Search Results (237)

Objectives: Papillary thyroid carcinoma (PTC) frequently presents with cervical lymph node metastasis, even in small tumors, and lateral lymph node involvement serves as an important prognostic factor. Therapeutic lateral neck dissection is typically recommended when nodal metastasis is clinically evident, usually including levels II–V. However, the necessity of routine level II dissection in patients without clinical or radiologic evidence of level II involvement remains controversial, given its association with increased surgical morbidity, particularly injury to the spinal accessory nerve. Identifying reliable clinicopathological predictors of occult level II metastasis may enable more selective surgical approaches that minimize unnecessary dissection while preserving oncologic safety. Therefore, this study aimed to identify clinicopathological risk factors associated with occult level II lymph node metastasis in patients with PTC who have clinically positive lateral nodes but no clinical evidence of level II involvement. Methods: We retrospectively analyzed 1247 patients who underwent thyroidectomy for PTC between 2015 and 2022. Of these, 67 patients with clinically positive lateral lymph node metastasis and clinically negative Level II nodes who underwent therapeutic lateral neck dissection were included. Clinicopathological features were compared between patients with and without occult Level II metastasis. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors. Results: Among the 67 patients analyzed, 24 (35.8%) had occult Level II metastasis. Compared to those without, patients with occult Level II metastasis had significantly larger primary tumors (2.18 ± 1.31 cm vs. 1.51 ± 1.02 cm, p = 0.024), a greater number of central lymph node metastases (5.88 ± 4.41 vs. 3.37 ± 2.66, p = 0.005), larger maximum size of metastatic central lymph node (1.44 ± 1.07 cm vs. 0.87 ± 0.48 cm, p = 0.004), and a higher number of metastatic lateral lymph nodes (7.63 ± 3.75 vs. 3.19 ± 2.21, p < 0.001). Multivariate analysis identified the number of metastatic lateral lymph node as the only independent predictor of occult Level II involvement (OR = 1.57, 95% CI: 1.213–2.044, p = 0.001). The final multivariate model demonstrated a Nagelkerke R² of 0.46. ROC curve analysis confirmed good predictive performance (AUC = 0.85), and the optimal cut-off value was ≥ 5 metastatic lateral lymph nodes. Conclusions: A substantial proportion of patients with clinically negative Level II nodes harbor occult metastasis. The number of metastatic lateral lymph nodes is an independent predictor of occult Level II involvement and may assist in tailoring the extent of lateral neck dissection in patients with PTC. Full article

This study presents a general 3 × 5 × 5 factorial experimental design to maximize the Power Coefficient (Cp) of an H-Darrieus hydrokinetic turbine equipped with external accessories. Five accessory configurations (standard, cycloidal, flat plate, curve, and blocking plate), three solidity levels, and five Tip-Speed Ratio (TSR) levels were evaluated as main factors under the hypothesis that these factors significantly influence Cp. The data analyzed were obtained from numerical simulations, and their processing was conducted using Analysis of Variance (ANOVA), linear regression models, and response surfaces in the software programs Minitab 21 and RStudio V4.4.2. ANOVA makes it possible to determine the statistical significance of the effect of each factor and their interactions on the obtained Cp, identifying the accessories, TSR, and solidity that have the greatest impact on turbine performance. The results indicate that the optimal configuration to maximize Cp includes the flat-plate accessory, a solidity of 1.0, and a TSR of 3.2. From the linear regression models, mathematical relationships describing the system’s behavior were established, while the response surface analysis identified optimal operating conditions. These findings provide an effective tool for optimizing H-Darrieus turbine designs, highlighting the positive impact of accessories on performance improvement. Full article

Human leukocyte antigen class I (HLA-I) molecules present intracellular peptides on the cell surface to enable CD8+ T cells to effectively control viral infections. Many viruses disrupt this antigen presentation pathway to evade immune detection. In this study, we demonstrate that SARS-CoV-2 Nsp1 impairs both the constitutive and interferon-γ (IFN-γ)-induced upregulation of HLA-I. Moreover, Nsp1 also blocks IFN-γ-induced expression of HLA-II. We found that, contrary to previously published work, the early SARS-CoV-2 B 1.1.7 Alpha variant lacking the accessory protein ORF8 retained full capacity to downregulate HLA-I, comparable to an ORF8-expressing wild-type isolate. While ectopic overexpression of ORF8 could reduce HLA-I surface levels, this effect was only observed at high expression levels. In contrast, moderate expression of the viral protein Nsp1 was sufficient to potently suppress both basal and IFN-γ-induced HLA-I, as well as HLA-II expression. To probe the underlying mechanism, we analyzed HLA-I-associated genes in previously published RNA-sequencing datasets and confirmed that Nsp1 reduces expression of components required for HLA-I biosynthesis and antigen processing. These findings identify Nsp1 as a key factor that impairs antigen presentation pathways, potentially contributing to the ability of SARS-CoV-2 to modulate immune recognition. Full article

