Simultaneous Screening of 172 Veterinary Drugs by Modified QuEChERS-LC-MS/MS in TCM Galli Gigerii Endothelium Corneum.

An analytical method was developed for the screening of 172 veterinary drugs in traditional Chinese medicine Galli Gigerii Endothelium Corneum by high-performance liquid chromatography tandem mass spectrometry. The samples were pretreated by a modified QuEChERS method. A Zorbax Eclipse plus C18 column (1.8 µm, 3.0 × 150 mm2, Agilent) was used for the separation of analytes by gradient elution. All analytes were detected by electrospray ionization mass spectrometry with multiple reaction monitoring mode. Good linearity with R ≥ 0.99 was exhibited for all analytes within the respective range. The recoveries of all monitored analytes ranged from 55.4 to 127.6% at three spiked levels (limit of quantitation-LOQ, 2-fold LOQ, 10-fold LOQ), with relative standard deviations <17.8%. The estimated LOQ levels were 0.2-20 µg/kg. The application of this method provides a reference for the safety control of traditional Chinese medicines.

3D parallel pulsed chaos LiDAR system.

We propose and experimentally demonstrate a parallel pulsed chaos light detection and ranging (LiDAR) system with a high peak power, parallelism, and anti-interference. The system generates chaotic microcombs based on a chip-scale Si3N4 microresonator. After passing through an acousto-optic modulator, the continuous-wave chaotic microcomb can be transformed into a pulsed chaotic microcomb, in which each comb line provides pulsed chaos. Thus, a parallel pulsed chaos signal is generated. Using the parallel pulsed chaos as the transmission signal of LiDAR, we successfully realize a 4-m three-dimensional imaging experiment using a microelectromechanical mirror for laser scanning. The experimental results indicate that the parallel pulsed chaos LiDAR can detect twice as many pixels as direct detection continuous wave parallel chaos LiDAR under a transmission power of -6 dBm, a duty cycle of 25%, and a pulse repetition frequency of 100 kHz. By further increasing the transmission power to 10 dBm, we acquire an 11 cm × 10 cm image of a target scene with a resolution of 30 × 50 pixels. Finally, the anti-jamming ability of the system is evaluated, and the results show that the system can withstand interferences of at least 15 dB.

Advancements of Macrophages Involvement in Pathological Progression of Colitis-Associated Colorectal Cancer and Associated Pharmacological Interventions.

Intestinal macrophages play crucial roles in both intestinal inflammation and immune homeostasis. They can adopt two distinct phenotypes, primarily determined by environmental cues. These phenotypes encompass the classically activated pro-inflammatory M1 phenotype, as well as the alternatively activated anti-inflammatory M2 phenotype. In regular conditions, intestinal macrophages serve to shield the gut from inflammatory harm. However, when a combination of genetic and environmental elements influences the polarization of these macrophages, it can result in an M1/M2 macrophage activation imbalance, subsequently leading to a loss of control over intestinal inflammation. This shift transforms normal inflammatory responses into pathological damage within the intestines. In patients with ulcerative colitis-associated colorectal cancer (UC-CRC), disorders related to intestinal inflammation are closely correlated with an imbalance in the polarization of intestinal M1/M2 macrophages. Therefore, reinstating the equilibrium in M1/M2 macrophage polarization could potentially serve as an effective approach to the prevention and treatment of UC-CRC. This paper aims to scrutinize the clinical evidence regarding Chinese medicine (CM) in the treatment of UC-CRC, the pivotal role of macrophage polarization in UC-CRC pathogenesis, and the potential mechanisms through which CM regulates macrophage polarization to address UC-CRC. Our objective is to offer fresh perspectives for clinical application, fundamental research, and pharmaceutical advancement in UC-CRC.

Cross-modal conflict deficit in children with attention-deficit/hyperactivity disorder.

The difference between the audiovisual incongruent condition and the audiovisual congruent condition is known as cross-modal conflict, which is an important behavioral index to measure the conflict control function. Previous studies have found conflict control deficits in children with attention-deficit/hyperactivity disorder (ADHD), but it is not clear whether and how cross-modal conflict occurs in children with ADHD at different processing levels. The current study adopted the cross-modal matching paradigm to recruit 25 children with ADHD (19 boys and 6 girls) and 24 TD children (17 boys and 7 girls), aiming to investigate the cross-modal conflict effect at the perception and response levels of children with ADHD. The results showed that both groups of children showed significant cross-modal conflict, and there was no significant difference between the ADHD and TD groups in the number of error trials and mean response time. However, the cross-modal conflict effect caused by auditory distractors was different between the ADHD and TD groups; the TD group had stronger auditory conflict at the response level, whereas the ADHD group had weaker auditory conflict. This indicates that the ADHD group had a deficit of auditory conflict at the response level.

