Search

Myelodysplastic neoplasm (MDS) is a heterogeneous group of clonal hematological disorders that originate from the hematopoietic and progenitor cells and present with cytopenias and morphologic dysplasia with a propensity to progress to bone marrow failure or acute myeloid leukemia (AML). Genetic evolution plays a critical role in the pathogenesis, progression, and clinical outcomes of MDS. This process involves the acquisition of genetic mutations in stem cells that confer a selective growth advantage, leading to clonal expansion and the eventual development of MDS. With the advent of next-generation sequencing (NGS) assays, an increasing number of molecular aberrations have been discovered in recent years. The knowledge of molecular events in MDS has led to an improved understanding of the disease process, including the evolution of the disease and prognosis, and has paved the way for targeted therapy. The 2022 World Health Organization (WHO) Classification and the International Consensus Classification (ICC) have incorporated the molecular signature into the classification system for MDS. In addition, specific germline mutations are associated with MDS development, especially in pediatrics and young adults. This article reviews the genetic abnormalities of MDS in adults with a brief review of germline predisposition syndromes.

With the invention of high-throughput screening technologies, innumerable drug sensitivity data for thousands of cancer cell lines and hundreds of compounds have been produced. Computational analysis of these data has opened a new horizon in the development of novel anti-cancer drugs. Previous deep-learning approaches to predict drug sensitivity showed drawbacks due to the casual integration of genomic features of cell lines and compound chemical features. The challenges addressed include the intricate interplay of diverse molecular features, interpretability of complex deep learning models, and the optimization of drug combinations for synergistic effects. Through the utilization of normalized discounted cumulative gain (NDCG) and root mean squared error (RMSE) as evaluation metrics, the models aim to concurrently assess the ranking quality of recommended drugs and the accuracy of predicted drug responses. The integration of the DRPO model into cancer drug response prediction not only tackles these challenges but also holds promise in facilitating more effective, personalized, and targeted cancer therapies. This paper proposes a new deep learning model, DRPO , for efficient integration of genomic and compound features in predicting the half maximal inhibitory concentrations (IC50). First, matrix factorization is used to map the drug and cell line into latent 'pharmacogenomic' space with cell line-specific predicted drug responses. Using these drug responses, we next obtained the essential drugs using a Normalized Discounted Cumulative Gain (NDCG) score. Finally, the essential drugs and genomic features are integrated to predict drug sensitivity using a deep model. Experimental results with RMSE 0.39 and NDCG 0.98 scores on Genomics of drug sensitivity in cancer (GDSC1) datasets show that our proposed approach has outperformed the previous approaches, including DeepDSC, CaDRRes, and KMBF. These good results show great potential to use our new model to discover novel anti-cancer drugs for precision medicine. [ABSTRACT FROM AUTHOR]

With the invention of high-throughput screening technologies, innumerable drug sensitivity data for thousands of cancer cell lines and hundreds of compounds have been produced. Computational analysis of these data has opened a new horizon in the development of novel anti-cancer drugs. Previous deep-learning approaches to predict drug sensitivity showed drawbacks due to the casual integration of genomic features of cell lines and compound chemical features. The challenges addressed include the intricate interplay of diverse molecular features, interpretability of complex deep learning models, and the optimization of drug combinations for synergistic effects. Through the utilization of normalized discounted cumulative gain (NDCG) and root mean squared error (RMSE) as evaluation metrics, the models aim to concurrently assess the ranking quality of recommended drugs and the accuracy of predicted drug responses. The integration of the DRPO model into cancer drug response prediction not only tackles these challenges but also holds promise in facilitating more effective, personalized, and targeted cancer therapies. This paper proposes a new deep learning model, DRPO, for efficient integration of genomic and compound features in predicting the half maximal inhibitory concentrations (IC50). First, matrix factorization is used to map the drug and cell line into latent ’pharmacogenomic’ space with cell line-specific predicted drug responses. Using these drug responses, we next obtained the essential drugs using a Normalized Discounted Cumulative Gain (NDCG) score. Finally, the essential drugs and genomic features are integrated to predict drug sensitivity using a deep model. Experimental results with RMSE 0.39 and NDCG 0.98 scores on Genomics of drug sensitivity in cancer (GDSC1) datasets show that our proposed approach has outperformed the previous approaches, including DeepDSC, CaDRRes, and KMBF. These good results show great potential to use our new model to discover novel anti-cancer drugs for precision medicine.

Medulloblastomas are the most common malignant brain tumors in the pediatric population. Based on the idea that tumors with identical radio-genomic features should behave similarly, the 4 molecular subtypes are now widely accepted as a guide for the management and prognosis. The radiological features of medulloblastomas can predict the molecular subtype; thus, anticipating the subsequent disease progression. However, this has not been evaluated comprehensively. We aim to thoroughly study the association between the molecular subtypes and radiological features of medulloblastomas. Moreover, we aim to investigate the efficacy of this correlation with the use of progression-free survival and 5-year survival rates. A retrospective analysis was conducted for all histopathological confirmed medulloblastomas in pediatric patients (<16 years old) that were operated on in Kuwait over the past ten years (n = 44). The radiological, histological, and molecular characteristics were justifiably evaluated and analyzed in our sample. The overall progression-free survival after one year was noticed among 27 cases (≈44%) and the nonspecific 5-year survival was seen in 31 cases (≈70%) after a 5-year follow-up. Sonic Hedgehog and Wingless had the best outcomes, while group 3 showed the worst outcomes. Our findings did not support the association between most of the typical magnetic resonance imaging characteristics and survival rate. We further established that Sonic Hedgehog and Wingless biological types have a better prognosis. There was no association observed between the radiographic features, specifically the location, and the molecular subtype. [ABSTRACT FROM AUTHOR]