Objectives: This study investigates whether scan time in the high-resolution magnetic resonance imaging (MRI) of human embryos can be reduced without compromising spatial resolution by applying zero-shot self-supervised learning (ZS-SSL), a deep-learning-based reconstruction method. Methods: Simulations using a numerical phantom were conducted to evaluate spatial resolution across various acceleration factors (AF = 2, 4, 6, and 8) and signal-to-noise ratio (SNR) levels. Resolution was quantified using a blur-based estimation method based on the Sparrow criterion. ZS-SSL was compared to conventional compressed sensing (CS). Experimental imaging of a human embryo at Carnegie stage 21 was performed at a spatial resolution of (30 μm)³ using both retrospective and prospective undersampling at AF = 4 and 8. Results: ZS-SSL preserved spatial resolution more effectively than CS at low SNRs. At AF = 4, image quality was comparable to that of fully sampled data, while noticeable degradation occurred at AF = 8. Experimental validation confirmed these findings, with clear visualization of anatomical structures—such as the accessory nerve—at AF = 4; there was reduced structural clarity at AF = 8. Conclusions: ZS-SSL enables significant scan time reduction in high-resolution MRI of human embryos while maintaining spatial resolution at AF = 4, assuming an SNR above approximately 15. This trade-off between acceleration and image quality is particularly beneficial in studies with limited imaging time or specimen availability. The method facilitates the efficient acquisition of ultra-high-resolution data and supports future efforts to construct detailed developmental atlases. Full article

Background and Objectives: The causes and clinical outcomes of renal perfusion abnormalities occurring after para-aortic lymphadenectomy (PANDx) for gynecologic malignancies are unknown. We investigated the potential involvement of accessory renal artery (ARA) obstruction in their development by reassessing perioperative contrast-enhanced computed tomography (CECT). Materials and Methods: This retrospective study investigated a clinical database to identify urinary contrast defects using CECT in all patients who had undergone PANDx between January 2020 and December 2024. The perfusion defects in the kidney detected by CECT were extracted by a gynecologic oncologist and evaluated by a radiologist and urologist for suspected obstruction of ARAs. Results: Postoperative renal contrast defects were observed in 3.8% (6/157) of patients. Renal parenchymal fibrosis, cortical atrophy, and parenchymal thinning were observed as universal findings in all patients showing renal contrast defects. In five of the six cases, ARAs supplying the infarcted renal segments were identified on preoperative CECT, and arterial obstruction was confirmed on postoperative imaging. The remaining case was considered to be latent pyelonephritis. All five patients underwent laparotomy, and preoperative CECT failed to detect ARAs. The median resected para-aortic lymph node was 23 nodes (range: 15–33) in five patients, showing no statistically significant difference compared to patients without perfusion abnormalities (p = 0.19). Postoperative serum creatinine levels remained stable. Conclusions: ARA obstruction appears to be a risk factor for segmental renal infarction after para-aortic lymphadenectomy in gynecological malignancies; however, the clinical impact on urinary function may be limited. Awareness of this potential complication is essential for gynecologic oncologists performing PANDx. Full article

Vpr, a virion-associated accessory virulence factor of HIV-1, promotes virus replication in both T cells and macrophages. Although Vpr’s early activity—antagonism of preintegration silencing and host restriction factors—has been documented, the relative contribution of virion-associated versus de novo expressed Vpr to HIV-1 replication fitness remains unclear. Here, we developed a T cell-based system that genetically separates early and late Vpr functions by combining tetracycline-inducible Vpr expression in CEM.SS T cells with vpr-deficient HIV-1 constructs and Gag p6 mutations that block Vpr packaging. CEM.SS T cells have been shown to recapitulate the positive effect of Vpr on HIV-1 replication observed in activated primary T cells. Using pairwise replication fitness assays under spreading infection conditions, we demonstrate that de novo synthesized Vpr exerts the dominant effect on HIV-1 replication in T cells, while virion-associated Vpr plays a lesser role. Somewhat unexpectedly, our findings reveal that antagonism of preintegration HIV-1 silencing by virion-associated Vpr is unlikely to be the major driver of enhanced HIV-1 replication in proliferating T cells. Instead, this function may play a more prominent role in the infection of non-dividing T cells and/or other cell types. Full article