Adsorption of phosphate over a novel magnesium-loaded sludge-based biochar.

The production of sludge-based biochar to recover phosphorus (P) from wastewater and reuse the recovered phosphorus as agricultural fertilizer is a preferred process. This article mainly studied the removal of phosphate (PO4-P) from aqueous solution by synthesizing sludge-based biochar (MgSBC-0.1) from anaerobic fermentation sludge treated with magnesium (Mg)-loading-modification, and compared it with unmodified sludge-based biochar (SBC). The physicochemical properties, adsorption efficiency, and adsorption mechanism of MgSBC-0.1 were studied. The results showed that the surface area of MgSBC-0.1 synthesized increased by 5.57 times. The material surface contained MgO, Mg(OH)2, and CaO nanoparticles. MgSBC-0.1 can effectively remove phosphate in the initial solution pH range of 3.00-7.00, with a fitted maximum phosphorus adsorption capacity of 379.52 mg·g-1. The adsorption conforms to the pseudo second-order kinetics model and Langmuir isotherm adsorption curve. The characterization of the adsorbed composite material revealed the contribution of phosphorus crystal deposition and electrostatic attraction to phosphorus absorption.

Liraglutide promotes UCP1 expression and lipolysis of adipocytes by promoting the secretion of irisin from skeletal muscle cells.

Although Liraglutide (Lira) increases serum irisin levels in type 2 diabetes mellitus (T2DM), it is unclear whether it induces expression of uncoupling protein 1 (UCP1) of adipocytes via promoting irisin secretion from skeletal muscle. Male T2DM rats were treated with 0.4 mg/kg/d Lira twice a day for 8 weeks, and the protein expression of phosphorylated AMP kinase (p-AMPK), phosphorylated acetyl-CoA carboxylase 1 (p-ACC1) and UCP1 in white adipose tissues were detected. Differentiated C2C12 cells were treated with palmitic acid (PA) and Lira to detect the secretion of irisin. Differentiated 3T3-L1 cells were treated with irisin, supernatant from Lira-treated C2C12 cells, Compound C or siAMPKα1, the triglyceride (TG) content and the related gene expression were measured. The transcriptome in irisin-treated differentiated 3T3-L1 cells was analyzed. Lira elevated serum irisin levels, decreased the adipocyte size and increased the protein expression of UCP1, p-AMPK and p-ACC1 in WAT. Moreover, it promoted the expression of PGC1α and FNDC5, the secretion of irisin in PA-treated differentiated C2C12 cells. The irisin and supernatant decreased TG synthesis and promoted the expression of browning- and lipolysis-related genes in differentiated 3T3-L1 cells. While Compound C and siAMPKα1 blocked AMPK activities and expression, irisin partly reversed the pathway. Finally, the transcriptome analysis indicated that differently expressed genes are mainly involved in browning and lipid metabolism. Overall, our findings showed that Lira modulated muscle-to-adipose signaling pathways in diabetes via irisin-mediated AMPKα/ACC1/UCP1/PPARα pathway. Our results suggest a new mechanism for the treatment of T2DM by Lira.

Efficacy of Intravitreal Injections Anti-Vascular Endothelial Growth Factor Treatment for Radiation Retinopathy: A Systematic Review and Meta-analysis.

