A practical method for the preparation of (diacetoxyiodo)arene ArI(OAc)2 is described. The use of commercially available sodium hypochlorite pentahydrate (NaClO·5H2O) enabled safe, rapid, and ...inexpensive oxidation of iodoarenes with electron-withdrawing and -donating substituents. The method allows tandem divergent access to synthetically useful organo-λ3-iodanes such as hydroxyl(tosyloxy)iodobenzene, iodosylbenzene, iodonium ylide, etc.
BACKGROUNDIn patients with fever or inflammation of unknown origin (fever of unknown origin FUO or inflammation of unknown origin IUO, respectively), expert consensus recommends the use of positron ...emission tomography with fluorine-18-fluorodeoxy glucose combined with computed tomography (FDG-PET/CT) when standard work-up fails to identify diagnostic clues. However, the clinical variables associated with successful localization of the cause by FDG-PET/CT remain uncertain. Moreover, the long-term outcomes of patients with unexplained FUO or IUO after negative FDG-PET/CT results are unknown. Therefore, we assessed predictors of successful diagnosis of FUO or IUO caused by FDG-PET/CT and associations of spontaneous remission of symptoms with FDG-PET/CT results. METHODSAll patients with FUO or IUO, who underwent FDG-PET/CT from 2013 to 2019 because diagnostic work-up failed to identify a cause, were retrospectively included. We calculated the diagnostic yield and performed multivariable logistic regression to assess characteristics previously proposed to be associated with successful localization of FUO or IUO causes. We also assessed whether the FDG-PET/CT results were associated with spontaneous remissions. RESULTSIn total, 50 patients with diagnostically challenging FUO or IUO (35 with FUO and 15 with IUO) were assessed. Other than one case of infection, all the identified causes were either malignancy or non-infectious inflammatory diseases (each with 18 patients), and FDG-PET/CT correctly localized the cause in 29 patients (diagnostic yield = 58%). None of the proposed variables was associated with successful localization. All 13 patients with sustained unexplained cause remained alive (median follow-up, 190 days). Spontaneous remission was observed in 4 of 5 patients with a negative FDG-PET/CT, and 1 of 8 with a positive result (P = 0.018). CONCLUSIONIn the current cohort, the proposed variables were not predictive for successful localization by FDG-PET/CT. A negative FDG-PET/CT scan may be prognostic for spontaneous remission in patients with sustained FUO or IUO.
Hydrogen is expected to be utilized for decarbonization of energy systems. One of the barriers to society’s implementation of hydrogen use is transportation costs. One method proposed to reduce ...transportation costs is to inject hydrogen into the existing natural gas grid and transport it as a gas mixture. Since the characteristics of the blended gas vary depending on the hydrogen concentration, the deployment of mixed gas transportation requires concentration control in the gas grid and in the gas supplied to customers. More specifically, the distribution of hydrogen concentration in the grid will vary spatially and temporally depending on the facility layout and operating conditions of the gas grid, and that complicates management of the hydrogen concentration in the grid. Therefore, this study proposed an evaluation indicator that enables selection of robust pathways that can stabilize hydrogen concentration at demand points. To avoid gas merging from multiple supply points in the gas grid and to unify the supply sources, a consolidation path ratio was defined using the gas distribution ratio as an indicator. This indicator was applied to a simulated grid, and the mainstream pathway was identified, even if the supply pressure changed. By shutting off the non-mainstream pathway, a pathway with stable demand point concentrations was established. Use of the consolidation path ratio is expected to allow robust paths to be extracted for demand points connected to the mixed gas grid.
Defects in T-cell immunity to SARS-CoV-2 have been linked to an increased risk of severe COVID-19 (even after vaccination), persistent viral shedding and the emergence of more virulent viral ...variants. To address this T-cell deficit, we sought to prepare and cryopreserve banks of virus-specific T cells, which would be available as a partially HLA-matched, off-the-shelf product for immediate therapeutic use. By interrogating the peripheral blood of healthy convalescent donors, we identified immunodominant and protective T-cell target antigens, and generated and characterized polyclonal virus-specific T-cell lines with activity against multiple clinically important SARS-CoV-2 variants (including 'delta' and 'omicron'). The feasibility of making and safely utilizing such virus-specific T cells clinically was assessed by administering partially HLA-matched, third-party, cryopreserved SARS-CoV-2-specific T cells (ALVR109) in combination with other antiviral agents to four individuals who were hospitalized with COVID-19. This study establishes the feasibility of preparing and delivering off-the-shelf, SARS-CoV-2-directed, virus-specific T cells to patients with COVID-19 and supports the clinical use of these products outside of the profoundly immune compromised setting (ClinicalTrials.gov number, NCT04401410).
