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Background: Early prediction of treatment response is crucial for the optimal treatment of advanced breast cancer. We aimed to explore whether monitoring early changes in plasma human epidermal growth factor receptor 2 (HER2) levels using digital PCR (dPCR) could predict the treatment response in advanced breast cancer. Methods: This was a multicenter, prospective, noninterventional clinical study of patients with advanced breast cancer. All enrolled patients underwent blood testing to measure the HER2 levels by digital PCR before treatment initiation and once every 3 weeks during the study. The primary endpoints werea the diagnostic value of dPCR for detecting HER2 status in the blood andb the relevance of potential changes in the plasma HER2 level at 3 weeks from baseline for predicting treatment response. Results: Overall, 85 patients were enrolled between October 9, 2018, and January 23, 2020. dPCR had a specificity of 91.67% (95% CI: 80.61% to 97.43%) for detecting HER2 amplification, and the area under the receiver operating characteristic (ROC) curve was 0.84 (p < 0.01). A clinically relevant specificity threshold of approximately 90%, which was equivalent to a ≥15% decrease in the plasma HER2 ratio at 3 weeks from baseline, showed a positive predictive value of 97.37% (95% CI: 77.11% to 98.65%) in terms of predicting clinical benefit. Patients whose plasma HER2 ratio was reduced by ≥15% had a longer median progression‐free survival (PFS) than those whose ratio was reduced by <15% (9.20 months vs. 4.50 months, p < 0.01). Conclusions: Early changes in the plasma HER2 ratio may predict the treatment response in patients with advanced breast cancer and could facilitate optimal treatment selection. [ABSTRACT FROM AUTHOR]

Background: Autosomal trisomy is a relatively rare abnormality observed in AML, occurring singly or as a secondary event in association with other karyotypic changes, and associated with prognosis. The molecular genetic and clinical characterizations of acute myeloid leukemia (AML) with isolated trisomy 4, 11, or 21 have been poorly investigated. Materials and Methods: Interphase fluorescence in situ hybridization, reverse transcriptase‐quantitative polymerase chain reaction for 41 chromosomal gene translocations/fusion genes, and next‐generation sequencing (NGS) were performed on 29 AML patients with trisomy 4, 11, or 21 as the sole chromosomal anomaly. Results: Of the 29 patients, one or more mutations were detected in 93.1% of patients. CEBPA had the highest mutation frequency, followed by TET2, NPM1, DNMT3A, and FLT3‐ITD. The sole +11 AML patients exhibited more mutations in FLT3‐ITD (P =.031) than the sole +21 AML patients, while CEBPA mutation was more frequently found in the sole +21 AML patients than that in the sole +11 AML patients(P =.07). The median overall survival (OS) and disease‐free survival (DFS) for patients with +11 were shorter than those with +4(P =.015, 0.046) or +21 (0.057, 0.064), but no difference was found between +4 patients and +21 patients. In the whole cohort, only the FLT3‐ITD mutation was significantly associated with inferior OS (18 vs. 35 months, P =.023) and DFS (12 months vs. NR, P =.046). There were no significant differences in OS and DFS according to the gene mutation status of CEBPA, TET2, NPM1, DNMT3A, and IDH1/2. Conclusion: There was a significantly different mutation profile among the sole +4, +11, +21 AML patients. Our research provided new insight into the molecular characteristics of AML with isolated trisomy. [ABSTRACT FROM AUTHOR]

Summary: To assess the prognostic significance of immunoglobulin (Ig) paraproteinaemia in mucosa‐associated lymphoid tissue (MALT) lymphoma, 218 patients diagnosed with MALT lymphoma were enrolled in this study. Serum Ig paraprotein was detected in 42 of 218 patients (19.3%), mostly IgM‐K (15, 35.7%), followed by IgM‐L and IgG‐L. Advanced age (p = 0.025), poor Eastern Cooperative Oncology Group performance status (p = 0.014), bone marrow involvement (p = 0.019), B symptoms (p = 0.039), advanced disease stage (III−IV) (p < 0.0001), elevated serum β2‐microglobulin level (p < 0.0001), multiple extranodal sites of involvement (p < 0.0001), nodal involvement (p < 0.0001), systemic therapy (p < 0.0001) and higher MALT‐lymphoma International Prognostic Index (MALT‐IPI) scores (p = 0.001) were significantly associated with the presence of serum Ig paraprotein. Multivariate Cox regression analysis showed that Ig paraproteinaemia was an independent prognostic predictor for inferior progression‐free survival (PFS) and overall survival. A new prognostic index based on MALT‐IPI and Ig paraproteinaemia, as assessed using receiver operating characteristic curves and the area under the curve statistics, showed better discriminative ability than MALT‐IPI in predicting PFS. In conclusion, Ig paraproteinaemia was a promising prognostic predictor for MALT lymphoma. Ig paraproteinaemia together with MALT‐IPI might contribute to optimising therapeutic management in clinical practice. [ABSTRACT FROM AUTHOR]

