Basal differentiation and expression status of SOX2 and KLF4 in basal layers are prognostic factors for disease-specific survival in oral squamous cell carcinoma.

BACKGROUND: Basal differentiation in oral squamous cell carcinoma is usually detected at invasive sites. However, its significance as a prognostic value has been poorly investigated. METHODS: COL17 was selected as a basal differentiation marker because of its stable expression in the basal-like cells of oral squamous cell carcinoma. Sixty-five cases of oral squamous cell carcinoma were subclassified into COL17-high (30 cases) and -low (35 cases) types, and the prognostic value was analyzed by Cox regression analysis. In addition, the stem cell markers such as SOX2, KLF4, MYC as well as the stem cell-related markers BMI1, EZH2, and YAP and its paralog TAZ, were immunohistochemically analyzed. Their prognostic values were investigated along with their COL17 status by Cox regression analysis. RESULTS: No significant difference was observed between the COL17-high and -low groups in the disease-specific survival and recurrence-free survival in oral squamous cell carcinoma. When the COL17-high and -low categories were combined with the SOX2, KLF4, EZH2, or YAP/TAZ status in the basal layers, together with gender and age as covariates, the hazard ratios reached 3.3, 3.7, 2.8, and 3.1, respectively. In addition, multivariate analysis, including COL17, SOX2, and KLF4, with gender and age as covariates, showed a significantly poor prognosis for disease-specific survival. CONCLUSION: Based on the relatively high hazard ratios, it is indicated that basal differentiation and the expression status of SOX2 and KLF4 in the basal layers are prognostic factors for oral squamous cell carcinoma.

Relationship between dietary fiber to carbohydrate ratio and mortality risk in US adults: NHANES 2007-2018.

BACKGROUND AND AIMS: The evidence is inconsistent regarding associations between relative proportions of macronutrient intake and disease risk, potentially due to limitations in accounting for differential effects of simple sugars and dietary fiber, grouped as "carbohydrates." We examined the association between the ratio of dietary fiber to carbohydrate intake (FC-R) measure, the relative proportion of macronutrients, and mortality risk in a nationally representative sample of U.S. adults. METHODS AND RESULTS: We performed a retrospective cohort study, using data from the National Health and Nutrition Examination Survey in 2007-2018 and linked mortality data among 15,789 adults aged ≥40 years. We categorized participants into three groups by tertile cutpoints of FC-R, and by percent calories from carbohydrate (<45 %, 45-65 %, and >65 %). Cox proportional hazards regression was performed to estimate hazard ratios (HR) for all-cause mortality with 95 % confidence intervals (95 % CI), adjusting for demographic, health history, and lifestyle factors. During a median follow-up of 6.5 years, 2044 deaths were observed. Compared to the low FC-R group, higher FC-R groups showed a reduction in mortality risk after adjusting for potential confounders (high vs low: HR = 0.71, 95 % CI = 0.62-0.83). The association persisted in those consuming 45-65 % and >65 % of calories from carbohydrate, while the association was attenuated in those with <45 % of calories from carbohydrate. Percent calories from carbohydrate showed no association with mortality risk. CONCLUSION: Higher FC-R was associated with lower all-cause mortality risk in adults with moderate to high levels of percent calories from carbohydrate. Mechanisms of the association warrant further investigation.

Local Low-dose Anti-PD-L1 Antibodies Improve Antitumor Effects in Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: Immune checkpoint inhibitors are highly effective for treating recurrent and metastatic head and neck cancers. However, they require systemic administration and are associated with immune-related adverse events (irAEs). Reducing therapeutic antibody doses to prevent irAEs is challenging. MATERIALS AND METHODS: Mouse buccal mucosa squamous cell carcinoma cells (Sq-1979) were transplanted into the backs of mice to induce tumors. The antitumor efficacy and tumor immunohistological environment in tumor-bearing mice were compared after administering a standard dose of programmed death-ligand 1 (PD-L1) antibodies systemically (200 mg/body) or 1/10th of the standard dose (20 mg/body) directly to tumors. Mice received four doses of antibody administered in 3-day intervals. Tumor reduction rates and antitumor efficacies were evaluated 21 days after initiating treatment. CD8+T cell counts and PD-L1, PD-1, perforin, and granzyme B levels; CD25 and Foxp3 expression levels; and tumor Tregs were assessed in the resected subcutaneous tumors. RESULTS: The antitumor efficacies in the local low-dose and systemic standard-dose groups were compared with that of the control group. The efficacies of the two treatment groups were similar, and both treatment groups revealed significant antitumor effects compared to the control group. Perforin and granzyme B levels were higher in the local low-dose group (p<0.05). CONCLUSION: Local low-dose administration of anti-PD-L1 antibodies exhibits antitumor efficacy similar to systemic standard-dose administration suggesting that local low-dose administration is useful for treating oral squamous cell carcinoma.

Intracellular Signaling Pathways Involved in the Regulation of Gene Expression by Pilocarpine.

