Early detection of low QRS voltage and its association with mortality in patients with sepsis.

Various electrocardiographic changes occur during sepsis, but data on the clinical importance of a low QRS voltage in sepsis are still limited. We aimed to evaluate the association between low QRS voltage identified early in sepsis and mortality in patients with sepsis. Between September 2019 and December 2020, all consecutive adult patients diagnosed with sepsis in the emergency room or general ward at Samsung Medical Center were enrolled. Patients without a 12-lead electrocardiogram recorded within 48 h of recognition of sepsis were excluded. In 432 eligible patients, 12-lead electrocardiogram was recorded within the median of 24 min from the first recognition of sepsis, and low QRS voltage was identified in 115 (26.6%) patients. The low QRS group showed more severe organ dysfunction and had higher levels of N-terminal pro-brain natriuretic peptide. The hospital mortality was significantly higher in the low QRS voltage group than in the normal QRS voltage group (49.6% vs. 28.1%, p < 0.001). Similarly, among the 160 patients who required intensive care unit admission, significantly more patients in the low QRS group died in the intensive care unit (35.9% vs. 18.2%, p = 0.021). Low QRS voltage was associated with increased hospital mortality in patients with sepsis.

Chromosome-level genome assembly of Korean holoparasitic plants, Orobanche coerulescens.

Orobanche coerulescens is a parasitic plant that cannot complete its life cycle without a host and is incapable of photosynthesis. The habitats of O. coerulescens span the coasts of Korea and its volcanic islands, Ulleungdo and Dokdo. Those on the volcanic islands exhibit morphological differences and have distinct hosts compared to those on the peninsula. The family of Orobanchaceae, encompassing both autotrophic and parasitic species, serves as a model for evolutionary studies of parasitic states. However, there are limited genome assemblies for the Orobanche genus. In our study, we produced approximately 100x ONT long reads to construct a chromosome-level genome of O. coerulescens. The resulting assembly has a total size of 3,648 Mb with an N50 value of 195 Mb, and 82.0% of BUSCO genes were identified as complete. Results of the repeat annotation revealed that 86.3% of the genome consisted of repeat elements, and 29,395 protein-coding genes were annotated. This chromosome-level genome will be an important biological resource for conserving biodiversity and further understanding parasitic plants.

Physical loads on upper extremity muscles while interacting with virtual objects in an augmented reality context.

Augmented reality (AR) environments are emerging as prominent user interfaces and gathering significant attention. However, the associated physical strain on the users presents a considerable challenge. Within this background, this study explores the impact of movement distance (MD) and target-to-user distance (TTU) on the physical load during drag-and-drop (DND) tasks in an AR environment. To address this objective, a user experiment was conducted utilizing a 5× 5 within-subject design with MD (16, 32, 48, 64, and 80 cm) and TTU (40, 80, 120, 160, and 200 cm) as the variables. Physical load was assessed using normalized electromyography (NEMG) (%MVC) indicators of the upper extremity muscles and the physical item of NASA-Task load index (TLX). The results revealed significant variations in the physical load based on MD and TTU. Specifically, both the NEMG and subjective physical workload values increased with increasing MD. Moreover, NEMG increased with decreasing TTU, whereas the subjective physical workload scores increased with increasing TTU. Interaction effects of MD and TTU on NEMG were also significantly observed. These findings suggest that considering the MD and TTU when developing content for interacting with AR objects in AR environments could potentially alleviate user load.

Evaluation of Pre-Transfusion Crossmatch Test Using Microscanner C3.

A pre-transfusion crossmatch test is crucial for ensuring safe blood transfusions by identifying the compatibility between donor and recipient blood samples. Conventional tube methods for crossmatching have limitations, including subjectivity in result interpretation and the potential for human error. In this study, we evaluated the diagnostic performance of a new crossmatch test using Microscanner C3, which can overcome these shortcomings. The crossmatch test results using the method were obtained in 323 clinical samples. The sensitivity, specificity, positive predictive value, negative predictive value, and concordance rate of the crossmatch test using Microscanner C3 were 98.20%, 100.00%, 100.00%, 98.11%, and 99.07%, respectively. The diagnostic performance of the new system offers a promising alternative to conventional tube methods for pre-transfusion crossmatch testing. Microscanner C3 could also increase the automation, standardization, and accuracy of crossmatch tests. The crossmatch test using Microscanner C3 is thought to increase the efficiency and reliability in identifying blood samples suitable for transfusion, thereby improving patient safety and optimizing the use of blood products in clinical settings.

