in all exposed groups. In contrast to the presence of heat-killed bacteria, the medium exhibited obvious effects on the amino acid composition of A. castellanii. After long-term exposure, the amino acid composition was more similar to that of the control group. A. castellanii may achieve amino acid homeostasis through pathways related to alanine, aspartate, citrulline, and serine. Discussion Under short-term exposure, compared to the presence of bacteria, the type of medium exerted a more powerful effect on the amino acid composition of the amoeba. Previous studies focused on the interaction of the amoeba and bacteria with effective secretion systems and effectors. This may have caused the effects of low-nutrient environments to be overlooked. Conclusion When A. castellanii was stimulated in the coculture system through various methods, such as the presence of bacteria and a low-nutrient environment, it accumulated intracellular amino acids within a short period. However, different stimulations correspond to different amino acid compositions. After long-term exposure, A. castellanii achieved an amino acid equilibrium by downregulating the biosynthesis of several amino acids.

ABSTRACTThe iron-regulated surface determinant protein B (IsdB) of Staphylococcus aureus is involved in the acquisition of iron from hemoglobin. Moreover, IsdB elicits an adaptive immune response in mice and humans. Here, we show that IsdB also has impact on innate immunity. IsdB induces the release of proinflammatory cytokines, including IL-6 and IL-1β, in innate immune cells of humans and mice. In silico analysis and thermophoresis show that IsdB directly binds to TLR4 with high affinity. TLR4 sensing was essential for the IsdB-mediated production of IL-6, IL-1β, and other cytokines as it was abolished by blocking of TLR4-MyD88-IRAK1/4-NF-κB signaling. The release of IL-1β additionally required activation of the NLRP3 inflammasome. In human monocytes infected with live S. aureus, IsdB was necessary for maximal IL-1β release. Our studies identify S. aureus IsdB as a novel pathogen-associated molecular pattern that triggers innate immune defense mechanisms.IMPORTANCEThe prevalence of multidrug-resistant Staphylococcus aureus is of global concern, and vaccines are urgently needed. The iron-regulated surface determinant protein B (IsdB) of S. aureus was investigated as a vaccine candidate because of its essential role in bacterial iron acquisition but failed in clinical trials despite strong immunogenicity. Here, we reveal an unexpected second function for IsdB in pathogen-host interaction: the bacterial fitness factor IsdB triggers a strong inflammatory response in innate immune cells via Toll-like receptor 4 and the inflammasome, thus acting as a novel pathogen-associated molecular pattern of S. aureus. Our discovery contributes to a better understanding of how S. aureus modulates the immune response, which is necessary for vaccine development against the sophisticated pathogen.

A solid-state semiconductor battery with the n-type WO3/silica-coated TiO2 core–shell nanoparticles/p-type NiO laminated structure for the rechargeable device has been developed. The electricity storage layer comprises poly-acrylonitrile mixed with core–shell nanoparticles containing n-type TiO2 particles coated with an insulating SiO2 shell. The average diameter size of nanoparticles was determined from 20 to 50 nm by a high-resolution transmission electron microscope and the relative atomic weight percentage of the Si on the coated TiO2 nanoparticles had been qualitatively determined by the energy dispersive spectrometer. The silica-coated TiO2 nanoparticles in the composite were assigned to the mixed phases of Anatase and Rutile by XRD analysis. Furthermore, photoluminescence analysis has verified the energy levels present in the bandgap of the silica-coated TiO2 core–shell nanoparticles. The device exhibits a constant-current discharge capacity of 0.16 mA h at a discharge voltage of 2.46 V. The energy density of the charging layer has been estimated to 12.3 Wh/kg. Finally, a mechanism of the solid-state semiconductor battery has also been proposed.

Abstract Background The poor outcome of patients with lung squamous cell carcinoma (LUSC) highlights the importance of the identification of novel effective prognostic markers and therapeutic targets. Long noncoding RNAs (lncRNAs) have generally been considered to serve important roles in tumorigenesis and the development of various types of cancer, including LUSC. Methods Here, we aimed to investigate the role of LINC02323 in LUSC and its potential mechanisms by performing comprehensive bioinformatic analyses. Results LINC02323 was elevated and positively associated with unfavorable prognosis of LUSC patients. LINC02323 exerted oncogenic function by competitively binding to miR‐1343‐3p and miR‐6783‐3p, thereby upregulating L1CAM expression. Indeed, we also determined that LINC02323 could interact with the RNA‐binding protein DDX3X, which regulates various stages of RNA expression and processing. Conclusion Taken together, we identified that LINC02323 and its indirect target L1CAM can act as novel biomarkers for determining the prognosis of patients with LUSC and thus deserves further study.

