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The purpose of this study was to investigate the presence of Cryptococcus neoformans species complex isolates from environmental sources in Croatia and to determine their molecular types and antifungal susceptibility. Swab samples of tree hollows and bird excreta in the soil beneath trees were collected. Samples included 472 (92.73%) samples obtained from tree hollows and 37 (7.27%) samples from bird excreta. Four C. neoformans species complex isolates were recovered from tree hollow swabs along the Mediterranean coast, while there were no isolates recovered from bird excreta or from the continental area. Three isolates were identified as molecular types VNI and one as VNIV. All tested antifungals showed high in vitro activity against the four isolates. This is the first report proving the presence of C. neoformans species complex in the environment of Croatia. The results of the study suggest a major risk of exposure for inhabitants living along the Croatian coast and that both VNI and VNIV molecular types can be expected in clinical cases of cryptococcosis. Susceptibility to antifungals confirmed that no resistance should be expected in patients with cryptococcosis at the present time.

The diagnosis of ependymoma has moved from a purely histopathological review with limited prognostic value to an integrated diagnosis, relying heavily on molecular information. However, as the integrated approach is still novel and some molecular ependymoma subtypes are quite rare, few studies have correlated integrated pathology and clinical outcome, often focusing on small series of single molecular types. We collected data from 2023 ependymomas as classified by DNA methylation profiling, consisting of 1736 previously published and 287 unpublished methylation profiles. Methylation data and clinical information were correlated, and an integrated model was developed to predict progression-free survival. Patients with EPN-PFA, EPN-ZFTA, and EPN-MYCN tumors showed the worst outcome with 10-year overall survival rates of 56%, 62%, and 32%, respectively. EPN-PFA harbored chromosome 1q gains and/or 6q losses as markers for worse survival. In supratentorial EPN-ZFTA, a combined loss of CDKN2A and B indicated worse survival, whereas a single loss did not. Twelve out of 200 EPN-ZFTA (6%) were located in the posterior fossa, and these tumors relapsed or progressed even earlier than supratentorial tumors with a combined loss of CDKN2A/B . Patients with MPE and PF-SE, generally regarded as non-aggressive tumors, only had a 10-year progression-free survival of 59% and 65%, respectively. For the prediction of the 5-year progression-free survival, Kaplan-Meier estimators based on the molecular subtype, a Support Vector Machine based on methylation, and an integrated model based on clinical factors, CNV data, and predicted methylation scores achieved balanced accuracies of 66%, 68%, and 73%, respectively. Excluding samples with low prediction scores resulted in balanced accuracies of over 80%. In sum, our large-scale analysis of ependymomas provides robust information about molecular features and their clinical meaning. Our data are particularly relevant for rare and hardly explored tumor subtypes and seemingly benign variants that display higher recurrence rates than previously believed.

Lung cancer has become a major public health concern, standing as the leading cause of cancer-related deaths worldwide. Among its subtypes, small-cell lung cancer (SCLC) is characterized by aggressive and rapid growth, poor differentiation, and neuroendocrine features. Typically, SCLC is diagnosed at an advanced stage (extensive disease, ED-SCLC), with distant metastases, and is strongly associated with tobacco smoking and has a poor prognosis. Recent clinical trials, such as CASPIAN and IMpower133, have demonstrated promising outcomes with the incorporation of immune checkpoint inhibitors in first-line chemotherapy, leading to prolonged progression-free survival and overall survival in patients with ED-SCLC compared to standard chemotherapy. Other studies have emphasized the potential for future development of molecularly targeted therapies in SCLC patients, including inhibitors of IGF-1R, DLL3, BCL-2, MYC, or PARP. The molecular subdivision of SCLC based on transcriptomic and immunohistochemical analyses represents a significant advancement in both diagnostic and clinical approaches in SCLC patients. Specific molecular pathways are activated within distinct transcriptome subtypes of SCLC, offering the potential for personalized treatment strategies, such as targeted therapies and immunotherapies. Such tailored approaches hold promise for significantly improving outcomes in SCLC patients.

As the second leading etiological agent of candidemia in Turkey and the cause of severe fluconazole-non-susceptible (FNS) clonal outbreaks, Candida parapsilosis emerged as a major health threat at Ege University Hospital (EUH). Evaluation of microbiological and pertinent clinical profiles of candidemia patients due to C . parapsilosis in EUH in 2019–2020. Candida parapsilosis isolates were collected from blood samples and identified by sequencing internal transcribed spacer ribosomal DNA. Antifungal susceptibility testing was performed in accordance with CLSI M60 protocol and ERG11 and HS1/HS2- FKS1 were sequenced to explore the fluconazole and echinocandin resistance, respectively. Isolates were typed using a multilocus microsatellite typing assay. Relevant clinical data were obtained for patients recruited in the current study. FNS C . parapsilosis isolates were recovered from 53% of the patients admitted to EUH in 2019–2020. Y132F was the most frequent mutation in Erg11. All patients infected with C . parapsilosis isolates carrying Y132F, who received fluconazole showed therapeutic failure and significantly had a higher mortality than those infected with other FNS and susceptible isolates (50% vs . 16.1%). All isolates carrying Y132F grouped into one major cluster and mainly recovered from patients admitted to chest diseases and pediatric surgery wards. The unprecedented increase in the number of Y132F C . parapsilosis , which corresponded with increased rates of fluconazole therapeutic failure and mortality, is worrisome and highlights the urgency for strict infection control strategies, antifungal stewardship, and environmental screening in EUH.