Background: Microsatellite instability-high (MSI-H) tumors are distinct molecular subtypes in gastric cancer. However, a few studies have comprehensively reported the molecular features of MSI-H tumors and their prognostic factors in locally advanced gastric cancer. This study aimed to clarify the molecular features and prognostic factors of locally advanced MSI-H gastric cancer. Methods: This study included 499 patients with locally advanced gastric cancer who underwent radical gastrectomy. We evaluated the MSI status and compared with previously published whole-exome sequencing, panel sequencing, and gene expression profiling data. Clinicopathological characteristics and molecular profiles were compared between patients with MSI-H and microsatellite stable (MSS) gastric cancer. A subgroup analysis of survival was performed in patients with MSI-H gastric cancer. Results: MSI-H tumors were detected in 79 of 499 patients (15.8%). MSI-H tumors were associated with an increased tumor mutational burden, MLH1 downregulation, CD274 (PD-L1) upregulation, and enrichment of cell cycle pathways. Among patients with MSI-H gastric cancer, the disease-specific survival (DSS) tended to be better in the surgery plus tegafur, gimeracil, and oteracil potassium (S-1) adjuvant chemotherapy group than in the surgery alone group, especially for stage III patients. Furthermore, DSS was better in the T cell-inflamed gene expression signature-high group, and it tended to be worse in the non-solid type poorly differentiated adenocarcinoma group. Conclusions: The molecular features and prognostic factors of locally advanced MSI-H gastric cancer were clarified. S-1 adjuvant chemotherapy appears to be beneficial, and the T cell-inflamed gene expression signature and histopathological type are prognostic factors in MSI-H tumors. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinicopathological and molecular features of appendiceal mucinous neoplasms (AMNs), compare the differences bewteen the LAMN and HAMN. Methods 32 cases of AMNs were collected between January 2015 and September 2021. They were hospitalized in the Affiliated Hospital of Southwest Medical University. 10 samples of them were selected for Next Generation Sequencing (NGS) analysis of 425 genes. Results The majority of AMNs were female (68.8%) . Most patients had positive tumor markers. The proportion of distant metastasis, recurrence and death in HAMN patients were higher than those in LAMN patients. KRAS, GNAS and BRAF gene mutations were common in AMNs patients. The SNP of MTHFR and NQO1 were common in AMNs patients. The TMB of LAMN and HAMN patients were both lower, and there was no statistical significance between them ( P > 0.05). Conclusion AMNs have special clinical pathological and molecular pathological changes, but there is no significant difference between HAMN and LAMN. [ABSTRACT FROM AUTHOR]

As one of the most prevalent digestive system tumours, colorectal cancer (CRC) poses a significant threat to global human health. With the emergence of immunotherapy and target therapy, the prognosis for the majority of CRC patients has notably improved. However, the subset of patients with BRAF exon 15 p.V600E mutation (BRAFV600E) has not experienced remarkable benefits from these therapeutic advancements. Hence, researchers have undertaken foundational investigations into the molecular pathology of this specific subtype and clinical effectiveness of diverse therapeutic drug combinations. This review comprehensively summarised the distinctive molecular features and recent clinical research advancements in BRAF‐mutant CRC. To explore potential therapeutic targets, this article conducted a systematic review of ongoing clinical trials involving patients with BRAFV600E‐mutant CRC. [ABSTRACT FROM AUTHOR]

Borderline ovarian tumours (BOTs) show intriguing characteristics distinguishing them from other ovarian tumours. The aim of the systematic review was to analyse the spectrum of molecular changes found in BOTs and discuss their significance in the context of the overall therapeutic approach. The systematic review included articles published between 2000 and 2023 in the databases: PubMed, EMBASE, and Cochrane. After a detailed analysis of the available publications, we qualified for the systematic review: 28 publications on proto-oncogenes: BRAF, KRAS, NRAS, ERBB2, and PIK3CA, 20 publications on tumour suppressor genes: BRCA1/2, ARID1A, CHEK2, PTEN, 4 on adhesion molecules: CADM1, 8 on proteins: B-catenin, claudin-1, and 5 on glycoproteins: E-Cadherin. In addition, in the further part of the systematic review, we included eight publications on microsatellite instability and three describing loss of heterozygosity in BOT. Molecular changes found in BOTs can vary on a case-by-case basis, identifying carcinogenic mutations through molecular analysis and developing targeted therapies represent significant advancements in the diagnosis and treatment of ovarian malignancies. Molecular studies have contributed significantly to our understanding of BOT pathogenesis, but substantial research is still required to elucidate the relationship between ovarian neoplasms and extraneous disease, identify accurate prognostic indicators, and develop targeted therapeutic approaches.

Objective: Mammographic calcifications are a common feature of breast cancer, but their molecular characteristics and treatment implications in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancer remain unclear. Methods: We retrospectively collected mammography records of an HR+/HER2− breast cancer cohort (n = 316) with matched clinicopathological, genomic, transcriptomic, and metabolomic data. On the basis of mammographic images, we grouped tumors by calcification status into calcification-negative tumors, tumors with probably benign calcifications, tumors with calcification of low-moderate suspicion for maligancy and tumors with calcification of high suspicion for maligancy. We then explored the molecular characteristics associated with each calcification status across multiple dimensions. Results: Among the different statuses, tumors with probably benign calcifications exhibited elevated hormone receptor immunohistochemical staining scores, estrogen receptor (ER) pathway activation, lipid metabolism, and sensitivity to endocrine therapy. Tumors with calcifications of high suspicion for malignancy had relatively larger tumor sizes, elevated lymph node metastasis incidence, Ki-67 staining scores, genomic instability, cell cycle pathway activation, and may benefit from cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. Conclusions: Our research established links between tumor calcifications and molecular features, thus proposing potential precision treatment strategies for HR+/HER2− breast cancer.

Myelodysplastic neoplasm (MDS) is a heterogeneous group of clonal hematological disorders that originate from the hematopoietic and progenitor cells and present with cytopenias and morphologic dysplasia with a propensity to progress to bone marrow failure or acute myeloid leukemia (AML). Genetic evolution plays a critical role in the pathogenesis, progression, and clinical outcomes of MDS. This process involves the acquisition of genetic mutations in stem cells that confer a selective growth advantage, leading to clonal expansion and the eventual development of MDS. With the advent of next-generation sequencing (NGS) assays, an increasing number of molecular aberrations have been discovered in recent years. The knowledge of molecular events in MDS has led to an improved understanding of the disease process, including the evolution of the disease and prognosis, and has paved the way for targeted therapy. The 2022 World Health Organization (WHO) Classification and the International Consensus Classification (ICC) have incorporated the molecular signature into the classification system for MDS. In addition, specific germline mutations are associated with MDS development, especially in pediatrics and young adults. This article reviews the genetic abnormalities of MDS in adults with a brief review of germline predisposition syndromes.

Abstract Objective This study aims to analyze the molecular characteristics of the novel coronavirus (SARS-CoV-2) Omicron variant BA.2.76 in Jining City, China. Methods Whole-genome sequencing was performed on 87 cases of SARS-CoV-2 infection. Evolutionary trees were constructed using bioinformatics software to analyze sequence homology, variant sites, N-glycosylation sites, and phosphorylation sites. Results All 87 SARS-CoV-2 whole-genome sequences were classified under the evolutionary branch of the Omicron variant BA.2.76. Their similarity to the reference strain Wuhan-Hu-1 ranged from 99.72 to 99.74%. In comparison to the reference strain Wuhan-Hu-1, the 87 sequences exhibited 77–84 nucleotide differences and 27 nucleotide deletions. A total of 69 amino acid variant sites, 9 amino acid deletions, and 1 stop codon mutation were identified across 18 proteins. Among them, the spike (S) protein exhibited the highest number of variant sites, and the ORF8 protein showed a Q27 stop mutation. Multiple proteins displayed variations in glycosylation and phosphorylation sites. Conclusion SARS-CoV-2 continues to evolve, giving rise to new strains with enhanced transmission, stronger immune evasion capabilities, and reduced pathogenicity. The application of high-throughput sequencing technologies in the epidemic prevention and control of COVID-19 provides crucial insights into the evolutionary and variant characteristics of the virus at the genomic level, thereby holding significant implications for the prevention and control of the COVID-19 pandemic.

