Bacteria Contaminants Detected by Organic Inverter-Based Biosensors.

The importance of bacteria detection lies in its role in enabling early intervention, disease prevention, environmental protection, and effective treatment strategies. Advancements in technology continually enhance the speed, accuracy, and sensitivity of detection methods, aiding in addressing these critical issues. This study first reports the fabrication of an inverter constructed using crosslinked-poly(4-vinylphenol) (C-PVP) as the dielectric layer and an organic complementary metal-oxide semiconductor (O-CMOS) based on pentacene and N,N'-ditridecylperylene-3,4,9,10-tetracarboxylic diimide (PTCDI-C13) as a diagnostic biosensor to rapidly detect bacterial concentration. Bacteria including Escherichia coli O157, Staphylococcus aureus ATCC25922, and Enterococcus faecalis SH-1051210 were analysed on the inverters at an ultra-low operating voltage of 2 V. The high density of negative charge on bacteria surfaces strongly modulates the accumulated negative carriers within the inverter channel, resulting in a shift of the switching voltage. The inverter-based bacteria sensor exhibits a linear-like response to bacteria concentrations ranging from 102 to 108 CFU/mL, with a sensitivity above 60%. Compared to other bacterial detectors, the advantage of using an inverter lies in its ability to directly read the switching voltage without requiring an external computing device. This facilitates rapid and accurate bacterial concentration measurement, offering significant ease of use and potential for mass production.

Diastolic/systolic blood pressure ratio for predicting febrile children with sepsis and progress to septic shock in the emergency department.

OBJECTIVE: Given the scarcity of studies analyzing the clinical predictors of pediatric septic cases that would progress to septic shock, this study aimed to determine strong predictors for pediatric emergency department (PED) patients with sepsis at risk for septic shock and mortality. METHODS: We conducted chart reviews of patients with ≥ 2 age-adjusted quick Sequential Organ Failure Assessment score (qSOFA) criteria to recognize patients with an infectious disease in two tertiary PEDs between January 1, 2021, and April 30, 2022. The age range of included patients was 1 month to 18 years. The primary outcome was development of septic shock within 48 h of PED attendance. The secondary outcome was sepsis-related 28-day mortality. Initial important variables in the PED and hemodynamics with the highest and lowest values during the first 24 h of admission were also analyzed. RESULTS: Overall, 417 patients were admitted because of sepsis and met the eligibility criteria for the study. Forty-nine cases progressed to septic shock within 48 h after admission and 368 were discharged without progression. General demographics, laboratory data, and hemodynamics were analyzed by multivariate analysis. Only the minimum diastolic blood pressure/systolic blood pressure ratio (D/S ratio) during the first 24 h after admission remained as an independent predictor of progression to septic shock and 28-day mortality. The best cutoff values of the D/S ratio for predicting septic shock and 28-day mortality were 0.52 and 0.47, respectively. CONCLUSIONS: The D/S ratio is a practical bedside scoring system in the PED and had good discriminative ability in predicting the progression of septic shock and in-hospital mortality in PED patients. Further validation is essential in other settings.

Safety and oncological outcome of early intraoperative intravesicle mitomycin C vs. deferred instillation in patients receiving robot-assisted radical nephroureterectomy.