Protocol for in vitro co-culture assay for rapid expansion of human T cell acute lymphoblastic leukemia.

T cell acute lymphoblastic leukemia (T-ALL) is a rare but aggressive hematological cancer that occurs primarily in children and adolescents. Here, we present a protocol for in vitro co-culture assay that enables robust expansion of primary T-ALL cells. We describe steps for seeding T-ALL and stromal cells in 3D organoids and subsequent flow analysis to capture the T-ALL cell growth for long-term culture. This protocol provides a valuable platform for in vitro functional studies and drug screenings using patient-derived cells. For complete details on the use and execution of this protocol, please refer to Rivera et al.1.

Hand-held all-in-one (HAO) self-test kit for rapid and on-site detection of SARS-CoV-2 with colorimetric LAMP.

Throughout the COVID-19 pandemic, individuals potentially infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were forcibly recalled to local or central hospitals, where the diagnostic results were obtained a couple of days after the liquid biopsies were subjected to conventional polymerase chain reaction (PCR). This slow output of such a complex and time-consuming laboratory procedure hindered its widespread application. To overcome the limitations associated with such a centralized diagnostic system, we developed a hand-held and all-in-one type test kit in which the analytical results can be obtained in only 30 min. The test kit consists of three major steps for on-site SARS-CoV-2 RNA detection: 1) virus lysis by heat, 2) RNA enrichment by membrane, and 3) real-time detection by colorimetric loop-mediated isothermal amplification (c-LAMP). The proposed device operates in a sample-to-answer format, is fully automated, and reduces dependence on traditional laboratory settings, facilitating large-scale population screening.

Development and validation of an interpretable model for predicting sepsis mortality across care settings.

There are numerous prognostic predictive models for evaluating mortality risk, but current scoring models might not fully cater to sepsis patients' needs. This study developed and validated a new model for sepsis patients that is suitable for any care setting and accurately forecasts 28-day mortality. The derivation dataset, gathered from 20 hospitals between September 2019 and December 2021, contrasted with the validation dataset, collected from 15 hospitals from January 2022 to December 2022. In this study, 7436 patients were classified as members of the derivation dataset, and 2284 patients were classified as members of the validation dataset. The point system model emerged as the optimal model among the tested predictive models for foreseeing sepsis mortality. For community-acquired sepsis, the model's performance was satisfactory (derivation dataset AUC: 0.779, 95% CI 0.765-0.792; validation dataset AUC: 0.787, 95% CI 0.765-0.810). Similarly, for hospital-acquired sepsis, it performed well (derivation dataset AUC: 0.768, 95% CI 0.748-0.788; validation dataset AUC: 0.729, 95% CI 0.687-0.770). The calculator, accessible at https://avonlea76.shinyapps.io/shiny_app_up/ , is user-friendly and compatible. The new predictive model of sepsis mortality is user-friendly and satisfactorily forecasts 28-day mortality. Its versatility lies in its applicability to all patients, encompassing both community-acquired and hospital-acquired sepsis.

Expansion of tumor-infiltrating lymphocytes in non-small cell lung cancer: Clinical potential and efficacy in EGFR mutation subsets.