Objective: This study aims to analyze the molecular characteristics of the novel coronavirus (SARS-CoV-2) Omicron variant BA.2.76 in Jining City, China. Methods: Whole-genome sequencing was performed on 87 cases of SARS-CoV-2 infection. Evolutionary trees were constructed using bioinformatics software to analyze sequence homology, variant sites, N-glycosylation sites, and phosphorylation sites. Results: All 87 SARS-CoV-2 whole-genome sequences were classified under the evolutionary branch of the Omicron variant BA.2.76. Their similarity to the reference strain Wuhan-Hu-1 ranged from 99.72 to 99.74%. In comparison to the reference strain Wuhan-Hu-1, the 87 sequences exhibited 77–84 nucleotide differences and 27 nucleotide deletions. A total of 69 amino acid variant sites, 9 amino acid deletions, and 1 stop codon mutation were identified across 18 proteins. Among them, the spike (S) protein exhibited the highest number of variant sites, and the ORF8 protein showed a Q27 stop mutation. Multiple proteins displayed variations in glycosylation and phosphorylation sites. Conclusion: SARS-CoV-2 continues to evolve, giving rise to new strains with enhanced transmission, stronger immune evasion capabilities, and reduced pathogenicity. The application of high-throughput sequencing technologies in the epidemic prevention and control of COVID-19 provides crucial insights into the evolutionary and variant characteristics of the virus at the genomic level, thereby holding significant implications for the prevention and control of the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

In recent decades, the prevalence of thyroid cancer has risen substantially, with papillary thyroid microcarcinoma (PTMC) constituting over 50% of cases. Although most PTMCs exhibit indolent growth and a favorable prognosis, some present an increased risk of recurrence and an unfavorable prognosis due to high-risk characteristics such as lymph node metastasis, extrathyroidal extension, and distant metastasis. The early identification of clinically progressing PTMC remains elusive. In this review, the authors summarize findings from PTMC progression-related literature, highlighting that factors such as larger tumor size, cervical lymph node metastasis, extrathyroidal extension, younger age, higher preoperative serum thyroid-stimulating hormone levels, family history, and obesity positively correlate with PTMC progression. The role of multifocality in promoting PTMC progression; however, remains contentious. Furthermore, recent studies have shed light on the impact of mutations, such as BRAF and TERT mutations, on PTMC progression. Researchers have identified several mRNAs, noncoding RNAs, and proteins associated with various features of PTMC progression. Some studies propose that peripheral and tumor tissue-infiltrating immune cells could serve as biomarkers for the clinical progression of PTMC. Collectively, these clinical and molecular features offer a rationale for the early detection and the development of precision theranostic strategies of clinically progressive PTMC. [ABSTRACT FROM AUTHOR]

Abstract As one of the most prevalent digestive system tumours, colorectal cancer (CRC) poses a significant threat to global human health. With the emergence of immunotherapy and target therapy, the prognosis for the majority of CRC patients has notably improved. However, the subset of patients with BRAF exon 15 p.V600E mutation (BRAFV600E) has not experienced remarkable benefits from these therapeutic advancements. Hence, researchers have undertaken foundational investigations into the molecular pathology of this specific subtype and clinical effectiveness of diverse therapeutic drug combinations. This review comprehensively summarised the distinctive molecular features and recent clinical research advancements in BRAF‐mutant CRC. To explore potential therapeutic targets, this article conducted a systematic review of ongoing clinical trials involving patients with BRAFV600E‐mutant CRC.

Abstract Objective This study aimed to investigate the clinicopathological features and prognostic indicators of alveolar soft part sarcoma (ASPS). Methods The characteristics of 26 ASPS patients diagnosed at our hospital between January 2011 and January 2019 were retrospectively analysed. Results The data for 12 male and 14 female patients, with a median age of 27.5 years, were assessed. The clinical symptoms mainly included painless enlarged masses in deep soft tissues. ASPS had a characteristic pathological morphology. Twenty-four patients were positive for TFE3, and TFE3 gene rearrangement was detected in 12 patients. Among the 26 patients who completed follow-up, 14 had metastasis, 1 had local recurrence, and 7 died. Kaplan–Meier survival analysis revealed that prognosis was significantly correlated with sex, tumour size and metastasis (P

The serrated pathway to colorectal cancers (CRCs) is a significant pathway encompassing five distinct types of lesions, namely hyperplastic polyps (HPs), sessile serrated lesions (SSLs), sessile serrated lesions with dysplasia (SSL-Ds), traditional serrated adenomas (TSAs), and serrated adenoma unclassified. In contrast to the conventional adenoma-carcinoma pathway, the serrated pathway primarily involves two mechanisms: BRAF/KRAS mutations and CpG island methylator phenotype (CIMP). HPs are the most prevalent non-malignant lesions, while SSLs play a crucial role as precursors to CRCs, On the other hand, traditional serrated adenomas (TSAs) are the least frequently encountered subtype, also serving as precursors to CRCs. It is crucial to differentiate these lesions based on their unique morphological characteristics observed in histology and colonoscopy, as the identification and management of these serrated lesions significantly impact colorectal cancer screening programs. The management of these lesions necessitates the crucial steps of removing premalignant lesions and implementing regular surveillance. This article provides a comprehensive summary of the epidemiology, histologic features, molecular features, and detection methods for various serrated polyps, along with recommendations for their management and surveillance. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is the most prevalent cancer diagnosis and the leading cause of cancer death worldwide. Therapeutic failure in lung cancer (LUAD) is heavily influenced by drug resistance. This challenge stems from the diverse cell populations within the tumor, each having unique genetic, epigenetic, and phenotypic profiles. Such variations lead to varied therapeutic responses, thereby contributing to tumor relapse and disease progression. Methods: The Genomics of Drug Sensitivity in Cancer (GDSC) database was used in this investigation to obtain the mRNA expression dataset, genomic mutation profile, and drug sensitivity information of NSCLS. Machine Learning (ML) methods, including Random Forest (RF), Artificial Neurol Network (ANN), and Support Vector Machine (SVM), were used to predict the response status of each compound based on the mRNA and mutation characteristics determined using statistical methods. The most suitable method for each drug was proposed by comparing the prediction accuracy of different ML methods, and the selected mRNA and mutation characteristics were identified as molecular features for the drug-responsive cancer subtype. Finally, the prognostic influence of molecular features on the mutational subtype of LUAD in publicly available datasets. Results: Our analyses yielded 1,564 gene features and 45 mutational features for 46 drugs. Applying the ML approach to predict the drug response for each medication revealed an upstanding performance for SVM in predicting Afuresertib drug response (area under the curve [AUC] 0.875) using CIT, GAS2L3, STAG3L3, ATP2B4-mut, and IL15RA-mut as molecular features. Furthermore, the ANN algorithm using 9 mRNA characteristics demonstrated the highest prediction performance (AUC 0.780) in Gefitinib with CCL23-mut. Conclusion: This work extensively investigated the mRNA and mutation signatures associated with drug response in LUAD using a machine-learning approach and proposed a priority algorithm to predict drug response for different drugs. [ABSTRACT FROM AUTHOR]