OBJECTIVES: Pilocarpine is commonly used clinically to treat dry mouth. The long-term administration of pilocarpine reportedly improves salivary secretion more effectively than short-term administration. Therefore, we hypothesized that pilocarpine alters gene expression in salivary glands via muscarinic receptor stimulation. This study aimed to investigate the effects of pilocarpine use on gene expression mediated by mitogen-activated protein kinase (MAPK) activity. METHODS: The effects of pilocarpine on gene expression were investigated in rats and human salivary gland (HSY) cells using several inhibitors of intracellular signaling pathways. Gene expression in the rat submandibular gland and HSY cells was determined using reverse transcription-quantitative polymerase chain reaction analysis of total RNA. RESULTS: In animal experiments, at 7 days after pilocarpine stimulation, Ctgf and Sgk1 expressions were increased in the submandibular gland. In cell culture experiments, pilocarpine increased Ctgf expression in HSY cells. The mitogen-activated protein kinase kinase inhibitor trametinib, the Src inhibitor PP2, and the muscarinic acetylcholine receptor antagonist atropine suppressed the effect of pilocarpine on gene expression. CONCLUSIONS: Pilocarpine enhances Ctgf and Sgk1 expressions by activating Src-mediated MAPK activity. Although further studies are required to fully understand the roles of Ctgf and Sgk1, changes in gene expression may play an important role in improving salivary secretions.

A Case of High-Dose Intravenous MgSO4 and Hemoperfusion for Aconite Poisoning with Chronic Kidney Disease.

Aconite contains four highly toxic diester-diterpene alkaloids, including aconitine, mesaconitine, hypaconitine, and jesaconitine, in all plant parts. Aconite has been used as for suicide, murder, and as an arrow poison since ancient Greek and Roman times. Ventricular tachyarrhythmias are the most common cause of death in aconite poisoning, and antiarrhythmic drugs and cardioversion are ineffective. A 61-year-old woman ingested the crushed raw roots of a single aconite plant. An ambulance brought her to the Tottori University Hospital 30 min after ingestion. She had a history of chronic stage 5 kidney disease but was not on dialysis. Her heart rate (HR) was 120 bpm upon arrival. The patient developed sustained supraventricular tachycardia (SVT) at an HR of 165 bpm with frequent premature ventricular contractions (PVCs) 15 min after arrival. She then developed sustained monomorphic ventricular tachycardia (VT) at an HR of 200 bpm 20 min after arrival, which progressed to pulseless polymorphic VT. Cardioversion was unsuccessful. External cardiac massage restored spontaneous circulation; however, her underlying rhythm remained sustained SVT with frequent PVCs. These arrhythmias repeatedly led to circulatory arrest. She was administered six intravenous boluses of 2 g of MgSO4 in the emergency department, which prevented her from going into sustained pulseless VT. Hemoperfusion (HP) with activated charcoal was performed 1.5 h after arrival. The aconitine, mesaconitine, and hypaconitine plasma concentrations were high at 8.9, 23.5, and 5.5 ng/mL, respectively, before the start of HP but decreased to 1.7, 4.0, and 2.7 ng/mL, respectively, after 7 h of HP. She returned to sinus rhythm on the second day of hospitalization; however, the patient required maintenance hemodialysis. We concluded that high-dose IV MgSO4 is an effective treatment for fatal tachyarrhythmias due to aconite poisoning, and that in cases of renal failure, HP may be required to remove aconite toxins from the body.

Three-dimensional sensing of surfaces by projection of invisible electroluminescence from organic light-emitting diodes.

Organic light-emitting diodes (OLEDs) that efficiently emit near-infrared (NIR) light and consume little power will create valuable applications for OLEDs beyond just displays. Here, we report such a NIR-OLED with high operational stability that can be used as a light source for three-dimensional sensing of object's surfaces. Using a narrow-energy-gap material as a host for producing NIR hyperfluorescence system, we fabricated a NIR-OLED exhibiting intense emission at 930 nm with a high external electroluminescence quantum efficiency of more than 1% at a current density of 100 milliamperes per square meter without any degradation even after more than 300 hours of operation. The NIR-OLEDs were integrated with dense complementary metal-oxide semiconductor circuits to make a micro-NIR-OLED projector (0.21 inch, 230,400 pixels). By actively driving the projector on a pixel by pixel and projecting their emission onto objects, we successfully scanned and sensed the surfaces in three dimensions with invisible NIR.

A case of primary lung adenocarcinoma mimicking metastatic papillary thyroid carcinoma.

A 61-year-old woman, who had a history of total thyroidectomy for follicular variant of papillary thyroid carcinoma (PTC), visited our hospital for assessment of an enlarging nodule which appeared in the lung with multiple metastatic lesions of PTC which had been stable for 17 years. Wedge resection of the lung was performed. Miliary nodules were confirmed to be metastatic PTCs based on their morphological as well as immunohistochemical findings. As for the main nodule, its morphological features suggested a diagnosis of metastatic PTC, while its immunohistochemical findings were identical with primary lung adenocarcinoma. Further genetic analysis provided no definitive information for the diagnosis of the main nodule. The present case shows the need of comprehensive analyses for differentiation between primary lung adenocarcinoma and metastatic PTCs.

