This study aimed to establish an effective prognostic nomogram with or without plasma Epstein-Barr virus DNA (EBV DNA) for nondisseminated nasopharyngeal carcinoma (NPC).
The nomogram was based on a ...retrospective study of 4630 patients who underwent radiotherapy with or without chemotherapy at Sun Yat-sen University Cancer Center from 2007 to 2009. The predictive accuracy and discriminative ability of the nomogram were determined by a concordance index (C-index) and calibration curve and were compared with EBV DNA and the current staging system. The results were validated using bootstrap resampling and a prospective cohort study on 1819 patients consecutively enrolled from 2011 to 2012 at the same institution. All statistical tests were two-sided.
Independent factors derived from multivariable analysis of the primary cohort to predict recurrence were age, sex, body mass index (BMI), T stage, N stage, plasma EBV DNA, pretreatment high sensitivity C-reactive protein (hs-CRP), lactate dehydrogenase (LDH), and hemoglobin level (HGB), which were all assembled into the nomogram with (nomogram B) or without EBV DNA (nomogram A). The calibration curve for the probability of recurrence showed that the nomogram-based predictions were in good agreement with actual observations. The C-index of nomogram B for predicting recurrence was 0.728 (P < .001), which was statistically higher than the C-index values for nomogram A (0.690), EBV DNA (0.680), and the current staging system (0.609). The C-index of nomogram B (0.730) and nomogram A (0.681) remained higher for predicting recurrence among patients treated with intensity-modulated radiotherapy (P < .001). The results were confirmed in the validation cohort.
The proposed nomogram with or without plasma EBV DNA resulted in more accurate prognostic prediction for NPC patients.
A novel dynamic model for rotating pre-twisted carbon nanotubes reinforced composite (CNTRC) blades with elastic boundary constraints is established based on the first-order shear deformation theory ...(FSDT). The effects of Coriolis and centrifugal forces are considered in the formulation. Based on the Euler-Lagrange equations, the natural frequencies and vibration modes of a rotating pre-twisted blade are obtained. The model's accuracy is verified by comparing it with the results in the literature and Ansys. The influence of distributions of CNTs, pre-twist angle, rotation speed, and stagger angle on the vibration of the ceramic matrix CNTRC blade is studied in detail.
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BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Over the past decade, artificial intelligence (AI) has contributed substantially to the resolution of various medical problems, including cancer. Deep learning (DL), a subfield of AI, is ...characterized by its ability to perform automated feature extraction and has great power in the assimilation and evaluation of large amounts of complicated data. On the basis of a large quantity of medical data and novel computational technologies, AI, especially DL, has been applied in various aspects of oncology research and has the potential to enhance cancer diagnosis and treatment. These applications range from early cancer detection, diagnosis, classification and grading, molecular characterization of tumors, prediction of patient outcomes and treatment responses, personalized treatment, automatic radiotherapy workflows, novel anti‐cancer drug discovery, and clinical trials. In this review, we introduced the general principle of AI, summarized major areas of its application for cancer diagnosis and treatment, and discussed its future directions and remaining challenges. As the adoption of AI in clinical use is increasing, we anticipate the arrival of AI‐powered cancer care.
This review introduced the general principle of AI, summarize major areas of its application for cancer diagnosis, treatment, and precision medicine and discuss its future directions and remaining challenges.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The prevalence of Lynch syndrome (LS) varies significantly in different populations, suggesting that ethnic features might play an important role. We enrolled 3330 consecutive Chinese patients who ...had surgical resection for newly diagnosed colorectal cancer. Universal screening for LS was implemented, including immunohistochemistry for mismatch repair (MMR) proteins, BRAFV600E mutation test and germline sequencing. Among the 3250 eligible patients, MMR protein deficiency (dMMR) was detected in 330 (10.2%) patients. Ninety‐three patients (2.9%) were diagnosed with LS. Nine (9.7%) patients with LS fulfilled Amsterdam criteria II and 76 (81.7%) met the revised Bethesda guidelines. Only 15 (9.7%) patients with absence of MLH1 on IHC had BRAFV600E mutation. One third (33/99) of the MMR gene mutations have not been reported previously. The age of onset indicates risk of LS in patients with dMMR tumors. For patients older than 65 years, only 2 patients (5.7%) fulfilling revised Bethesda guidelines were diagnosed with LS. Selective sequencing of all cases with dMMR diagnosed at or below age 65 years and only of those dMMR cases older than 65 years who fulfill revised Bethesda guidelines results in 8.2% fewer cases requiring germline testing without missing any LS diagnoses. While the prevalence of LS in Chinese patients is similar to that of Western populations, the spectrum of constitutional mutations and frequency of BRAFV600E mutation is different. Patients older than 65 years who do not meet the revised Bethesda guidelines have a low risk of LS, suggesting germline sequencing might not be necessary in this population.
What's new?