ABSTRACT Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a major public health threat globally, especially during the beginning of the pandemic in 2020. Reverse transcription-quantitative PCR (RT-qPCR) is utilized for viral RNA detection as part of control measures to limit the spread of COVID-19. Collecting nasopharyngeal swabs for RT-qPCR is a routine diagnostic method for COVID-19 in clinical settings, but its large-scale implementation is hindered by a shortage of trained health professionals. Despite concerns over its sensitivity, saliva has been suggested as a practical alternative sampling approach to the nasopharyngeal swab for viral RNA detection. In this study, we spiked saliva from healthy donors with inactivated SARS-CoV-2 from an international standard to evaluate the effect of saliva on viral RNA detection. On average, the saliva increased the cycle threshold (CT) values of the SARS-CoV-2 RNA samples by 2.64 compared to the viral RNA in viral transport medium. Despite substantial variation among different donors in the effect of saliva on RNA quantification, the outcome of the RT-qPCR diagnosis was largely unaffected for viral RNA samples with CT values of

Matrix metalloproteinases (MMPs), which are proteolytic enzymes, promote blood–brain barrier (BBB) disruption, leading to neuronal damage and neuroinflammation. Among them, MMP-9 upregulation serves as an inflammatory biomarker in the central nervous system (CNS). Currently, the development of marine organism-derived bioactive compounds or metabolites as anti-inflammatory drugs has received considerable attention. The 9,11-secosteroid, 3β,11-dihydroxy-9,11-secogorgost-5-en-9-one (4p3f), is a novel sterol compound extracted from the soft coral Sinularia leptoclado with potential anti-inflammatory activity. However, the effect of and potential for brain protection of 4p3f on brain astrocytes remain unclear. Herein, we used rat brain astrocytes (RBAs) to investigate the effects and signaling mechanisms of 4p3f on lipopolysaccharide (LPS)-induced MMP-9 expression via zymographic, quantitative reverse transcription–polymerase chain reaction (qRT-PCR), Western blot, immunofluorescence staining, promoter–reporter, and cell migration analyses. We first found that 4p3f blocked LPS-induced MMP-9 expression in RBAs. Next, we demonstrated that LPS induced MMP-9 expression via the activation of ERK1/2, p38 MAPK, and JNK1/2, which is linked to the STAT3-mediated NF-κB signaling pathway. Finally, 4p3f effectively inhibited LPS-induced upregulation of MMP-9-triggered RBA cell migration. These data suggest that a novel sterol from soft coral, 4p3f, may have anti-inflammatory and brain-protective effects by attenuating these signaling pathways of MMP-9-mediated events in brain astrocytes. Accordingly, the soft coral-derived sterol 4p3f may emerge as a potential candidate for drug development or as a natural compound with neuroprotective properties.

Abstract Background With the continuous emergence of new SARS-CoV-2 variants that feature increased transmission and immune escape, there is an urgent demand for a better vaccine design that will provide broader neutralizing efficacy. Methods We report an mRNA-based vaccine using an engineered “hybrid” receptor binding domain (RBD) that contains all 16 point-mutations shown in the currently prevailing Omicron and Delta variants. Results A booster dose of hybrid vaccine in mice previously immunized with wild-type RBD vaccine induced high titers of broadly neutralizing antibodies against all tested SARS-CoV-2 variants of concern (VOCs). In naïve mice, hybrid vaccine generated strong Omicron-specific neutralizing antibodies as well as low but significant titers against other VOCs. Hybrid vaccine also elicited CD8+/IFN-γ+ T cell responses against a conserved T cell epitope present in wild type and all VOCs. Conclusions These results demonstrate that inclusion of different antigenic mutations from various SARS-CoV-2 variants is a feasible approach to develop cross-protective vaccines.

