Key drivers of the oxidative potential of PM2.5 in Beijing in the context of air quality improvement from 2018 to 2022.

The mass concentration of atmospheric particulate matter (PM) has been continuously decreasing in the Beijing-Tianjin-Hebei region. However, health endpoints do not exhibit a linear correlation with PM mass concentrations. Thus, it is urgent to clarify the prior toxicological components of PM to further improve air quality. In this study, we analyzed the long-term oxidative potential (OP) of water-soluble PM2.5, which is generally considered more effective in assessing hazardous exposure to PM in Beijing from 2018 to 2022 based on the dithiothreitol assay and identified the crucial drivers of the OP of PM2.5 based on online monitoring of air pollutants, receptor model, and random forest (RF) model. Our results indicate that dust, traffic, and biomass combustion are the main sources of the OP of PM2.5 in Beijing. The complex interactions of dust particles, black carbon, and gaseous pollutants (nitrogen dioxide and sulfur dioxide) are the main factors driving the OP evolution, in particular, leading to the abnormal rise of OP in Beijing in 2022. Our data shows that a higher OP is observed in winter and spring compared to summer and autumn. The diurnal variation of the OP is characterized by a declining trend from 0:00 to 14:00 and an increasing trend from 14:00 to 23:00. The spatial variation in OP of PM2.5 was observed as the OP in Beijing is lower than that in Shijiazhuang, while it is higher than that in Zhenjiang and Haikou, which is primarily influenced by the distribution of black carbon. Our results are of significance in identifying the key drivers influencing the OP of PM2.5 and provide new insights for advancing air quality improvement efforts with a focus on safeguarding human health in Beijing.

Potential pre-industrial-like new particle formation induced by pure biogenic organic vapors in Finnish peatland.

Pure biogenic new particle formation (NPF) induced by highly oxygenated organic molecules (HOMs) could be an important mechanism for pre-industrial aerosol formation. However, it has not been unambiguously confirmed in the ambient due to the scarcity of truly pristine continental locations in the present-day atmosphere or the lack of chemical characterization of NPF precursors. Here, we report ambient observations of pure biogenic HOM-driven NPF over a peatland in southern Finland. Meteorological decoupling processes formed an "air pocket" (i.e., a very shallow surface layer) at night and favored NPF initiated entirely by biogenic HOM from this peatland, whose atmospheric environment closely resembles that of the pre-industrial era. Our study sheds light on pre-industrial aerosol formation, which represents the baseline for estimating the impact of present and future aerosol on climate, as well as on future NPF, the features of which may revert toward pre-industrial-like conditions due to air pollution mitigation.

Diversity, integration, and variability of intergenerational relationships in old age: New insights from personal network research.

Relationships between family members from different generations have long been described as a source of solidarity and support in aging populations and, more recently, as a potential risk factor for COVID-19 contagion. Personal or egocentric network research offers a powerful kit of conceptual and methodological tools to study these relationships, but this has not yet been employed to its full potential in the literature. We investigate the heterogeneity, social integration, and individual correlates of intergenerational relationships in old age analyzing highly granular data on the personal networks of 230 older adults (2747 social ties) from a local survey in one of the areas of the world at the forefront of global aging trends (northern Italy). Using information on different layers in broad egocentric networks and on the structure of connectivity among the social contacts of aging people, we propose multiple conceptualizations and measures of intergenerational connectedness. Results show that intergenerational relationships are strongly integrated, but also highly diverse and variable, in older adults' social networks. Different types of intergenerational ties exist in different network layers, with various relational roles, degrees of tie strength, and patterns of association with individual and tie characteristics. We discuss how new and existing personal network data can be leveraged to consider novel questions and hypotheses about intergenerational relationships in contemporary aging families.

Coexistence of Trigonocephaly and Sylvian Arachnoid Cysts: A Coincidence?