Stroke represents a significant public health burden, ranking as a leading cause of death and disability globally. The prevalence of stroke increases with age, with ischemic stroke accounting for nearly 87% of cases globally. The pathophysiology of stroke is characterized by neuronal injury, neuroinflammation, and oxidative stress, which exacerbate brain damage and hinder recovery. Myeloid Differentiation Factor 2 (MD2), an accessory protein of Toll-like receptor 4 (TLR4), has emerged as a key player in mediating inflammatory responses in stroke. This short review discusses the molecular mechanisms by which MD2 contributes to neuroinflammation and neuronal death following stroke and highlights MD2 as a promising therapeutic target for stroke treatment. Subsequently, we investigate the potential of MD2 inhibitors, their underlying mechanisms, and the therapeutic prospects of such inhibitors in reducing stroke-induced brain damage. Full article

AIDS-related malignant lymphomas (ARLs) are the lymphomas that develop in association with HIV infection. According to the introduction of combination antiretroviral therapy (cART), the life expectancy of People Living with HIV (PLWH) has markedly improved; however, approximately one-third of PLWH have passed away from the complications of malignancies, even in well-controlled PLWH. HIV itself is not tumorigenic, and most of these tumors are due to co-infection with oncogenic viruses. γ-herpes viruses (Epstein–Barr virus: EBV and Kaposi sarcoma-associated herpesvirus: KSHV) are the most significant risk factors for ARLs. Immunodeficiency, chronic inflammation, accelerated aging, and genetic instability caused by HIV infection, as well as HIV accessory molecules, are thought to promote lymphomagenesis. The prognosis of ARLs is comparable to that of non-HIV cases in the cART era. Intensive chemotherapy with autologous stem cell transplantation is also available for relapsed/refractory ARLs. Since the early stage of HIV infection has no symptoms, significant numbers of HIV-infected individuals have not noticed HIV infection until the onset of AIDS (so-called Ikinari AIDS). Since the ratio of these patients is more than 30% in Japan, hematologists should carefully consider the possibility of HIV infection in cases of lymphoma. Even in an era of cART, ARL remains a critical complication in PLWH, warranting continuous surveillance. Full article

Fusarium oxysporum f. sp. vasinfectum (Fov) is a devastating cotton pathogen. Australian Fov strains are distinguished by their ability to infect plants without nematode interaction and are genetically distinct from global Fov, classified into two vegetative compatibility groups (VCG-01111 and VCG-01112). Here, we present chromosome-level genome assemblies of a historical isolate for each Australian Fov VCG. The end-to-end gapless genome assemblies demonstrate high contiguity and completeness, with 97.7% BUSCO completeness for both isolates. Phylogenetic analysis indicates that the Australian Fov lineages diverged from other known Fov genomes over 3.6 million years ago, while VCG-01111 and VCG-01112 separated approximately 1.1 million years ago. Comparative genomics analysis identified four accessory chromosomes unique to the Australian isolates. Functional annotations revealed 14,495 and 15,342 genes in VCG-01111 and VCG-01112, respectively, with accessory chromosomes containing significantly fewer genes than core chromosomes. Ortholog analysis uncovered unique gene clusters enriched in key metabolic pathways, pathogenicity, and cell division processes. Additionally, we identified several novel lineage-specific peptides unique to each Australian isolate. This comprehensive genomic characterization provides the first insights into the unique evolutionary history of Australian Fov, distinguishing them from global Fov races. Our findings lay the foundation for understanding the genetic factors underlying their exceptional virulence, which makes Australian Fov among the most aggressive cotton pathogens worldwide. Full article

