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Background: Klebsiella pneumoniae invasive syndrome (KPIS) is characterized by primary pyogenic liver abscess associated with metastatic infections. Although rare, Klebsiella endocarditis carries a high mortality risk., Case Presentation: A 60-year-old lady with type II diabetes mellitus presented with fever, malaise, right hypochondriac pain and vomiting for two weeks. Ultrasound abdomen revealed a collection within liver, and distended gallbladder with echogenic debris within. 3 days after ultrasound guided pigtail drainage of gallbladder empyema, newly presence murmur detected. Pus, urine, and blood cultures obtained were positive for Klebsiella pneumonia. Echocardiogram exhibited oscillating mass attached to anterior mitral valve leaflet. After 6 weeks of intravenous ceftriaxone, follow-up echocardiogram and ultrasound showed complete resolution of mitral valve vegetation, hepatic and gallbladder collection., Conclusion: Concomitant extrahepatic infective endocarditis (IE) should raise concerns in daily practice for patients with Klebsiella pneumoniae liver abscesses, despite the rarity of Klebsiella endocarditis. In the absence of diagnostic suspicion, antibiotic treatment regimens may be shortened, and adverse effects from IE infection may ensue., (© 2024. The Author(s).)

Extracellular vesicles (EVs) have emerged as a promising source of disease biomarkers for noninvasive early stage diagnoses, but a bottleneck in EV sample processing restricts their immense potential in clinical applications. Existing methods are limited by a low EV yield and integrity, slow processing speeds, low sample capacity, and poor recovery efficiency. We aimed to address these issues with a high-throughput automated workflow for EV isolation, EV lysis, protein extraction, and protein denaturation. The automation can process clinical urine samples in parallel, resulting in protein-covered beads ready for various analytical methods, including immunoassays, protein quantitation assays, and mass spectrometry. Compared to the standard manual lysis method for contamination levels, efficiency, and consistency of EV isolation, the automated protocol shows reproducible and robust proteomic quantitation with less than a 10% median coefficient of variation. When we applied the method to clinical samples, we identified a total 3,793 unique proteins and 40,380 unique peptides, with 992 significantly upregulated proteins in kidney cancer patients versus healthy controls. These upregulated proteins were found to be involved in several important kidney cancer metabolic pathways also identified with a manual control. This hands-free workflow represents a practical EV extraction and profiling approach that can benefit both clinical and research applications, streamlining biomarker discovery, tumor monitoring, and early cancer diagnoses.

We have demonstrated a compact and cost-effective ytterbium-doped all-fiber laser operating at 976 nm. By utilizing a commercially available ytterbium-doped fiber with a length of only 18 cm, we achieved a lasing power of 10.3 W, with a slope efficiency of 25.4%. To our knowledge, our work presents the shortest gain fiber ever documented in the literature capable of delivering tens-of-watt 976-nm lasing power. The design is compatible with conventional fiber components, simplifying the monolithic assembly process. Notably, the incorporation of such a short gain fiber obviated the need for additional measures to suppress the strong 1.03-µm emission.

