Central Front Research Articles

Spatial transcriptomics reveals cancer and stromal cell heterogeneity between center and invasive front of pancreatic cancer.

Intratumor heterogeneity is considered a major cause of treatment failure in pancreatic ductal adenocarcinoma (PDAC). In recent years, marked heterogeneity at the genomic and transcriptional level has been revealed, but the spatial distribution of the heterogeneous cell populations has not been considered. Yet, it is assumed that cancer cells at the invasive front are endowed with enhanced migratory and invasive properties, although evidence is scanty, and cancer-associated fibroblasts (CAFs) in this location have not been characterized. In this study, digital spatial profiling was used to compare the transcriptional profiles of cancer cells and CAFs in the tumor center versus the invasive front of human PDAC. Four well differentiated PDACs with conventional morphology were investigated with the GeoMx system (Nanostring). Regions of interest were analyzed in the tumor center and at the invasive front using a whole transcriptome assay in cancer cell and CAF segments separately. Three of the PDACs harbored mutated KRAS, while the fourth case was confirmed wild-type KRAS. Substantial inter-regional heterogeneity was identified, with increased activity of pathways associated with cellular stress (including TNFα-signaling via NFκB, hypoxia, P53 pathway), proliferation (MYC targets, mitotic spindle), glycolysis, and epithelial-mesenchymal transition at the invasive front in both the cancer cell and CAF segments compared to the center of the tumor. Immunohistochemical validation on 17 PDACs of well, moderate and poor differentiation confirmed significant inter-regional heterogeneity in the expression level of markers of EMT and glycolysis. The results of this study show that in PDAC, transcriptional profiles of both cancer cells and CAFs differ between the center of the tumor and the invasive front.

Unveiling the dynamics of shallow fronts in Australia during Southerly Buster episodes (1994–2020)

A Frontal Identification System (FIS), initially designed to track Galernas in the Bay of Biscay, has been adapted to monitor cold fronts across Australia using wind shifts derived from ERA5 hourly reanalysis data. This high-resolution system tracks shallow, cloud-free fronts during the warm season, which can trigger bushfires, dust storms, extreme heat, and coastal weather extremes like Southerly Busters (SB) on the east coast. SB episodes, marked by sudden, squally south winds, pose hazards for boating and aviation. Our analysis of 35 SB events from 1994 to 2020 indicates that SBs originate from frontogenesis in Bass Strait (40 %) or from prefrontal troughs crossing the strait (60 %). Preceding synoptic conditions involve a Southern Ocean cold front driving cool maritime winds into the Australian thermal low, creating shallow convergence fronts (∼1000 m deep) facing warm continental winds. Onshore acceleration into the thermal low sharpens these new fronts (Type 2 fronts of the southern coast) and weakens the trailing primary ocean front, which may disappear due to high-pressure wave propagation, cold advection, and subsidence over the sea. These fronts can penetrate deep inland (Central Australian fronts) and initiate SBs on the southeast coast after interacting with the Great Dividing Range. All 35 SB events show active shallow front frontogenesis/frontolysis affecting the southern coast and inland regions. Upper-level reversed pressure gradients between the thermal low over the continent and the ocean depression maintain a wind shear region over the shallow inland cold advection. Intense warm north-westerlies south of the surface front, with wind speeds of 35–50 m s−1 between 700 and 550 hPa, contribute to mesofront formation preceding SB episodes. This jet also sustains strong cross-mountain winds over the Great Dividing Range, causing the lee trough at the coastal strip that precedes all SB episodes on the eastern coast. Understanding these dynamics can help predict and manage these events more effectively.

Dissecting the immune infiltrate of primary luminal B-like breast carcinomas in relation to age.

