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Abstract Objectives Podoplanin (PDPN) expression in cancer‐associated fibroblasts (CAFs) (CAF‐PDPN) is considered a poor prognostic factor in nonsmall cell lung cancer, but little is known about its clinical significance in high‐grade neuroendocrine carcinoma of the lung (HGNEC). This study examines the association between CAF‐PDPN and stromal programmed death‐ligand 1 (PD‐L1) expression and the prognostic implications of CAF‐PDPN and PD‐L1 expression status in surgically resected HGNEC patients. Methods Immunohistochemical analyses were performed on 121 resected HGNEC specimens using antibodies against PDPN and PD‐L1. Correlations between CAF‐PDPN, stromal PD‐L1 expression, and clinicopathologic features and their implications for survival were analyzed statistically. Results There were substantially more large‐cell neuroendocrine carcinomas in the stromal PD‐L1‐positive group and more vascular invasion in the tumoral PD‐L1‐positive group. PDPN expression in CAF was moderately correlated with stromal PD‐L1 expression (ρ = 0.567, p

Abstract In this study, we focused on calcification and diffusion restriction, which sometimes appear around the resection cavity or periventricular white matter in patients with high-grade glioma (HGG) treated with bevacizumab (BVZ), as candidate imaging biomarkers for BVZ treatment efficacy. We investigated the timing of the appearance of diffusion restriction and calcification using magnetic resonance imaging and computed tomography in 35 patients with newly diagnosed or recurrent HGG treated with BVZ. In 17 (48.6%) patients, calcification was identified around the resection cavity or periventricular white matter at a median of 12 months after the initiation of BVZ treatment. Patients with calcification had significantly longer progression-free survival (16 vs. 7 months; p = 0.0023) and overall survival (36 vs. 12 months; p = 0.0006) than those without calcification. Histopathological examination revealed the presence of scattered microcalcifications within areas of necrosis, which suggested dystrophic calcification induced by BVZ. Diffusion-restricted lesions that appeared in patients with calcification had significantly lower apparent diffusion coefficients than those in patients without calcifications, indicating the presence of treatment-related necrosis but not hypercellularity. In conclusion, the radiological finding of diffusion restriction followed by calcification could be a potential imaging biomarker for favorable clinical course in patients with HGG treated with BVZ.

Abstract Reference materials are critical in assay development for calibrating and assessing their suitability. The devasting nature of the COVID-19 pandemic and subsequent proliferation of vaccine platforms and technologies has meant that there is even a greater need for standards for immunoassay development, which are critical to assess and compare vaccines’ responses. Equally important are the standards needed to control the vaccine manufacturing processes. Standardized vaccine characterization assays throughout process development are essential for a successful Chemistry, Manufacturing and Controls (CMC) strategy. In this perspective paper, we advocate for reference material incorporation into assays and their calibration to International Standards from preclinical vaccine development through control testing and provide insight into why this is necessary. We also provide information on the availability of WHO international antibody standards for CEPI-priority pathogens.

Abstract Objectives MYC family genes including MYC, MYCN, and MYCL are amplified and overexpressed as oncogenic drivers in high‐grade neuroendocrine carcinoma of the lung (HGNEC), but little is known about their clinical significance. This study evaluated the prognostic impact of MYC family protein expression in patients with surgically resected HGNEC. Methods Immunohistochemical analyses were performed on 83 resected specimens of HGNEC using antibodies against MYC family proteins (c‐MYC, n‐MYC, and l‐MYC). When nuclear staining of any intensity in ≥10% of tumor cells showed immunoreactivity with any one or more of c‐MYC, n‐MYC, or l‐MYC, the specimens were defined as MYC family‐positive. Results A total of 83 patients were analyzed. MYC family‐positive status was observed in 33.7% (28 of 83 cases) and was not correlated with clinicopathological factors. The protein expression was mutually exclusive and no duplicate cases were observed. A log‐rank test showed that MYC family‐positive status was significantly associated with shorter overall survival (OS) (p = 0.003) and recurrence‐free survival (RFS) (p = 0.039). According to Cox multivariate analysis, MYC family‐positive status had a significant effect on shorter OS (hazard ratio [HR] = 2.217, 95% confidence interval [CI] 1.179–4.169, p = 0.014) and RFS (HR = 1.802, 95% CI 1.014–3.202, p = 0.045). In patients with pathological stage I, MYC family‐positive status also showed significantly poor OS (HR = 2.847, 95% CI 1.236–6.557, p = 0.014) and RFS (HR = 2.088, 95% CI 1.006–4.332, p = 0.048) in the multivariate analysis. Conclusions MYC family protein expression could be an independent unfavorable prognostic factor in patients with surgically resected HGNEC.

Introduction Brain and spinal cord metastases from testicular cancer occur rarely, and metastases with seminoma are extremely rare. Case presentation A 42‐year‐old man who was diagnosed with seminoma and multiple metastases underwent first‐line and salvage chemotherapy. Brain metastases were noted; consequently, surgery, third‐line chemotherapy, and whole‐brain irradiation were performed. Subsequently, paralysis developed, and spinal cord metastases were detected. He received fourth‐line chemotherapy but died. Pathological autopsy revealed metastases only in the spinal cord. The cause of death was considered respiratory failure due to cervical spinal cord involvement from spinal metastases. Conclusion Brain and spinal cord metastases from seminoma are rare. Thus, similar future cases should be treated appropriately.