By presenting a comprehensive analysis of low-grade serous carcinomas (LGSCs), a subset of epithelial ovarian cancers, this review delves into their distinct molecular characteristics, clinicopathological features and systemic therapy options, emphasizing their differences from high-grade serous carcinomas (HGSCs). Notably, LGSCs exhibit prevalent RAS/RAF/MEK/MAPK pathway activation, KRAS and BRAF mutations, and infrequent p53 mutations. While chemotherapy is commonly employed, LGSCs display lower responsiveness compared to HGSCs. Hormone therapy, particularly endocrine maintenance therapy, is explored due to the higher estrogen receptor expression. Novel therapeutic approaches involving CDK4/6 inhibitors, MEK inhibitors, and antiangiogenic agents like bevacizumab are also investigated. Ongoing clinical trials are striving to enhance LGSC treatment strategies, offering valuable insights for future therapeutic advancements in this challenging ovarian cancer subtype.

Abstract Background Previous studies on cancer of unknown primary (CUP) mainly focus on treatment and prognosis in western populations and lacked clinical evaluation of different IHC markers, so this study aimed to evaluate characteristics of CUP and recommend a diagnostic strategy from a single center in China. Methods and results Data of 625 patients with CUP were retrospectively collected and reviewed. The patients ranged in age from 20 to 91 years, with a female-to-male ratio of 1.3:1. The predominant histological type was poor or undifferentiated adenocarcinomas (308; 49.3%). The results of Canhelp-Origin molecular testing for the identification of the tissue of origin in 262 of 369 patients (71.0%) were considered predictable (similarity score > 45), with the most common predicted primary tumor site being the breast (57, 21.8%). Unpredictable molecular results correlated with more aggressive clinical parameters and poor survival. Thee positivity rates of several targeted antibodies (GATA3, GCDFP15, TTF1, Napsin A, and PAX8), based on the clinically predicted site, were lower than those reported for the corresponding primary tumors. Nonetheless, TRPS1 and INSM1 were reliable markers of predicted breast carcinoma (75.0%) and neuroendocrine tumors (83.3%), respectively. P16 expression, as well as HPV and EBER testing contributed significantly to the diagnosis of squamous cell carcinomas. Survival analysis revealed that older ages (> 57), ≥ 3 metastatic sites, non-squamous cell carcinomas, bone/liver/lung metastases, unpredictable molecular results, and palliative treatment correlated with poor overall survival. Conclusions We recommend a CUP diagnostic strategy involving the use of targeted antibody panels as per histological findings that is potentially applicable in clinical practice. The markers TRPS1, INSM1, and P16 expression, as well as HPV and EBER testing are particularly valuable in this aspect. Molecular testing is also predictive of survival rates.

Abstract Background The human gut microbiome (HGM), consisting of trillions of microorganisms, is crucial to human health. Adverse drug use is one of the most important causes of HGM disorder. Thus, it is necessary to identify drugs or compounds with anti-commensal effects on HGM in the early drug discovery stage. This study proposes a novel anti-commensal effects classification using a machine learning method and optimal molecular features. To improve the prediction performance, we explored combinations of six fingerprints and three descriptors to filter the best characterization as molecular features. Results The final consensus model based on optimal features yielded the F1-score of 0.725 ± 0.014, ACC of 82.9 ± 0.7%, and AUC of 0.791 ± 0.009 for five-fold cross-validation. In addition, this novel model outperformed the prior studies by using the same algorithm. Furthermore, the important chemical descriptors and misclassified anti-commensal compounds are analyzed to better understand and interpret the model. Finally, seven structural alerts responsible for the chemical anti-commensal effect are identified, implying valuable information for drug design. Conclusion Our study would be a promising tool for screening anti-commensal compounds in the early stage of drug discovery and assessing the potential risks of these drugs in vivo.

Background: Previous studies on cancer of unknown primary (CUP) mainly focus on treatment and prognosis in western populations and lacked clinical evaluation of different IHC markers, so this study aimed to evaluate characteristics of CUP and recommend a diagnostic strategy from a single center in China. Methods and results: Data of 625 patients with CUP were retrospectively collected and reviewed. The patients ranged in age from 20 to 91 years, with a female-to-male ratio of 1.3:1. The predominant histological type was poor or undifferentiated adenocarcinomas (308; 49.3%). The results of Canhelp-Origin molecular testing for the identification of the tissue of origin in 262 of 369 patients (71.0%) were considered predictable (similarity score > 45), with the most common predicted primary tumor site being the breast (57, 21.8%). Unpredictable molecular results correlated with more aggressive clinical parameters and poor survival. Thee positivity rates of several targeted antibodies (GATA3, GCDFP15, TTF1, Napsin A, and PAX8), based on the clinically predicted site, were lower than those reported for the corresponding primary tumors. Nonetheless, TRPS1 and INSM1 were reliable markers of predicted breast carcinoma (75.0%) and neuroendocrine tumors (83.3%), respectively. P16 expression, as well as HPV and EBER testing contributed significantly to the diagnosis of squamous cell carcinomas. Survival analysis revealed that older ages (> 57), ≥ 3 metastatic sites, non-squamous cell carcinomas, bone/liver/lung metastases, unpredictable molecular results, and palliative treatment correlated with poor overall survival. Conclusions: We recommend a CUP diagnostic strategy involving the use of targeted antibody panels as per histological findings that is potentially applicable in clinical practice. The markers TRPS1, INSM1, and P16 expression, as well as HPV and EBER testing are particularly valuable in this aspect. Molecular testing is also predictive of survival rates. [ABSTRACT FROM AUTHOR]