Introduction The association between trigonocephaly and sylvian fissure arachnoid cysts (ACs) has been occasionally reported in the literature [1,2]. However, the real incidence of this association and its clinical relevance remain unknown. Methods The authors collected and retrospectively reviewed all clinical charts and CT scans of patients surgically treated for trigonocephaly at the Pediatric Neurosurgical Department of Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS from January 2014 to June 2023. Results During the study period, 136 patients with trigonocephaly underwent surgery. Analysis of the clinical charts revealed that in 39.7% of the cases (54/136), pre-operative CT scan depicted the presence of a sylvian fissure arachnoid cyst. Of these, AC was bilateral in 23 cases and unilateral in the remaining 31. All unilateral ACs were on the left side. The ACs were classified as Galassi grade I in 52 cases (96.3%) and Galassi grade II in 2 cases (3.7%)[3]. Interestingly, in one case we reported a Galassi grade I AC enlargement during follow-up, thereby necessitating surgical fenestration. Conclusion ACs and trigonocephaly are well-known conditions for pediatric neurosurgeons; however, their association is poorly defined. Despite the lack of reports on the incidence and clinical significance of this association, it is worth knowing that radiological follow-up is essential be in monitoring AC evolution.

Do Minimally Invasive Approaches to Pediatric Orbital Tumors Provide an Advantage on Outcome and Efficiency?

OBJECTIVE: The present study evaluated whether minimally invasive approaches to orbital lesions could improve surgical, clinical, and aesthetic outcomes compared with more invasive ones. This is the first study specifically addressing this topic in children. METHODS: Children consecutively operated on from January 2010 to January 2020 were analyzed. Thirty patients matched the inclusion criteria and were divided into group A: 14 cases treated with traditional surgical approaches; and group B: 16 cases managed by minimally invasive approaches. RESULTS: There were no significant differences between the 2 groups in terms of demographic data and extent of tumor resection. Mean surgical time for the approach (40 minutes vs. 70 minutes, P < 0.0001), surgical complication such as periorbital edema (37% vs. 78%, P = 0.02) and dural tear (0 vs. 21%, P = 0.05), and procedures cost (P < 0.0001) were significantly reduced in group B. Regarding clinical outcomes, group B showed a significant reduction both in terms of postoperative pain (mean score based on visual pain scale was 2.9 vs. 4.1 P = 0.003) and mean hospitalization time (4.5 days vs. 5.5 days, P = 0.0004). The cosmetic outcome according to the Sloan classification was significantly better in group B as well (81% vs. 36% class I patients, P = 0.005). CONCLUSIONS: The use of mini-invasive approaches to orbital tumor has clear advantages in terms of surgical, clinical, and cosmetic outcomes in comparable patients; therefore, they should be preferred whenever feasible. Craniotomic approaches remain necessary for very large tumors.

Oxidized organic molecules in the tropical free troposphere over Amazonia.

New particle formation (NPF) in the tropical free troposphere (FT) is a globally important source of cloud condensation nuclei, affecting cloud properties and climate. Oxidized organic molecules (OOMs) produced from biogenic volatile organic compounds are believed to contribute to aerosol formation in the tropical FT, but without direct chemical observations. We performed in situ molecular-level OOMs measurements at the Bolivian station Chacaltaya at 5240 m above sea level, on the western edge of Amazonia. For the first time, we demonstrate the presence of OOMs, mainly with 4-5 carbon atoms, in both gas-phase and particle-phase (in terms of mass contribution) measurements in tropical FT air from Amazonia. These observations, combined with air mass history analyses, indicate that the observed OOMs are linked to isoprene emitted from the rainforests hundreds of kilometers away. Based on particle-phase measurements, we find that these compounds can contribute to NPF, at least the growth of newly formed nanoparticles, in the tropical FT on a continental scale. Thus, our study is a fundamental and significant step in understanding the aerosol formation process in the tropical FT.