PURPOSE: This study aims to appraise the therapeutic effectiveness of intravitreal injections anti-vascular endothelial growth factor (anti-VEGF) vs alternative therapies in managing radiation retinopathy (RR). DESIGN: Systematic review and meta-analysis. METHODS: We obtained comprehensive data retrieval using PubMed, Embase, Web of Science, Scopus, and the Cochrane Library from their inception until December 15, 2023. This review included randomized controlled trials (RCTs) and nonrandomized studies (NRSs) reporting on best-corrected visual acuity (BCVA) among RR patients treated with intravitreal anti-VEGF. Study selection and data extraction were meticulously performed by 2 independent reviewers. The Cochrane Risk of Bias Tool 2.0 (RoB 2.0) and Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) scales were utilized for bias risk assessment. Quantification of heterogeneity was executed using Q, H, and I2 statistics. The primary endpoint was the BCVA at the final observation point of each study. Secondary endpoints included central retinal thickness (CRT), foveal avascular zone (FAZ) area, and capillary density (CD) at the level of superficial capillary plexus. Subgroup analyses were undertaken to explore potential heterogeneity sources possibly due to treatment duration and study design. Sensitivity analyses were conducted to ascertain result stability. RESULTS: This analysis incorporated 7 studies (including 3 RCTs) encompassing 922 patients afflicted with RR. Relative to other treatment modalities, intravitreal anti-VEGF therapy was associated with a statistically significant mean decrease in BCVA of -0.34 logMAR (95% CI, -0.39 to -0.30 logMAR; I2 = 87.70%; P < .001), and a substantial reduction in CRT of -34.65 µm (95% CI, -50.70 to -18.60 µm; I2 = 30.40%; P < .001). Additionally, a reduction in the FAZ area by -0.69 mm² (95% CI, -0.91 to -0.46 mm², I2 = 0%; P < .001) was observed. A positive tendency was noted in CD at the superficial capillary plexus between anti-VEGF and other therapeutic interventions. CONCLUSIONS: Intravitreal anti-VEGF injections, in comparison to other treatments, demonstrate superior efficacy in enhancing BCVA and reducing CRT, thereby underscoring the potential of anti-VEGF in ameliorating radiation retinopathy outcomes. However, the conclusions are constrained by the incorporation of data from some NRSs and the small sample sizes.

Application of dental pulp stem cells for bone regeneration.

Bone defects resulting from severe trauma, tumors, inflammation, and other factors are increasingly prevalent. Stem cell-based therapies have emerged as a promising alternative. Dental pulp stem cells (DPSCs), sourced from dental pulp, have garnered significant attention owing to their ready accessibility and minimal collection-associated risks. Ongoing investigations into DPSCs have revealed their potential to undergo osteogenic differentiation and their capacity to secrete a diverse array of ontogenetic components, such as extracellular vesicles and cell lysates. This comprehensive review article aims to provide an in-depth analysis of DPSCs and their secretory components, emphasizing extraction techniques and utilization while elucidating the intricate mechanisms governing bone regeneration. Furthermore, we explore the merits and demerits of cell and cell-free therapeutic modalities, as well as discuss the potential prospects, opportunities, and inherent challenges associated with DPSC therapy and cell-free therapies in the context of bone regeneration.

A phase 1 trial of the MEK inhibitor selumetinib in combination with pembrolizumab for advanced or metastatic solid tumors.

MEK inhibitors have immunomodulatory activity and potential for synergistic activity when combined with PD-1 inhibitors. We evaluated selumetinib (inhibitor of MEK1/2) plus pembrolizumab (anti‒PD-1 antibody) in patients with advanced/metastatic solid tumors. In this phase 1b study, adults with previously treated advanced/metastatic solid tumors received pembrolizumab 200 mg intravenously every 3 weeks plus selumetinib on days 1‒14 per 3-week cycle (2 weeks on/1 week off); selumetinib dosing began at 50 mg orally twice daily with escalation in 25 mg increments for ≤ 35 cycles. Primary endpoints were dose-limiting toxicities (DLTs), adverse events (AEs), and treatment discontinuations due to AEs. Thirty-two patients were enrolled. Dose escalation was completed up to selumetinib 125 mg twice daily. The target DLT rate of 30% was not reached at any dose level. In the selumetinib 100 mg group, 2/11 patients (18.2%) experienced DLTs (n = 1 grade 3 diarrhea, n = 1 grade 3 fatigue). In the selumetinib 125 mg group, 3/14 (21.4%) experienced DLTs (n = 1 grade 2 retinal detachment, n = 1 grade 3 retinopathy, n = 1 grade 3 stomatitis). Dose-related changes in pharmacokinetic exposures were observed for selumetinib and N-desmethyl selumetinib up to 100 mg (saturation at 125 mg). Two patients achieved partial responses (1 each with selumetinib 75 mg and 125 mg) for an objective response rate of 6%. The study was stopped early because of insufficient efficacy. Although the target DLT rate was not reached at any dose level and no new safety signals were identified, selumetinib plus pembrolizumab had limited antitumor activity in this population. Trial registration: ClinicalTrials.gov , NCT03833427.

