Anesthetic management of airway stent placement by rigid bronchoscopy with superior laryngeal nerve block while preserving spontaneous breathing: a case reportToshio Okada1), Mio Yoshida1), Tomoko Matsushita1), Yusuke Ishida1), Kinya Furukawa2), and Michihiro Murozono3)1) Department of Anesthesiology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan2) Department of Thoracic Surgery, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuo, Amimachi, Inashiki-gun, Ibaraki 300-0395, Japan3) Department of Anesthesiology, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuo, Amimachi, Inashiki-gun, Ibaraki 300-0395, JapanCorresponding author: Toshio OkadaDepartment of AnesthesiologyTokyo Medical University6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, JapanTel.: +81-03-3342-6111; Fax: +81-03-5381-6650Email: [email protected]
Glioblastoma (GBM) is the most common and aggressive brain tumor with poor outcome. Immune checkpoint inhibitors (ICIs) have been tested in GBM and, despite disappointing results, the identification of a small subgroup of responders underlies the need to improve our understanding of the tumor microenvironment (TME) immunity. The aim of this study was to determine whether the expression of selected immune checkpoints on tissue-resident memory T cells (Trm) may predict patient outcome. We conducted a single cohort observational study. Tumor samples were collected from 45 patients with histologically confirmed, IDH wild type, GBM (WHO grade IV) and processed to obtain single cell suspensions. Using multiparametric flow cytometry and uni/multivariate analyses, patients were assessed for the correlation of Trm with overall survival (OS) and progression-free survival (PFS). High and low frequency of Trm expressing PD1 and TIM3 was found to be linked to clinical outcome. In fact, low frequency of Trm expressing PD1 or TIM3 or both markers defined subgroups as independent positive prognostic factors for patient survival. On multivariate analysis, low CD8+CD103+PD1+TIM3+ Trm and KPS ≥70 were confirmed to be the most predictive independent factors associated with longer OS (HR [95%CI]: 0.14 [0.04 - 0.52] p˂0.001, 0.39 [0.16 - 0.96] p=0.04, respectively). The CD8+CD103+ Trm subgroups also resulted age-linked predictors for survival in GBM.
Despite belonging to the most abundant and widespread genus of freshwater fishes in the region, the carp gudgeons of eastern Australia (genus Hypseleotris) have proved taxonomically and ecologically problematic to science since the 19th century. Several molecular studies and a recent taxonomic revision have now shed light on the complex biology and evolutionary history that underlies this group. These studies have demonstrated that carp gudgeons include a sexual/unisexual complex (five sexual species plus an assortment of hemiclonal lineages), many members of which also co-occur with an independent sexual relative, the western carp gudgeon (H. klunzingeri). Here we fill yet another knowledge gap for this important group by presenting a detailed molecular phylogeographic assessment of the western carp gudgeon across its entire and extensive geographic range. We use a suite of nuclear genetic markers (SNPs and allozymes) plus a matrilineal genealogy (cytb) to demonstrate that H. klunzingeri s.l. also displays considerable taxonomic and phylogeographic complexity. All molecular datasets concur in recognizing the presence of multiple candidate species, two instances of historic between-species admixture, and the existence of a natural hybrid zone between two of the three candidate species found in the Murray Darling Basin. We also discuss the major phylogeographic patterns evident within each taxon. Together these analyses provide a robust molecular, taxonomic, and distributional framework to underpin future morphological and ecological investigations on this prominent member of regional freshwater ecosystems in eastern Australia.