Introduction: Radical nephroureterectomy with concurrent bladder cuff excision (RNUBCE) is the gold standard surgical approach for high-risk primary upper tract urothelial carcinoma (UTUC). Given the notably high incidence of bladder tumor recurrence following this procedure, this study aimed to evaluate the effect and safety of intraoperative mitomycin-C (MMC) instillation vs. deferred instillation on overall oncological outcomes following robot-assisted RNUBCE. Methods: This is a retrospective chart review study. Patients with non-invasive (N0, not T3/T4) UTUC who underwent robotic RNUBCE combined an intraoperative MMC instillation or a deferred MMC instillation after surgery at a medical center in Taiwan between November 2013 and June 2020 were eligible for inclusion. Patients with prior bladder UC, carcinomas of other origins, received neoadjuvant chemotherapy, and had undergone kidney transplantation were excluded. All surgeries were executed by a single surgical team under the guidance of the same surgeon. The primary outcomes was the risk of bladder tumor recurrence between patients received intraoperative (IO) vs. deferred MMC instillation postoperatively (PO) during one-year follow-up. The secondary outcome was postoperative adverse events assessed by the Clavien-Dindo classification. Univariate and multivariable Cox regression analyses were performed to determine the associations between study variables and the outcomes. Results: A total of 54 patients were included in the analysis. 12 (22.2%) patients experienced a bladder tumor recurrence during follow-up (IO: 7.7%, PO: 35.7%, p < 0.021). After adjustment in the multivariable, intraoperative MMC instillation was significantly associated with lower risk of bladder recurrence [adjusted hazard ratio (aHR) = 0.15, 95% CI: 0.03-0.81, p = 0.028]. No MMC-related Clavien-Dindo Grade III-IV adverse events were found in either group. Conclusion: IIntraoperative MMC instillation is safe and associated with a lower bladder tumor recurrence risk in patients undergoing robotic RNUBCE for UTUC than deferred instillation. Future large, prospective studies are still warranted to confirm the findings.

Current updates for hyperuricemia and gout in age-related macular degeneration.

The escalating prevalence of metabolic syndrome poses a significant public health challenge, particularly among aging populations, with metabolic dysfunctions contributing to pro-inflammatory states. In this review, we delved into the less recognized association between hyperuricemia (HUA), a manifestation of metabolic syndrome and a primary risk factor for gout, and age-related macular degeneration (AMD), a sight-threatening ailment predominantly affecting the elderly. In recent years, inflammation, particularly its involvement in complement pathway dysregulation, has gained prominence in AMD pathophysiology. The contradictory role of uric acid (UA) in intercellular and intracellular environments was discussed, highlighting its antioxidant properties in plasma and its pro-oxidant effects intracellularly. Emerging evidence suggests a potential link between elevated serum uric acid levels and choroid neovascularization in AMD, providing insights into the role of HUA in retinal pathologies. Various pathways, including crystal-induced and non-crystal-induced mechanisms, were proposed to indicate the need for further research into the precise molecular interactions. The implication of HUA in AMD underscores its potential involvement in retinal pathologies, which entails interdisciplinary collaboration for a comprehensive understanding of its impact on retina and related clinical manifestations.

The Removal of Strontium Ions from an Aqueous Solution Using Na-A Zeolites Synthesized from Kaolin.

Sr2+ ions in an aqueous solution were removed using Na-A zeolites synthesized from kaolin, a natural mineral. Na-A zeolites with high crystallinity were synthesized using NaOH/kaolin mass ratios of 0.6 (ZK06) and 0.9 (ZK09). The adsorption reached equilibrium within 120 min. The adsorption data obtained from experiments for Sr2+ using ZK06 and ZK09 were appropriately analyzed with pseudo-second-order kinetic and Langmuir isotherm models. Comparing the maximum adsorption capacities (qm) of ZK06 and ZK09 for Sr2+, the highest values were obtained at 1.90 and 2.42 mmol/g, respectively. Consequently, the Na-A zeolites synthesized from kaolin can be evaluated as adsorbents with high adsorption capacities for the removal of Sr2+, proportional to the degree of their crystallinity.

Anti-SARS-CoV-2 nucleocapsid antibody positivity 3 years after COVID-19.

The accurate identification of individuals without prior infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pivotal for seroepidemiological research and vaccine trials. Because of widespread COVID-19 vaccination, the anti-nucleocapsid antibody continues to serve as a valuable marker for individuals without a history of COVID-19. This study aimed to comprehensively assess anti-nucleocapsid antibody positivity using diverse commercial and in-house immunoassays among individuals who contracted COVID-19 more than 3 years ago. We enrolled 44 participants with laboratory-confirmed COVID-19 between January and May 2020 from Seoul National University Hospital and its community treatment centers. The results showed anti-nucleocapsid antibody positivities ranged from 45.5% to 87.9% depending upon the immunoassay used. The study highlights the importance of considering the limited anti-nucleocapsid antibody positivity in participants with a distant COVID-19 history in seroepidemiological or vaccine research.

Urgent Management of Penetrating Ocular Injury: A Case Report and Review of the Literature.