Macrod1 suppresses diabetic cardiomyopathy via regulating PARP1-NAD+-SIRT3 pathway.

Diabetic cardiomyopathy (DCM), one of the most serious long-term consequences of diabetes, is closely associated with oxidative stress, inflammation and apoptosis in the heart. MACRO domain containing 1 (Macrod1) is an ADP-ribosylhydrolase 1 that is highly enriched in mitochondria, participating in the pathogenesis of cardiovascular diseases. In this study, we investigated the role of Macrod1 in DCM. A mice model was established by feeding a high-fat diet (HFD) and intraperitoneal injection of streptozotocin (STZ). We showed that Macrod1 expression levels were significantly downregulated in cardiac tissue of DCM mice. Reduced expression of Macrod1 was also observed in neonatal rat cardiomyocytes (NRCMs) treated with palmitic acid (PA, 400 µM) in vitro. Knockout of Macrod1 in DCM mice not only worsened glycemic control, but also aggravated cardiac remodeling, mitochondrial dysfunction, NAD+ consumption and oxidative stress, whereas cardiac-specific overexpression of Macrod1 partially reversed these pathological processes. In PA-treated NRCMs, overexpression of Macrod1 significantly inhibited PARP1 expression and restored NAD+ levels, activating SIRT3 to resist oxidative stress. Supplementation with the NAD+ precursor Niacin (50 µM) alleviated oxidative stress in PA-stimulated cardiomyocytes. We revealed that Macrod1 reduced NAD+ consumption by inhibiting PARP1 expression, thereby activating SIRT3 and anti-oxidative stress signaling. This study identifies Macrod1 as a novel target for DCM treatment. Targeting the PARP1-NAD+-SIRT3 axis may open a novel avenue to development of new intervention strategies in DCM. Schematic illustration of macrod1 ameliorating diabetic cardiomyopathy oxidative stress via PARP1-NAD+-SIRT3 axis.

Optimizing auxiliary laser heating for Kerr soliton microcomb generation.

Auxiliary laser heating has become a widely adopted method for Kerr soliton frequency comb generation in optical microcavities, thanks to its reliable and easy-to-achieve merits for solving the thermal instability during the formation of dissipative Kerr solitons. Here, we conduct optimization of auxiliary laser heating by leveraging the distinct loss and absorption characteristics of different longitudinal and polarization cavity modes. We show that even if the auxiliary and pump lasers enter orthogonal polarization modes, their mutual photothermal balance can be efficient enough to maintain a cavity thermal equilibrium as the pump laser enters the red-detuning soliton regime, and by choosing the most suitable resonance for the auxiliary and pump lasers, the auxiliary laser power can be reduced to 20% of the pump laser and still be capable of warranting soliton generation. Moreover, we demonstrate soliton comb generation using integrated laser modules with a few milliwatt on-chip pump and auxiliary powers, showcasing the potential for further chip integration of the auxiliary laser heating method.

40 Gb/s multimode all-optical regenerator based on the low-loss silicon-based nanowaveguide.

With the increasing demand for communication capacity, all-optical regeneration of multimode signals is a helpful technology of network nodes and optical signal processors. However, the difficulty of regenerating signal in higher-order modes hinders the practical application of multimode all-optical regenerators. In this study, we experimentally demonstrate the 40 Gb/s all-optical regeneration of NRZ-OOK signal in TE0 and TE1 modes via four-wave mixing (FWM) in the low-loss silicon-based nanowaveguide. By optimizing the parameters of waveguide section to enhance FWM conversion efficiency of two modes, and introducing Euler bending to reduce crosstalk between modes, the transmission loss of the silicon waveguide is 0.3 dB/cm, and the FWM conversion efficiency of the multimode regenerator is as high as -9.6 dB (TE0) and -13.0 dB (TE1). Both modes achieve extinction ratio enhancement of about 6 dB after regeneration. This silicon-based all-optical regenerator has great application potential in all-optical signal processing systems.

Efficient visible light-driven photodegradation of glyphosate utilizing Bi2WO6 with oxygen vacancies: Performance, mechanism, and toxicity assessment.