Exploration of grape pomace peels and amaranth flours as functional ingredients in the elaboration of breads: phenolic composition, bioaccessibility, and antioxidant activity.

This study evaluated the incorporation of two ingredients as a source of bioactive compounds: amaranth flour (AF) and grape pomace peels flour (GP) to improve the nutritional qualities and functional properties of a wheat bread, emphasising the revalorisation of agricultural residues from grape winemaking as an ethical and economically viable source of bioactive compounds. Specifically, wheat flour (WF) substitutions were carried out for the individual ingredients, replacing 20% WF (A20 bread) or 5% GP (GP5 bread) and a mixture of both ingredients 20% WF and 5% GP (A20GP5 bread), and the antioxidant potential of the breads was analysed. The effect of simulated gastrointestinal digestion (SGID) on the phenolic profile and antioxidant activity of the fortified breads was also investigated. The substitution of WF by AF or GP introduced several phenolic compounds, digestion increased the bioaccessibility of phenolic compounds and reshaped their phenolic composition profiles. The combined presence of AF and GP in the breads modified the phenolic compounds composition and improved their antioxidant activity after SGID. Interactions between the phenolic compounds and other AF components (possibly proteins) were observed, which could protect the phenols from degradation during SGID, allowing them to be released after SGID.

Rollout of the 2022/2023 Seasonal Influenza Vaccination and Correlates of the Use of Enhanced Vaccines among Italian Adults.

In Italy, several types of seasonal influenza vaccines (SIVs) are available for older adults, but for the 2022/2023 season there were no guidelines on their specific use. This cross-sectional study assessed the frequency and determinants of the use of enhanced (adjuvanted and high-dose) SIVs in Italian older adults, as compared to standard-dose non-adjuvanted formulations. Of 1702 vaccines administered to a representative outpatient sample of adults aged ≥ 60 years and residing in Genoa, 69.5% were enhanced SIVs. Older age (adjusted odds ratio (aOR) for each 1-year increase 1.10; p < 0.001), and the presence of cardiovascular disease (aOR 1.40; p = 0.011) and diabetes (aOR 1.62; p = 0.005) were associated with the use of enhanced vaccines. Compared with the adjuvanted SIV, subjects immunized with the high-dose vaccine were older (aOR for each 1-year increase 1.05; p < 0.001) and had higher prevalence of respiratory diseases (aOR 1.85; p = 0.052). Moreover, usage of the enhanced SIVs was driven by the period of immunization campaign, place of vaccination and physician. Despite their superior immunogenicity and effectiveness, the adoption of enhanced SIVs in Italy is suboptimal, and should be increased. Enhanced formulations are mostly used in the oldest, and in subjects with some co-morbidities.

Evaluation of an institutional series of low-grade oncocytic tumor (LOT) of the kidney and review of the mutational landscape of LOT.

The 2022 WHO classification of urinary and male genital tumors introduced several novel kidney entities exhibiting eosinophilic/oncocytic features with specific mutational backgrounds. Thus, molecular techniques, such as next-generation sequencing (NGS), became more commonly used for their evaluation. We studied 12 low-grade oncocytic tumors (LOT) of the kidney (from 11 patients), identified in a cohort of 210 eosinophilic/oncocytic renal tumors, diagnosed in our institution between October 2019 and May 2023, which represented 5.7% (12/210) of all eosinophilic/oncocytic renal tumors during this period. We reviewed their clinicopathologic, histologic, and immunohistochemical features, as well as their mutational profiles. We also reviewed the literature on NGS-derived data of LOT, by selecting papers in which LOT diagnosis was rendered according to the criteria proposed initially. Median age was 65 years (mean: 63.5; range 43-79) and median tumor size was 2.0 cm (mean: 2.2; range: 0.9-3.1). All tumors were positive for PAX8, CK7, and GATA3, and negative or focally positive for CD117/KIT. We found the following gene mutations: MTOR ((6/11), 54.5%)), TSC1 ((2/11), 18.2%)), and 1 had both NOTCH1 and NOTCH4 ((1/11), 9.1%)). Wild-type status was found in 2/11 (18.2%) patients and one tumor was not analyzable. A review of 8 previous studies that included 79 LOTs revealed frequent mutations in the genes that regulate the mammalian target of rapamycin (mTOR) pathway: MTOR (32/79 (40.5%)), TSC1 (21/79 (26.6%)), and TSC2 (9/79 (11.4%)). Other mutated genes included PIK3CA, NF2, and PTEN, not typically known to affect the mTOR pathway, but potentially acting as upstream and downstream effectors. Our study shows that LOT is increasingly diagnosed in routine practice when applying the appropriate diagnostic criteria. We also confirm that the mTOR pathway is strongly implicated in the pathogenesis of this tumor mainly through MTOR, TCS1, and TSC2 mutations, but other genes could also be involved in the pathway activation, especially in LOTs without "canonical" mutations.