The pandemic of Coronavirus Disease 2019 has triggered a worldwide public health emergency. Its pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has developed multiple strategies for effectively evading the host immune defenses, including inhibition of interferon (IFN) signaling. Several viral proteins of SARS-CoV-2 are believed to interfere with IFN signaling. In this study, we found that the SARS-CoV-2 accessory protein ORF7a considerably impaired IFN-activated Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling via suppression of the nuclear translocation of IFN-stimulated gene factor 3 (ISGF3) and the activation of STAT2. ORF7a dampened STAT2 activation without altering the expression and phosphorylation of Janus kinases (JAKs). A co-immunoprecipitation (co-IP) assay was performed to gather ORF7a protein, but it failed to precipitate STAT2. Interestingly, mass spectrometry and immunoblotting analyses of the ORF7a co-IP product revealed that ORF7a interacted with an RNA-binding protein, heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1), and HNRNPA2B1 was related to the inhibitory effect of ORF7a on STAT2 phosphorylation. Moreover, examination of ORF7a deletion constructs revealed that the C-terminal region of ORF7a (amino acids 96 to 122) is crucial for suppressing IFN-induced JAK/STAT signaling activation. In conclusion, we discovered that SARS-CoV-2 ORF7a antagonizes type I IFN-activated JAK/STAT signaling by interacting with HNRNPA2B1, and the C-terminal region of ORF7a is responsible for its inhibitory effect. Full article

The COVID-19 pandemic, caused by SARS-CoV-2, has had a profound impact on global health, with nearly 800 million cases reported in the Americas alone. The clinical presentation of the disease is highly variable, with approximately half of all patients experiencing severe symptoms. This variability confounds the complex interplay between immune responses and disease severity. Severe cases are often characterized by elevated levels of inflammatory cytokines. Over 88% of COVID-19 patients have multiple comorbidities; factors such as age and pre-existing conditions further modulate immune responses and contribute to the severity of the disease. While some studies have reported differences in cytokine profiles between severity groups, larger, well-designed cohorts are needed to clarify these relationships. Natural Killer cells, which are critical for the innate immune response against SARS-CoV-2, are often impaired and contribute to immune exhaustion. In addition, SARS-CoV-2 evades innate immune defenses through accessory proteins that inhibit interferon signaling and exacerbate cytokine storms and inflammation. This integrative review aims to synthesize findings from 2020 onward and provide insights into the innate immune responses induced by SARS-CoV-2 and their contributions to disease pathogenesis. Understanding cytokine dynamics, NK cell behaviors, and viral immune evasion strategies is critical for advancing therapeutic approaches. Full article

The evolution of regional anesthesia in total hip arthroplasty (THA) has significantly impacted perioperative management, particularly in older adults, where age-related physiological vulnerability requires optimized strategies. Adequate pain control is crucial in enhancing recovery, minimizing opioid consumption, and reducing complications. Traditional nerve blocks such as lumbar plexus and femoral nerve blocks have long been the mainstay of analgesia. However, they are associated with significant motor impairments, which delay mobilization and increase the fall risks. Introducing motor-sparing regional anesthesia techniques represents a substantial advancement in optimizing postoperative pain management while preserving muscle function. Motor-sparing techniques, including the pericapsular nerve group (PENG) block, supra-inguinal fascia iliaca block (SI-FIB), erector spinae plane block (ESPB), and quadratus lumborum block (QLB), have been developed to provide adequate analgesia without compromising motor control. The PENG block selectively targets the articular branches of the femoral, obturator, and accessory obturator nerves, ensuring superior pain relief while minimizing quadriceps weakness. Similarly, the SI-FIB provides extensive sensory blockade with minimal motor involvement, allowing for earlier ambulation. The ESPB and QLB extend analgesia beyond the hip region while preserving motor function, reducing opioid consumption, and facilitating early rehabilitation. Compared to traditional motor-impairing blocks, these newer techniques align with Enhanced Recovery After Surgery (ERAS) protocols by promoting early mobility and reducing the hospital length of stay. Studies suggest that motor-sparing blocks lead to improved functional recovery, lower postoperative pain scores, and decreased opioid requirements, which are critical factors in geriatric THA patients. Moreover, these techniques present a safer alternative, reducing the risk of postoperative falls—a significant concern in elderly patients undergoing hip replacement. Despite their advantages, motor-sparing nerve blocks are still evolving, and further research is necessary to standardize the protocols, optimize the dosing strategies, and evaluate the long-term functional benefits. Integrating these techniques into routine perioperative care may significantly enhance patient outcomes and revolutionize pain management in geriatric THA. As regional anesthesia advances, motor-sparing techniques will improve postoperative recovery, ensuring patient safety and functional independence. Full article