Our study aimed to expand tumor-infiltrating lymphocytes (TILs) from primary non-small cell lung cancers (NSCLCs) and evaluate their reactivity against tumor cells. We expanded TILs from 103 primary NSCLCs using histopathological analysis, flow cytometry, IFN-γ release assays, cell-mediated cytotoxicity assays, and in vivo efficacy tests. TIL expansion was observed in all cases, regardless of EGFR mutation status. There was also an increase in the median CD4+/CD8+ ratio during expansion. In post-rapid expansion protocol (REP) TILs, 13 out of 16 cases, including all three cases with EGFR mutations, exhibited a two-fold or greater increase in IFN-γ secretion. The cytotoxicity assay revealed enhanced tumor cell death in three of the seven cases, two of which had EGFR mutations. In vivo functional testing in a patient-derived xenograft model showed a reduction in tumor volume. The anti-tumor activity of post-REP TILs underscores their potential as a therapeutic option for advanced NSCLC, irrespective of mutation status.

Pepper SUMO protease CaDeSI2 positively modulates the drought responses via deSUMOylation of clade A PP2C CaAITP1.

Posttranslational modification of multiple ABA signaling components is an essential process for the adaptation and survival of plants under stress conditions. In our previous study, we established that the pepper group A PP2C protein CaAITP1, one of the core components of ABA signaling, undergoes ubiquitination mediated by the RING-type E3 ligase CaAIRE1. In this study, we discovered an additional form of regulation mediated via the SUMOylation of CaAITP1. Pepper plants subjected to drought stress were characterized by reductions in both the stability and SUMOylation of CaAITP1 protein. Moreover, we identified a SUMO protease, Capsicum annuum DeSUMOylating Isopeptidase 2 (CaDeSI2), as a new interacting partner of CaAITP1. In vitro and in vivo analyses revealed that CaAITP1 is deSUMOylated by CaDeSI2. Silencing of CaDeSI2 in pepper plants led to drought-hypersensitive and ABA-hyposensitive phenotypes, whereas overexpression of CaDeSI2 in transgenic Arabidopsis plants resulted in the opposite phenotypes. Importantly, we found that the CaAITP1 protein was stabilized in response to the silencing of CaDeSI2, and CaDeSI2 and CaAITP1 co-silenced pepper plants were characterized by drought-tolerant phenotypes similar to those observed in CaAITP1-silenced pepper. Collectively, our findings indicate that CaDeSI2 reduces the stability of CaAITP1 via deSUMOylation, thereby positively regulating drought tolerance.

Dynamic liver volume change in predicting hepatic decompensation and long-term effects of stereotactic body radiation therapy.

BACKGROUND AND AIM: This study aimed to investigate the association between liver volume change and hepatic decompensation and compare the risk of hepatic decompensation in patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC) who underwent stereotactic body radiation therapy (SBRT). METHODS: A retrospective review of SBRT-treated HCC and compensated LC without HCC patients was conducted. Liver volume was measured using auto-segmentation software on liver dynamic computed tomography scans. The decompensation event was defined as the first occurrence of refractory ascites, esophageal variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis. We evaluated the association between the rate of liver volume decrease and hepatic decompensation and compared decompensation events between the SBRT and LC cohorts using propensity score matching. RESULTS: A total of 138 patients from the SBRT cohort and 488 from the LC cohort were analyzed. The rate of liver volume decrease was associated with the risk of decompensation events in both cohorts. The 3-year rate of decompensation events was significantly higher in the group with a liver volume decreasing rate > 7%/year compared with the group with a rate < 7%/year. In the propensity score-matched cohort, the 3-year rate of decompensation events after a single session of SBRT was not significantly different from that in the LC cohort. CONCLUSIONS: The rate of liver volume decrease was significantly associated with the risk of hepatic decompensation in both HCC patients who received SBRT and LC patients. A single session of SBRT for HCC did not result in a higher decompensation rate compared with LC.

The development of hair follicles and nail.

The hair follicle and nail unit develop and regenerate through epithelial-mesenchymal interactions. Here, we review some of the key signals and molecular interactions that regulate mammalian hair follicle and nail formation during embryonic development and how these interactions are reutilized to promote their regeneration during adult homeostasis and in response to skin wounding. Finally, we highlight the role of some of these signals in mediating human hair follicle and nail conditions.

The association of arterial partial oxygen pressure with mortality in critically ill sepsis patients: a nationwide observational cohort study.

