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Adverse events in the thyroid: Anti–programmed cell death–1 (PD-1) antibody blockade has revolutionized cancer treatment by enhancing immune responses against tumors. However, anti–PD-1 treatment can also induce immune-related adverse events by promoting autoreactive immune responses. In this study, Yasuda et al. investigated the immune cell type responsible for promoting destructive thyroiditis, a common adverse event observed in patients treated with anti–PD-1 antibody. The authors found that CD4+ T cells are required for the onset of destructive thyroiditis in a mouse model, which was supported by analysis of circulating CD4+ T cells isolated from patients. These results suggest that CD4+ T cells may mediate destructive thyroiditis in patients with cancer after anti–PD-1 treatment. Immune-related adverse events induced by anti–programmed cell death–1 antibodies (PD-1-Ab), including destructive thyroiditis (thyroid-irAE), are thought to be caused by activated T cells. However, the T cell subsets that are directly responsible for damaging self-organs remain unclear. To clarify which T cell subsets are involved in the development of thyroid-irAE, a mouse model of thyroid-irAE was analyzed. PD-1-Ab administration 2.5 months after immunization with thyroglobulin caused destructive thyroiditis. Thyroiditis was completely prevented by previous depletion of CD4+ T cells and partially prevented by depleting CD8+ T cells. The frequencies of central and effector memory CD4+ T cell subsets and the secretion of interferon-γ after stimulation with thyroglobulin were increased in the cervical lymph nodes of mice with thyroid-irAE compared with controls. Histopathological analysis revealed infiltration of CD4+ T cells expressing granzyme B in thyroid glands and major histocompatibility complex class II expression on thyrocytes in mice with thyroid-irAE. Adoptive transfer of CD4+ T cells from cervical lymph nodes in mice with thyroid-irAE caused destruction of thyroid follicular architecture in the irradiated recipient mice. Flow cytometric analyses showed that the frequencies of central and effector memory CD4+ T cells expressing the cytotoxic marker CD27 were higher in peripheral blood mononuclear cells collected from patients with thyroid-irAE induced by PD-1-Ab versus those without. These data suggest a critical role for cytotoxic memory CD4+ T cells activated by PD-1-Ab in the pathogenesis of thyroid-irAE. [ABSTRACT FROM AUTHOR]

This study was aimed to assess the outcomes of simultaneous phototherapeutic keratectomy (PTK) and photoastigmatic keratectomy (PAK), with special attention to astigmatic correction. We comprised 70 eyes of 70 patients who underwent simultaneous PTK and PAK in patients having granular corneal dystrophy and band keratopathy with refractive astigmatism of 1 diopter (D) or more. Preoperatively and 6 months postoperatively, we assessed corrected uncorrected distance visual acuity (UDVA), distance visual acuity (CDVA), manifest spherical equivalent, refractive astigmatism, corneal astigmatism, and higher-order aberrations (HOAs). LogMAR CDVA significantly improved, from 0.27 ± 0.27 preoperatively, to 0.13 ± 0.21 postoperatively (Paired t test, p < 0.001). LogMAR UDVA also significantly improved, from 0.70 ± 0.32 preoperatively, to 0.57 ± 0.41 postoperatively (p = 0.043). Refractive astigmatism significantly decreased, from 2.12 ± 0.95 D preoperatively, to 0.89 ± 0.81 D postoperatively (p < 0.001). Corneal astigmatism also significantly decreased, from 2.17 ± 0.90 D preoperatively, to 1.08 ± 0.71 D postoperatively (p < 0.001). Corneal HOAs did not significantly change, from 0.54 ± 0.30 µm preoperatively, to 0.48 ± 0.20 µm postoperatively (p = 0.140). No significant complications occurred in any eye. Simultaneous PTK and PAK treatment is effective not only for improving visual acuity, but also for reducing astigmatism. [ABSTRACT FROM AUTHOR]