The impact of aging on the immune landscape of luminal breast cancer (Lum-BC) is poorly characterized. Understanding the age-related dynamics of immune editing in Lum-BC is anticipated to improve the therapeutic benefit of immunotherapy in older patients. To this end, here we applied the 'multiple iterative labeling by antibody neo-deposition' (MILAN) technique, a spatially resolved single-cell multiplex immunohistochemistry method. We created tissue microarrays by sampling both the tumor center and invasive front of luminal breast tumors collected from a cohort of treatment-naïve patients enrolled in the prospective monocentric IMAGE (IMmune system and AGEing) study. Patients were subdivided into three nonoverlapping age categories (35-45 = 'young', n = 12; 55-65 = 'middle', n = 15; ≥70 = 'old', n = 26). Additionally, depending on localization and amount of cytotoxic T lymphocytes, the tumor immune types 'desert' (n = 22), 'excluded' (n = 19), and 'inflamed' (n = 12) were identified. For the MILAN technique we used 58 markers comprising phenotypic and functional markers allowing in-depth characterization of T and B lymphocytes (T&B-lym). These were compared between age groups and tumor immune types using Wilcoxon's test and Pearson's correlation. Cytometric analysis revealed a decline of the immune cell compartment with aging. T&B-lym were numerically less abundant in tumors from middle-aged and old compared to young patients, regardless of the geographical tumor zone. Likewise, desert-type tumors showed the smallest immune-cell compartment and were not represented in the group of young patients. Analysis of immune checkpoint molecules revealed a heterogeneous geographical pattern of expression, indicating higher numbers of PD-L1 and OX40-positive T&B-lym in young compared to old patients. Despite the numerical decline of immune infiltration, old patients retained higher expression levels of OX40 in T helper cells located near cancer cells, compared to middle-aged and young patients. Aging is associated with important numerical and functional changes of the immune landscape in Lum-BC. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Spatial Heterogeneity of Immune Regulators Drives Dynamic Changes in Local Immune Responses, Affecting Disease Outcomes in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is considered a low-immunogenic (LI) tumor with a "cold" tumor microenvironment and is mostly unresponsive to immune checkpoint blockade therapies. In this study, we decipher the impact of intratumoral heterogeneity of immune determinants on antitumor responses. We performed spatial proteomic and transcriptomic analyses and multiplex immunofluorescence on multiple tumor regions, including tumor center (TC) and invasive front (IF), from 220 patients with PDAC, classified according to their transcriptomic immune signaling into high-immunogenic PDAC (HI-PDAC, n = 54) and LI PDAC (LI-PDAC, n = 166). Spatial compartments (tumor: pancytokeratin+/CD45- and leukocytes: pancytokeratin-/CD45+) were defined by fluorescence imaging. HI-PDAC exhibited higher densities of cytotoxic T lymphocytes with upregulation of T-cell priming-associated immune determinants, including CD40, ITGAM, glucocorticoid-induced TNF-related receptor, CXCL10, granzyme B, IFNG, and HLA-DR, which were significantly more prominent at the IF than at the TC. In contrast, LI-PDAC exhibited immune-evasive tumor microenvironments with downregulation of immune determinants and a negative gradient from TC to IF. Patients with HI-PDAC had significantly better outcomes but showed more frequently exhausted immune phenotypes. Our results indicate strategic differences in the regulation of immune determinants, leading to different levels of effectiveness of antitumor responses between HI and LI tumors and dynamic spatial changes, which affect the evolution of immune evasion and patient outcomes. This finding supports the coevolution of tumor and immune cells and may help define therapeutic vulnerabilities to improve antitumor immunity and harness the responsiveness to immune checkpoint inhibitors in patients with PDAC.