Background Ferroptosis is closely associated with the pathophysiological processes of many diseases, such as infection, and is characterized by the accumulation of excess lipid peroxides on the cell membranes. However, studies on the ferroptosis-related diagnostic markers in tuberculosis (TB) is still lacking. Our study aimed to explore the role of ferroptosis-related biomarkers and molecular subtypes in TB. Methods GSE83456 dataset was applied to identify ferroptosis-related genes (FRGs) associated with TB, and GSE42826, GSE28623, and GSE34608 datasets for external validation of core biomarkers. Core FRGs were identified using weighted gene co-expression network analysis (WGCNA). Subsequently, two ferroptosis-related subtypes were constructed based on ferroptosis score, and differently expressed analysis, GSEA, GSEA, immune cell infiltration analysis between the two subtypes were performed.Affiliations: Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.correctly Results A total of 22 FRGs were identified, of which three genes (CHMP5, SAT1, ZFP36) were identified as diagnostic biomarkers that were enriched in pathways related to immune-inflammatory response. In addition, TB patients were divided into high- and low-ferroptosis subtypes (HF and LF) based on ferroptosis score. HF patients had activated immune- and inflammation-related pathways and higher immune cell infiltration levels than LF patients. Conclusion Three potential diagnostic biomarkers and two ferroptosis-related subtypes were identified in TB patients, which would help to understand the pathogenesis of TB.Author names: Kindly check and confirm the process of the author names [2,4]correctly

C2N-ring-based molecular chains were designed at the molecular level and theoretically demonstrated to show distinctive and valuable electron transport properties that were superior to the parent carbonaceous system and other similar nanoribbon-based molecular chains. This new -type molecular chain presented an exponential attenuation of the conductance and electron transmission with the length. Essentially, the molecular chain retained the electron-resonant tunneling within 7 nm and the dominant transport orbital was the LUMO. Shorter molecular chains with stronger conductance anomalously possessed a larger tunnel barrier energy, attributing to the compensation of a much smaller HOMO–LUMO gap, and these two internal factors codetermined the transport capacity. Some influencing factors were also studied. In contrast to the common O impurity with a tiny effect on electron transmission of the C2N rings chain, the common H impurity clearly improved it. When the temperature was less than 400 K, the electron transmission varied with temperature within a narrow range, and the structural disorder deriving from proper heating did not greatly modify the transmission possibility and the exponentially decreasing tendency with the length. In a non-equilibrium condition, the current increased overall with the bias but the growth rate varied with size. A valuable negative differential resistance (NDR) effect appeared in longer molecular chains with an even number of big carbon–nitrogen rings and strengthened with size. The emergence of such an effect originated from the reduction in transmission peaks. The conductance of longer molecular chains was enhanced with the voltage but the two shortest ones presented completely different trends. Applying the bias was demonstrated to be an effective way for C2N-ring-based molecular chains to slow down the conductance decay constant and affect the transport regime. C2N-ring-based molecular chains show a perfect application in tunneling diodes and controllable molecular devices.

Human Adenovirus (HAdV) is a significant pathogen for acute respiratory infections(ARIs) in children. However, its epidemiological patterns, serotype distribution changes, and molecular mechanisms associated with severe pneumonia during and after the COVID-19 pandemic require further elucidation through large-scale and molecular typing studies. This study used a retrospective cohort design to analyze 28060 respiratory specimens from Tianjin Children's Hospital from March 2022 to March 2024. HAdV detection and typing were performed through targeted high-throughput sequencing and PCR-based amplification of Penton, Hexon, and Fiber genes for phylogenetic analysis. Additionally, clinical data were compared to assess differences in clinical presentations among pediatric patients infected with different HAdV types. The overall HAdV detection rate was 8.9% (2,484/28,060), with significant male predominance (9.2% . 8.4%, = 0.019) and age-specific susceptibility peaking in school-aged children (10.4%, < 0.001). Seasonal patterns demonstrated winter predominance (15.9%), contrasting with other seasons ( < 0.001). Genotyping of 1,914 positive specimens demonstrated HAdV-3 dominance (53.4%, 1,022), followed by HAdV-7 (17.7%, 338), HAdV-2 (8.4%, 160), HAdV-1 (7.9%, 152), and HAdV-21 (6.4%, 122). The diagnosis mainly included pneumonia, bronchitis, adenopharyngitis, and upper respiratory tract infections (URTIs). Genotype-clinical correlations showed distinct patterns: HAdV-3 (55.6%) and HAdV-7 (20.9%) predominated in pneumonia cases, with HAdV-7 linked to severe pneumonia ( <0.001). HAdV-3 (40.6%) and HAdV-2 (16.7%) were more common in adenopharyngitis, while HAdV-3 and HAdV-21 were more common in bronchitis (51.2% and 11.1%) and URTIs (31.9% and 19.1%). Molecular characterization revealed structural conservation in the Penton protein of HAdV-C and identified Hexon as the most polymorphic region with 85 variable sites, indicating divergent evolutionary pressures across viral domains. HAdV-3, HAdV-7, HAdV-2, and HAdV-1 were the predominant HAdV types in children hospitalized with ARIs in Tianjin. Moreover, not only the epidemiological characteristics of different HAdV types vary, but there are also certain differences in the clinical symptoms and outcomes of children infected with different types of HAdV. Therefore, it is essential to differentiate HAdV types for epidemiological surveillance and clinical management purposes.