Multilayered metal–organic frameworks (MOF) thin films, called MOF-on-MOF thin films, generate integrated and multiple functionalities toward high-performance sensing, electrochemical, and optical devices. Although epitaxy at the MOF/MOF interfaces in these multilayered MOF films plays a crucial role for high functionalities, the effect of structural consistency at a molecular scale at the epitaxial interface on the quality of the films (e.g., crystallite size and degree of orientation of MOF-on-MOF thin films) has not been explored. Here, we report the factors governing such physical parameters by revealing a relationship between lattice mismatch ratios and orientations of MOF-on-MOF thin films with epitaxial interfaces (referred as to "e-MoM thin films"). Highly oriented e-MoM thin films were successfully obtained by considering not only lattice mismatch ratios but also stacking order depending on the lattice parameters of MOF components. Because of the chemical and structural tunability of e-MoM materials, the present finding will offer insight into fabricating e-MoM thin films for designing future MOF-based devices. [ABSTRACT FROM AUTHOR]

We previously reported that ROR1 is a crucial downstream gene for the TTF‐1/NKX2‐1 lineage‐survival oncogene in lung adenocarcinoma, while others have found altered expression of ROR1 in multiple cancer types. Accumulated evidence therefore indicates ROR1 as an attractive molecular target, though it has yet to be determined whether targeting Ror1 can inhibit tumor development and growth in vivo. To this end, genetically engineered mice carrying homozygously floxed Ror1 alleles and an SP‐C promoter–driven human mutant EGFR transgene were generated. Ror1 ablation resulted in marked retardation of tumor development and progression in association with reduced malignant characteristics and significantly better survival. Interestingly, gene set enrichment analysis identified a hypoxia‐induced gene set (HALLMARK_HYPOXIA) as most significantly downregulated by Ror1 ablation in vivo, which led to findings showing that ROR1 knockdown diminished HIF‐1α expression under normoxia and clearly hampered HIF‐1α induction in response to hypoxia in human lung adenocarcinoma cell lines. The present results directly demonstrate the importance of Ror1 for in vivo development and progression of lung adenocarcinoma, and also identify Ror1 as a novel regulator of Hif‐1α. Thus, a future study aimed at the development of a novel therapeutic targeting ROR1 for treatment of solid tumors such as seen in lung cancer, which are frequently accompanied with a hypoxic tumor microenvironment, is warranted. [ABSTRACT FROM AUTHOR]

Objective: Owing to variations in the exterior appearances of noncancerous diseases in the oral cavity, clinicians may have difficulty diagnosing oral squamous cell carcinoma (OSCC). Tissue biopsy is confirmatory, but invasive. Therefore, reliable tumor markers for OSCC are required. Here, exosomal Alix (exoAlix) levels were measured in serum/salivary samples from patients with OSCC and healthy controls (HCs). Methods: Fifty‐seven patients admitted to Nagoya University Hospital from 2017 through 2019 were enrolled, and serum samples (OSCC, n = 29; HC, n = 21) and/or saliva samples (OSCC, n = 23; HC, n = 20) were collected. Exosomal fractions were isolated using ultracentrifugation. ExoAlix levels were measured using enzyme‐linked immunosorbent assay. Results: Serum/salivary exoAlix levels were significantly higher in patients with OSCC than in HCs. Receiver operating characteristic analyses revealed that sensitivity, specificity, positive predictive value, and area under the curve were 0.345, 1.000, 1.000, and 0.685, respectively, for serum exoAlix and 0.348, 1.000, 1.000, and 0.712, respectively, for salivary exoAlix at optimal cut‐off values (serum, 0.205; saliva, 0.193). All tested OSCC tissue sections (n = 21) were immuno‐reactive for Alix. Conclusion: Serum and salivary exoAlix were identified as potential diagnostic OSCC biomarkers. Serum exoAlix was suitable for prediction of therapeutic responses. [ABSTRACT FROM AUTHOR]

Molecular structures of siloxane materials should be highly controlled for achieving advanced functionalities. However, it is still difficult to precisely control the structure of siloxane materials by the sol–gel processing. In the present study, we focused on the silanol groups in the intermediate oligomers and resultant siloxane materials as a key structural unit for controlling the molecular structure. Thermal stability and chemical reactivity of silanol groups were found to be highly dependent on the steric effects of the surrounding side chains and siloxane skeletons. The present work suggests that controlling the steric effects around silanol groups in the intermediate oligomers allows modulating the crosslink density of siloxane skeletons. The selective molecular modification tunes the structure and chemical properties of the resultant siloxane materials. Highlights: Hydroxyl groups in oraganically modified siloxane oligomers exhibit a diffrent reactivity depending on the local environments. Molecular structures of siloxane materials should be highly controlled for achieving advanced functionalities. The selective molecular modification tunes the structure and chemical properties of the resultant siloxane materials. [ABSTRACT FROM AUTHOR]