CSChighE-cadherinlow immunohistochemistry panel predicts poor prognosis in oral squamous cell carcinoma

Identifying marker combinations for robust prognostic validation in primary tumour compartments remains challenging. We aimed to assess the prognostic significance of CSC markers (ALDH1, CD44, p75NTR, BMI-1) and E-cadherin biomarkers in OSCC. We analysed 94 primary OSCC and 67 metastatic lymph node samples, including central and invasive tumour fronts (ITF), along with clinicopathological data. We observed an increase in ALDH1+/CD44+/BMI-1- tumour cells in metastatic lesions compared to primary tumours. Multivariate analysis highlighted that elevated p75NTR levels (at ITF) and reduced E-cadherin expression (at the tumour centre) independently predicted metastasis, whilst ALDH1high exhibited independent predictive lower survival at the ITF, surpassing the efficacy of traditional tumour staging. Then, specifically at the ITF, profiles characterized by CSChighE-cadherinlow (ALDH1highp75NTRhighE-cadherinlow) and CSCintermediateE-cadherinlow (ALDH1 or p75NTRhighE-cadherinlow) were significantly associated with worsened overall survival and increased likelihood of metastasis in OSCC patients. In summary, our study revealed diverse tumour cell profiles in OSCC tissues, with varying CSC and E-cadherin marker patterns across primary tumours and metastatic sites. Given the pivotal role of reduced survival rates as an indicator of unfavourable prognosis, the immunohistochemistry profile identified as CSChighE-cadherinlow at the ITF of primary tumours, emerges as a preferred prognostic marker closely linked to adverse outcomes in OSCC.

Flame morphology and laminar flame assessments affected by flames interaction using multi-ignition sources of NH3/H2-air flames

A detailed assessment of flame–flame interaction and laminar flame evolution using multi-ignition sources is experimentally studied. To understand the flame interaction, the centrally ignited flame is measured and calculated for comparison with multi-ignition sources hydrogen–ammonia/flame. The location of the external ignition source, the delay time, the hydrogen blending, and the mixture equivalence ratio at an initial pressure of 0.1 MPa affect the propagation and morphology of the flame. It can be observed that the advancement of the pressure wave of the external flame causes deformation to the central flame front; This deformation occurs even before the interaction of the flames. The deformation can be decomposed into horizontal deformation, which decelerates the flame front as a result of the drag or accelerates due to the thrust of the flow field on the flame front. At the same time, vertical deformation is influenced by drag and thrust-lift forces. Therefore, the equivalent flame decelerates with time. This effect gives a nonsymmetric shape for expanding flame, and the shape changes from spherical to ellipsoidal, then a triaxial quasi-ellipsoid flame (scalene). The equivalent flame speed and laminar burning velocity are maximized near stoichiometry for all delay times and locations of the ignition source. As the delay time of the stoichiometric hydrogen ammonia/air increases, the equivalent laminar flame speed and laminar burning velocity monotonously decrease, as well as the time and location of the interaction. The equivalent flame speed and laminar burning velocity for ignition sources 1 and 2 decreases with delay time, and this becomes evident on the rich side. While employing a third ignition source increases with delay time since the drag force get eliminated from the horizontal axis. Furthermore, the hydrogen blending effect enhances and highlights these tendencies.

The Feat of the Gunners of the 3rd Fighter Brigade in Defensive Battles on the Northern Face of the Kursk Bulge

Relevance lies in the need to preserve the historical truth about the events of the Great Patriotic War and one of its most important battles – the Battle of Kursk. Despite the significant historiographical groundwork, the generalization of the experience of fighting in the defense zone of the Central Front troops continues to be actively developed. The retrospective factography of participation in the battles of individual units and formations requires further clarification, researchers should pay attention to the restoration of the destinies and names of the heroes of the summer battles of 1943. Whose example continues to inspire the exploits of modern defenders of the Fatherland.Purpose. On the basis of documentary sources from the Central Archive of the Ministry of Defense of the Russian Federation, to reveal the specifics of the organization of defensive battles at Teplov heights by the forces of the gunners of the 3rd fighter brigade.Objectives: to identify and study archival materials about the defensive battles of the 3rd Fighter Brigade on the northern face of the Kursk Bulge; to note the role of gunners in deterring the offensive of German troops on July 5-12, 1943; to determine the behavior of individual servicemen who distinguished themselves during the summer battles, to characterize the problems of establishing their destinies.Methodology. During the research, the author adhered to the principles of objectivity and historicism. The information revealed in the sources was systematized and analyzed, allowing to reveal the problems of using artillery in defensive battles during the Battle of Kursk.Results. The generalization of the experience of combat operations of the 3rd Fighter Brigade during defensive battles on the northern face of the Kursk Bulge indicates a well-thought-out and successfully implemented tactics of using individual artillery units in the organization of anti-tank defense.Conclusion. An example of the courage and bravery of the soldiers of the 3rd fighter Brigade during the battles at Teplovsky Heights testifies to their high moral and volitional qualities, as well as the rational alignment of forces and means at the occupied defense lines, which ensured the successful fulfillment of the combat tasks assigned to the gunners.