BACKGROUND: Although several trials were conducted to optimize the oxygenation range in intensive care unit (ICU) patients, no studies have yet reached a universal recommendation on the optimal a partial pressure of oxygen in arterial blood (PaO2) range in patients with sepsis. Our aim was to evaluate whether a relatively high arterial oxygen tension is associated with longer survival in sepsis patients compared with conservative arterial oxygen tension. METHODS: From the Korean Sepsis Alliance nationwide registry, patients treated with liberal PaO2 (PaO2 ≥ 80 mm Hg) were 1:1 matched with those treated with conservative PaO2 (PaO2 < 80 mm Hg) over the first three days after ICU admission according to the propensity score. The primary outcome was 28-day mortality. RESULTS: The median values of PaO2 over the first three ICU days in 1211 liberal and 1211 conservative PaO2 groups were, respectively, 107.2 (92.0-134.0) and 84.4 (71.2-112.0) in day 1110.0 (93.4-132.0) and 80.0 (71.0-100.0) in day 2, and 106.0 (91.9-127.4) and 78.0 (69.0-94.5) in day 3 (all p-values < 0.001). The liberal PaO2 group showed a lower likelihood of death at day 28 (14.9%; hazard ratio [HR], 0.79; 95% confidence interval [CI] 0.65-0.96; p-value = 0.017). ICU (HR, 0.80; 95% CI 0.67-0.96; p-value = 0.019) and hospital mortalities (HR, 0.84; 95% CI 0.73-0.97; p-value = 0.020) were lower in the liberal PaO2 group. On ICU days 2 (p-value = 0.007) and 3 (p-value < 0.001), but not ICU day 1, hyperoxia was associated with better prognosis compared with conservative oxygenation., with the lowest 28-day mortality, especially at PaO2 of around 100 mm Hg. CONCLUSIONS: In critically ill patients with sepsis, higher PaO2 (≥ 80 mm Hg) during the first three ICU days was associated with a lower 28-day mortality compared with conservative PaO2.

Clinical outcomes of colorectal neoplasm with positive resection margin after endoscopic submucosal dissection.

A positive resection margin after colorectal endoscopic submucosal dissection (ESD) is associated with an increased risk of recurrence. We aimed to identify the clinical significance of positive resection margins in colorectal neoplasms after ESD. We reviewed 632 patients who had en bloc colorectal ESD at two hospitals between 2015 and 2020. The recurrence rates and presence of residual tumor after surgery were evaluated. The rate of additional surgery after ESD and recurrence rate were significantly higher in patients with incomplete resection (n = 75) compared to patients with complete resection (n = 557). When focusing solely on non-invasive lesions, no significant differences in recurrence rates were observed between the groups with complete and incomplete resection (0.2% vs. 1.9%, p = 0.057). Among 84 patients with submucosal invasive carcinoma, 39 patients underwent additional surgery due to non-curative resection. Positive vertical margin and lymphovascular invasion were associated with residual tumor. Lymphovascular invasion was associated with lymph node metastasis. However, no residual tumor nor lymph node metastases were found in patients with only one unfavorable histological factor. In conclusion, a positive resection margin in non-invasive colorectal lesions, did not significantly impact the recurrence rate. Also, in T1 colorectal cancer with a positive vertical resection margin, salvage surgery can be considered in selected patients with additional risk factors.

Severe Human Parainfluenza Virus Community- and Healthcare-Acquired Pneumonia in Adults at Tertiary Hospital, Seoul, South Korea, 2010-2019.

The characteristics of severe human parainfluenza virus (HPIV)-associated pneumonia in adults have not been well evaluated. We investigated epidemiologic and clinical characteristics of 143 patients with severe HPIV-associated pneumonia during 2010-2019. HPIV was the most common cause (25.2%) of severe virus-associated hospital-acquired pneumonia and the third most common cause (15.7%) of severe virus-associated community-acquired pneumonia. Hematologic malignancy (35.0%), diabetes mellitus (23.8%), and structural lung disease (21.0%) were common underlying conditions. Co-infections occurred in 54.5% of patients admitted to an intensive care unit. The 90-day mortality rate for HPIV-associated pneumonia was comparable to that for severe influenza virus-associated pneumonia (55.2% vs. 48.4%; p = 0.22). Ribavirin treatment was not associated with lower mortality rates. Fungal co-infections were associated with 82.4% of deaths. Clinicians should consider the possibility of pathogenic co-infections in patients with HPIV-associated pneumonia. Contact precautions and environmental cleaning are crucial to prevent HPIV transmission in hospital settings.