Optic Pathway Gliomas: The Trends of Basic Research to Reduce the Impact of the Disease on Visual Function.

Pediatric optic pathway gliomas (OPG) are low-grade brain tumors characterized by slow progression and invalidating visual loss. Common therapeutic strategies include surgery, radiotherapy, chemotherapy, and combinations of these modalities, but despite the different treatment strategies, no actual treatment exists to prevent or revert visual impairment. Nowadays, several reports of the literature show promising results regarding NGF eye drop instillation and improvement of visual outcome. Such results seem to be related with the NGF-linked prevention in caspase activation, which reduces retinal ganglion cell loss.Reducing retinal ganglion cell loss results clinically in visual field improvement as well as visual electric potential and optical coherence tomography gain. Nonetheless, visual acuity fails to show significant changes.Visual impairment represents nowadays one of the major issues in dealing with OPGs. Secondary to the interesting results offered by NGF eye drop administration, further studies are warranted to better comprehend potential treatment strategies.

Adamantinomatous craniopharyngioma: evolution in the management.

BACKGROUND: In spite of the continuous progresses in pediatric neurosurgery, adamantinomatous craniopharyngioma (AC) remains a challenging tumor due to its proximity to optic pathways, pituitary gland, hypothalamus, and Willis' circle, which can result in significant endocrine, cognitive, and neurological morbidity after treatment with subsequent impact on the patient's quality of life (QoL). The relevance that QoL has today explains the changes in the management of AC observed over the time. The goal of the present article is to provide a historical background, to show the milestones in the changes of the AC treatment, and to analyze the current main options to manage such a challenging tumor. MATERIAL AND METHODS: The pertinent literature has been reviewed. Moreover, a comparison between the past and recent personal series is reported. RESULTS: Three main eras have been identified. The first (named Cushing era) was characterized by the need to realize a harmless surgery and to define the best way to approach AC; the second (microscope era) was characterized by a tremendous technical and technological development, with remarkable results in term of safe tumor resection and control but relatively poor QoL outcomes; and the third one (current period) is characterized by an increasing integration between surgery and adjuvant treatments, with relatively minor tumor control but significant improvement of QoL (comparable overall survival). The authors' experience reflects these changes. Two groups of children were compared: 52 cases (mean follow-up: 17.5 years) belong to the historical series (group 1, 1985-2003, aggressive surgical management) and 41 (mean follow-up: 8.5 years) to the current one (Group 2, 2004-2021, integrated management). No significant differences between the two groups were detected about recurrence rate, surgical mortality, and overall survival. However, Group 2 showed significant lower rates of postoperative panhypopituitarism, obesity, and visual deterioration. CONCLUSIONS: Radical surgery allows for a good AC control with a low rate of recurrence but high risk of permanent morbidity. Despite the greater number of recurrences and surgeries, the more conservative policy, based on a combination of treatments, seems to provide the same tumor control with a better QoL. The advances in trans-nasal and trans-ventricular endoscopy, in proton therapy and in the management of the AC cyst are the main factors that allowed such an improvement.