Copyright of Die Pathologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The molecular classification of endometrial cancer has previously been shown to be associated with clinical outcomes. However, there are insufficient data to support the routine use of molecular classification for the treatment of patients seeking fertility preservation. Methods: Here, we retrospectively investigated 90 patients received fertilitysparing treatment. We used a next generation sequencing (NGS) panel to classify these patients into four subtypes. All patients received hormonal therapy combined with hysteroscopy. Therapeutic effects were evaluated by hysteroscopy every three months during the treatment. Results: Patients with POLE mutations had the highest disease progression rate (50.0%, P=0.013), while the microsatellite instability-high (MSI-H) group had the highest recurrence rate (50.0%, P=0.042). PIK3CA mutation (hazard ratio (HR): 0.61; 95% confidence interval (CI): 0.37-0.99; P=0.046), overweight (HR: 0.56; 95% CI: 0.32-0.96; P=0.033) and obesity (HR: 0.44; 95% CI: 0.20-0.95; P=0.036) were associated with a significantly lower cumulative complete response (CR) rate. The combination of gonadotropin-releasing hormone analogues (GnRH-a) and letrozole (HR: 3.43; 95% CI: 1.81-6.52; P< 0.001) was associated with a significantly higher cumulative CR rate. KRAS mutation was significantly associated with disease progression (P=0.002). In wild-type TP53 patients, PTEN and PIK3CA mutations significantly prolonged the duration of treatment to achieve CR (log rank P=0.034; P=0.018). Conclusion: The implementation of molecular classification for EC patients undergoing fertility-sparing treatment is promising and can facilitate the selection of appropriate medical regimes to achieve better outcomes in patients with EC who require fertility preservation treatment. [ABSTRACT FROM AUTHOR]

Deep eutectic solvents may develop a pivotal role in future technologies considering sustainability and safety as pivotal aspects for chemistry developments. The possible application of these fluids for heat transfer operations is of great relevance for which the knowledge of thermal properties such as thermal conductivity is required as well as inferring structure–property relationships which allow reverse design of the fluids according to the technological requirements. Considering the technological relevance of this property, the available literature on the thermal conductivity for deep eutectic solvents is critically discussed showing strengths and weaknesses. The analysis of the state-of-the-art shows the future needs in this research field considering the application of these solvents for thermal-related technologies. The review indicates the scarcity of reliable experimental data and the need of predictive methods, which could be used for process design and solvent screening purposes. Likewise, considering the relevance of developing predictive methods for in silico design of these fluids according to industrial needs, the available predictive theoretical approaches are analysed showing their reliability as well as future needs. Finally, considering the need of developing suitable and reliable structure–property relationship, the molecular level basis of thermal conductivity in deep eutectic solvents is discussed, showing the role of hydrogen bonding and the effects rising from the involved hydrogen bond donors and acceptors as well as the eutectic compositions. This work reports the first literature review and analysis on thermal conductivity for deep eutectic solvents considering an experimental and theoretical approach as well as providing support for the molecular basis of this technologically relevant property, thus contributing to the development of environmentally friendly materials for thermal-related technologies. [ABSTRACT FROM AUTHOR]

Marshes in high plateaus are critical in governing carbon cycle because of their huge but labile soil organic carbon (SOC) storage, which of even a small proportion of carbon contained in SOC can lead to high variations in the atmospheric CO2 levels. The Yarlung Zangbo River (YZR) is the world's highest river, flowing from west to east across Tibet. There are widespread alpine marshes and meadows along the YZR basin, with huge SOC storage but extremely vulnerable to climate change. However, few studies were carried out to explore the potential effects of environmental factors on SOC pool along the YZR. In the present work, effects of climate, plant biomass, soil nutrients, and molecular features of organic matter on SOC storage were systematically evaluated. Results indicated that SOC contents varied from 0.86% to 29.68%, with an average of 7.29%, and an estimated 5887 Gg (109g) of carbon was stored in marsh soils along the YZR. Soil accretion rates ranged from 1.66 to 2.73 mm yr−1, while carbon sequestration rates ranged from 43.65 gC m−2 yr−1 to 125.4 gC m−2 yr−1, with an average of 75.89 gC m−2 yr−1. It was estimated that 34.58 Gg of carbon was sequestrated by wetlands along the YZR every year. The abundance of lignin‐derived components, total nitrogen, and soil moisture contents (SWC) were the main drivers promoting SOC contents. SOC storage was significantly related to mean annual temperature (Temp) but decreased with the ratio of annual precipitation (Pre) to Temp. Compared with the chemical decomposition resistance of organic matter, more SOC variations arose from climate, and climate warming had adverse impacts on SOC pool. SWC were proved to be the most powerful promoter of SOC increase. Rising temperatures are expected to have a detrimental impact on SOC storage when the climate is warming in the future. [ABSTRACT FROM AUTHOR]

Are there any differences between conjoined twin fetuses at the molecular level? Skin tissues were collected from thoracopagus conjoined twins at 15+4 weeks of gestation. The skin tissues were collected from the thigh side of conjoined twins after the abortion procedure. All specimens were obtained after written informed patient consent and were fully anonymized. All relevant ethical regulations were followed. Every specimen underwent multiomics sequencing analysis to determine associations among the DNA methylome, transcriptome and mutations in the exon regions in the conjoined twins. The global methylation pattern was similar in the two fetuses of conjoined twins, while significant differences were seen in local regions such as CpG islands (P = 0.026), enhancers (P < 0.001) and various repetitive elements (P < 0.05), which showed significant differences. The conjoined twins also differed in genes related to growth and development, cellular component morphogenesis and cellular stress, both in terms of DNA methylation levels and gene expression levels. Exon data analysis revealed that the common mutations in conjoined twins mainly occurred in neural development, lipid metabolism and microtubule morphogenesis. Specific mutations were associated with cellular component biosynthesis, behaviour and germ cell development. Conjoined twins were similar to each other globally, but there were significant differences related to growth and development, cellular component morphogenesis and cellular stress. The current study reveals the molecular features of conjoined twins for the first time, laying the foundation for future exploration of the mechanism of conjoined twins. [ABSTRACT FROM AUTHOR]

Introduction: The blood--brain barrier (BBB) is a semipermeable border that is responsible for maintaining central nervous system (CNS) homeostasis in the brain. Screening compounds based on their BBB permeability is an important consideration for CNS-acting drug development. Several studies have attempted to link physicochemical properties to specific BBB permeability; however, there is no widely accepted rule that can determine how and to what extent molecular properties affect the BBB permeability of compounds. To understand the complex phenomenon of BBB permeability, we explored the vast molecular space of the compounds to determine whether some features could differentiate the compounds based on their BBB permeability. Materials and Methods: A dataset of 1951 compounds containing 1246 BBB-permeable and 705 BBB-nonpermeable molecules was used in the study. Each compound encoded 499 molecular features. Feature selection was performed using feature selection algorithms, feature-to-feature, and feature-to-permeability correlation analysis. The findings of the feature selection algorithms were merged to select the best set of 53 features. Results: The descriptive analysis of the molecular features suggests that nCXr (number of X on ring C[sp3]) feature values for BBB nonpermeable compounds are zero for all considered compounds except for compounds with PubChem ID 71260, Flurithromycin. In addition, the majority of compounds were found to have nCrq (number of ring quaternary C[sp3]) feature values of zero for BBB nonpermeable compounds. For BBB-permeable compounds, MACCS fingerprints 8 feature values for all 1951 compounds were found to be zero except for the compound with PubChem ID 146291, Dezinamide. Conclusion: The descriptive and nonparametric tests confirm that molecular feature distributions are significantly different for BBB permeable and BBB nonpermeable compounds. [ABSTRACT FROM AUTHOR]