Bacterial resistance caused by metallo‐β‐lactamases (MβLs) has become an emerging public health threat, and the development of MβLs inhibitor is an effective way to overcome the resistance. In this study, thirteen novel O‐aryloxycarbonyl hydroxamates were constructed and assayed against MβLs. The obtained molecules specifically inhibited imipenemase‐1 (IMP‐1) and New Delhi metallo‐β‐lactamase‐1, exhibiting an IC50 value in the range of 0.10–18.42 and 0.23–22.33 μM, respectively. The hydroxamate 5 was found to be the most potent inhibitor, with an IC50 of 0.1 and 0.23 μM using meropenem and cefazolin as substrates. ICP‐MS analysis showed that 5 did not coordinate to the Zn(II) ions at the active site of IMP‐1, while the rapid dilution, thermal shift and MALDI‐TOF assays revealed that the hydroxamate formed a covalent bond with the enzyme. Cytotoxicity assays indicated that the hydroxamates have low toxicity in MCF‐7 cells. This work provided a potent scaffold for the development of MβLs inhibitors. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that marital status was associated with stages and survival in patients with melanoma or Merkel cell carcinoma. To date, the impacts of marital status on stage and survival in patients with mycosis fungoides (MF) have not been determined yet. Methods: A total of 3375 eligible cases diagnosed from 2004 to 2015 were included from the Surveillance, Epidemiology, and End Results (SEER) database. Association of marital status with stage and survival in patients with MF was analyzed. Results: Married patients were more likely to be diagnosed at T1 stage (p = 0.041). And married patients were less likely to present with lymph node involvement (p = 0.007). More favorable overall survival (p < 0.001) and cancer‐specific survival (p < 0.001) were demonstrated in married patients as compared with divorced patients or widowed patients. A clinically feasible prognostic model including marital status, age, sex, race, and stage at presentation was constructed. Conclusion: Married marital status was associated with earlier stage at diagnosis and longer survival compared with divorced or widowed marital status in patients with MF. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis (OP) is a bone disease characterized by reduced amount and quality of bone. This study was designed to explore the role and mechanism of lncRNA IGF2‐AS in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Methods: Human lncRNA and miRNA microarray analyses were performed to measure the differential expression levels of lncRNAs and miRNAs in undifferentiated and osteogenically differentiated BMSCs. lncRNA IGF2‐AS, miR‐3,126‐5p, and KLK4 levels were measured by real‐time quantitative polymerase chain reaction (RT‐qPCR). Osteogenic differentiation of BMSCs was assessed by alkaline phosphatase (ALP) staining and Alizarin Red staining (ARS). Protein levels of osterix (Osx), osteocalcin (OCN), and runt‐related transcription factor 2 (RUNX2) were examined by RT‐PCR and western blot assays. The binding relationship between miR‐3,126‐5p and lncRNA IGF2‐AS or KLK4 was predicted by TargetScan (http://www.targetscan.org/vert%5f72/) and then verified with a dual‐luciferase reporter assay. Results: lncRNA IGF2‐AS and KLK4 were highly expressed and miR‐3,126‐5p was weakly expressed in osteogenically differentiated BMSCs. Moreover, lncRNA IGF2‐AS overexpression enhanced the osteogenic differentiation of BMSCs. In contrast, lncRNA IGF2‐AS knockdown showed the opposite trend. Moreover, miR‐3,126‐5p overexpression abolished the lncRNA IGF2‐AS‐mediated osteogenic differentiation of BMSCs. lncRNA IGF2‐AS functions as a sponge of miR‐3,126‐5p to regulate KLK4 expression. Conclusion: lncRNA IGF2‐AS enhances the osteogenic differentiation of BMSCs by modulating the miR‐3,126‐5p/KLK4 axis, suggesting a promising therapeutic target for bone‐related diseases. [ABSTRACT FROM AUTHOR]

The temperature-salinity (T-S) diagram is widely used in water mass analysis, but the boundaries between water masses are vaguely distinguished by conventional T-S-based methods. Herein, we propose a new method based on the potential density-potential spicity (sigma-pi) diagram. The new method has been applied to the conductivity-temperature-depth data collected in the northern South China Sea during a spring cruise in 2011. The water masses in the study region are classified into 13 types according to both the standard deviation of potential spicity in each potential density layer and the water volumetric distribution in the sigma-pi space. The results suggest that this new method is reasonable and robust for classifying water masses in the sigma-pi space as compared to previous methods based on the traditional T-S space. In addition, the westward intrusion of the West Pacific Ocean water to the northern South China Sea can be clearly detected by the tongue-like potential spicity structure and relatively high potential spicity patches on potential density layers, further verifying the robustness and efficiency of our method in the water mass analysis. [ABSTRACT FROM AUTHOR]