Role of sesquiterpenes in biogenic new particle formation.

Biogenic vapors form new particles in the atmosphere, affecting global climate. The contributions of monoterpenes and isoprene to new particle formation (NPF) have been extensively studied. However, sesquiterpenes have received little attention despite a potentially important role due to their high molecular weight. Via chamber experiments performed under atmospheric conditions, we report biogenic NPF resulting from the oxidation of pure mixtures of ß-caryophyllene, α-pinene, and isoprene, which produces oxygenated compounds over a wide range of volatilities. We find that a class of vapors termed ultralow-volatility organic compounds (ULVOCs) are highly efficient nucleators and quantitatively determine NPF efficiency. When compared with a mixture of isoprene and monoterpene alone, adding only 2% sesquiterpene increases the ULVOC yield and doubles the formation rate. Thus, sesquiterpene emissions need to be included in assessments of global aerosol concentrations in pristine climates where biogenic NPF is expected to be a major source of cloud condensation nuclei.

A visual-language foundation model for pathology image analysis using medical Twitter.

The lack of annotated publicly available medical images is a major barrier for computational research and education innovations. At the same time, many de-identified images and much knowledge are shared by clinicians on public forums such as medical Twitter. Here we harness these crowd platforms to curate OpenPath, a large dataset of 208,414 pathology images paired with natural language descriptions. We demonstrate the value of this resource by developing pathology language-image pretraining (PLIP), a multimodal artificial intelligence with both image and text understanding, which is trained on OpenPath. PLIP achieves state-of-the-art performances for classifying new pathology images across four external datasets: for zero-shot classification, PLIP achieves F1 scores of 0.565-0.832 compared to F1 scores of 0.030-0.481 for previous contrastive language-image pretrained model. Training a simple supervised classifier on top of PLIP embeddings also achieves 2.5% improvement in F1 scores compared to using other supervised model embeddings. Moreover, PLIP enables users to retrieve similar cases by either image or natural language search, greatly facilitating knowledge sharing. Our approach demonstrates that publicly shared medical information is a tremendous resource that can be harnessed to develop medical artificial intelligence for enhancing diagnosis, knowledge sharing and education.

The Potential of Wine Lees as a Fat Substitute for Muffin Formulations.

The current study evaluates the prospect of wine lees (WL), a costless by-product from Amarone winemaking, as a fat replacer in muffin formulation. WL have elsewhere replaced sunflower oil, allowing the creation of 0, 25, 50, 75, and 100% fat-substituted muffins named ML0, ML25, ML50, ML75, and ML100, respectively. Batter rheology, in addition to the textural and colorimetric characteristics, the pore dimension, and the sensory aspect of the different formulations were evaluated. The batter consistency (K) of fat-replaced muffins was lower than that of the control, while the hardness and chewiness of the end products were higher. ML25 and ML50 samples reached the highest volume, while the baking loss decreased due to WL's fiber components. ML25, ML50, ML75, and ML100 accounted for caloric reductions of 9, 18, 22, and 26%, respectively, compared to full-fat muffins. Muffins with WL showed a darker crust and crumb as lightness (L*) decreased. Moreover, a* parameter increased with the increment of WL in the formulation, leading to a redder and less yellow-hued fat-replaced muffin. In conclusion, WL could effectively replace fat in the 25-50% range in muffins, achieving a final product with reduced calories, a higher dietary fiber content, higher volume, and promising sensory aspects.

NO at low concentration can enhance the formation of highly oxygenated biogenic molecules in the atmosphere.