Analysis of the immunological markers BTLA, TIM-3, and PD-L1 at the invasion front and tumor center in clear cell renal cell carcinoma.

Immune checkpoint inhibitors (ICI) are then backbone in the therapy of metastatic renal cell carcinoma (RCC). The aim of this analysis was to explore the different expression of the ICI PD-L1, BTLA, and TIM-3 at the different tumor locations of the invasion front and the tumor center. Large-area sections of the tumor center and invasion front of 44 stage pT1-4 clear cell RCCs were examined immunohistochemically using antibodies against BTLA, TIM-3, and PD-L1 and subsequently correlated with clinicopathologic data. TIM-3 was most strongly expressed at the invasion front (mean ± SD: 84.1 ± 46.6, p = 0.094). BTLA expression was highest in normal tissue, with weak staining in the tumor center and at the invasion front [110.2 vs. 18.6 (p < 0.001) vs. 32.2 (p = 0.248)]. PD-L1 was weakly expressed at the tumor center (n = 5/44) and at the invasion front (n = 5/44). Correlation with clinicopathological parameters revealed significantly higher BTLA expression in ≥ T3 tumors compared to T1/2 tumors (tumor center p = 0.009; invasion front p = 0.005). BTLA-positive tumors at the tumor center correlated with worse CSS (median 48.46 vs. 68.91months, HR 4.43, p = 0.061). PD-L1 expression was associated with worse CSS (median 1.66 vs. 4.5years, HR 1.63, p = 0.652). For TIM-3, there were no significant associations with clinicopathological parameters and survival. The present results show heterogeneous intratumoral and intertumoral expression of the investigated checkpoint receptors PD-L1, BTLA, and TIM-3. In the clinical practice tumor sampling should include different tumor locations, and multiple inhibition of different checkpoint receptors seems reasonable to increase the therapeutic success.

Further development of the LNMRI/IRD's TNF2 thermal system for flexible dose rate irradiation.

The 'Inverse Square Law' (ISL)( 1) requires the existence of a point radiation source to be validated, but in some cases where there is more than one source, its use is possible as long as a point is determined where a virtual source can be positioned and from this point the points correspond to the ISL. Ambient dose equivalent rate values were obtained by simulation and measurements at various points along the LNMRI Thermal Neutron Flux 2 (TNF2) central axis front face, determining a function corresponding to the inverse square of the distance and the font position at the virtual point 'y0', so that the ISL is respected. This function will help in the neutron monitors calibration, previously estimating the ambient dose equivalent at a certain distance from the face.

Immunohistochemical Assessment of Microvessel Density in OSCC: Spatial Heterogeneity of Angiogenesis and Its Impact on Survival.