Correction: Limitations of rapid diagnostic tests in malaria surveys in areas with varied transmission intensity in Uganda 2017-2019: Implications for selection and use of HRP2 RDTs.

[This corrects the article DOI: 10.1371/journal.pone.0244457.].

Dermal ß-Catenin Is Required for Hedgehog-Driven Hair Follicle Neogenesis.

Hair follicle neogenesis (HFN) occurs after large skin excisions in mice, serving as a rare regenerative model in mammalian wound healing. Wound healing typically results in fibrosis in mice and humans. We previously showed that small skin excisions in mice result in scarring devoid of HFN, displaying features of nonregenerative healing, and hedgehog (Hh) activation in the dermis of such wounds can induce HFN. In this study, we sought to verify the role of dermal Wnt/ß-catenin signaling in HFN because this pathway is essential for hair follicle development but is also paradoxically well-characterized in fibrosis of adult wounds. By deletion of ß-catenin in large wound myofibroblasts, we show that Wnt/ß-catenin signaling is required for endogenous mechanisms of HFN. By utilizing a combined mouse model that simultaneously induces deletion of ß-catenin and constitutive activation of Smoothened in myofibroblasts, we also found that ß-catenin is required for Hh-driven dermal papilla formation. Transcriptome analysis confirms that Wnt/ß-catenin and Hh pathways are activated in dermal papilla cells. Our results indicate that Wnt-active fibrotic status may also create a permissive state for the regenerative function of Hh, suggesting that activation of both Wnt and Hh pathways in skin wound fibroblasts must be ensured in future strategies to promote HFN.

Simultaneous Analysis of 272 Pesticides in Agricultural Products by the QuEChERS Method and Gas Chromatography with Tandem Mass Spectrometry.

The aim of this study is to develop a rapid and accurate method for simultaneous analysis of multi-residue pesticides and conduct pesticide monitoring in agricultural products produced by the production and distribution stage in Korea. The representative agricultural products were selected as brown rice, soybean, potato, mandarin, and green pepper and developed using gas chromatography with tandem mass (GC-MS/MS) for the analysis of 272 pesticide residues. The experimental samples were extracted by the QuEChERS-EN method and then cleaned up by using d-SPE, including MgSO4 and primary secondary amine (PSA) sorbents. The established method was validated in accordance with Codex CAC-GL/40, and the limit of quantitation (LOQ) was determined to be 0.01 mg/kg. A total of 243 pesticides satisfied the guidelines in five samples at three levels with values of 60 to 120% (recovery) and ≤45% (coefficient of variation, CV). The remaining 29 pesticides did not satisfy the guidelines, and these pesticides are expected to be used as a screening method for the routine inspection of agricultural products. As a result of analyzing 223 agricultural products in South Korea by applying the simultaneous analysis method, none of the detected levels in the samples exceeded the standard values based on maximum residue limits (MRLs). The developed method in this study will be used to inspect residual pesticides in agricultural products, and it is anticipated to contribute to the distribution of safe agricultural products to consumers.

Loop-Mediated Isothermal Amplification and Lateral Flow Immunochromatography Technology for Rapid Diagnosis of Influenza A/B.