Caseous mitral annulus calcification mimicking a cardiac tumor Henda Nèji a,b,c, Emna Bennour b,d, , Ines Baccouche a,c, Salma Kechaou a,c, Ikram Kammoun b,d, Meriem Affes a,b,cSaoussen Hantous-Zannad a,b,ca: Imaging Department, Abderrahmen Mami Hospital, Ariana – Tunisiab: Faculty of Medicine of Tunis, University Tunis El Manar, Tunisiac: Cardio-thoracic imaging Research Laboratoryd: Cardiology Department
IntroductionPancreatic neuroendocrine tumors are a subset of Neuroendocrine tumors (NET) that mainly originate from the neuroendocrine system. They account for less than 10% of total NETs and have a general incidence of 0.5 per 100,000 persons per year . Only 10 to 30% of these tumors are hormone-secreting, with the majority being insulinomas. The tumors are often found incidentally in the pancreas or GI system on imaging. Pathological specimens are generally positive for Chromogranin A and Synaptophysin but can additionally be positive for other serum markers such as Insulin, Gastrin, and VIP, depending on the subtype of NET . General management includes surgery for localized disease and surgery/chemotherapy in combination for extensive disease. Prognosis is poor for those with liver metastases, with an overall mortality rate greater than > 80%. Functional tumors are generally localized and rarely present as metastatic disease .Among functional NETs, Insulinomas are the most common. Incidence is around 1 to 3 cases per million and is usually present in the pancreas over 99% of the time . Diagnosis is established with symptomatic hypoglycemia in the setting of elevated insulin and c-peptide levels after a 72-hour fasting test. Blood glucose levels usually improve with Glucagon or Dextrose administration. These lesions are amenable to treatments such as alcohol ablation, radiofrequency ablation, embolization, or surgical resection. Surgical resection is the preferred option for isolated lesions as it is often curative . Symptomatic management of hypoglycemia involves dextrose administration and Diazoxide. Diazoxide inhibits the release of insulin from insulinoma cells and is often the only effective measure prior to surgery . Somatostatin analogs such as octreotide are also used in combination with diazoxide in more severe cases but can lead to episodes of hypoglycemia . Cases involving surgical management have a good prognosis [6,7].Malignant insulinomas only account for about 5% of all insulinomas at presentation [8,9]. In patients with distant metastases, surgical resection with lymph node dissection improves prognosis. However, the overall difference is minimal, and the data is limited in these cases . Overall, these patients do quite poorly due to limited treatment options. There are very few case reports that discuss the conversion of non-functional metastatic NET into a malignant insulinoma. This case report presents such a conversion in an elderly female patient.
Tilapia farmers would benefit tremendously if they could decrease aggression among fish. Conspecific aggression affects growth, feed conversion and general wellbeing of fish. Previous studies established an inverse relationship between blood cholesterol levels and aggression in fish, whereby a decrease in cholesterol led to an increase in aggression. The present study assessed the effect of an increase of dietary cholesterol on blood cholesterol and possible decrease in aggression of Nile tilapia Oreochromis niloticus. Nile tilapia were stocked in an outdoor recirculation system then offered one of five diets: 0% cholesterol, 0.5% cholesterol, 1% cholesterol, 1.5% cholesterol and 2% cholesterol. Five fish of each treatment were moved to a glass tank and monitored for signs of aggression for 10 minutes, twice a day. This experimental procedure was repeated five times using a new set of fish every time. Results show an increase in cholesterol levels in the blood but that there are no significant differences in aggression among treatments. Accordingly, the present study suggests that an increase in dietary cholesterol increases blood cholesterol in fish but does not have a significant effect on antagonistic patterns in Nile tilapia.
Fucosylation plays a critical role in cell-to-cell interactions and disease progression. However, the effects of fucosylation on splenocytes and their interactions with T cells remain unclear. In this study, we aimed to explore the transcriptome profiles of splenocytes deficient in fucosyltransferase (FUT) 1, an enzyme that mediates fucosylation, and investigate their impact on the proliferation and differentiation of T cells. We analyzed and compared the transcriptomes of splenocytes isolated from Fut1 knockout (KO) mice and those from wild-type (WT) mice using RNA-seq. Additionally, we examined the effects of Fut1 KO splenocytes on CD4 T cell proliferation and differentiation, in comparison to WT splenocytes, and elucidated the mechanisms involved. The comparative analysis of transcriptomes between Fut1 KO and WT splenocytes revealed that thrombospondin (THBS)-1, among the genes related to immune response and inflammation, was the most highly downregulated gene in Fut1 KO splenocytes. The reduced expression of THBS1 was further confirmed using qRT-PCR and flow cytometry. In coculture experiments, Fut1 KO splenocytes promoted the proliferation of CD4 T cells and drove their differentiation towards Th1 and Th17 cells, compared to WT splenocytes. Moreover, the levels of IL-2, IFN-γ and IL-17 were increased, while IL-10 was decreased, in T cells cocultured with Fut1 KO splenocytes compared to those with WT splenocytes. These effects of Fut1 KO splenocytes on T cells were reversed when THBS1 was replenished. Taken together, our results demonstrate that splenocytes with Fut1 deficiency promote CD4 T cell proliferation and Th1/Th17 differentiation at least in part through THBS1 downregulation.
