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Evaluating, ranking, and clustering (ERC) stand as fundamental tasks in scientific research, each requiring a mathematical foundation. This study presents an ERC system anchored in the CCHZ-DISO (Chen, Chen, Hu, and Zhou-Distance between Indices of Simulation and Observation) system. Previous research underscores the optimality achieved by the CCHZ-DISO system (Hu et al., 2022). Since the inception of CCHZ- DISO-series research by Hu et al. (2019), DISO has found extensive applications across various domains including geography, hydrology, and economics. Analogous to the CCHZ-DISO system's construction, the ERC system employs the Euclidean distance to perform evaluating, ranking, and clustering tasks. Furthermore, illustrative examples are provided to elucidate the application of the ERC system. In fact, the ERC system unified the evaluating, ranking, and clustering tasks in one simple equation which is more flexible and simpler than the present system. It will have a more widely application than CCHZ-DISO in diverse scientific domains. [ABSTRACT FROM AUTHOR]

Gaining a comprehensive understanding of the characteristics and propagation of precipitation-based meteorological drought to terrestrial water storage (TWS)-derived hydrological drought is of the utmost importance. This study aims to disentangle the frequency–time relationship between precipitation-derived meteorological and TWS-based hydrological drought from June 2002 to June 2017 based on the Standardized Precipitation Index (SPI) and Standardized Terrestrial Water Storage Index (STI) by employing wavelet coherence rather than a traditional correlation coefficient. The possible influencing factors on drought propagation in 28 regions across the world are examined. The results show that the number of drought months detected by the STI is higher than that detected by the SPI worldwide, especially for slight and moderate drought. Generally, TWS-derived hydrological drought is triggered by and occurs later than precipitation-based meteorological drought. The propagation characteristics between meteorological and hydrological droughts vary by region across the globe. Apparent intra-annual and interannual scales are detected by wavelet analysis in most regions, but not in the polar climate region. Drought propagation differs in phase lags in different regions. The phase lag between hydrological and meteorological drought ranges from 0.5 to 4 months on the intra-annual scale and from 1 to 16 months on the interannual scale. Drought propagation is influenced by multiple factors, among which the El Niño–Southern Oscillation, North Atlantic Oscillation, and potential evapotranspiration are the most influential when considering one, two, or three factors, respectively. The findings of this study improve scientific understanding of drought propagation mechanisms over a global scale and provide support for water management in different subregions. [ABSTRACT FROM AUTHOR]

Background: Most of the current progression of immune checkpoint inhibitors for malignant melanoma is based on data from Caucasians in Western countries, but the benefit of Chinese patients is limited, mainly due to different pathological subtypes. The patients in western countries are mainly skin melanoma (about 90%), while the acral and mucosal types are dominant in China, accounting for 41.8% and 22.6% respectively. Acral and mucosal melanoma have lower response rates to immunotherapy and chemotherapy. Objective: Whether immune checkpoint inhibitors can improve the survival of Chinese patients with malignant melanoma, therefore, we conducted a retrospective analysis. Methods: We analyzed 53 patients with metastatic melanoma treated in our hospital to evaluate the efficacy and safety of PD‐1 mAb in Chinese patients with metastatic melanoma, and performed univariate and multivariate analyses of prognostic factors that may affect overall survival (OS). Results: In a study of 125 patients with advanced malignant melanoma, 53 patients participated, with a median follow‐up of 16 months. Among these, 69.8% died, and 30.2% remained on treatment. Median progression‐free survival (PFS) was 6 months, and median OS was 19 months. Patients treated with immune checkpoint inhibitors had improved outcomes, with a median PFS of 7 months and a median OS of 24 months. Patients with bone metastasis and aberrant Lactate dehydrogenase (LDH) post‐treatment had worse prognoses, while immunotherapy was a protective factor. Subgroup analysis showed the benefits of immunotherapy across various patient characteristics. No unexpected toxicities were observed. Conclusion: The study highlights the efficacy of immune checkpoint inhibitors, particularly PD‐1 mAb, in improving survival outcomes for Chinese patients with metastatic melanoma. [ABSTRACT FROM AUTHOR]

The N6-methyladenosine (m6A) RNA binding protein YTHDF1 is frequently overexpressed in colorectal cancer (CRC) and drives chemotherapeutic resistance. To systematically identify druggable targets in CRC with high expression of YTHDF1, we employed a CRISPR/Cas9 screening strategy that revealed RUVBL1 and RUVBL2 as putative targets.RUVBL1/2 were overexpressed in primary CRC samples and represented independent predictors of poor patient prognosis. Functionally, loss of RUVBL1/2 preferentially impaired the growth ofYTHDF1-high CRC cells, patient-derived primary CRC organoids, and subcutaneous xenografts. Mechanistically, YTHFD1 and RUVBL1/2 formed a positive feed-forward circuit to accelerate oncogenic translation. YTHDF1 bound to m6A-modified RUVBL1/2 mRNA to promote translation initiation and protein expression. Co-IP and mass spectrometry identified that RUVBL1/2 reciprocally interacted with YTHDF1 at 40S translation initiation complexes. Consequently, RUVBL1/2 depletion stalled YTHDF1-driven oncogenic translation and nascent protein biosynthesis, leading to proliferative arrest and apoptosis. Ribo-seq revealed that RUVBL1/2 loss impaired the activation of MAPK, RAS and PI3K-AKT signaling induced by YTHDF1. Finally, blockade of RUVBL1/2 by the pharmacological inhibitor CB6644 or vesicle-like nanoparticle-encapsulated siRNAs preferentially arrested the growth of YTHDF1-expressing CRC in vitro and in vivo. Together, this study uncovered that RUVBL1/2 are potential prognostic markers and druggable targets that regulate protein translation in YTHDF1-high CRC.

Objectives: Homopolymer (HP) sequencing is error-prone in next-generation sequencing (NGS) assays, and may induce false insertion/deletions and substitutions. This study aimed to evaluate the performance of dichromatic and tetrachromatic fluorogenic NGS platforms when sequencing homopolymeric regions., Results: A HP-containing plasmid was constructed and diluted to serial frequencies (3%, 10%, 30%, 60%) to determine the performance of an MGISEQ-2000, MGISEQ-200, and NextSeq 2000 in HP sequencing. An evident negative correlation was observed between the detected frequencies of four nucleotide HPs and the HP length. Significantly decreased rates (P < 0.01) were found in all 8-mer HPs in all three NGS systems at all four expected frequencies, except in the NextSeq 2000 at 3%. With the application of a unique molecular identifier (UMI) pipeline, there were no differences between the detected frequencies of any HPs and the expected frequencies, except for poly-G 8-mers using the MGI 200 platform. UMIs improved the performance of all three NGS platforms in HP sequencing., Conclusions: We first constructed an HP-containing plasmid based on an EGFR gene backbone to evaluate the performance of NGS platforms when sequencing homopolymeric regions. A highly comparable performance was observed between the MGISEQ-2000 and NextSeq 2000, and introducing UMIs is a promising approach to improve the performance of NGS platforms in sequencing homopolymeric regions., (© 2024. The Author(s).)