Rationale: Hashimoto's thyroiditis (HT) is a common autoimmune disease. However, its presentation and management in the context of COVID-19 are unclear, and COVID-19-triggered HT, along with myopathy and persistent creatine kinase (CK) levels, have not been previously reported. Moreover, no literature review is currently available on HT in the context of COVID-19. This study is a case report and systematic review of the literature., Patient Concerns: A 33-year-old man was admitted with acute-onset myalgia, anosmia, loss of taste, fever, and upper respiratory tract symptoms., Diagnoses: He was diagnosed with coronavirus disease (COVID-19) during hospitalization and had abnormal CK levels. The elevated CK level persisted even after the resolution of COVID-19. After excluding myopathies and cardiac factors, HT was diagnosed., Interventions: CK levels did not decrease appreciably until 14 d after levothyroxine administration., Outcomes: The patient was discharged from the hospital in good health. In the systematic literature review, 7 case reports on COVID-19-associated HT were observed, although no incidence of associated myopathy or persistent elevation of CK was noted., Lessons: This case report highlights the potential link between COVID-19 and autoimmune thyroid diseases. In particular, this study underscores the significance of recognizing new-onset autoimmune thyroid disease in COVID-19-positive patients with elevated CK levels that cannot be attributed to other factors. This systematic review offers additional perspectives for diagnosing and managing HT in COVID-19 settings. Overall, the findings of this study could have important clinical implications for the care of COVID-19 patients, as early identification and treatment of autoimmune thyroid disease could help prevent long-term complications. Additional research is essential to elucidate the fundamental correlations between COVID-19 and HT and assess the effectiveness of therapeutic approaches for autoimmune thyroid conditions related to COVID-19., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been recognized as genetic risk factors for Parkinson's disease (PD). However, compared to cancer, fewer genetic mutations contribute to the cause of PD, propelling the search for protein biomarkers for early detection of the disease., Methods: Utilizing 138 urine samples from four groups, healthy individuals (control), healthy individuals with G2019S mutation in the LRRK2 gene (non-manifesting carrier/NMC), PD individuals without G2019S mutation (idiopathic PD/iPD), and PD individuals with G2019S mutation (LRRK2 PD), we applied a proteomics strategy to determine potential diagnostic biomarkers for PD from urinary extracellular vesicles (EVs)., Results: After efficient isolation of urinary EVs through chemical affinity followed by mass spectrometric analyses of EV peptides and enriched phosphopeptides, we identify and quantify 4476 unique proteins and 2680 unique phosphoproteins. We detect multiple proteins and phosphoproteins elevated in PD EVs that are known to be involved in important PD pathways, in particular the autophagy pathway, as well as neuronal cell death, neuroinflammation, and formation of amyloid fibrils. We establish a panel of proteins and phosphoproteins as novel candidates for disease biomarkers and substantiate the biomarkers using machine learning, ROC, clinical correlation, and in-depth network analysis. Several putative disease biomarkers are further partially validated in patients with PD using parallel reaction monitoring (PRM) and immunoassay for targeted quantitation., Conclusions: These findings demonstrate a general strategy of utilizing biofluid EV proteome/phosphoproteome as an outstanding and non-invasive source for a wide range of disease exploration., (© 2023. The Author(s).)

Translating the research capability and knowledge in cancer signaling into clinical settings has been slow and ineffective. Recently, extracellular vesicles (EVs) have emerged as a promising source for developing disease phosphoprotein markers to monitor disease status. This study focuses on the development of a robust data-independent acquisition (DIA) using mass spectrometry to profile urinary EV phosphoproteomics for renal cell cancer (RCC) grades differentiation. We examined gas-phase fractionated library, direct DIA (library-free), forbidden zones, and several different windowing schemes. After the development of a DIA mass spectrometry method for EV phosphoproteomics, we applied the strategy to identify and quantify urinary EV phosphoproteomes from 57 individuals representing low-grade clear cell RCC, high-grade clear cell RCC, chronic kidney disease, and healthy control individuals. Urinary EVs were efficiently isolated by functional magnetic beads, and EV phosphopeptides were subsequently enriched by PolyMAC. We quantified 2584 unique phosphosites and observed that multiple prominent cancer-related pathways, such as ErbB signaling, renal cell carcinoma, and regulation of actin cytoskeleton, were only upregulated in high-grade clear cell RCC. These results show that EV phosphoproteome analysis utilizing our optimized procedure of EV isolation, phosphopeptide enrichment, and DIA method provides a powerful tool for future clinical applications., Competing Interests: Conflict of interests The authors declare a competing financial interest. A. I. and W. A. T. are principals at Tymora Analytical Operations, which developed EVtrap beads and commercialized PolyMAC enrichment kit., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Gout is the most common type of inflammatory arthritis, and its impact on cardiovascular health and quality of life is often underestimated. The prevalence and incidence of gout are increasing globally. Further, ischemic heart disease (IHD) and chronic kidney disease (CKD) are prevalent in gout patients. Some unmet needs for gout management include physicians' low initiation rate of urate-lowering therapy (ULT) and poor treatment adherence in patients with gout. There is also a lack of randomized controlled trials that establish safe doses of acute and long-term treatment for gout, particularly in patients with IHD and stage 4 CKD and above (including end-stage renal failure). Furthermore, there is also a lack of studies showing optimal serum uric acid (SUA) target and validated clinical outcome measures, including disease activity and remission criteria for gout tailored to treat-to-target approaches and the high cost of newer gout medications. The causal relationship between asymptomatic hyperuricemia or gout with comorbidities such as IHD and CKD has yet to be fully elucidated. There is a pressing need for collaborative international efforts to address the overall suboptimal management of gout., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Lee et al.)