As two dimensional materials (2D materials) demonstrate unique and diverse properties, clean transfer methods can serve a cornerstone for creative assembly of these 2D building blocks for both fundamental explorations and versatile applications. One of the major challenges for preserving the pristine properties of 2D materials during transfer and construction is to debond 2D materials from original substrates without inducing structural damage and external contamination. In this work, through both molecular dynamic studies and experimental demonstration, it is found that droplets of ethanol, a common and environmental friendly solvent, can be used to effectively reduce the adhesion energy between 2D materials and substrates, and therefore enable a clean transfer method for 2D materials. Various assembled structures based on 2D building blocks, such as van der Waals heterostructures, predesigned artificial patterns, 2D materials on suspended devices are all demonstrated. Thermal conductivity measurements of MoS2 nanosheets on a suspended microbridge device also confirm the successful application of suspended 2D transfer. It is expected that this ethanol assisted transfer method can enable clean assembly of 2D building blocks for construction of novel structures and suspended devices. [ABSTRACT FROM AUTHOR]

Red blood cell distribution width (RDW), which measures the range of variation of red blood cell volume, has been explored as a prognostic factor in multiple types of cancer. However, the role of RDW in mantle cell lymphoma (MCL), a rare type of non‐Hodgkin lymphoma with poor outcomes, remains to be determined. Therefore, we investigated the prognostic role of RDW in MCL. We found that 21 of 76 MCL patients (27.6%) had an abnormally elevated RDW (>15.7%). Abnormally elevated RDW was significantly associated with presence of B symptoms (P = 0.0020), elevated lactate dehydrogenase (LDH) (P = 0.0010), higher leukocyte count (P = 0.0345), higher simplified Mantle Cell International Prognostic Index (sMIPI) (P = 0.0194), and lower level of hemoglobin (Hb) (P < 0.0001). It was marginally associated with increased C‐reactive protein (P = 0.0862). RDW was significantly correlated with Hb level (r2 = 0.42) and LDH level (r2 = 0.19). 15.8% was determined as the best cutoff of RDW in predicting the survival outcome by the X‐tile software. Survival analysis revealed that high RDW (>15.8%) predicted shorter progression‐free survival (PFS) (hazards ratio [HR]: 3.14; P = 0.0005) and shorter overall survival (OS) (HR: 4.04; P < 0.0001). High RDW independently predicted both shorter PFS (P = 0.0493) and OS (P = 0.0118). RDW also improved the prognostic stratification based on sMIPI. In conclusion, our study identified RDW as a novel prognostic factor of clinical feasibility in the prognostication of MCL. [ABSTRACT FROM AUTHOR]

The article discusses research on the prevalence of immunoglobulin (Ig) paraproteinemia in diffuse large B cell lymphoma (DLBCL) populations and its prognostic influence. Topics covered include baseline characteristics and their associations with Ig paraprotein in patients, survival analysis regarding the association of Ig paraprotein with both progression-free survival (PFS) and overall survival (OS), and the association between survival and type of Ig paraprotein.

The aim of this study was to evaluate the prognostic effect of low triiodothyronine (T3) syndrome on patients with diffuse large B cell lymphoma ( DLBCL). A hundred and eighty-eight patients with detailed thyroid hormone levels at diagnosis of DLBCL were enrolled. Low T3 syndrome was defined as a low serum free T3 ( FT3) level with low or normal serum free tetraiodothyronine ( FT4) and thyroid stimulating hormone levels. Multivariate Cox regression analysis was used to screen prognostic factors associated with progression-free survival ( PFS) and overall survival ( OS). Receiver-operator characteristic curves and the corresponding areas under the curve were calculated to assess the predictive accuracy of International Prognostic Index ( IPI) and low T3 syndrome. Twenty-four patients were diagnosed with low T3 syndrome, which was associated with worse PFS and OS in the rituximab era. It was an independent prognostic factor for PFS and OS, especially for those with IPI 0−2, extranodal sites ≤1 and stage III−IV. Synchronously low FT3 and FT4 had poorer survival outcome compared to only low FT3 and adding criterion of low T3 syndrome improved the prognostic capacity of IPI for predicting PFS and OS in DLBCL. Low T3 syndrome was found to be a strong prognostic predictor in DLBCL. [ABSTRACT FROM AUTHOR]

A major objective of quantitative trait locus (QTL) studies is to find genes/markers that can be used in breeding programs via marker assisted selection (MAS). We surveyed the QTLs for yield and yieldrelated traits and their genomic distributions in common wheat (Triticum aestivum L.) in the available published reports. We then carried out a meta-QTL (MQTL) analysis to identify the major and consistent QTLs for these traits. In total, 55 MQTLs were identified, of which 12 significant MQTLs were located on wheat chromosomes 1A, 1B, 2A, 2D, 3B, 4A, 4B, 4D and 5A. Our study showed that the genetic control of yield and its components in common wheat involved the important genes such as Rht and Vrn. Furthermore, several significant MQTLs were found in the chromosomal regions corresponding to several rice genomic locations containing important QTLs for yield related traits. Our results demonstrate that meta-QTL analysis is a powerful tool for confirming the major and stable QTLs and refining their chromosomal positions in common wheat, which may be useful for improving the MAS efficiency of yield related traits. [ABSTRACT FROM AUTHOR]

A facile method to synthesize cyanochlorin from a formyl-substituted chlorin by oxidation of methyl (pyro)pheophorbide-a is accomplished. [ABSTRACT FROM AUTHOR]