Cryptococcosis, a potentially fatal mycosis, is caused by members of the Cryptococcus neoformans and Cryptococcus gattii species complexes. In Latin America, cryptococcal meningitis is still an important health threat with a significant clinical burden. Analysis of publicly available molecular data from 5686 clinical, environmental, and veterinary cryptococcal isolates from member countries of the Latin American Cryptococcal Study Group showed that, as worldwide, C. neoformans molecular type VNI is the most common cause of cryptococcosis (76.01%) in HIV-infected people, followed by C. gattii molecular type VGII (12.37%), affecting mostly otherwise healthy hosts. These two molecular types also predominate in the environment (68.60% for VNI and 20.70% for VGII). Among the scarce number of veterinary cases, VGII is the predominant molecular type (73.68%). Multilocus sequence typing analysis showed that, in Latin America, the C. neoformans population is less diverse than the C. gattii population (D of 0.7104 vs. 0.9755). Analysis of antifungal susceptibility data showed the presence of non-wild-type VNI, VGI, VGII, and VGIII isolates in the region. Overall, the data presented herein summarize the progress that has been made towards the molecular epidemiology of cryptococcal isolates in Latin America, contributing to the characterization of the genetic diversity and antifungal susceptibility of these globally spreading pathogenic yeasts.

Endometrial cancer represents one of the most common gynecological cancers in women. In recent years, there has been increasing interest in immunotherapy, including the use of pembrolizumab, particularly for the treatment of cancers with deficient mismatch repair (dMMR) and microsatellite instability-high (MSI-H). A systematic review of the literature from 2020 to 2025 was conducted according to the PICO model. Six studies were included in this review, comprising four randomized clinical trials (RCTs) and two pre-specified subgroup analyses derived from previous RCTs involving a total of 3684 patients with early-stage or advanced disease or metastatic or recurrent endometrial cancer. Interventions included the use of pembrolizumab in monotherapy and in combination with chemotherapy or lenvatinib. Pembrolizumab showed a significant improvement in progression-free survival (PFS) and overall survival (OS) in the dMMR patient groups. Therapeutic benefit was limited in the proficient mismatch repair (pMMR) groups. The incidence of side effects was high but comparable to the control group. Pembrolizumab, especially in combination therapy with lenvatinib, is a promising therapeutic option for patients with dMMR/MSI-H endometrial cancer. The results suggest a potential long-term treatment effect, although the limitations of the RCT and the variability in the therapeutic regimens require further research.

Background: Breast tubular carcinoma is a special pathological type of invasive breast cancer, accounting for about 0.8% to 10.0% of breast cancer cases, and it is a rare type of breast cancer. Currently, there is still a lack of relevant diagnostic and treatment consensus. Exploring the relationship between the pathological characteristics, molecular subtypes, and prognosis of ductal breast cancer is of great scientific value and clinical significance for improving patients’ survival rate and quality of life. Methods: The clinical data of 22 patients with tubular breast carcinoma diagnosed by pathology in The First Medical Center of PLA General Hospital from January 2001 to December 2021 were collected, and their pathological features, molecular classification, and prognosis were analyzed retrospectively. Results: The clinicopathological features of 22 patients with tubular breast carcinoma were age ≥ 35 years, married, tumor ≤ 2 cm, single focal, mixed type, no lymph node metastasis, estrogen receptor (ER) positive, progesterone receptor (PR) positive, Ki‐67 ≤ 14%, CyclinD1 negative, less recurrence, and metastasis. Twenty‐two patients with breast tubular carcinoma were followed up for 5 years after surgery, and the survival rate of disease‐free survival (DFS) was 90.9% (20/22). The positive rates of ER, PR, and human epidermal growth factor receptor‐2 (HER‐2) are 100.0%, 100.0%, and 40.9%, respectively. The proportion of tumor cells expressing Ki‐67 is 45.4%. Among them, the difference of HER‐2 level, recurrence and metastasis, and postoperative comprehensive treatment showed different prognoses. Conclusion: Tubular breast carcinoma is a kind of tumor with a low malignant degree. The prognosis is significantly related to its HER‐2 level, recurrence and metastasis, and postoperative comprehensive treatment by univariate analysis, in which HER‐2 is an independent risk factor, postoperative comprehensive treatment is a protective factor, but postoperative recurrence and metastasis have nothing to do with the prognosis by the multivariate analysis.