Global environmental deterioration poses a major risk to ecological security and human health, and emerging technologies are urgently needed to deal with it. Therefore, the exploitation of photocatalysts with favorable activity for efficient degradation of pesticide contaminants is one of the strategies to achieve environmental remediation. Herein, oxygen vacancy-rich Bi2WO6 (Ov-BWO) was prepared through a solvothermal method utilizing ethylene glycol (EG), which exhibited excellent photocatalytic efficiency in photodegradation of glyphosate. The formation of oxygen vacancies (Ovs) in Ov-BWO was demonstrated utilizing XPS and EPR. PL, TRPL, photocurrent tests, and EIS analyses revealed that Ovs accelerated effective transfer of photogenerated charge, extended lifetime of charge carriers, promoted production of active species and significantly improved the photocatalytic performance. Compared with the low-activity Bi2WO6 (BWO, 59.6%), Ov-BWO showed outstanding photocatalytic activity, achieving a degradation efficiency of 91% for glyphosate at 120 min of visible light irradiation. Moreover, Ov-BWO also displayed outstanding recyclable stability after four repeated uses. Based on the characterization of photoelectric properties, a feasible photocatalytic reaction was put forth, along with glyphosate degradation pathways. Furthermore, the degradation intermediates of glyphosate were analyzed in detail employing HPLC-MS. The toxicity assessment indicated that degraded products had been proven to be non-toxic to the ecological system. This work presents the potential of photocatalysts with Ovs for the photodegradation of pesticides, providing a viable strategy for environmental renovation.

Organic-Hydrochloride-Modified ZnO Electron Transport Layer for Efficient Defect Passivation and Stress Release in Rigid and Flexible all Inorganic Perovskite Solar Cells.

All inorganic CsPbI2Br perovskite (AIP) has attracted great attention due to its excellent resistance against thermal stress as well as the remarkable capability to deliver high-voltage output. However, CsPbI2Br perovskite solar cells (PeSCs) still encounter critical challenges in attaining both high efficiency and mechanical stability for commercial applications. In this work, formamidine disulfide dihydrochloride (FADD) modified ZnO electron transport layer (ETL) has been developed for fabricating inverted devices on either rigid or flexible substrate. It is found that the FADD modification leads to efficient defects passivation, thereby significantly reducing charge recombination at the AIP/ETL interface. As a result, rigid PeSCs (r-PeSCs) deliver an enhanced efficiency of 16.05% and improved long-term thermal stability. Moreover, the introduced FADD can regulate the Young's modulus (or Derjaguin-Muller-Toporov (DMT) modilus) of ZnO ETL and dissipate stress concentration at the AIP/ETL interface, effectively restraining the crack generation and improving the mechanical stability of PeSCs. The flexible PeSCs (f-PeSCs) exhibit one of the best performances so far reported with excellent stability against 6000 bending cycles at a curvature radius of 5 mm. This work thus provides an effective strategy to simultaneously improve the photovoltaic performance and mechanical stability.

Identification and Validation of Hub Genes Related to Neutrophil Extracellular Traps-Mediated Cell Damage During Myocardial Infarction.

Purpose: Studies have shown that neutrophil-mediated formation of neutrophil extracellular traps (NETs) leads to increased inflammatory response and cellular tissue damage during myocardial infarction (MI). We aimed to identify and validate possible hub genes in the process of NETs-mediated cell damage. Methods: We performed an immune cell infiltration analysis of the MI transcriptome dataset based on CIBERSORT and ssGSEA algorithms. Gene expression profiles of NETs formation (GSE178883) were used to analyze the physiological processes of peripheral blood neutrophils after phorbol myristate acetate (PMA) stimulation. Bioinformatics and machine learning algorithms were utilized to find candidate hub genes based on NETs-related genes and transcriptome datasets (GSE66360 and GSE179828). We generated the receiver operating curve (ROC) to evaluate the diagnostic value of hub genes. Next, the correlation between hub genes and immune cells was analyzed using CIBERSORT, ssGSEA and xCell algorithms. Finally, we used quantitative real-time PCR (qRT-PCR) and immunohistochemistry to verify gene expression. Results: Immune cell infiltration analysis revealed that inflammatory cells such as neutrophils were highly expressed in the peripheral blood of patients with MI. Functional analysis of differentially expressed genes (DEGs) in GSE178883 indicated that the potential pathogenesis lies in immune terms. Using weighted gene co-expression network analysis (WGCNA) and machine learning algorithms, we finally identified the seven hub genes (FCAR, IL1B, MMP9, NFIL3, CXCL2, ICAM1, and ZFP36). The qRT-PCR results showed that IL-1B, MMP9, and NFIL3 mRNA expression was up-regulated in the MI group compared to the control. Immunohistochemical results showed high MMP9, IL-1B, and NFIL3 expression in the infarcted area compared to the non-infarcted area and sham-operated groups. Conclusion: We identified seven hub genes associated with NETs-mediated cellular damage during MI. Our results may provide insights into the mechanisms of neutrophil-mediated cell injury during MI.