The interaction between nitrogen monoxide (NO) and organic peroxy radicals (RO2) greatly impacts the formation of highly oxygenated organic molecules (HOM), the key precursors of secondary organic aerosols. It has been thought that HOM production can be significantly suppressed by NO even at low concentrations. Here, we perform dedicated experiments focusing on HOM formation from monoterpenes at low NO concentrations (0 - 82 pptv). We demonstrate that such low NO can enhance HOM production by modulating the RO2 loss and favoring the formation of alkoxy radicals that can continue to autoxidize through isomerization. These insights suggest that HOM yields from typical boreal forest emissions can vary between 2.5%-6.5%, and HOM formation will not be completely inhibited even at high NO concentrations. Our findings challenge the notion that NO monotonically reduces HOM yields by extending the knowledge of RO2-NO interactions to the low-NO regime. This represents a major advance towards an accurate assessment of HOM budgets, especially in low-NO environments, which prevails in the pre-industrial atmosphere, pristine areas, and the upper boundary layer.

FoxA2 is a reliable marker for the diagnosis of yolk sac tumour postpubertal-type.

AIMS: Yolk sac tumour postpubertal-type (YSTpt) shows a wide range of histological patterns and is challenging to diagnose. Recently, forkhead box transcription factor A2 (FoxA2) emerged as a driver of YSTpt formation and a promising marker for diagnosing YSTpt. However, FoxA2 has not been tested in the different patterns of YSTpt. This study aimed to assess the staining pattern of FoxA2 in te different patterns of YSTpt and other germ cell tumours of the testis (GCTT), comparing it with glypican-3 (GPC3) and α-fetoprotein (AFP). METHODS AND RESULTS: FOXA2, GPC3 and AFP immunohistochemistry was performed on 24 YSTpt (24 microcystic/reticular, 10 myxoid, two macrocystic, five glandular/alveolar, two endodermal sinus/perivascular, four solid, two polyembryoma/embryoid body and two polyvesicular vitelline) and 81 other GCTT. The percentage of positive cells (0, 1+, 2+, 3+) and the intensity (0, 1, 2, 3) were evaluated regardless of and within each YSTpt pattern. FoxA2 was positive in all YSTpt (24 of 24) and all but one (23 of 24) exhibited 2+/3+ stain, with higher intensity [median value (mv): 2.6] than AFP (1.8) and GPC3 (2.5). Both FoxA2 and GPC3 were positive in all microcystic/reticular (24 of 24), myxoid (10 of 10), macrocystic (two of two), endodermal sinus/perivascular (four of four) and polyembryoma/embryoid body (two of two) patterns. Nevertheless, only FoxA2 was positive in all glandular/alveolar (five of five), solid (four of four) and polyvesicular vitelline (two of two) patterns. The intensity of FoxA2 was higher than AFP and GPC3 in almost all YST patterns. In the other GCTT, FoxA2 was positive only in teratoma postpubertal-type (Tpt) [13 of 20 (65%)], with staining almost exclusively confined to the mature gastrointestinal/respiratory tract epithelium. CONCLUSIONS: FoxA2 is a highly sensitive and specific biomarker that supports the diagnosis of YSTpt. FoxA2 is superior to GPC3 and AFP, especially in rare and difficult-to-diagnose histological patterns of YSTpt, but mature glands of Tpt could represent a potential diagnostic pitfall.

Chiari I malformation: management evolution and technical innovation.

BACKGROUND AND DEFINITION: In recent years thanks to the growing use of radiological assessment, Chiari I malformation became one of the major diseases for a neurosurgeon to deal with. CIM can be classified according to the extent of cerebellar tonsil tip into the foramen magnum being a protrusion over five mm considered pathological. Such a disease is a heterogeneous condition with a multifactorial pathogenetic mechanism that can subdivided into a primary and secondary form. Regardless of the form, it seems that CIM is the result of an imbalance between the volume of the braincase and its content. Acquired CIMs are secondary to conditions causing intracranial hypertension or hypotension while the pathogenesis of primary forms is still controversial. PATHOGENESIS AND TREATMENT: There are several theories in the literature but the most accepted one implies an overcrowding due to a small posterior cranial fossa. While asymptomatic CIM do not need treatment, symptomatic ones prompt for surgical management. Several techniques are proposed being the dilemma centered in the need for dural opening procedures and bony decompression ones. CONCLUSION: Alongside the paper, the authors will address the novelty presented in the literature on management, diagnosis and pathogenesis in order to offer a better understanding of such a heterogeneous pathology.