Background: Various biomarkers are being developed for the early diagnosis of cancer and for predicting its prognosis. The aim of this study is to evaluate the diagnostic significance of serum CD109 in head and neck squamous cell carcinoma (HNSCC). Methods: The serum CD109 levels in a total of 112 serum samples collected before and after surgery from 56 HNSCC patients were analyzed with an enzyme‐linked immunosorbent assay (ELISA). The clinical factor that showed a statistically significant association with both the preoperative serum CD109 level, and the CD109 index: which was defined as the ratio of the preoperative serum CD109 level to the postoperative serum CD109 level, were assessed. The correlations between the serum CD109 levels and lymph node density (LND), pathological features such as lymphatic invasion, and serum SCC antigen levels were also assessed. Results: The ELISA measurement revealed that preoperative serum CD109 levels were elevated in patients with node metastasis‐positive and stage IV disease, in comparison to those with node metastasis‐negative and Stage I+II+III disease, respectively. A multiple regression analysis indicated that serum CD109 level was significantly associated with the node metastasis status. A Spearman's rank correlation analysis also revealed a positive correlation between the preoperative serum CD109 level and LND. Furthermore, the probabilities of the overall and relapse‐free survival were significantly lower in patients with a preoperative serum CD109 level of ≥38.0 ng/ml and a CD109 index of ≥1.6, respectively, than in others. There was no significant correlation between the serum CD109 and SCC antigen levels. Conclusions: The serum CD109 levels were elevated in patients with advanced stage disease, reflecting the node metastasis status. CD109 in sera could be a novel prognostic marker for HNSCC involving lymph node metastasis. [ABSTRACT FROM AUTHOR]

This study was aimed to review the etiology and the outcomes of current posterior chamber phakic intraocular lens (Visian ICL, STAAR Surgical) extraction. This review comprised 770 eyes of 403 consecutive patients undergoing ICL extraction. We evaluated prevalence, etiology, uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), predictability, and patient satisfaction. ICL extraction was required in 8 of 770 (1.0%) eyes. The most common reason was the progression of the pre-existing cataract formation in 5 eyes (63%), followed by residual refractive errors in 3 eyes (38%). Of the 7 eyes targeted for emmetropia, 7 (100%) and 6 (86%) achieved UDVAs of 20/40 and 20/20 or better, respectively. Three eyes (38%) showed no change in CDVA, 3 eyes (38%) gained 1 line, 2 eyes (25%) gained 3 or more lines. 88% and 100% were within ± 0.5 and 1.0 diopter (D), respectively, of the targeted correction. Patient satisfaction improved significantly, from 3.0 ± 1.4 preoperatively, to 8.0 ± 2.4 postoperatively. No vision-threatening complications occurred. ICL extraction was required in approximately 1% of ICL-implanted eyes. Visual and refractive outcomes were good, and patient satisfaction was overall high, even in ICL-extracted eyes. [ABSTRACT FROM AUTHOR]

Investigation of the Er concentration dependence of up-conversion intensity under 800 nm excitation in transparent oxyfluoride glass-ceramics has demonstrated the presence of intense up-conversion emissions at around 525 nm, 550 nm and 660 nm. Weak emissions were seen at 410 nm, 450 nm and 490 nm. X-ray diffraction measurement revealed that the nanocrystals have fluorite-type structure. The average nanocrystalline size was around 25 nm in diameter, regardless of the kind of rare earth element.

Activation of REarranged during Transfection (RET) proto-oncogene is responsible for various human cancers such as papillary and medullary thyroid carcinomas and non-small cell lung carcinomas. RET activation in these tumors is caused by point mutations or gene rearrangements, resulting in constitutive activation of RET tyrosine kinase. Physiologically, RET is activated by glial cell line–derived neurotrophic factor (GDNF) ligands that bind to coreceptor GDNF family receptor alphas (GFRαs), leading to RET dimerization. GDNF-GFRα1-RET signaling plays crucial roles in the development of the enteric nervous system, kidney and lower urinary tract as well as in spermatogenesis. Intracellular tyrosine phosphorylation in RET and recruitment of adaptor proteins to phosphotyrosines are essential for various biological functions. Significance of intracellular RET signaling pathways activated by GDNF is discussed and summarized in this review. [ABSTRACT FROM AUTHOR]