Achieving Bright and Long-Lived Aqueous Room-Temperature Phosphorescence of Carbon Nitrogen Dots Through In Situ Host-Guest Binding.

The development of bright and long-lived aqueous room-temperature phosphorescent (RTP) materials holds paramount importance in broadening the application scope of RTP material system. However, the conventional RTP materials usually exhibit low efficiency and short lifetime in aqueous solution. Herein, an in situ host-guest strategy is proposed to achieve cyanuric acid (CA)-derived phosphorescent carbon nitrogen dots (CNDs) composite (CNDs@CA) that demonstrates a significant enhancement of both quantum yield (QY) and lifetime mediated by water. Detailed investigations reveal that the robust hydrogen bonding networks between CNDs@CA and water effectively stabilize triplet excitons and suppress nonradiative decays, as well as facilitate efficient energy transfer from CA to CNDs, thereby prolonging the lifetime and enhancing the efficiency of RTP. The phosphorescent QY and lifetime of CNDs@CA can be increased to 26.89% (3.9-fold increase) and 951.25 ms (5.5-fold increase), respectively, with the incorporation of 50 wt% water under ambient conditions. Even in fully aqueous environments (with up to 400 wt% water added), CNDs@CA exhibits persistent water-boosted RTP properties, demonstrating exceptional stability. The robust water-boosted RTP property of CNDs@CA in aqueous solutions presents significant potential for high signal-to-noise ratio afterglow bioimaging as well as advanced information encryption.

The oral-brain axis: can periodontal pathogens trigger the onset and progression of Alzheimer's disease?

Alzheimer's disease (AD) is the most prevalent form of dementia, characterized by a progressive cognitive decline. Sporadic AD, accounting for more than 95% of cases, may arise due to the influence of environmental factors. It was reported that periodontitis, a common oral ailment, shares several risk factors with AD, including advanced age, smoking, diabetes, and hypertension, among others. Periodontitis is an inflammatory disease triggered by dysbiosis of oral microorganisms, whereas Alzheimer's disease is characterized by neuroinflammation. Many studies have indicated that chronic inflammation can instigate brain AD-related pathologies, including amyloid-ß plaques, Tau protein hyperphosphorylation, neuroinflammation, and neurodegeneration. The potential involvement of periodontal pathogens and/or their virulence factors in the onset and progression of AD by the oral-brain axis has garnered significant attention among researchers with ongoing investigations. This review has updated the periodontal pathogens potentially associated with AD, elucidating their impact on the central nervous system, immune response, and related pathological processes in the brain to provide valuable insights for future research on the oral-brain axis.

Radiation Dose and Image quality of coronary CT angiography performed with whole-heart coverage CT scanner with 0.25s rotation time in patients with irregular heart rhythm.

Objectives: To evaluate radiation exposure, image quality, and diagnostic performance of coronary CT angiography (CCTA) using the invasive coronary angiography (ICA) as the reference standard in patients with irregular heart rhythm on a 0.25 s rotation time, 16 cm coverage, single-beat, CT scanner with AI-assisted motion correction. Methods: CCTA data-sheets of 427 patients using a CT scanner with an ECG monitoring system and motion correction algorithm were collected retrospectively. All the patients were divided into two groups: regular heart rhythm (357 patients) and irregular heart rhythm (70 patients). 22 patients in irregular heart rhythm underwent ICA. Image quality and effective dose in both groups were evaluated and compared. Image quality was evaluated on 5-point scales. The diagnostic performance of CCTA in irregular heart rhythm group was compared with the results of ICA. Results: The image quality in both groups was similar (4.34 ± 0.47 vs 4.37 ± 0.48, p > 0.05). No significant difference was observed in effective dose between two groups (2.7 ± 0.7 vs 2.9 ± 1.3, p > 0.05). The diagnostic accuracy was 90.91% in a patient-based analysis, 96.97% in a vessel-based analysis, and 98.61% in a segment-based analysis. In irregular heart rhythm group, gender was an important factor affecting the number of CCTA scans in a single examination and the radiation dose exposed to the patient. Conclusions: For patients with irregular heart rhythm, a CT scanner with an ECG monitoring system and motion correction algorithm can not only reduce the radiation dose to the same level as patients with normal heart rhythms, but also ensure that the images with high diagnostic accuracy.