Iniencephaly and long-term survival: a possible association-case report and review of the literature.

BACKGROUND: Iniencephaly is a rare, complex, and severe form of neural tube defect (NTD), usually associated with wide systemic involvement and poor prognosis. The malformation involves the occiput and the inion, variably combined with rachischisis of the upper cervical and thoracic spine. Although most patients are either stillborn or perish within a few hours after birth, there are reports linking iniencephaly and long survival. For the neurosurgeon, associated encephalocele and secondary hydrocephalus represent the main challenges in this setting of patients, together with proper prenatal counseling. MATERIAL AND METHODS: Herein, the authors performed a thorough review of the pertinent literature, looking for reports of long-term survivors. RESULTS: To date, only five long-term survivors have been reported, with surgical repair attempted in four of them. Furthermore, the authors added their personal experience about two children with long-term survival who underwent surgery, thus accurately comparing them with the analogous cases previously reported in literature, with the ultimate aim of providing novel information on the pathology and the therapeutic options needed to offer proper treatment to these patients. CONCLUSIONS: Although no distinctive anatomic differences have been prior identified between long-term survivors and other patients, some variations emerged to occur, regarding age of presentation, the extension of the CNS malformation, the systemic involvement, and the surgical procedures offered. Although the authors shed some light on the topic, further studies are warranted to better define this rare and complex disease, and survival.

TAMs PD-L1(+) in the reprogramming of germ cell tumors of the testis.

BACKGROUND: In recent years, several studies focused on the process of reprogramming of seminoma (S) cells, which regulates the transition from pure S (P-S) to S component (S-C) of mixed germ cell tumors of the testis (GCTT) and finally to embryonal carcinoma (EC) and other nonseminomatous GCTT (NS-GCTT). The accepted pathogenetic model is driven and regulated by cells (macrophages, B- and T-lymphocytes) and molecules of the tumor microenvironment (TME). Herein, we tested a series of GCTT with double staining (DS) for CD68-PD-L1 to evaluate tumor-associated macrophages (TAMs) expressing programmed death-ligand 1 (PD-L1) [TAMs PD-L1(+)] and clarify if these cells may be involved in establishing the fate of GCTT. METHODS: We collected 45 GCTT (comprising a total of 62 different components of GCTT). TAMs PD-L1(+) were evaluated with three different scoring systems [TAMs PD-L1(+)/mm2, TAMs PD-L1(+)/mm2H-score, TAMs PD-L1(+) %], and compared using pertinent statistic tests (Student's t-test and Mann-Whitney U test). RESULTS: We found that TAMs PD-L1(+) values were higher in S rather than EC (p = 0.001, p = 0.015, p = 0.022) and NS-GCTT (p < 0.001). P-S showed statistically significant differences in TAMs PD-L1(+) values compared to S-C (p < 0.001, p = 0.006, p = 0.015), but there were no differences between S-C and EC (p = 0.107, p = 0.408, p = 0.800). Finally, we found statistically significant differences also in TAMs PD-L1(+) values between EC and other NS-GCTT (p < 0.001). CONCLUSIONS: TAMs PD-L1(+) levels gradually decrease during the reprogramming of S cells {P-S [(high values of TAMs PD-L1(+)] → S-C and EC [(intermediate values of TAMs PD-L1(+)] → other NS-GCTT [(low values of TAMs PD-L1(+)], supporting a complex pathogenetic model where the interactions between tumor cells and TME components [and specifically TAMs PD-L1(+)] play a key role in determining the fate of GCTT.