Populations of Monacha atacis from southern Occitania in France and of M. samsunensis from northern Anatolia in Turkey (Atakum/Samsun and Kastamonu) were investigated by an integrative approach based on morphological (shell and genitalia) and molecular (mitochondrial and nuclear gene sequences) features. Morphological examination revealed a complex pattern of variation within and between geographically separated populations, while molecular analysis showed strong similarity between the two species, confirming earlier suggestions that the species are conspecific. Pfeiffer’s name Helix samsunensis introduced in 1868 has priority over the name M. atacis given by Gittenberger & de Winter in 1985.

Objective: To summarize the clinicopathological characteristics of uterine serous carcinoma (USC), and to investigate its molecular classification and human epidermal growth factor receptor 2 (HER2) expression. Methods: The clinical data of 20 USC patients were collected. HE, immunohistochemistry, Sanger sequencing and FISH were used to detect in USC patients, and the molecular typing and HER2 expression were analyzed. Results: USC accounted for 8% of endometrial cancers, with FIGO stage Ⅰ in 5 cases (25%), stage Ⅱ in 1 case (5%), stage Ⅲ in 9 cases (45%), and stage Ⅳ in 5 cases (25%). Three histological structures of papilla, glandular and solid were seen in the carcinoma tissue. The nipple is wide or small, the cells are easy to fall off, the edge is not smooth and the glandular lumen is mostly fissured. The cytoplasm was clear or eosinophilic and vascular invasion was observed in 13 cases (65%). The positive rates of ER, PR, Vimentin, WT1 and P16 were 40%, 25%, 10%, 35% and 100%, respectively, and the positive rates of Ki-67 were 30%-80%. POLE mutation was not detected in 20 UCS patients, MLH1, PMS2, MSH2 and MSH6 were all positive. There were 16 cases (75%) with P53 missense mutation and 4 cases (25%) with nonsense mutation. HER2 3+ was labeled by immunohistochemistry in 5 cases (25%), and amplified signal was detected by FISH in 4 cases. Conclusions: The incidence of USC was low and the pathological morphology of USC was diverse. Immunohistochemical staining was helpful for its diagnosis. The molecular typing of USC was abnormal P53, and HER2 was expected to be a therapeutic target. [ABSTRACT FROM AUTHOR]

The incidence of ampulla of Vater carcinoma, a type of periampullary cancer, has been increasing at an annual percentage rate of 0.9%. However, patients with ampulla of Vater carcinoma have quite different prognoses due to the heterogeneities of the tissue origin of this carcinoma. In addition to TNM staging, histological subtypes and molecular features of ampulla of Vater carcinoma are the key factors for predicting the clinical outcomes of patients. Fortunately, with the development of testing technology, information on the histological subtypes and molecular features of ampulla of Vater carcinoma is increasingly being analyzed in-depth. Patients with the pancreaticobiliary subtype have shorter survival times. In immunohistochemical examination, high cutoff values of positive MUC1 staining can be used to accurately predict the outcome of patients. Mutant KRAS, TP53, negative SMAD4 expression, and microsatellite stability are related to poor prognosis, while the clinical value of BRCA1/BRCA2 mutations is limited for prognosis. Testing the histological subtypes and molecular characteristics of ampulla of Vater carcinoma not only is the key to prognosis analysis but also provides extra information for targeted treatment to improve the clinical outcomes of patients. [ABSTRACT FROM AUTHOR]

Somatic MET exon 14 skipping mutations (MET ex14) are targetable driver mutations for non-small cell lung cancer (NSCLC), responsive to MET inhibitors. Objective: This study seeks to further characterize the clinicopathologic features and mutational profile of MET ex14 variant NSCLC. Design: Retrospective review of all MET ex14 tested NSCLC. Testing for selected BRAF, EGFR, HER2, KRAS, and MET mutations was performed using a clinically validated NGS assay, followed by MiSeq sequencing. Variants were classified as significant (Tier1/2) or variants of uncertain significance (VUS) per 2017 AMP/ASCO/CAP Joint Consensus Guidelines. PD-L1 expression was assessed by immunohistochemistry. Results: Of 2296 NSCLCs tested between 2017-7/2019, MET ex14 variants were present in 44 (1.9%). A total of 32 of 44 variants were MET exon 14 skipping, while the other 12 mutations were significant missense (3) or VUS (9). Of nine VUS, five were adjacent to the canonical splice site and likely to impact splicing. Four cases had concomitant mutations. Of 35 cases with known clinical staging, stage 1-2 = 20 (57%), stage 3 = 3 (9%), and stage 4 = 12 (34%). Of 19 resected NSCLSs, histological types and growth pattern included 7 lepidic pattern-predominant. A high percentage of tumors with MET ex14 mutations are positive for PD-L1, and the percentage of cases with PD-L1 expression >50% trends higher in more advanced disease. Conclusions: Most MET variants identified in our cohort (73%) are MET ex14 skipping. The prevalence of MET ex14 variants is 1.9%, and a large percentage of tumors has lower clinical stage and less aggressive pathologic features. [ABSTRACT FROM AUTHOR]

Simple Summary: Mucinous ovarian cancer (MOC) is a rare tumor that can be classified according to stage in early MOC and advanced MOC. Early MOC is characterized by a good prognosis and, in most cases, surgical treatment alone represents the mainstay of therapy. Despite the good prognosis, some early-stage MOCs can relapse and exhibit aggressive behavior, and new biomarkers are emerging to better stratify these patients. Advanced MOC, instead, is characterized by a poor prognosis. Radical surgery is still the mainstay of treatment since these tumors are chemo-resistant. New targeted therapies are being studied to improve the prognosis in this setting, but unfortunately, none of these have been approved yet. This review focuses on the most relevant clinical, pathological, and molecular features and treatment options according to prognosis. This review includes state-of-the-art prognostic and predictive factors of mucinous ovarian cancer (MOC), a rare tumor. Clinical, pathological, and molecular features and treatment options according to prognosis are comprehensively discussed. Different clinical implications of MOC are described according to the The International Federation of Gynecology and Obstetrics (FIGO) stage: early MOC (stage I-II) and advanced MOC (stage III-IV). Early MOC is characterized by a good prognosis. Surgery is the mainstay of treatment. Fertility-sparing surgery could be performed in patients who wish to become pregnant and that present low recurrence risk of disease. Adjuvant chemotherapy is not recommended, except in patients with high-risk clinical and pathological features. Regarding the histological features, an infiltrative growth pattern is the major prognostic factor of MOC. Furthermore, novel molecular biomarkers are emerging for tailored management of early-stage MOC. In contrast, advanced MOC is characterized by poor survival. Radical surgery is the cornerstone of treatment and adjuvant chemotherapy is recommended, although the efficacy is limited by the intrinsic chemoresistance of these tumors. Several molecular hallmarks of advanced MOC have been described in recent years (e.g., HER2 amplification, distinct methylation profiles, peculiar immunological microenvironment), but target therapy for these rare tumors is not available yet. [ABSTRACT FROM AUTHOR]