Ocular globe injury is a severe ophthalmic emergency that requires immediate attention in the emergency department. In this case report, we present a 35-year-old male who suffered a penetrating ocular injury and globe rupture caused by a nail puncture. The patient presented with severe pain and visual loss and was treated with tetanus vaccination, empirical antibiotics, and pain control, followed by an urgent orbital computed tomography (CT) scan and consultation with an ophthalmologist. The CT scan revealed a retained nail in the ocular space, and an urgent operation was performed to repair the eyeball rupture, remove the intraocular foreign body, and perform an anterior vitrectomy. The patient was discharged 6 days after the operation with a visual acuity of 20/400 and an ocular trauma score of 34. This case highlights the importance of initial emergency physician decision-making and the need for a thorough history-taking and examination when encountering penetrating ocular injuries.

Corrigendum to "Development and Asian-wide validation of the Grade for Interpretable Field Triage (GIFT) for predicting mortality in pre-hospital patients using the Pan-Asian Trauma Outcomes Study (PATOS)" [The Lancet Regional Health - Western Pacific 34 (2023) 100733].

[This corrects the article DOI: 10.1016/j.lanwpc.2023.100733.].

Absence of the Klotho Function Causes Cornea Degeneration with Specific Features Resembling Fuchs Endothelial Corneal Dystrophy and Bullous Keratopathy.

The Klotho loss-of-function mutation is known to cause accelerated senescence in many organs, but its effects on the cornea have not been published. The present study aims to investigate the effects of the Klotho null mutation on cornea degeneration and to characterize the pathological features. Mouse corneas of Klotho homozygous, heterozygous, and wild-type mice at 8 weeks of age for both genders were subject to pathological and immunohistological examinations. The results show an irregular topography on the corneal surface with a Klotho null mutation. Histological examinations revealed a reduced corneal epithelial cell density, endothelial cell-shedding, and decreased cornea stromal layer thickness in the absence of the Klotho function. Furthermore, guttae formation and the desquamation of wing cells were significantly increased, which was comparable to the characteristics of Fuchs endothelial corneal dystrophy and bullous keratopathy. The mechanism analysis showed multi-fold abnormalities, including oxidative stress-induced cornea epithelium apoptosis and inflammation, extracellular matrix remodeling in the stroma, and a disruption of epithelial repair, presumably through the epithelial-mesenchymal transition. In conclusion, cornea degeneration was observed in the Klotho loss-of-function mutant mice. These pathological features support the use of Klotho mutant mice for investigating age-related cornea anomalies, including Fuchs endothelial corneal dystrophy, bullous keratopathy, and dry eye diseases.

Musculoskeletal Pain, Physical Activity, Muscle Mass, and Mortality in Older Adults: Results from the Korean Longitudinal Study on Health and Aging (KLoSHA).

Background and objectives: Musculoskeletal (MSK) pain significantly impacts physical activity and quality of life in older adults, potentially influencing mortality. This study explored the relationship between MSK pain, physical activity, muscle mass, and mortality among older adults. Material and Methods: We studied 1000 participants in the Korean Longitudinal Study on Health and Aging (KLoSHA), a prospective, population-based cohort study of people aged 65 years or older. Survival status was tracked over a 5-year period. Correlations between low back pain (LBP), knee pain, regular exercise, appendicular skeletal muscle mass (ASM), and other variables were analyzed. Logistic regression analyses were used to identify independent risk factors for mortality. Results: Of the total participants, 829 (82.9%) survived over a 5-year period. Survivors tended to be younger, had a higher BMI, and were more active in regular exercise. In contrast, non-survivors exhibited a higher prevalence of both LBP and knee pain, along with increased instances of multiple MSK pains. Lower ASM correlated moderately with LBP and knee pain, whereas higher ASM was associated with regular exercise. There was a moderate correlation between LBP and knee pain, both of which were associated with a lack of regular exercise. Age, sex, ASM, and regular exercise were significant predictors, even though MSK pain itself did not directly predict all-cause mortality. Conclusions: This study demonstrated the independent association between ASM, regular exercise, and mortality. Although MSK pain did not directly correlate with all-cause mortality, the non-survivor group had higher levels of both single and multiple MSK pains. Recognizing the interplay of MSK pain, physical activity, and muscle mass for older adults, the research underscores the need for holistic strategies to enhance health outcomes in older individuals with MSK pain.