Carbon dioxide can be converted into functional heterocycles known as cyclic carbonates, whose recent reactivity has been expanded towards the formation of tailor-made engineering polymers. This minireview gives an overview of the most topical developments in this area with a special focus on the synthetic methods employed to prepare these CO2 based synthons. In addition, their application potential in the area of polymer science using a variety of polymerization techniques is discussed that have in common the ring-opening of the carbonate monomers. Future perspectives are provided that provide impetus for the scientific communities aligning research to the use of sustainable processes for polymers from recyclable carbon sources such as CO2.
Since 2004, the U.S. Centers for Disease Control and Prevention (CDC) Influenza Division (ID) has supported seven countries in the Eastern Mediterranean region and the World Health Organization Regional Office for the Eastern Mediterranean to establish and strengthen influenza surveillance. There has been substantial growth in influenza surveillance capacities in the region over two decades that demonstrates commitment by national governments to strengthen national programs and contribute to global influenza surveillance. CDC ID remains committed to continuing support to the region and supporting partners to translate surveillance data into policies and programs effectively.
Several Asian countries are undergoing rapid economic development driven by diverse factors. This development is leading to continuous land use changes, including deforestation, urbanization, and agricultural conversion. Such transformations threaten essential ecosystem functions and services, like food provision, climate regulation, and cultural benefits. Land-use changes, influenced by economic activities and policies, carry extensive consequences, impacting ecosystem productivity, water resources, and climate stability. Remote sensing technology significantly aids in monitoring and quantifying these changes, offering valuable insights for land management and policy decisions. The NASA Land-Cover and Land-Use Change (LCLUC) Program within NASA’s Earth Science Division program aims to establish global assessments of land changes using space-based methods (https://lcluc.umd.edu/). The South/Southeast Asia Research Initiative (SARI), funded by NASA LCLUC, focuses on advancing LCLUC science in the region and fostering collaborations between US and Asian researchers. Utilizing geospatial data from remote sensing and models, SARI employs a comprehensive approach, considering biophysical and socioeconomic aspects of land systems and their interactions. SARI has been enhancing LCLUC science through science projects, partnerships, training, workshops, and capacity building exchanges since 2015. This Special Issue, stemming from SARI meetings in the Philippines and Malaysia in 2018 and 2019, gathers articles focusing on LCLUC, degradation, and ecosystem services in Asia. Of over 90 submissions, 30 have been accepted, providing insights into these issues and their regional impacts. The articles are summarized into various sub-themes below.
Mutations in T lymphocytes (T-cells) are informative quantitative markers for environmental mutagen exposures, but risk extrapolations from rodent models to humans also requires understanding how T-cell development and proliferation kinetics impact mutagenic outcomes. Rodent studies have shown that patterns in chemical-induced mutations in the hypoxanthine-guanine phosphoribosyltransferase (Hprt) gene of T-cells differ between lymphoid organs. The current work was performed to obtain knowledge of the relationships between maturation events during T-cell development and changes in chemical-induced mutant frequencies over time in differing immune compartments of a mouse model. A novel RTPCR based method was developed to determine the specific T-cell receptor beta (Tcrb) gene mRNA expressed in mouse T-cell isolates, enabling sequence analysis of the PCR product that then identifies the specific hypervariable CDR3 junctional region of the expressed Tcrb gene for individual isolates. Characterization of spontaneous Hprt mutant isolates from the thymus, spleen, and lymph nodes of control mice for their Tcrb gene expression found evidence of in vivo clonal amplifications of Hprt mutants and their trafficking between tissues in the same animal. Concurrent analyses of Hprt mutations and Tcrb gene rearrangements in different lymphoid tissues of control versus N-ethyl-N-nitrosourea-exposed mice permitted elucidation of the localization and timing of mutational events in T-cells, establishing that mutagenesis occurs primarily in the pre-rearrangement replicative period in pre-thymic/thymic populations. These findings demonstrate that chemical-induced mutagenic burden is determined by the combination of mutagenesis and T-cell clonal expansion, processes with roles in immune function and the pathogenesis of autoimmune disease and cancer.