Purpose
Diagnostic and neurosurgical procedures require the precise localization of small intracranial arteries, but this may be difficult using conventional computed tomography angiography (CTA). ...This study was conducted to evaluate the quality of CTA images acquired using a prototype ultra-high-resolution computed tomography (U-HRCT) system compared with those acquired using a conventional computed tomography (C-CT) system.
Materials and methods
From July through September 2015, 10 adult patients (6 women and 4 men) previously scanned by C-CT were examined using U-HRCT to locate and assess cerebral aneurysms. The bilateral ophthalmic artery (Opth A), anterior choroidal artery (Acho A), and thalamoperforating arteries (TPAs) were visually evaluated in randomly presented CTA images. Images were graded on a 5-point scale, and differences in scores between U-HRCT and C-CT were evaluated by the Wilcoxon signed-rank test. A
p
value < 0.05 was considered statistically significant.
Results
Visual evaluation scores for images of the Opth A, Acho A, and TPAs were significantly higher for U-HRCT than for C-CT. U-HRCT images achieved good visualization (score > 3) for C-CT images with poor visualization (score < 3) in 66.7–100% of all the small arteries.
Conclusion
U-HRCT is superior to C-CT for detecting and evaluating clinically significant small intracranial arteries.
Reliable and sensitive characterization assays are important determinants of the successful clinical translation of immunotherapies. For the assessment of cytolytic potential, the chromium 51 (
Cr) ...release assay has long been considered the gold standard for testing effector cells. However, attaining the approvals to access and use radioactive isotopes is becoming increasingly complex, while technical aspects i.e. sensitivity, short (4-6 hours) assay duration may lead to suboptimal performance. This has been the case with our ex vivo expanded, polyclonal (CD4+ and CD8+) multivirus-specific T cell (multiVST) lines, which recognize 5 difficult-to-treat viruses Adenovirus (AdV), BK virus (BKV), cytomegalovirus (CMV), Epstein Barr virus (EBV), and human herpes virus 6 (HHV6) and when administered to allogeneic hematopoietic stem cell (HCT) or solid organ transplant (SOT) recipients have been associated with clinical benefit. However, despite mediating potent antiviral effects
, capturing
cytotoxic potential has proven difficult in a traditional
Cr release assay. Now, in addition to cytotoxicity surrogates, including CD107a and Granzyme B, we report on an alternative, vital dye -based, flow cytometric platform in which superior sensitivity and prolonged effector:target co-culture duration enabled the reliable detection of both CD4- and CD8-mediated
cytolytic activity against viral targets without non-specific effects.
Purpose:
Adoptively transferred, ex vivo expanded multi-antigen-targeted T cells (multiTAA-T) represent a new, potentially effective, and nontoxic therapeutic approach for patients with breast cancer ...(BC). In this first-in-human trial, we investigated the safety and clinical effects of administering multiTAA T cells targeting the tumor-expressed antigens, Survivin, NY-ESO-1, MAGE-A4, SSX2, and PRAME, to patients with relapsed/refractory/metastatic BC.
Materials and methods:
MultiTAA T-cell products were generated from the peripheral blood of heavily pre-treated patients with metastatic or locally recurrent unresectable BC of all subtypes and infused at a fixed dose level of 2 × 107/m2. Patients received two infusions of cells 4 weeks apart and safety and clinical activity were determined. Cells were administered in an outpatient setting and without prior lymphodepleting chemotherapy.
Results:
All patients had estrogen receptor/progesterone receptor positive BC, with one patient also having human epidermal growth factor receptor 2-positive. There were no treatment-related toxicities and the infusions were well tolerated. Of the 10 heavily pre-treated patients enrolled and infused with multiTAA T cells, nine had disease progression while one patient with 10 lines of prior therapies experienced prolonged (5 months) disease stabilization that was associated with the in vivo expansion and persistence of T cells directed against the targeted antigens. Furthermore, antigen spreading and the endogenous activation of T cells directed against a spectrum of non-targeted tumor antigens were observed in 7/10 patients post-multiTAA infusion.
Conclusion:
MultiTAA T cells were well tolerated and induced disease stabilization in a patient with refractory BC. This was associated with in vivo T-cell expansion, persistence, and antigen spreading. Future directions of this approach may include additional strategies to enhance the therapeutic benefit of multiTAA T cells in patients with BC.
PDF