A community challenge to predict clinical outcomes after immune checkpoint blockade in non-small cell lung cancer.

BACKGROUND: Predictive biomarkers of immune checkpoint inhibitor (ICI) efficacy are currently lacking for non-small cell lung cancer (NSCLC). Here, we describe the results from the Anti-PD-1 Response Prediction DREAM Challenge, a crowdsourced initiative that enabled the assessment of predictive models by using data from two randomized controlled clinical trials (RCTs) of ICIs in first-line metastatic NSCLC. METHODS: Participants developed and trained models using public resources. These were evaluated with data from the CheckMate 026 trial (NCT02041533), according to the model-to-data paradigm to maintain patient confidentiality. The generalizability of the models with the best predictive performance was assessed using data from the CheckMate 227 trial (NCT02477826). Both trials were phase III RCTs with a chemotherapy control arm, which supported the differentiation between predictive and prognostic models. Isolated model containers were evaluated using a bespoke strategy that considered the challenges of handling transcriptome data from clinical trials. RESULTS: A total of 59 teams participated, with 417 models submitted. Multiple predictive models, as opposed to a prognostic model, were generated for predicting overall survival, progression-free survival, and progressive disease status with ICIs. Variables within the models submitted by participants included tumor mutational burden (TMB), programmed death ligand 1 (PD-L1) expression, and gene-expression-based signatures. The best-performing models showed improved predictive power over reference variables, including TMB or PD-L1. CONCLUSIONS: This DREAM Challenge is the first successful attempt to use protected phase III clinical data for a crowdsourced effort towards generating predictive models for ICI clinical outcomes and could serve as a blueprint for similar efforts in other tumor types and disease states, setting a benchmark for future studies aiming to identify biomarkers predictive of ICI efficacy. TRIAL REGISTRATION: CheckMate 026; NCT02041533, registered January 22, 2014. CheckMate 227; NCT02477826, registered June 23, 2015.

Growth Patterns of Prostate Cancers Undetected by Prostate 3T Multiparametric MRI.

BACKGROUND/AIM: The multiparametric magnetic resonance imaging (mpMRI)-ultrasound (US) fusion targeted biopsy (TB) is a useful diagnostic device for men with suspected prostate cancer (PC) and can increase the detection rate for clinically significant PCs (csPC). However, few studies have shown pathological findings of undetectable csPCs on the prostate mpMRI. PATIENTS AND METHODS: This study investigated the growth patterns of csPC undetected in prostate mpMRI. The study enrolled 248 patients with suspected PCs and ≥PI-RADS 2 lesions, who then underwent mpMRI-US fusion TB and nearly prostate-mapping systematic biopsies (SB). A total 248 biopsies included 404 regions of interest in TB and 2976 mapping-regions in SB. RESULTS: The detection rates of csPC, defined as PC grade group (GG) ≥2, were 42% in TB and 44% in SB, and the highest detection rate was 50%, using both TB and SB. Approximately 79% of PI-RADS 3/4/5 with any PC showed csPC. A total 201 PI-RADS 3/4/5 lesions showed benign prostatic hyperplasia, lymphocytic prostatitis, or fibromuscular stroma only in the core tissues. Notably, 22 csPCs detected in SB but undetected in prostate mpMRI preferentially showed a pattern of mixed well-formed and fused PC glands. The other patterns including cribriform glands and poorly formed glands with intracytoplasmic vacuoles were also seen. Approximately 85% of the 22 csPCs showed tumor volume less than 50% of core tissues. CONCLUSION: Changes in prostatic stroma amounts, inflammation severity, tumor volume and growth patterns of PC glands affected the detectability of prostate mpMRI.

A systematic review and meta-analysis of the relationship between heavy smoking and probability discounting.