In March 2023, over 800 researchers, clinicians, patients, survivors, and advocates from the pediatric oncology community met to discuss the progress, plans, and future priorities of the National Cancer Institute’s Childhood Cancer Data Initiative. We present here the status of the initiative’s efforts in building its data ecosystem to provide access to childhood cancer data; updates on the Molecular Characterization Initiative; plans for implementing a Coordinated National Initiative for Rare Cancers in Children and Young Adults; and efforts to establish a framework for computable consent.
In recent years, penetration testing (pen-testing) has emerged as a crucial process for evaluating the security level of network infrastructures by simulating real-world cyber-attacks. Automating pen-testing through reinforcement learning (RL) facilitates more frequent assessments, minimizes human effort, and enhances scalability. However, real-world pen-testing tasks often involve incomplete knowledge of the target network system. Effectively managing the intrinsic uncertainties via partially observable Markov decision processes (POMDPs) constitutes a persistent challenge within the realm of pen-testing. Furthermore, RL agents are compelled to formulate intricate strategies to contend with the challenges posed by partially observable environments, thereby engendering augmented computational and temporal expenditures. To address these issues, this study introduces EPPTA (Efficient POMDP-Driven Penetration Testing Agent), an agent built on an asynchronous RL framework, designed for conducting pen-testing tasks within partially observable environments. We incorporate an implicit belief module in EPPTA, grounded on the belief update formula of the traditional POMDP model, which represents the agent’s probabilistic estimation of the current environment state. Furthermore, by integrating the algorithm with the high-performance RL framework, Sample Factory, EPPTA significantly reduces convergence time compared to existing pen-testing methods, resulting in an approximately 20-fold acceleration. Empirical results across various pen-testing scenarios validate EPPTA’s superior task reward performance and enhanced scalability, providing substantial support for efficient and advanced evaluation of network infrastructure security.
This study aims to investigate the effect of NaOH immersion time and concentration on the activation of carbon from Oil Palm Frond (OPF), specifically focusing on the surface morphology and characteristics as the electrodes to biobattery application. The method employed involves carbonization and activation with NaOH at various concentrations: 0.5 M, 1 M, 1.5 M, 2 M, and 2.5 M, along with different immersion times of 12, 18, 24, 30, and 36 hours. Subsequently, the activated carbon is analyzed using a Scanning Electron Microscope (SEM) to observe its morphology, and the Brunauer Emmett Teller (BET) method is utilized to determine the carbon surface area. Furthermore, a voltage test uses a multimeter to assess the electric potential properties. Another outcome of this study is developing a prototype bio-battery POWER. Activated carbon from oil palm frond (OPF) testing resulted in 1 M NaOH, giving the highest surface area of 336.493 m 2g -1, and immersion time at 30 hours gave the optimum result of 396,808 m 2g -1. At the same time, the biobattery electrical test voltage of 0,653 V at a concentration of 1 M and 0,902 V at 30 hours of immersion.
The cochlea forms a key element of the human auditory system in the temporal bone. Damage to the cochlea continues to produce significant impairment for sensory reception of environmental stimuli. To improve this impairment, the optical cochlear implant forms a new research approach. A prerequisite for this method is to understand how light propagation, as well as scattering, reflection and absorption, takes place within the cochlea. We offer a method to study the light distribution in the human cochlea through phantom materials and Monte-Carlo simulations. The calculation of an angular distribution after scattering requires a phase function. Often approximate functions like Henyey-Greenstein, two-term Henyey-Greenstein or Legendre polynomial decompositions are used as phase function. An alternative is to exactly calculate a Mie distribution for each scattering event. This method provides a better fit to the data measured in this work.