Abstract Background A thymoma with chest pain and multilocular thymic cysts (MTCs) is very rare. Case presentation A 49-year-old man presented to another hospital complaining of an anterior chest pain. Chest computed tomography (CT) showed an anterior mediastinal tumor 60 × 30 × 55 mm in size. The boundary with the pericardium or left brachiocephalic vein seemed to be partially unclear while enhanced by the contrast medium, and so the tumor could have invaded them. No definitive diagnosis of myasthenia gravis was made although the serum anti-acetylcholine receptor antibody count was high. We performed an extended thymectomy with combined partial resection of left brachiocephalic vein, left upper lobe, and left phrenic nerve. He was discharged with no chest pain and no complications post-surgery. The tumor was pathologically type B2 thymoma with hemorrhage necrosis and MTCs, and we diagnosed Masaoka stage II because of no histological infiltration to the organs. Conclusions We speculated that hemorrhagic necrosis due to infarction in tumor caused the inflammation to spread to the surrounding organs, which was related to the chest pain and the development of MTCs.

Persistent left superior vena cava (PLSVC) is the most common congenital anomaly of the SVC. In most cases, the PLSVC drains via the coronary sinus into the right atrium, but in some cases, it drains into the left atrium instead. This anomaly is of particular importance during central venous catheter (CVC) placement, especially during a left-sided approach, as manipulation within the coronary sinus has been associated with hemodynamic instability and shock. PLSVC is usually suspected when confirmatory plain radiograph shows the catheter traveling along the left mediastinal border. We are reporting the case of a 3-year-old female patient with CVC placement into her left subclavian vein and subsequently a PLSVC. Portable chest radiography showed the catheter coursing along the lateral border of the left mediastinum. An echocardiogram showed flow from the subclavian vein into the right atrium; therefore, the catheter most likely terminated in a PLSVC draining into the right atrium. The catheter had excellent flow and was kept in place for six days without any complications or sequelae before it was removed.

The Ecosystem Services concept has been developed in recent decades through both academic and international institutions. Nowadays, most of the literature agrees that ecosystem services constitute a crucial contribution to human well-being. Most studies focus on final ecosystem services which are directly identifiable amongst society’s consumption habits. Ecosystem services generally named “Provisioning Services” seem to be the masterpiece of ecosystem services provided by nature, and their contribution to human well-being is linked to their economic relevance. In most cases this can be easily determined as there are markets already developed to evaluate these services. Nonetheless, final ecosystem services are supported by often-overlooked Intermediate Ecosystem Services, which do not have a structured market and yet hold an economic relevance that could directly affect society. Similarly, cultural ecosystem services are often difficult to economically assess as it is very difficult to put a price on intrinsic values. T hough Regulating and Cultural Ecosystem Services are difficult to value, they are of vital importance to society and must be evaluated when making any assessment locally or regionally. In order to yield a better understanding of the importance of all ecosystem service categories, we propose a spatial-temporal limited study to pinpoint the synergies and trade-offs between Ecosystem services, Biodiversity conservation, and Commodity production in Allpahuayo Mishana National Reserve, and to highlight the possible environmental and economic outcomes according to different management scenario

Vitamin D and folate are associated with decreased colorectal cancer risk and their association with colorectal cancer prognosis is under investigation. We assessed the levels of plasma 25-hydroxyvitamin D3 (25(OH)D3), folate and vitamin B12 in an international pilot study in order to determine variability of these biomarkers based on geographical location. Plasma 25(OH)D3, folate and vitamin B12 concentrations were measured in 149 invasive, newly diagnosed colorectal cancer cases from Heidelberg (Germany), Seattle (WA, USA), and Tampa (FL, USA) and in ninety-one age- and sex-matched controls. Their associations with potential predictors were assessed using multivariate linear regression analyses. Plasma 25(OH)D3, folate and vitamin B12 concentrations differed by location. Other predictors were season for 25(OH)D3 and tumour stage (vitamin B12). Season-corrected average 25(OH)D3 concentrations were higher in Heidelberg (31·7 ng/ml; range 11·0–83·0 ng/ml) than in Seattle (23·3 ng/ml; range 4·0–80·0 ng/ml) and Tampa (21·1 ng/ml; range 4·6–51·6 ng/ml). In Heidelberg, a strong seasonal variation was observed. Folate (11·1 ng/ml) and vitamin B12 (395 pg/ml) concentrations in Heidelberg were lower than those in Seattle (25·3 ng/ml and 740 pg/ml, respectively) and Tampa (23·8 ng/ml and 522 pg/ml, respectively). Differences in plasma 25(OH)D3 and folate concentrations between Heidelberg and the US sites were observed, probably reflecting variation in outdoor activities and sun-avoidance behaviour during summer as well as in folic acid fortification and supplement use. Intra-site differences at each study location were greater than between-location variability, suggesting that individual health behaviours play a significant role. Nevertheless, the intra-site differences we observed may be due to chance because of the limited sample size. Our pilot study illustrates the value of an international cohort in studying colorectal cancer prognosis to discern geographical differences in a broad range of exposures.