(1) Background Oral squamous cell carcinomas (OSCC) are a common malignancy of the oral cavity and are often diagnosed when they have already spread to the regional lymph nodes. Advanced stages of cancer are characterized by the development of distant metastases. Angiogenesis, a hallmark of cancer, is known to contribute to cancer progression and metastasis. High microvessel density (MVD) has been linked to poor clinical outcomes in various types of cancer. (2) Methods: In this study, we aimed to investigate the spatial heterogeneity of blood vessels by comparing the tumor center and invasion front and to evaluate its prognostic value in OSCC. A total of 71 OSCC patient specimens were collected. The tissue was immunohistochemically stained using CD31 antibody to assess the MVD in the tumor center and the invasion front. Furthermore, the associations between the histopathological parameters, including MVD, disease-free survival (DFS), and overall survival (OS) were computed. (3) Results: In our study, we found a significantly higher presence of blood vessels at the invasion front of OSCCs compared to the tumor center. However, we did not observe any significant differences in MVD between different tumor stages. High intratumoral MVD was shown to be a positive prognostic factor for DFS (p = 0.047). (4) Conclusions: To the best of our knowledge, we were the first to analyze MVD as a prognostic factor by considering its spatial heterogeneity in OSCC. However, further studies are warranted to further elucidate the complexity of microvascular spatial heterogeneity and its influence on prognosis.

GLDC promotes colorectal cancer metastasis through epithelial-mesenchymal transition mediated by Hippo signaling pathway.

Cancer metastasis remains a major cause of death in cancer patients, and epithelial-mesenchymal transition (EMT) plays a decisive role in cancer metastasis. Recently, abnormal expression of Glycine Decarboxylase (GLDC) has been demonstrated in tumor progression, and GLDC is up-regulated in cancers, such as lung, prostate, bladder, and cervical cancers. However, the exact role of GLDC in colorectal cancer (CRC) progression remains to be elucidated. The aim of our study was to explore the role of GLDC in CRC metastasis. The GSE75117 database was used to investigate GLDC expression in tumor center and invasive front tissues and we found that GLDC expression levels were higher in theinvasive front tissue. GLDC expression levels were negatively correlated with the prognosis of CRC patients. In vitro studies have showed that GLDC can promote invasion and migration of CRC cells by inhibiting the Hippo signaling pathway and regulating the EMT process. Blocking the Hippo signaling pathway with Verteporfin reduced the effect of GLDC on CRC metastasis. In vivo metastasis assays further confirmed that tail vein injection of GLDC+/+ cells induced morelung metastasis, compared to normal CRC cells. The results of this study suggest that GLDC promotes EMT through the Hippo signaling pathway, providing a new therapeutic target for CRC metastasis.

Apoptosis-related Prognostic Factors in Advanced Colorectal Cancer Determined Using Tissue Microarrays.

Cancer cells evade apoptosis in colorectal cancer (CRC); however, overlap between apoptosis and poor prognosis marker proteins in the invasive front of tumors has not been reported. Here, we aimed to clarify the relationship between apoptosis, apoptosis-related protein expression, and prognosis in the central and invasive front regions of CRC using tissue microarrays. Data of 207 patients with pathological stage 3 CRC, who underwent radical surgery between October 2010 and November 2014, were retrospectively reviewed. We assessed apoptosis using M30 CytoDEATH, CD163, and p53 immunostaining in tumor sections in the center and invasive front using tissue microarrays and correlated the results with the survival outcomes. M30 CytoDEATH staining was negative; 134 cases (64.7%) were apoptosis-negative in the center and 103 (49.8%) were apoptosis-negative at the invasive front. CD163 positivity was observed in 16 cases (7.8%) in the center and in 36 cases (17.6%) at the invasive front; p53 positivity was observed in 33 (15.9%) and 64 (30.9%) cases in the center and invasive front, respectively. CD163 and p53 expression was not associated with survival outcomes; however, the apoptosis-negative group at the invasive front had significantly poorer survival outcomes (overall survival: p=0.044, relapse-free survival: p=0.001). We identified cases with a poor prognosis by combining apoptosis and CD163 expression. A lower apoptosis percentage at the invasive front is associated with a poorer prognosis. CRC cases with a poor prognosis can be identified by evaluating apoptosis and CD163 expression in the invasive front.