Biomarker Testing Journey Among Patients with Advanced Solid Tumors and Treatment Patterns by Homologous Recombination Repair Status: A Clinico-Genomic Database Study.

INTRODUCTION: Defects in the homologous recombination repair (HRR) pathway can include mutations in BRCA1 and BRCA2 (BRCAm) and other HRR genes (HRRm). These mutations are associated with a homologous recombination deficiency (HRD) phenotype. We evaluated testing journey and treatment patterns by BRCAm, HRRm, and HRD status in a real-world dataset. METHODS: Deidentified data for patients who had undergone comprehensive genomic profiling using FoundationOne®CDx were collected through December 31, 2020, from a real-world multi-tumor clinico-genomic database (CGDB) capturing data from clinics in the United States. Patients eligible for inclusion in this analysis had a confirmed diagnosis with advanced or metastatic disease between January 1, 2018, and December 31, 2019, for 1 of 15 solid tumor types. Objectives were to evaluate patient treatment patterns by BRCAm, HRRm, and HRD status and to describe the timing of when (throughout disease course) comprehensive genomic profiling was performed. RESULTS: Among 9457 patients included in the overall population with evaluable biomarker status, 7856 (83.1%) received ≥ 1 systemic therapy. Among the 7856 patients who received systemic therapy, 2324 (30.0%) underwent testing before first-line therapy, 4114 (52.4%) were tested after receiving first-line therapy and before receiving subsequent therapy (if any), 970 (12.3%) were tested after second-line therapy and before receiving subsequent therapy (if any), and 447 (5.7%) patients underwent testing after receiving third-line therapy. A higher proportion of patients with BRCAm, HRRm, or HRD-positive status were treated with poly(ADP-ribose) polymerase (PARP) inhibitors across all lines of therapy. There was no evidence of a meaningful difference in the proportion of patients who received other treatment (including chemotherapy and immunotherapy) by BRCAm, HRRm, or HRD status. CONCLUSION: The majority of patients from this real-world dataset underwent FoundationOne®CDx testing after initiation of first-line treatment. Testing appeared to influence treatment patterns, with a higher proportion of patients with BRCAm, HRRm, and HRD-positive disease receiving PARP inhibitors.

Enhancing clinical awareness: retrospective analysis of neurosyphilis cases and diagnostic predictors for early recognition and treatment.

OBJECTIVE: This is a retrospective analysis of clinical data from individuals diagnosed with neurosyphilis, aiming to enhance healthcare professionals' understanding of the disease and expedite early diagnosis and intervention. METHODS: A retrospective analysis was conducted on the clinical records of 50 patients who received a diagnosis of symptomatic neurosyphilis and were admitted to the Neurology Department during the period spanning January 2012 to December 2022. RESULTS: Clinical manifestations encompassed diverse phenotypes, with syphilitic meningitis accounting for 16% of cases, characterized by symptoms such as headache, blepharoptosis, paralysis, blurred vision, and tinnitus. Meningovascular syphilis presented in 36% of cases, exhibiting episodic loss of consciousness, limb numbness, and limb convulsion. Paralytic dementia manifested in 36% of cases, featuring symptoms such as memory loss, sluggish response, and slow movement. Tabes dorsalis was observed in 12% of cases, presenting with weakness, numbness, and staggering. Routine cerebrospinal fluid (CSF) analysis indicated abnormal white blood cell counts in 60% of patients, while biochemical testing revealed abnormal protein content in 52% of patients. Notably, statistically significant differences were observed between patients with interstitial and parenchymatous neurosyphilis (Z = 2.023, P = 0.044) in terms of CSF protein content. Electroencephalogram (EEG) results were abnormal in six patients, and imaging studies unveiled diverse findings in 46 patients. CONCLUSION: The study highlights the importance of neurological and/or ocular symptoms in diagnosing symptomatic neurosyphilis. Individuals with hypomnesia should be closely monitored for potential neurosyphilis. Integrating clinical manifestations, laboratory tests, EEG, and imaging can reduce misdiagnosis. This comprehensive approach shows promise in improving early identification and management of neurosyphilis.