Background: To compare the endothelial cell density and morphology in the peripheral cornea before and after corneal cross-linking (CXL).Methods: This study evaluated thirty-one eyes of 31 patients who were treated with standard CXL for progressive keratoconus. Preoperatively and 6 months postoperatively, we compared the corneal endothelial cell density (ECD), the coefficient of variation in cell size (CV), and the percentage of hexagonal cells (HEX), in the peripheral regions of the cornea, using a non-contact specular microscope (EM-3000, Tomey).Results: All keratoconic eyes in this series were measurable in the peripheral regions. No significant differences were found in the peripheral ECD preoperatively and 6 months postoperatively at each point (Wilcoxon signed-rank test, superior, p = 0.16, nasal superior, p = 0.12, temporal superior, p = 0.17, inferior, p = 0.37, nasal inferior, p = 0.28, temporal inferior, p = 0.17). The mean percentage of the ECD loss was 1.3, 1.3, 1.0, 1.4, 0.7, and 1.4%, respectively. No significant differences in the peripheral CV or HEX were found preoperatively and 6 months postoperatively at each point.Conclusions: Standard CXL does not cause significant changes in endothelial cell density, polymegethism, or polymorphism, in the peripheral regions of the cornea. It is suggested that CXL is a minimally invasive surgical approach for progressive keratoconus, even in terms of peripheral endothelial cells.Trial Registration: University Hospital Medical Information Network Clinical Trial Registry (000031162). [ABSTRACT FROM AUTHOR]

Acute lupus myocarditis and pulmonary arterial hypertension (PAH) are rare complications associated with systemic lupus erythematosus (SLE). No previous reports have shown the coexistence of these disorders. Here we present a 41-year-old patient with SLE who concurrently developed severe acute lupus myocarditis and PAH with digital gangrene as an initial manifestation. Acute lupus myocarditis and PAH were successfully treated with prednisolone and intravenous cyclophosphamide pulse therapy (600–700 mg × 6) along with anticoagulant therapy. Catheter-directed thrombolysis was required for digital gangrene caused by vasculitis. Concurrent development of these rare disorders may represent a common mechanism such vasculitis as an underlining cause of SLE. [ABSTRACT FROM AUTHOR]

Purpose: To compare the predictability of intraocular lens (IOL) power calculation using several corneal power measurements in eyes that underwent phototherapeutic keratectomy (PTK). Study design: Retrospective case series. Methods: We reviewed the clinical charts of 42 eyes of 25 consecutive patients who underwent cataract surgery after PTK for granular corneal dystrophy or band keratopathy. IOL power calculations were performed using the SRK/T formula with four corneal power measurements [automated keratometry (AK) measured with a partial coherence interferometer, simulated keratometry (Sim K), true net power (TNP), and total corneal refractive power (TCRP) measured with a rotating Scheimpflug camera]; we determined the prediction error, absolute error, and percentage within ± 1.0 D of the targeted refraction, 1 month postoperatively. Results: The prediction error in the TCRP group was significantly better than those in the AK, Sim K, and TNP groups. The absolute error was also significantly better than those in the AK and Sim K groups, but not significantly different from that in the TNP group. The percentages of within ± 0.5 and 1.0 D in the TCRP group were significantly higher than those in the AK and Sim K groups, but not significantly different from that in the TNP group. Conclusions: The TCRP provides the highest predictability of IOL power calculation in post-PTK eyes. This result suggests that the use of the TCRP, rather than of conventional anterior keratometry, may be clinically helpful for improving the refractive accuracy of post-PTK eyes. [ABSTRACT FROM AUTHOR]

The photochemical reaction of Ge[sup 2+] in 10GeO[sub 2]-90SiO[sub 2] optical fiber preform and the origin of the 5.7 eV optical absorption band induced by intense ultraviolet laser excitation have been investigated using a near-ultraviolet XeF excimer laser (3.7 eV) as the main excitation source. Based on the previous and present experimental results, it is concluded that the 5.7 eV optical absorption band does not originate from the Ge(2) electron trapped center. In place of this model, we have proposed an alternative structural model for the origin of the 5.7 eV band taking into account the experimental fact that the corresponding center is diamagnetic. In addition, it is found that the site selective excitation of the Ge[sup 2+] center can be achieved by using laser sources with different photon energies. [ABSTRACT FROM AUTHOR]