BACKGROUND AND OBJECTIVES: Probability discounting (PD), which refers to the process of adjusting the value of future probabilities when making decisions, is a method of measuring impulsive decision-making; however, the relationship between PD and nicotine remains unclear. The current study aimed at investigating the significance of PD in individuals who smoke. METHODS: According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched the PubMed, Embase, PsycINFO, and Web of Science databases for articles comparing individuals who smoke and their tobacco-naïve controls using PD task as outcome measure from inception to May 2023. The main outcome was an overall difference in PD function, while subgroup analysis and meta-regression were conducted to examine the analysis methods and the moderators of PD. RESULTS: Fourteen studies in total involving 384 individuals who smoke and 493 controls (mean age = 24.32 years, range = 15.1-38.05 years) were analyzed. The effect of smoking on PD was significant (g = 0.51, p = .02). The discounting parameter from the equation, compared to the area under the curve, was more sensitive to estimating PD function (p = .01). Regression analysis showed positive correlations of PD with female percentage, age, and the number of probability options (all p < .04), but not with the number of choices at each probability and maximum reward magnitude (all p > .07). There was no significant publication bias across the eligible studies (p = .09). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Our findings, which are the first to demonstrate a smaller PD (i.e., prone to risk-taking) in individuals who smoke, shed light on the appropriate analysis method, gender effect, age, and probability options on the PD function.

Preclinical Animal Study and Pilot Clinical Trial of Using Enriched Peripheral Blood-Derived Mononuclear Cells for Intervertebral Disc Degeneration.

Low back pain (LBP) is a leading cause of long-term disability globally. Intervertebral disk degeneration (IVDD) is mainly responsible for discogenic pain in LBP-affected young patients. There is no effective therapy to reverse disease severity and IVDD progression. This study investigates the effect of human peripheral blood-derived mononuclear cells (PBMCs) on pain relief and life quality improvement in IVDD patients. The enriched monocytes of the PBMCs could differentiate into CD14 and CD206 double-positive M2 macrophages in vitro. Preclinical evidence in rats showed that the transplanted PBMCs exhibited anti-inflammatory and moderate tissue-repair effects on controlling IVDD progress in the rat model. The PBMCs significantly steered the aggrecan and type II collagen expressions and attenuated the pro-inflammatory cytokines in the affected disk. Based on the animal results, 36 patients with chronic low back pain (CLBP) were included in clinical trials. The control group was conservative care only, and the experimental group was platelet-rich plasma (PRP) and PBMCs intradiscal injections. We first confirmed the single lumbar disk causing the discogenic pain by provocative discography or magnetic resonance imaging (MRI). Discogenic LBP participants received one intradiscal injection of autologous PBMCs and followed for 6 months. Our clinical trial showed that patients' LBP and disability were significantly ameliorated after the PBMCs transplantation rather than PRP. These preclinical and pilot clinical studies indicate that intradiscal injection of the enriched PBMCs might be a feasible and potential cell therapy to control pain and disability in IVDD patients.

Combination of XEOL, TR-XEOL and HB-T interferometer at the TPS 23A X-ray nanoprobe for exploring quantum materials.

In this study, a combination of X-ray excited optical luminescence (XEOL), time-resolved XEOL (TR-XEOL) and the Hanbury-Brown and Twiss (HB-T) interferometer at the Taiwan Photon Source (TPS) 23A X-ray nanoprobe beamline for exploring quantum materials is demonstrated. On the basis of the excellent spatial resolution rendered using a nano-focused beam, emission distributions of artificial micro-diamonds can be obtained by XEOL maps, and featured emission peaks of a selected local area can be obtained by XEOL spectra. The hybrid bunch mode of the TPS not only provides a sufficiently high peak power density for experiments at each beamline but also permits high-quality temporal domain (∼200 ns) measurements for investigating luminescence dynamics. From TR-XEOL measurements, the decay lifetime of micro-diamonds is determined to be approximately 16 ns. Furthermore, the XEOL spectra of artificial micro-diamonds can be investigated by the HB-T interferometer to identify properties of single-photon sources. The unprecedented strategy of combining XEOL, TR-XEOL and the HB-T interferometer at the X-ray nanoprobe beamline will open new avenues with significant characterization abilities for unraveling the emission mechanisms of single-photon sources for quantum materials.

Direction-selective Resistance to Cerebrospinal Fluid Flow as the Cause of Syringomyelia.