The prevalence of Lynch syndrome (LS) varies significantly in different ethnic populations. In this study, the authors screened more than 3000 Chinese colorectal cancer patients for mutations associated with LS, including mismatch repair (MMR) and BRAFV600E mutations. They found that, while the prevalence of LS in Chinese patients is similar to that of Western populations, the spectrum of mutations is different, including many not previously reported. Older patients had a decreased risk of LS, suggesting that germline sequencing may not be necessary in this population.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A straightforward tandem column separation procedure is presented for the separation of Sr, Nd, Pb, and Hf from silicate materials. It allows rapid purification, without any intervening evaporation, ...of these four elements of great interest in Earth science and cosmochemistry. After sample loading, the upper Sr Spec column adsorbs Sr and Pb, while the lower TODGA Spec column adsorbs Hf and Nd. Strontium-lead and hafnium-neodymium elements are then back-extracted from the Sr Spec and TODGA Spec columns, respectively. The whole separation procedure, including column setup, cleaning, and pre-conditioning, takes approximately eight hours for separating a batch of 25 samples. The proposed procedure offers significant improvement in separation efficiency of these often-used four elements, compared with conventional four column methods. Fractions of Sr, Nd and Pb are then measured by TIMS and the Hf fraction is determined by MC-ICP-MS. The stability of this procedure was demonstrated by replicate measurements of
87
Sr/
86
Sr,
143
Nd/
144
Nd,
176
Hf/
177
Hf,
206
Pb/
204
Pb,
207
Pb/
204
Pb and
208
Pb/
204
Pb isotope ratios of eight international silicate rock reference materials, spanning a wide range of bulk compositions. The analytical results obtained in this study agree well with published data. The external reproducibility (2RSD,
n
= 8) of standard BCR-2 was ±0.0026% for
87
Sr/
86
Sr, ±0.0020% for
143
Nd/
144
Nd, ±0.0049% for
176
Hf/
177
Hf, and ±0.026-0.034% for
206
Pb/
204
Pb,
207
Pb/
204
Pb and
208
Pb/
204
Pb isotope ratios.
A straightforward tandem column separation procedure is presented for the separation of Sr, Nd, Pb, and Hf from silicate materials.
Nd can be ionized to NdO
+
about 5-10 fold more efficiently than to Nd
+
by thermal ionization mass spectrometry (TIMS). However, with the NdO
+
method, Ce and Pr must be separated from Nd as ...completely as possible to reduce CeO
+
and PrO
+
isobaric interferences on NdO
+
(
e.g.
141
Pr
18
O
+
on
143
Nd
16
O
+
). With previously reported methods, it is difficult to achieve an efficient Pr-Nd separation although a perfect Sm-Nd separation can be achieved. In this study, a rapid, single column scheme for the separation of Nd and Sm from geological samples, based on TODGA resins (1 mL resin bed volume, 50-100 μm particle size), was developed. The total column separation time, including column cleaning steps, was about 8 h. With this method, not only Nd and Sm could be efficiently separated from the sample matrix, but also a perfect separation of Nd from Ce, Pr and Sm could be obtained. The recovery yield was greater than 90% for Nd and 95% for Sm. Furthermore, since only a single TODGA column separation step was involved, low procedural blanks (Sm < 5 pg; Nd < 10 pg) could be achieved. Therefore, the method is particularly useful for the separation of low levels of Nd from geological samples for isotope analysis as NdO
+
by TIMS. Finally, several rock reference materials, including BCR-2, BHVO-2, BIR-1a and UB-N, with different column loads, were analyzed to verify the reliability of the chemical procedure, and the analytical results show good agreement with the recommended values for the
143
Nd/
144
Nd isotopic ratios and Sm and Nd concentrations.
A single-stage TODGA column for the separation of Nd from geological materials for isotope analysis as NdO
+
by TIMS.
Total hip arthroplasty (THA) of Crowe type IV developmental dysplasia of the hip (DDH) is challenging. Although traditional (lateral, posterolateral, and posterior) THA approaches have been used with ...great anatomic success, they damage periarticular muscles, which are already quite weak in type IV DDH. The recently developed direct anterior approach (DAA) can provide an inter‐nerve and inter‐muscle approach for THA of type IV dysplasia hips. However, femur exposure with the DAA could be difficult during surgery and it is hard to apply femoral shortening osteotomy. THA techniques used for type IV DDH include anatomic hip center techniques (true acetabular reconstruction) and high hip center techniques, wherein an acetabulum is reconstructed above the original one. Although anatomic construction of the hip center is considered “the gold standard” treatment, it is impossible if the anatomical acetabular is too small and shallow. Procedures used to support type IV DDH reduction with anatomic hip center techniques include greater trochanter osteotomy, lesser trochanter osteotomy, and subtrochanteric osteotomy. However, these techniques have yet to be standardized, and it is unclear which is best for type IV DDH. One‐state and two‐state non‐osteotomy reduction techniques have also been introduced to treat type IV DDH. Potential complications of THA performed in patients with type IV DDH include leg length discrepancy (LLD), peri‐operative femur fracture, nonunion of the osteotomy site, and nerve injury. It is worth noting that nowadays an increasing number of Crowe type IV DDH patients are more sensitive to postoperative LLD.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
•High-affinity monoclonal antibodies that recognize EDTA-Cu2+ were obtained through mouse immunization.•The prepared copper antibody has a lower detection limit when used in ic-ELISA to detect copper ...ions.•The ic-ELISA method based on this copper antibody was compared with the ICP-MS method, and it was found that the results of the two methods were highly correlated when detecting trace amounts of copper ions in pork products. Provide a convenient method for detecting copper elements in pork products.