Clinical significance of the expression of FOXP3 and TIGIT in Merkel cell carcinoma

The pathogenesis of 80% of Merkel cell carcinoma (MCC) cases is associated with Merkel cell polyomavirus (MCPyV). Forkhead helix transcription factor P3 (FOXP3) and the T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT)–CD155 pathway, which are targets for immunotherapy, were assessed as prognostic factors of MCC. We analyzed mRNA expression data of 111 patients with MCC and performed immunohistochemical analysis to detect the expression of programmed death ligand 1 (PD-L1), CD8, FOXP3, TIGIT, and CD155 in 65 cases of MCC. In CD8 and FOXP3 immunostaining, the number of expressing-infiltrating cells was determined by dividing the region into tumor center and invasive front areas. FOXP3 expression was evaluated separately in cells with high and low intensities. Aberrant TIGIT expression and weak CD155 staining were observed in MCC cells. CD8- and FOXP3-positive cell infiltrations were higher in the invasive front than in the tumor center. Multivariate Cox hazard analysis revealed that high infiltration of cells with low-intensity FOXP3 expression in the invasive front is a favorable prognostic factor (p = 0.025). Thus, targeting TIGIT–CD155 signaling and FOXP3 as well as PD-L1 may be a therapeutic strategy for MCC.

E-Cadherin Expression Varies Depending on the Location within the Primary Tumor and Is Higher in Colorectal Cancer with Lymphoid Follicles.

Reliable indicators of cancer advancement have actively been sought recently. The detection of colorectal cancer progression markers is essential in improving diagnostic and therapeutic protocols. The aim of the study was to investigate the profile of E-cadherin expression in colorectal cancer tissue depending on the TNM staging and its correlation with several clinical and histopathological features. The study included 55 colorectal cancer patients admitted to the surgical ward for elective surgery. Tissue samples were obtained from resected specimens. Different distributions of E-cadherin expression within tumors were observed; the highest percentage of positive E-cadherin expression was found in the invasive front and in the tumor center. Additionally, the different cellular distribution of E-cadherin expression was noticed; weak membranous E-cadherin expression was the highest in the invasive front and in the budding sites, but a strong membranous pattern was most frequent in the tumor center. Various distributions of E-cadherin expression depending on cancer progression were also found; E-cadherin expression in node-positive patients was lower in the tumor center and in the tumor invasive front, whereas, in patients with distant metastases, the expression of E-Cadherin was lower in the budding sites. In patients with higher TNM stages, E-cadherin expression was lower within the tumor (in the budding sites, tumor center, and invasive front). In tumors with lymphoid follicles, E-cadherin expression was higher in all localizations within the primary tumor. E-cadherin expression in the tumor center was also lower in tumors with some higher tumor budding parameters (areas of poorly differentiated components and poorly differentiated clusters). E-cadherin expression was found to be lower at the tumor center in younger individuals, at the budding sites in men, and at the surrounding lymph nodes in rectal tumors. Low E-cadherin expression appears to be a reliable indicator of higher cancer staging and progression. When assessing the advancement of cancer, apart from the TNM classification, it is beneficial to also consider the expression of E-cadherin. High tumor budding, the poverty of lymphoid follicles, and low E-cadherin expression analyzed simultaneously may contribute to a reliable assessment of colorectal cancer staging. These three histopathological features complement each other, and their investigation, together with conventional tumor staging and grading, may be very helpful in predicting the prognosis of colorectal cancer patients and qualifying them for the best treatment. The role of E-cadherin in the diagnosis and treatment of colorectal cancer, as a part of a personalized medicine strategy, still requires comprehensive, prospective clinical evaluations to precisely target the optimal therapies for the right patients at the right time.