Abstract Meridians constitute the theoretical foundation of acupuncture in traditional Chinese medicine (TCM), and they have been described for 2000 years. Classical TCM advocates for the directionality of meridians. Finding an accurate method to verify this directionality is an important goal of TCM doctors and researchers. In this study, we objectively explored the physical properties of meridians, such as response current from electrical stimulation, to explore their directionality. The Agilent B1500A semiconductor measurement analyzer was utilized to input the alternating current waveforms and detect the response current on the meridians. The results showed that the direction of the meridians influences the intensity of the response current. Therefore, the mechanisms behind the directions of ion transportation and the meridians were investigated using the response time and the intensity of the response current. Thereafter, we propose a model to explain this mechanism. Afterward, a comparison between the direction of the meridian in this experiment and ancient Chinese medicine classics was performed.

Abstract Purpose This study aimed to determine the pathological complete response (pCR), overall survival (OS), and disease-free survival (DFS) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) using post-neoadjuvant chemoradiotherapy (nCRT) F-18-fluorodeoxyglucose (18FDG). Methods This is a retrospective study of patients with locally advanced ESCC receiving nCRT and then esophagectomy between January 2011 and December 2018 in the Tri-Service General Hospital, Taipei, Taiwan. A total of 50 patients were enrolled in the study. Survival analysis was performed using the Kaplan–Meier method and Cox proportional hazards model. Univariate and multivariate analysis were used to determine the independent prognostic factors. Results Fifty patients were enrolled in the study, and 18 had pathological complete response. Post-nCRT SUVmax ≥ 3 is a poor prognostic factor associated with overall survival (HR: 3.665, P = 0.013) and disease-free survival (HR: 3.417, P = 0.011). Poor prognosis was found in the non-pCR plus post-nCRT SUVmax ≥ 3 group compared with pCR plus post-nCRT SUVmax

Abstract A method of using non‐volatile and fast ferroelectric field‐effect transistor (FeFET) devices to realize Boolean logic is proposed. First, the internal states are initialized. Then, the gate and body function as input terminals, which are used to write the states of the device, based on the voltage. Finally, the output signals can be easily read through the drain current. Of the 10 Institute of Electrical and Electronics Engineers (IEEE) standard logic gates, eight can be implemented using the proposed operation method alone and by following the definitions listed herein. Thus, to enable FeFET devices to act as functional logic gates, a simple operating method is proposed, providing substantial contributions to the development of computing in memory. The experimental results provide evidence of the efficacy of this method.

IntroductionAnaplastic lymphoma kinase (ALK) fusion mutation is more common in younger and never-smoking lung cancer patients. The association of smoking and ALK-tyrosine kinase inhibitors (TKIs) on overall survival (OS) of treatment-naïve ALK-positive advanced lung adenocarcinoma remains unclear in real-world.MethodsThis retrospective study evaluated all 33170 lung adenocarcinoma patients registered in the National Taiwan Cancer Registry from 2017 to 2019, of whom 9575 advanced stage patients had ALK mutation data.ResultsAmong the 9575 patients, 650 (6.8%) patients had ALK mutation with the median follow-up survival time 30.97 months (median age, 62 years; 125 [19.2%] were aged ≥75 years; 357 (54.9%) females; 179 (27.5) smokers, 461 (70.9%) never-smokers, 10 (1.5%) with unknown smoking status; and 544 (83.7%) with first-line ALK-TKI treatment). Overall, of 535 patients with known smoking status who received first-line ALK-TKI treatment, never-smokers and smokers had a median OS of 40.7 months (95% confidence interval (CI), 33.1-47.2 months) and 23.5 months (95% CI, 11.5-35.5 months) (P=0.015), respectively. Among never-smokers, those who received first-line ALK-TKI treatment had a median OS of 40.7 months (95% CI, 22.7-57.8 months), while those ALK-TKI not as first-line treatment had a median OS of 31.7 months (95% CI, 15.2-42.8 months) (P=0.23). In smokers, the median OS for these patients was 23.5 months (95% CI, 11.5-35.5 months) and 15.6 months (95% CI, 10.2-21.1 months) (P=0.026), respectively.Conclusions and relevanceFor patients with treatment-naïve advanced lung adenocarcinoma, the ALK test should be performed irrespective of smoking status and age. Smokers had shorter median OS than never-smokers among treatment-naïve-ALK-positive patients with first-line ALK-TKI treatment. Furthermore, smokers not receiving first-line ALK-TKI treatment had inferior OS. Further investigations for the first-line treatment of ALK-positive smoking advanced lung adenocarcinoma patients are needed.