Adding an appropriate amount of copper to feed can promote the growth and development of livestock; however, a large amount of heavy metal copper can accumulate in livestock through the enrichment effect, which poses a serious threat to human health. Traditional Cu2+ detection relies heavily on complex and expensive instruments, such as inductively coupled plasma-optical emission spectrometry (ICP-OES) and inductively coupled plasma-mass spectrometry (ICP-MS); thus, convenient and simple rapid detection technologies are urgently needed. In this paper, synthesized copper antigens were used to immunize mice and highly specific anticopper monoclonal antibodies were obtained, which were verified to exhibit high affinity and specificity. Based on the above antibodies, an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) was established for the rapid detection of copper content in pork. The standard inhibition curve of the method was obtained by antigen–antibody working concentration screening, in which the half inhibitory concentration (IC50) was 11.888 ng/mL, the limit of detection (LOD) was 0.841 ng/mL and the correlation coefficient R2 of the curve was 0.998. In the additive recovery experiment, the recovery rate ranged from 90% to 110%, and the coefficient of variation (CV) was less than 10%, indicating that the method achieved high accuracy and precision. Finally, the results of ic-ELISA combined with Bland-Altman analysis showed a high correlation with ICP-MS, and the correlation coefficient (R2) reached 0.990 when the copper concentration was less than 200 ng/mL. Thus, the ic-ELISA method exhibits high reliability.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The Dexing adakitic porphyries (quartz diorite–granodiorite porphyries), associated with giant porphyry Cu deposits, are located in the interior of a continent (South China). They exhibit relatively ...high MgO, Cr, Ni and Sr contents, high La/Yb and Sr/Y ratios, but low Yb and Y contents, similar to adakites produced by slab melting associated with subduction. However, they are characterized by bulk Earth-like Nd–Sr isotope compositions (εNd(t) = −1·14 to +1·80 and (87Sr/86Sr)i = 0·7044 – 0·7047), and high Th (12·6–27·2 ppm) contents and Th/Ce (0·19–0·94) ratios, which are different from those of Cenozoic slab-derived adakites. Sensitive High-Resolution Ion Microprobe (SHRIMP) geochronology studies of zircons reveal that the Dexing adakitic porphyries have a crystallization age of 171 ± 3 Ma. This age is contemporaneous with Middle Jurassic extension within the Shi-Han rift zone, and within-plate magmatism elsewhere in South China, indicating that the Dexing adakitic porphyries were probably formed in an extensional tectonic regime in the interior of the continent rather than in an arc setting. Their high Th contents and Th/Ce ratios, and Middle Jurassic age, argue against an origin from a Neoproterozoic (∼1000 Ma) stalled slab in the mantle. Taking into account available data for the regional metamorphic–magmatic rocks, and the present-day crustal thickness (∼31 km) in the area, we suggest that the Dexing adakitic porphyries were most probably generated by partial melting of delaminated lower crust, which was possibly triggered by upwelling of the asthenospheric mantle due to the activity of the Shi-Hang rift zone. Moreover, the Dexing adakitic magmas must have interacted with the surrounding mantle peridotite during their ascent, which elevated not only their MgO, Cr and Ni contents, but also the oxygen fugacity (fO2) of the mantle. The high fO2 could have induced oxidation of metallic sulfides in the mantle and mobilization of chalcophile elements, which are required to produce associated Cu mineralization. Therefore, the Cu metallogenesis associated with the Dexing adakitic porphyries is probably related to partial melting of delaminated lower crust, similar to the metallogenesis accompanying slab melting.
The high prevalence of alternative splicing among genes implies the importance of genomic complexity in regulating normal physiological processes and diseases such as gastric cancer (GC). The ...standard form of stem cell marker CD44 (CD44S) and its alternatives with additional exons are reported to play important roles in multiple types of tumors, but the regulation mechanism of CD44 alternative splicing is not fully understood.
Here the expression of hnRNPK was analyzed among the Cancer Genome Atlas (TCGA) cohort of GC. The function of hnRNPK in GC cells was analyzed and its downstream targeted gene was identified by chromatin immunoprecipitation and dual luciferase report assay. Finally, effect of hnRNPK and its downstream splicing regulator on CD44 alternative splicing was investigated.
The expression of hnRNPK was significantly increased in GC and its upregulation was associated with tumor stage and metastasis. Loss-of-function studies found that hnRNPK could promote GC cell proliferation, migration, and invasion. The upregulation of hnRNPK activates the expression of the splicing regulator SRSF1 by binding to the first motif upstream the start codon (- 65 to - 77 site), thereby increasing splicing activity and expression of an oncogenic CD44 isoform, CD44E (has additional variant exons 8 to 10, CD44v8-v10).
These findings revealed the importance of the hnRNPK-SRSF1-CD44E axis in promoting gastric tumorigenesis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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