Immune cell infiltration, tumour budding, and the p53 expression pattern are important predictors in penile squamous cell carcinoma: a retrospective study of 152 cases

Penile squamous cell carcinoma (pSCC) is a rare malignancy with a slowly increasing incidence and variable prognosis. Regional lymph node involvement signifies poor prognosis but represents a late sign, and more prognostic markers for effective patient risk stratification are urgently needed. In this retrospective study, 152 tumour samples with formalin-fixed, paraffin-embedded tissue were analysed for traditional pathological variables, tumour budding, p53, p16, and mismatch repair proteins (MMR) immunohistochemistry. The density of tumour lymphocytic infiltrate was also determined, using subjective evaluation by two pathologists (brisk/non-brisk/absent) and also using the immunoscore method, which categorised the cohort into five immunoscore groups according to the number of CD3+ and CD8+ T-cells in both the tumour centre and tumour invasion front. Only one case (0.6%) was MMR-deficient. Tumour budding count ≥5 tumour buds/20× power field and non-brisk/absent lymphocytic infiltrate were significant negative predictors of both the overall survival (OS) and cancer-specific survival (CSS), whereas a low immunoscore was a significant marker of shorter OS but not CSS. Advanced pT stage (3+4) was a significant marker of shorter CSS but not OS. In the multivariate analysis, high-grade budding was a significant parameter if adjusted for the patient's age and associated variables, except for the pN stage. The lymphocytic infiltrate retained its prognostic significance if adjusted for age and associated variables. The negative prognostic significance of the previously described parameters (lymphatic, venous, and perineural invasion, regional lymph node metastasis, and p53 mutated profile) were confirmed in our study. Grade, histological subtype, and HPV status (as determined by p16 immunohistochemistry) showed, surprisingly, little or no prognostic significance.

Reconfigurable metatiles with circular maze-like space-coiling-based acoustic metastructure for low-to-mid frequency sound attenuation

This study presents a compact, lightweight, and reconfigurable acoustic metatile for sound mitigation applications. The metatile prototype is designed based on a circular maze-like acoustic metastructure, which utilizes a space-coiling technique for enhanced acoustic performance in low-to-mid frequencies. The proposed labyrinthine acoustic metadisk structure comprises a central hollow front face sheet and two coiling-up backing cavities. Experimental results show that the metadisk has high absorption peaks of 0.81 and 0.75 at 574 and 1436 Hz, respectively, and exhibits high sound transmission loss (STL) values ( ≥25 dB) in separate wide frequency bands between 100–580 Hz and 820–1600 Hz. Based on the metadisk samples, metatiles are constructed, which are 30.5 × 30.5 cm 2 in size. The acoustic performance of these metatiles is investigated in two distinct scenarios. Two prototypes of the acoustic metatile are presented: the metacage and the metapanel. The metacage is a cubical box-shaped structure constructed using five metatiles, which showed a wideband insertion loss of ≥10 dB in 200–16 000 Hz and ≥20 dB over 400–5000 Hz. On the other hand, the metapanel is constructed using nine metatiles, which exhibited STL values of &amp;gt;20 dB over 125–5000 Hz and had a sound transmission class rating of 34. The study highlights the potential of circular maze-like space-coiling-based acoustic disk metastructures to be reconfigured into metatiles and assembled into a metacage or metapanel for practical sound mitigation applications.

Tumor Immune Microenvironment Heterogeneity at the Invasion Front and Tumor Center in Oral Squamous Cell Carcinoma as a Perspective of Managing This Cancer Entity

Evaluating the tumor microenvironment and its influence on clinical management and therapy response is becoming increasingly important. However, only a few studies deal with the spatial distribution of immune cells within the tumor. This study aimed to describe the topology of immune cells in the microenvironment of oral squamous cell carcinoma (OSCC) sectioned by tumor invasion front and tumor center and to test their prognostic relevance regarding patient survival. A total of 55 OSCC patient specimens were collected retrospectively. The cancer tissue was immunohistochemically stained using an automated tissue stainer Ventana Benchmark Ultra (Roche) and analyzed using discrete expression marker profiles on immune cells. We investigated CD4+ lymphocytes, CD8+ lymphocytes, CD68+ macrophages, CD163+ macrophages, and M1 macrophages regarding their spatial distribution. The statistical analysis revealed that the quantity and distribution of CD4+ (p = 0.007), CD8+ (p < 0.001), CD68+ (p < 0.001), CD163+ cells (p = 0.004), and M1 (p < 0.001) macrophages were significantly higher at the invasion front compared to the tumor center in all observed cases. However, high and low immune cell counts in the tumor center and invasion front were not associated with overall survival. Our results show two distinct immune microenvironments of the tumor center compared to the invasion front. Future studies are needed to explore how these results can be leveraged to improve patient therapy and outcome.