Influenza viruses cause highly contagious respiratory diseases that cause millions of deaths worldwide. Rapid detection of influenza viruses is essential for accurate diagnosis and the initiation of appropriate treatment. We developed a loop-mediated isothermal amplification and lateral flow assay (LAMP-LFA) capable of simultaneously detecting influenza A and influenza B. Primer sets for influenza A and influenza B were designed to target conserved regions of segment 7 and the nucleoprotein gene, respectively. Optimized through various primer set ratios, the assay operated at 62 °C for 30 min. For a total of 243 (85 influenza A positive, 58 influenza B positive and 100 negative) nasopharyngeal swab samples, the performance of the influenza A/B multiplex LAMP-LFA was compared with that of the commercial AllplexTM Respiratory Panel 1 assay (Seegene, Seoul, Korea). The influenza A/B multiplex LAMP-LFA demonstrated a specificity of 98% for the non-infected clinical samples, along with sensitivities of 94.1% for the influenza A clinical samples and 96.6% for the influenza B clinical samples, respectively. The influenza A/B multiplex LAMP-LFA showed high sensitivity and specificity, indicating that it is reliable for use in a low-resource environment.

Development of a multiplex Loop-Mediated Isothermal Amplification (LAMP) for the diagnosis of bacterial periprosthetic joint infection.

BACKGROUND: Periprosthetic joint infection (PJI) is one of the most serious and debilitating complications that can occur after total joint arthroplasty. Therefore, early diagnosis and appropriate treatment are important for a good prognosis. Recently, molecular diagnostic methods have been widely used to detect the causative microorganisms of PJI sensitively and rapidly. The Multiplex Loop-Mediated Isothermal Amplification (LAMP) method eliminates the complex temperature cycling and delays caused by temperature transitions seen in polymerase chain reaction (PCR) methods, making it faster and easier to perform compared to PCR-based assays. Therefore, this study developed a multiplex LAMP assay for diagnosing bacterial PJI using LAMP technology and evaluated its analytical and clinical performance. METHODS: We developed a multiplex LAMP assay for the detection of five bacteria: Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus agalactiae, Pseudomonas aeruginosa, and Escherichia coli, frequently observed to be the causative agents of PJI. The method of analytical sensitivity and cross-reactivity were determined by spiking standard strains into the joint synovial fluid. The analytical sensitivity of the multiplex LAMP assay was compared with that of a quantitative real-time PCR (qPCR) assay. Clinical performance was evaluated using 20 joint synovial fluid samples collected from patients suspected of having bacterial PJI. RESULTS: The analytical sensitivity of the gram-positive bacterial multiplex LAMP assay and qPCR were 105/104 CFU/mL, 103/103 CFU/mL, and 105/104 CFU/mL against S. agalactiae, S. epidermidis, and S. aureus, respectively. For P. aeruginosa and E. coli, the analytical sensitivity of the multiplex LAMP and qPCR assays were 105/104 and 106/104 CFU/mL, respectively. The multiplex LAMP assay detects target bacteria without cross-reacting with other bacteria, and exhibited 100% sensitivity and specificity in clinical performance evaluation. CONCLUSIONS: This multiplex LAMP assay can rapidly detect five high-prevalence bacterial species causing bacterial PJI, with excellent sensitivity and specificity, in less than 1 h, and it may be useful for the early diagnosis of PJI.

Successful Transcatheter Arterial Embolization of Abdominal Wall Hematoma from the Left Deep Circumflex Iliac Artery after Abdominal Paracentesis in a Patient with Liver Cirrhosis: Case Report and Literature Review.

The occurrence of an abdominal wall hematoma caused by abdominal paracentesis in patients with liver cirrhosis is rare. This paper presents a case of an abdominal wall hematoma caused by abdominal paracentesis in a 67-year-old woman with liver cirrhosis with a review of the relevant literature. Two days prior, the patient underwent abdominal paracentesis for symptom relief for refractory ascites at a local clinic. Upon admission, a physical examination revealed purpuric patches with swelling and mild tenderness in the left lower quadrant of the abdominal wall. Abdominal computed tomography revealed advanced liver cirrhosis with splenomegaly, tortuous dilatation of the para-umbilical vein, a large volume of ascites, and a large acute hematoma at the left lower quadrant of the abdominal wall. An external iliac artery angiogram showed the extravasation of contrast media from the left deep circumflex iliac artery. Embolization of the target arterial branches using N-butyl-2-cyanoacrylate was then performed, and the bleeding was stopped. The final diagnosis was an abdominal wall hematoma from the left deep circumflex iliac artery after abdominal paracentesis in a patient with liver cirrhosis.