Sauce-flavor Baijiu is one of the most complex and typical types of traditional Chinese liquor, whose trace components have an important impact on its taste and quality. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) is one of the most favorable analytical tools to reveal trace molecular components in complex samples. This study analyzed the chemical diversity of several representative sauce-flavor Baijiu using the combination of electrospray ionization (ESI) and FT-ICR MS. The results showed that ESI+ and ESI− exhibited different chemical features characteristic of trace components. Overall, sauce-flavor Baijiu was dominated by CHO class compounds, and the main specific compound types were aliphatic, highly unsaturated with low oxygen, and peptide-like compounds. The mass spectral parameters resolved by FT-ICR MS of several well-known brands were relatively similar, whereas the greatest variability was observed from an internally supplied brand. This study provides a new perspective on the mass spectrometry characteristics of trace components of sauce-flavor Baijiu and offers a theoretical foundation for further optimization of the gradients in Baijiu. [ABSTRACT FROM AUTHOR]

Primary mediastinal germ cell tumors (PMGCTs) are a rare type of cancer affecting young adults. They have different molecular and clinical features compared to testicular germ cell tumors. Non-seminoma PMGCTs have the shortest 5-year overall survival and the poorest prognosis among all of the germ cell tumor presentations, while seminomas share the same survival and prognosis as their testicular counterparts. There is an unmet need for better treatment options for patients with non-seminoma PMGCTs in both first-line and salvage therapy, as the available options are associated with underwhelming outcomes. Identifying biological and genetic factors to predict treatment responses would be helpful in improving the survival of these patients. [ABSTRACT FROM AUTHOR]

Background: The significance of nucleotide metabolism and neuroendocrine in cellular immune response and cancer is becoming more well-established. However, the mechanisms underlying nucleotide metabolism and neuroendocrine involvement in stomach adenocarcinoma (STAD) remain unclear. Methods: First, a pan-cancer overview of nucleotide metabolism and neuroendocrine-related genes (NMNGs) was explored through the integration of expression profiles, prognostic values, mutation information, methylation levels, and pathway-regulation relationships. We next extensively assessed variations in prognosis and tumor microenvironment (TME) features across the various modification patterns, based on an extensive analysis of the NMNG modification patterns of 808 STAD samples based on 46 NMNGs. Utilizing principal component analysis methodologies, the NMNGscore was developed to measure NMNG alteration patterns of individual tumors. Results: Pan-cancer analysis shows that NMNGs mostly act as risk genes in multiple cancer types, especially in STAD. Based on the NMNGs we detected two different NMNG modification patterns in STAD. Both patterns showed distinct immune cell infiltration features and biological behavior, with NMNGcluster A exhibiting a worse prognosis and a larger amount of immune infiltration. Differentially expressed genes with prognostic relevance were used to classify the STAD samples into three genomic subgroups. Analysis of survival rates revealed that cluster B genes were associated with longer life expectancy than clusters A and C. Individual STAD patients’ NMNG alteration patterns were analyzed by analyzing their NMNGscore signatures. NMNGscore and immune cells showed a statistically significant adverse correlation with each other. Increased longevity, a higher incidence of mutations, and a better response to immunotherapy were associated with patients’ NMNG scores. Conclusions: Our findings provide a personalized prediction tool for prognosis and immunotherapy sensitivity in patients, as well as a promising knowledge of nucleotide metabolism and neuroendocrine in STAD. [ABSTRACT FROM AUTHOR]

Alternansucrase (ASR), classified in GH70, produces unique α-glucans with alternating α-1,3 and α-1,6 glycosidic linkages in the backbone chain from renewable sucrose which is easily obtained from nature with low cost. ASR has synthesized many products with valuable functionalities that hold enormous commercial interest and promising applications. The influence of biocatalysis and fermentation parameters on the yields, and properties of products are critical for the propositions made to promote the enzyme application. Investigations on ASR have been compiled in the review to provide information on the enzyme, products and parameters. This review summarizes studies on the characteristics, conversion mechanism, products, and beneficial applications of ASR and exhibits structure-based technologies to improve enzyme activity, specificity, and thermostability for industrial applications. Finally, prospects for further development are also proposed for various ASR applications in food and other fields. • Systematically elaborate the origin, biocatalysis, and current application status of alternansucrases for its applications in foods. • The limitations in practical applications of alternansucrase are explained in depth. • Thorough overview of strategies for engineering or remodeling alternausucrase for industrial application. • Future perspectives were proposed to cope with the challenges of design and applications of the alternausucrase. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer. High fibrosis, marked by increased collagen fibers, is widespread in TNBC and correlated with tumor progression. However, the molecular features of fibrosis and why it results in a poor prognosis remain poorly understood. Based on multiomics datasets of TNBC, we evaluated the pathological fibrosis grade of 344 samples for further analysis. Genomic, transcriptomic, and immune changes were analyzed among different subgroups of fibrosis. High fibrosis was an independent adverse prognosis predictor and had interactions with low stromal tumor-infiltrating lymphocytes. Genomic analysis identified copy number gains of 6p22.2–6p22.1 (TRIM27) and 20q13.33 (CDH4) as genomic hallmarks of tumors with high fibrosis. Transcriptome analysis revealed the transforming growth factor-beta pathway and hypoxia pathway were key pro-oncogenic pathways in tumors with high fibrosis. Moreover, we systematically evaluate the relationship between fibrosis and different kinds of immune and stromal cells. Tumors with high fibrosis were characterized by an immunosuppressive tumor microenvironment with limited immune cell infiltration and increased fibroblasts. This study proposes new insight into the genomic and transcriptomic alterations potentially driving fibrosis. Moreover, fibrosis is related to an immunosuppressive tumor microenvironment that contributes to the poor prognosis.