Ukrainian scientists — chief infectious disease specialists and epidemiologists of the central medical service, fronts (fleets), armies and military districts during the Second World War

The article considers the role of Ukrainian scientists — chief infectious disease specialists and epidemiologists of the central medical service, fronts (fleets), armies and military districts in ensuring the sanitary and epidemiological well-being of the troops during the Second World War.

A Quantitative Assessment on Perceived Physiological Comfort of Clothing during Lactation

Background: Physiological comfort refers to sensorial comfort including temperature, fit and fabric weight. Because pregnant and lactating women undergo various physiological changes, it is important to identify optimal comfort features regarding clothing. This will promote and increase breastfeeding duration. The purpose of this research is to compare physiological comfort of two types of clothing. They include designed clothing (DC) ,such as side flaps to access breasts and a strap which gets unhooked ), and conventional clothing(CC), like center front button closure, center front zipper, knitted V-neck shirt, and a t-shirt.&#x0D; Methods: This was a quantitative research study conducted to examine perceived physiological comfort of clothing during lactation (IRB# 1-1056432-1). Data were collected from 217 lactating women who were on lactated related social media sites (e.g., BabyCenter blog). A validated and reliable survey was developed by interviewers. It was a series of questions including demographic ones and assessed seven physiological features. Data were analyzed using descriptive statistics, frequencies (number and percent), and, a sample t-test. &#x0D; Results: After comparing DC with CC, authors found that DC provided greater physiological comfort. Statistically significant differences (p≤ .05) were found between garment coverage in reference to temperature (i.e. warmth) and satisfaction with the length of the garment.&#x0D; Conclusions: The results have practical implications for a variety of professions including apparel designers and lactation health care providers. Currently, there is little to no research which investigated physiological comfort of outerwear clothing for lactating mothers.&#x0D;

조선 후기 학창의 연구

Hakchangui is an article of clothing derived from Taoism and called Hakchang. Based on the relevance to Hakchang in the Ming dynasty, this study examines the public reaction to, function, and form of Hakchangui in the 17th and 18th century Joseon Dynasty and attempts to understand the change of Hakchangui in the 19th century. In the Ming Dynasty, Hakchangui was worn by the Taoists, the scholars who escaped power and lived a life of the world and the people in general. Jikryeong has no closures at the center front and no slits at the sides or back. In the 17th and 18th centuries, Hakchangui of the Joseon Dynasty was worn as a daily attire of the Scholar-officials. It is similar to the Hakchang of the Ming Dynasty in that it has wide sleeves, collars, sleeves, and hemlines. However, it is a combined shape of a cloak and differs in composition, shape, collars, and front closure. In the 19th century, Hakchangui was a with a black line on the Changui and had a back slit in the form of Jikryonggyoim, whose collar is straight and the hem crossed with back slits. Hakchangui was inner under official attire in the early 19th century, and it is estimated that it began to be used at the end of the 18th century when the policy of changing the Changui worn as an inner robe of court uniform to a white unlined garment worn as a base when wearing a uniform was implemented. The sleeveless Queja type of Hakchangui has been worn since the 17th century, and it lasted until the 19th century and was worn as innerwear like the Jikryonggyoim type of Hakchangui. Based on the Hakchang system of the Ming Dynasty in the 17th and 18th centuries, Hakchangui in the late Joseon Dynasty showed a small portion of its composition characteristics. Around the 19th century, it was separated from Hakchang in the Ming Dynasty and developed into a unique style of Joseon.