The Prospective Natural History Study of Patients with Intractable Venous Malformation and Klippel-Trenaunay Syndrome to Guide Designing a Proof-of-Concept Clinical Trial for Novel Therapeutic Intervention.

Background: The natural history of venous malformation (VM) and Klippel-Trenaunay Syndrome (KTS) has not been quantitatively studied. To obtain benchmarks to guide designing clinical trials to assess safety and efficacy of novel drug candidates, the clinical course of the patients was followed for 6 months. Methods and Results: This is a multicenter prospective observational study evaluating the change rate in lesion volume from baseline with magnetic resonance images, as the primary endpoint. In addition, disease severities, performance status (PS), pain visual analog scale (VAS) score, quality of life (QoL), infections, and coagulation markers were also evaluated. Thirty-four patients (VM = 17, KTS = 17, 1-53 of age; median 15.9 years) with measurable lesion volume were analyzed. There was no statistically significant difference in the lesion volume between baseline and day 180, and the mean change rate (standard deviation) was 1.06 (0.28). There were no baseline characteristics that affected the change in lesion volume over 6 months. However, there were patients who showed more than 20% volume change and it was suggested that the lesion volume was largely impacted by local infection. There were no statistically significant changes in pain VAS score, severity, PS, QoL score, D-dimer, and platelet count over 6 months within all patients analyzed. Conclusion: The results showed the representative natural course of VM and KTS for a 6-month period with objective change of lesion volume and other factors, suggesting that it is scientifically reasonable to conduct a Phase 2 proof-of-concept study without a placebo arm, using the results of this study as the control. Clinical Trial Registration: NCT04285723, NCT04589650.

Autoecologia das espécies florestais em regime de plantio de enriquecimento em linha na floresta primária da Amazônia Central / Autoecology of forest species in line plannting enrichment system in primary forest in Central Amazonia

A autoecologia das três espécies florestais em linhas de enriquecimento foi avaliada junto com o monitoramento do microclima e fertilidade do solo na floresta primária de terra-firme da Amazônia brasileira. A área situa-se no município de Novo Aripuanã Amazonas - Brasil (5°18'S, 60°04'W.). Nas três diferentes larguras de linhas (3, 5 e 7m) foram monitoradas os parâmetros de radiação com fotografias hemisféricas e sensor RFA. As linhas de 5 e 7m classificam-se como grande abertura de dossel (19,77-20,78 por cento), a de 3m mostrou maior variação na radiação RFA. Quanto à análise química do solo observou-se, uma redução significativa de K e Ca em relação ao aumento das larguras das linhas. Também foram monitorados os crescimentos em altura e diâmetro, índice de ganho foliar e o teor de clorofila nas plântulas das três espécies estidadas: Astronium lecointei Ducke, Cordia goeldiana Huber e Scleronema micranthum Ducke. Todas espécies sofreram devido à alta radiação e ao estresse hídrico. Astronium lecointei apresentou uma maior resistência tanto durante forte seca, como também ao excesso de chuva. Scleronema micranthum apresentou diferenças de crescimento entre linhas, principalmente na estação chuvosa. Beneficiou-se positivamente com a radiação direta nas linhas largas de enriquecimento. As duas apresentaram alta amplitude de nicho entre tolerante à sombra a intermediária. Já C.goeldiana apresentou maior variação em seu crescimento (CV: Cordia goeldiana: 113> Astronium lecointei: 60,6> Scleronema micranthum: 59,7). A largura de linha de 5m na floresta primária de terra-firme foi suficiente para estabelecimento de espécies tolerante à sombra e intermediária.

In this study, autoecological traits of three Amazonian terra-firme tree species grown in enrichment plantation lines were evaluated. The microclimatological parameters also were assessed in these lines. The study site is located in Novo Aripuanã, Amazonas State, Brazil (5(0)18'S, 60(0)04'W). Light condition in the three width lines (3, 5 and 7m) were assessed using hemispherical photographs and PAR sensor focusing radiation parameters. Although lines of 5 and 7m widths can be classified as large canopy opening (19,77-20,78 percent), lines of 3m represented major PAR variation. For soil chemical analysis, a significant reduction of K ans Ca was observed. Three tree species seedlings, Astronium lecointei Ducke, Cordia goeldiana Huber and Scleronema micranthum Ducke were set in the enrichment plantation lines. The relative growth rate (stem diameter+height) and chlorophyll contents were monitored in these plants. All species were subjected to high direct and diffuse radiation, low levels of nutrients and water stress. Astronium lecointei Ducke showed high drought resistance. Scleronema micranthum in the rainy season also benefited in the wider enrichment lines, showing positive responses to direct radiation. These two species showed features of intermediate to shade tolerant species (broad niche) when growth patterns were compared. On the other hand, C.goeldiana showed greater growth fluctuation than others (VC: Cordia goeldiana: 113> Astronium lecointei: 60,6> Scleronema micranthum: 59,7). Lines with five meters widths of primary terra-firme forests should be sufficient to establish shade tolerant and intermediate species.