The pathophysiology of syringomyelia remains poorly understood. Two prevailing challenges stand out: the need for a comprehensive understanding of its diverse types and the yet-to-be-explained mechanism of cerebrospinal fluid (CSF) retention in the syrinx despite its higher pressure than that in the adjacent subarachnoid space. Expanding on our previous proposal that direction-selective resistance to subarachnoid CSF flow drives syringomyelia genesis, this study uses a computer model to explore this mechanism further. We developed a computer simulation model to study spinal CSF dynamics, employing a lumped parameter approach with multiple compartments. This model replicated the to-and-fro movement of CSF in the spinal subarachnoid space and within an intraspinal channel. Subsequently, a direction-selective resistance-opposing only the caudal subarachnoid CSF flow-was introduced at a specific location within the subarachnoid space. Following the introduction of the direction-selective resistance, a consistent pressure increase was observed in the intraspinal channel downstream of the resistance. Importantly, this increase in pressure accumulated with every cycle of to-and-fro CSF flow. The accumulation results from the pressure drop across the resistance, and its effect on the spinal cord matrix creates a pumping action in the intraspinal channel. Our findings elucidate the mechanisms underlying our hypothesis that a direction-selective resistance to subarachnoid CSF flow causes syringomyelia. This comprehensively explains the various types of syringomyelia and resolves the puzzle of CSF retention in the syrinx despite a pressure gradient.

Sumoylation of SAP130 regulates its interaction with FAF1 as well as its protein stability and transcriptional repressor function.

BACKGROUND: Fas-associated factor 1 (FAF1) is a multidomain protein that interacts with diverse partners to affect numerous cellular processes. Previously, we discovered two Small Ubiquitin-like Modifier (SUMO)-interacting motifs (SIMs) within FAF1 that are crucial for transcriptional modulation of mineralocorticoid receptor. Recently, we identified Sin3A-associated protein 130 (SAP130), a putative sumoylated protein, as a candidate FAF1 interaction partner by yeast two-hybrid screening. However, it remained unclear whether SAP130 sumoylation might occur and functionally interact with FAF1. RESULTS: In this study, we first show that SAP130 can be modified by SUMO1 at Lys residues 794, 878 and 932 both in vitro and in vivo. Mutation of these three SUMO-accepting Lys residues to Ala had no impact on SAP130 association with Sin3A or its nuclear localization, but the mutations abrogated the association of SAP130 with the FAF1. The mutations also potentiated SAP130 trans-repression activity and attenuated SAP130-mediated promotion of cell growth. Additionally, SUMO1-modified SAP130 was less stable than unmodified SAP130. Transient transfection experiments further revealed that FAF1 mitigated the trans-repression and cell proliferation-promoting functions of SAP130, and promoted SAP130 degradation by enhancing its polyubiquitination in a sumoylation-dependent manner. CONCLUSIONS: Together, these results demonstrate that sumoylation of SAP130 regulates its biological functions and that FAF1 plays a crucial role in controlling the SUMO-dependent regulation of transcriptional activity and protein stability of SAP130.

Enhancing Electrochemical Non-Enzymatic Dopamine Sensing Based on Bimetallic Nickel/Cobalt Phosphide Nanosheets.

In this study, the successful synthesis of bimetallic nickel/cobalt phosphide nanosheets (Ni-Co-P NSs) via the hydrothermal method and the subsequent high-temperature phosphorization process were both confirmed. Ni-Co-P NSs exhibited excellent electrocatalytic activity for the electrochemical non-enzymatic DA sensing. The surface morphologies and physicochemical properties of Ni-Co-P NSs were characterized by atomic force microscopy (AFM), field-emission scanning (FESEM), field-emission transmission electron microscopy (FETEM), and X-ray diffraction (XRD). Further, the electrochemical performance was evaluated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The metallic nature of phosphide and the synergistic effect of Ni/Co atoms in Ni-Co-P NSs provided abundant catalytic active sites for the electrochemical redox reaction of DA, which exhibited a remarkable consequence with a wide linear range from 0.3~50 µM, a high sensitivity of 2.033 µA µM-1 cm-2, a low limit of detection of 0.016 µM, and anti-interference ability. As a result, the proposed Ni-Co-P NSs can be considered an ideal electrode material for the electrochemical non-enzymatic DA sensing.