Process Capability Indices (PCIs) are devices widely used in the industry to evaluate process quality. The commonly used process capability indices all contain accuracy indices and precision indices. As the accuracy index is closer to zero, the process accuracy is higher. The precision index mainly represents the extent of process variation. As the value is smaller, the process variation is smaller, that is, the precision is higher. In fact, process capability indices are the functions of accuracy indices and precision indices. Obviously, as long as accuracy indices and precision indices are controlled, the process capability indices can be controlled as well. Therefore, this study first derived accuracy and precision control charts to observe not only process accuracy but also process precision. Then, this study adopted in-control data to acquire a 100 (1 − α)% confidence region of an accuracy index and a precision index, with which statistical tests were performed. Subsequently, according to the definition of the six sigma quality level, both indices were examined. Furthermore, based on the testing results, suggestions for process improvement were proposed, including correcting the direction of process deviation and deciding whether to reduce process variation. Finally, this study demonstrated the applicability of the proposed model using an empirical example.

Background: Epidermal growth factor receptor (EGFR) gene mutation is a known predictor of the response to EGFR tyrosine kinase inhibitors. However, detecting EGFR mutations is a potential challenge because of the ground-glass opacity component, and its prognostic value for stage IA lung adenocarcinoma remains controversial. This study aimed to investigate the associations between EGFR mutation status, clinicopathological characteristics, and prognosis in surgically resected stage IA non-small cell lung cancer (NSCLC). Materials and Methods: We retrospectively examined the data of patients who underwent surgical resection for lung cancer between 2004 and 2014. The clinical data, imaging characteristics of nodules, surgical approaches, and outcomes were analyzed. Results: A total of 429 patients (female, n = 303; male, n = 126) with surgically resected stage IA NSCLC were analyzed and 343 were nonsmokers. The EGFR mutation rate was 48.3% (n = 207). Of the patients, 192 (44.8%) had stage IA1, 165 (38.5%) had stage IA2, and 72 (16.8%) had stage IA3 NSCLC. In the analysis of the correlations between clinicopathological features and EGFR status, older age (P = 0.032), nonsmoking history (P = 0.039), and pathological stage (P < 0.05) were related to EGFR mutation. Patients with stage IA2 NSCLC had a higher positive expression of EGFR than patients with stages IA1 and IA3. The 5-year overall survival rates and disease-free survival rates were better in the EGFR mutation group; however, the difference was not statistically significant. Conclusion: EGFR mutations are common in older and nonsmoking patients with stage IA NSCLC. Further separate analyses of EGFR gene mutations and pathological stage could improve the diagnostic performance and predict patients with unavailable EGFR gene testing who may benefit from targeted drug treatment.

Objectives: Circulating microRNAs (miRNAs) have been discovered to play a novel role in intercellular communication and cancer biology. They are emerging candidates for noninvasive molecular biomarkers of cancer and other diseases. However, current translational researches have been limited by the lack of consensus on the optimal endogenous control of circulating miRNAs quantitation. In this study, we compared two promising miRNAs, miR-1228 and miR-16, as an endogenous control. The effects of normalizers on the relative quantification of circulating miR-31 in plasma samples of colorectal cancer (CRC) were also assessed. Materials and Methods: The cel-miR-39 was a spiked-in RNA used as an external control and added to plasma samples before RNA extraction. Quantitative real-time polymerase chain reaction technology was used to analyze the expression levels of circulating miRNAs in plasma samples of 4 healthy controls and 14 CRC patients. The expression stability of the candidate controls was compared by Ct analysis and NormFinder algorithms. Results: There was no significant difference in expression level of miR-16 and miR-1228 between healthy control group and before or after therapy of CRC patient groups. The expression of miR-1228 has smaller the range Ct values (28.25-25.64) compared with those of miR-16 (24.91-20.34). The stability value of miR-1228 (0.102) is lower than that of miR-16 (0.350). The expression of miR-1228 endogenous reference candidate has lower stability value and smaller the range Ct values compared with those in miR-16. According to the range Ct values and stability value, miR-1228 is better than miR-16 as endogenous control in CRC patients. There are significant differences in circulating miR-31 expression between healthy control and CRC patients when miR-1228 was used to standardize miR-31 expression. Conclusions: miR-1228 is recommended as a better endogenous control in quantification of circulating miRNAs in CRC patients.