Background: The aim of this case series is to describe technical considerations and preliminary outcomes of preventive aneurysm sac embolization during fenestrated or branched EVAR (embo F/BEVAR technique). Methods: Five male patients suffering from juxtarenal or pararenal abdominal aortic aneurysms, preoperatively identified as being at “high risk” of type 2 endoleak (EL2) development, were treated with embo F/BEVAR. The patients presented at least two of these risk factors: patent inferior mesenteric artery (IMA) > 3 mm; more than three pairs of patent lumbar arteries (LAAs); more than two pairs of LAAs, associated with an accessory efferent artery or at least a pair of intercostal arteries; aneurysm thrombus volume < 40%; aneurysm sac diameter > 65 mm. Embo F/BEVAR was performed with 15 × 20 mm MReye Inconel coils (Cook Medical, Limerick, Ireland), using different aortic endografts. Results: Technical success was 100%, with no complications related to perioperative or postoperative coils implantation. An average number of 11 ± 4.4 coils/patient was deployed. No reinterventions were observed during the follow-up (12.4 ± 3.6 months). One case of EL2 (20%) was detected during the follow-up, without aneurysm sac enlargement. Conclusions: According to this preliminary experience, embo F/BEVAR technique with Inconel coils seems a feasible adjunctive procedure to manage the risk of EL2 after FEVAR or BEVAR, allowing a simple follow-up with low levels of scatter artifacts, and ensuring limited additional procedural costs. Moreover, embo F/BEVAR can be used with different endografts, requiring minimal increases in operating times. Further studies with larger cohorts of patients and longer follow-up periods are mandatory to better define the potential of this technique and its limitations. Full article

Staphylococcus aureus (S. aureus) colonizes the nasal cavities of both healthy individuals and patients with chronic rhinosinusitis (CRS) with (CRSwNP) and without (CRSsNP) nasal polyps. Treatment-resistant S. aureus biofilms and intracellular persistence are common in CRS patients, requiring the expression of specific virulence factor genes to transition into these forms. We hypothesized that S. aureus isolates from non-diseased controls, CRSsNP patients, and CRSwNP patients would exhibit distinct virulence factor patterns contributing to persistence and intracellular survival in CRS patients. Nasal swabs from seventy-seven individuals yielded S. aureus cultures in eight non-diseased controls, eight CRSsNP patients, and five CRSwNP patients. Whole-genome sequencing analyzed stress, antimicrobial resistance, and virulence genes, including plasmids and prophages. Four virulence factor gene patterns emerged: a core set (hlgA, icaC, hlgB, hlgC, hld, and aur) present in all isolates, and accessory sets, including the enterotoxin gene cluster (seo, sem, seu, sei, and sen) and a partial/complete invasive virulence factor set (splE, splA, splB, lukE, and lukD) (p = 0.001). CRSwNP isolates exhibited incomplete carriage of the core set, with frequent loss of scn, icaC, and hlgA (p < 0.05). These findings suggest that S. aureus has clusters of virulence factors that may act in concert to support the survival and persistence of the bacteria, resulting in enhanced pathogenicity. This may manifest clinically with resistant disease and refractoriness to antibiotics. Full article

Viral protein X (Vpx) is a unique accessory protein encoded by the genome of the human immunodeficiency virus type 2 (HIV-2) and lineages of the simian immunodeficiency virus of sooty mangabeys. So far, counteracting the cellular restriction factor SAMHD1 and mediating the efficient translocation of viral pre-integration complex have been recognized as key functions of Vpx; however, a thorough exploration of its effects on the cellular transcriptome and cytokine milieu has not yet been undertaken. In this study, we carried out the transcriptomic analysis of THP-1 cells and determined differential gene expressions induced by HIV-2 Vpx, utilizing vectors coding for the wild-type and K68-R70 functionally restricted proteins. Significantly altered genes were then validated and quantified through real-time quantitative PCR (qPCR); additionally, replication-competent virions were also used to confirm the findings. Moreover, we analyzed the effect of Vpx expression on the secretion of key cytokines in the medium of transfected cells. Our findings revealed that wild-type HIV-2 Vpx can significantly alter the expression of genes coding for helicases, zinc finger proteins, chaperons, transcription factors and proteins involved in DNA methylation. Differentially altered genes were involved in negative regulation of viral processes, the type I interferon-signaling pathway, DNA-template transcription, elongation, the positive regulation of interferon beta production and the negative regulation of innate immune response. Importantly, Vpx was also found to decrease the expression of HIV-1 Tat, possibly through the downregulation of a crucial splicing factor, required for the maturation of Tat. Additionally, studies on cellular cytokine milieu showed that this accessory protein induced key proinflammatory cytokines. Our study provides important information about the complex role played by HIV-2 Vpx in priming and taming the cellular environment to allow for the establishment of the infection. Full article