Background and Aim: Real-world data on sofosbuvir/velpatasvir with and without ribavirin (SOF/VEL ± RBV), particularly among patients with genotype 3 (GT3) decompensated cirrhosis, prior treatment, coinfection, and hepatocellular carcinoma (HCC), are scarce. We aimed to assess the efficacy and safety of SOF/VEL ± RBV in a real-world setting that included both community and incarcerated GT3 hepatitis C virus (HCV) patients., Methods: We included all GT3 HCV patients treated with SOF/VEL ± RBV in our institution. The primary outcome measure was the overall sustained virological response 12 weeks after treatment (SVR12), reported in both intention-to-treat (ITT) and per-protocol analyses. The secondary outcome measures were SVR12 stratified by the presence of decompensated cirrhosis, prior treatment, HCC, and HIV/hepatitis C virus coinfection and the occurrence rate of serious adverse events requiring treatment cessation or hospitalization., Results: A total of 779 HCV patients were treated with 12 weeks of SOF/VEL ± RBV, of which 85% were treated during incarceration. Among the 530 GT3 HCV patients, 31% had liver cirrhosis, and 6% were treatment-experienced. The overall SVR12 for GT3 was 98.7% (95% confidence interval: 97.3%, 99.5%) and 99.2% (95% confidence interval: 98.1%, 99.8%) in ITT and per-protocol analyses, respectively. High SVR12 was also seen in ITT analysis among GT3 HCV patients with decompensated cirrhosis (88%), prior treatment (100%), HCC (100%), and HIV/hepatitis B virus coinfection (100%). Apart from one patient who developed myositis, no other serious adverse events were observed., Conclusion: The SOF/VEL ± RBV is a safe and efficacious treatment option for GT3 HCV patients in a real-world setting. SOF/VEL with RBV may be considered for decompensated GT3 HCV patients., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

We theoretically explore the mechanism in a thulium Q -switched ytterbium-doped all-fiber fiber laser using a set of rate equations to model the correlations between the photons and the five energy levels of thulium involved in the Q switching mechanism. We demonstrate that by coupling with a gain-switched resonator, the Q -switched laser is stabilized up to the maximum pulsing rate that is limited by the lifetime of level 3 H 5 . To the best of our knowledge, this is the first study that revealed that level 3 H 5 plays an essential role in reinitialization, achieving sequential pulses, and limiting the maximum repetition rate.

In this paper, we proposed and numerically demonstrated a novel method to effectively minimize Fresnel reflection from a perpendicularly cleaved fiber using a uniform fiber Bragg grating (FBG) inscribed at the fiber end. By matching the reflectivity of an in-line FBG with the reflectivity caused by the glass-air boundary, the FBG acts as a virtual boundary, which provides destructive interference and suppresses Fresnel reflection. We achieved an anti-reflection FBG with a return loss of more than 80 dB by ensuring that the product of the index contrast and grating period number is almost constant, with a value of 0.2695.

Intense lensless intracavity focusing in a saturable absorber Q-switched all-fiber laser resonator by use of loss arrangement and mode-field-area mismatch between the fibers is investigated for the first time. The intracavity power distribution was related to the locations and values of the cavity losses as the saturable absorption loss, the reflection loss of the output coupler, and the splicing loss between the gain fiber and the absorber fiber. With a mode-field-area mismatch and a reduced splicing loss with the gain fiber, a power density in the absorber fiber was achieved that was 11.9 times higher than that in the gain fiber.

We propose and demonstrate an all-fiber self-Q-switched erbium laser system that is saturable-absorber Q switched by the mismatch of the mode-field areas in the resonator and stabilized with a saturable-amplifier pump switch. Sequential pulses with a pulse energy of 8-6 microJ and a pulse duration of 80-320 ns, corresponding to a pulse repetition rate of 0.25-1 kHz, were obtained using a cw 980 nm laser-diode pump. A peak pulse power of near 100 W was achieved.