The Notch signaling has an important role in multiple cellular processes and is related to carcinogenic process. To understand the potential molecular features of the crucial Notch pathway, a comprehensive multi-omics analysis is performed to explore its contributions in cancer, mainly including analysis of somatic mutation landscape, pan-cancer expression, ncRNA regulation and potential prognostic power. The screened 22 Notch core genes are relative stable in DNA variation. Dynamic expression patterns are associated with the Notch activity, which are mainly regulated by multiple ncRNAs via interactions of ncRNA:mRNA and ceRNA networks. The Notch pathway shows a potential prognostic ability through integrating multi-omics features as well as their targets, and it is correlated with immune infiltration and maybe available drug targets, implying the potential role in individualized treatment. Collectively, all of these findings contribute to exploring crucial role of the key pathway in cancer pathophysiology and gaining mechanistic insights into cross-talks among RNAs and biological pathways, which indicates the possible application of the well-conserved Notch signaling pathway in precision medicine.

BackgroundThe significance of nucleotide metabolism and neuroendocrine in cellular immune response and cancer is becoming more well-established. However, the mechanisms underlying nucleotide metabolism and neuroendocrine involvement in stomach adenocarcinoma (STAD) remain unclear.MethodsFirst, a pan-cancer overview of nucleotide metabolism and neuroendocrine-related genes (NMNGs) was explored through the integration of expression profiles, prognostic values, mutation information, methylation levels, and pathway-regulation relationships. We next extensively assessed variations in prognosis and tumor microenvironment (TME) features across the various modification patterns, based on an extensive analysis of the NMNG modification patterns of 808 STAD samples based on 46 NMNGs. Utilizing principal component analysis methodologies, the NMNGscore was developed to measure NMNG alteration patterns of individual tumors.ResultsPan-cancer analysis shows that NMNGs mostly act as risk genes in multiple cancer types, especially in STAD. Based on the NMNGs we detected two different NMNG modification patterns in STAD. Both patterns showed distinct immune cell infiltration features and biological behavior, with NMNGcluster A exhibiting a worse prognosis and a larger amount of immune infiltration. Differentially expressed genes with prognostic relevance were used to classify the STAD samples into three genomic subgroups. Analysis of survival rates revealed that cluster B genes were associated with longer life expectancy than clusters A and C. Individual STAD patients’ NMNG alteration patterns were analyzed by analyzing their NMNGscore signatures. NMNGscore and immune cells showed a statistically significant adverse correlation with each other. Increased longevity, a higher incidence of mutations, and a better response to immunotherapy were associated with patients’ NMNG scores.ConclusionsOur findings provide a personalized prediction tool for prognosis and immunotherapy sensitivity in patients, as well as a promising knowledge of nucleotide metabolism and neuroendocrine in STAD.

Populations of Monacha atacis from southern Occitania in France and of M. samsunensis from northern Anatolia in Turkey (Atakum/Samsun and Kastamonu) were investigated by an integrative approach based on morphological (shell and genitalia) and molecular (mitochondrial and nuclear gene sequences) features. Morphological examination revealed a complex pattern of variation within and between geographically separated populations, while molecular analysis showed strong similarity between the two species, confirming earlier suggestions that the species are conspecific. Pfeiffer's name Helix samsunensis introduced in 1868 has priority over the name M. atacis given by Gittenberger & de Winter in 1985. [ABSTRACT FROM AUTHOR]

Large granular lymphocyte leukemia is a rare chronic lymphoproliferative disease of cytotoxic lymphocytes. The diagnosis, according to the WHO, is based on a persistent (>6 months) increase in the number of LGL cells in the peripheral blood without an identifiable cause. A further distinction is made between T-LGL and NK-LGL leukemia. The molecular sign of LGL leukemia is the mutation of STAT3 and other genes associated with the JAK/STAT pathway. The most common clinical features are neutropenia, anemia, and thrombocytopenia, and it is often associated with various autoimmune conditions. It usually has an indolent course. Due to the rarity of the disease, no specific treatment has yet been identified. Immunosuppressive therapy is used and may allow for disease control and long-term survival, but not eradication of the leukemic clone. Here, we discuss the clinical presentation, diagnostic challenges, pathophysiology, and different treatment options available for alpha/beta T-LGL leukemia, which is the most common disease (85%), in order to better understand and manage this often misunderstood disease. [ABSTRACT FROM AUTHOR]

Soil-derived dissolved organic matter (DOM) links soil and water carbon pools and is an important source of photochemically produced reactive intermediates (PPRIs) in aquatic environments. Despite its importance, the variations in photochemical reactivity of soil-derived DOM molecules in producing PPRIs across broad geographical regions, and the factors driving these variations, remain unclear. Herein, we resolved the apparent quantum yields (Φ(PPRIs)) of hydroxyl radicals (•OH), singlet oxygen ( 1 O 2 ), and excited triplet-state DOM ( 3 DOM*) for irradiated DOM from 22 representative soil reference materials in China, and linked them to soil pH, mineral weathering degree, and DOM characteristics. Generally, the average Φ(PPRIs) values of the soil-derived DOM followed the order of Φ( 3 DOM*) (1.67× 10 -2 ) > Φ( 1 O 2 ) (1.47× 10 -2 ) > Φ(•OH) (7.31× 10 -5 ). The DOM from less weathered soils showed higher Φ(•OH) and Φ( 3 DOM*) and comparable Φ( 1 O 2 ) than that from more weathered soils. The differences were mainly regulated by the abundance of humic-, lignin-, tannin-, and aromatic-like compounds, as indicated by the correlation and random forest model analyses. Partial least squares and multiple linear regression analyses identified DOM molecular weight, nominal oxidation state of carbon, and soil chemical index of alteration as effective predictors of •OH yields. Soil chemical index of alteration emerged as a prioritized predictor of 3 DOM* yields, while the electron-donating capacity and humic-like compound content of the soil-derived DOM were effective predictors of 1 O 2 yields. This study advances our understanding of how mineral weathering processes regulate the photochemical reactivity of soil-derived DOM in the aquatic environment across wide geographical regions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Abstract Background The combination of bevacizumab and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) could prolong progression-free survival (PFS) in patients with EGFR-mutant advanced non-small-cell lung cancer (NSCLC). Our study investigated the clinical and molecular factors that affect the efficacy of first-generation EGFR-TKI with or without bevacizumab and identify the subset of patients who can benefit from combination therapy. Methods Our study included 318 patients with EGFR-mutant locally advanced/advanced NSCLC treated with either first-generation EGFR-TKI combined with bevacizumab (A+T; n = 159) or EGFR-TKI monotherapy (T; n = 159). Two nomogram models to predict PFS and overall survival (OS), respectively, were constructed using two factors that impact EGFR-TKI efficacy: metastatic site and presence of concurrent mutations. The study cohort was stratified into 2 cohorts for training (n = 176) and validation (n = 142) of the nomogram model. Using the median score from the nomogram, the patients were stratified into two groups to analyze their survival outcome. Results The A+T group had significantly longer PFS (14.0 vs. 10.5 months; p