基于多序列MRI与多体系影像组学模型预测子宫颈癌淋巴结转移的研究

背景与目的：术前寻找可早期用于准确评估淋巴结转移与否的生物标志物极具临床应用价值。探讨MRI影像组学参数预测子宫颈癌淋巴结转移的价值,建立和验证用于术前预测子宫颈癌淋巴结转移的影像组学模型。方法：回顾性分析2015年6月—2019年9月在复旦大学附属肿瘤医院经术后病理学检查证实的子宫颈癌非淋巴结转移患者和子宫颈癌淋巴结转移患者共202例的临床资料,所有患者均经过术前MRI检查。选用MRI图像分别为T2加权图像（T2 weighted image,T2WI）和T1增强图像（T1 contrast +,T1C+）。使用ITK-SNAP软件进行三维手动分割子宫颈癌肿瘤区域。通过开源的python包Pyradiomics和python编程平台jupyter notebook,经过10种图像类型体系和6种特征体系来提取影像组学特征,选取子宫颈癌患者202例,其中未发生淋巴结转移的104例,发生淋巴结转移的98例。T2WI序列和T1C+序列模型分别提取1 923个特征,T2WI联合T1C+序列提取3 846个特征。通过建立影像组学标签,经过机器学习模型验证影像组学标签。最后将训练集和测试集的曲线下面积（area under curve,AUC）、准确率、阳性预测值（positive predictive value,PPV）和阴性预测值（negative predictive value,NPV）作为评估影像组学标签的定量表现。结果：T2WI序列选取特征排序前14名的特征进行分类器训练,训练集AUC=0.810,测试集AUC=0.773。对于T1C+序列选取了特征排序前16名的特征进行分类器训练,训练集AUC=0.819,测试集AUC=0.781。在T2WI联合T1C+序列中选取了特征排序前16名的特征进行分类器训练,训练集AUC=0.841,测试集AUC=0.803。结论：T2WI联合T1C+序列影像组学模型对早期子宫颈癌淋巴结转移有较好的预测能力。     

Elevated MARCKS phosphorylation contributes to unresponsiveness of breast cancer to paclitaxel treatment

Accumulating evidence has suggested that myristoylated alanine-rich C-kinase substrate (MARCKS) is critical for regulating multiple pathophysiological processes. However, the molecular mechanism underlying increased phosphorylation of MARCKS at Ser159/163 (phospho-MARCKS) and its functional consequence in neoplastic disease remain to be established. Herein, we investigated how phospho-MARCKS is regulated in breast carcinoma, and its role in the context of chemotherapy. In a screen of patients with breast tumors, we find that the abundance of phospho-MARCKS, not MARCKS protein per se, increased in breast cancers and positively correlated with tumor grade and metastatic status. Among chemotherapeutic agents, mitotic inhibitors, including paclitaxel, vincristine or eribulin, notably promoted phospho-MARCKS accumulation in multiple breast cancer cells. We further show that phospho-MARCKS acted upstream of Src activation upon paclitaxel exposure. Reduction of phospho-MARCKS by knockdown of MARCKS or pharmacological agents increased paclitaxel sensitivity. Particularly, a known phospho-MARCKS inhibitor, MANS peptide, was demonstrated to increase paclitaxel efficacy and attenuate angiogenesis/metastasis of xenografted breast cancer cells by decreasing abundance of phospho-MARCKS and messages of inflammatory mediators. Our data suggest that unresponsiveness of breast cancer to paclitaxel treatment is, at least in part, mediated by phospho-MARCKS and also provide an alternative therapeutic strategy against breast cancer by improving taxanes sensitivity.     

Imaging findings in phyllodes tumors of the breast

Purpose

To study the radiological appearance and pathological features of breast phyllodes tumors (PTs), and to enhance the recognition of the tumor.

Materials and methods

Clinical and imaging findings were retrospectively reviewed in 24 women with PTs confirmed by surgical pathology. All of the 24 patients had preoperative MRI and sonography, and 10 had preoperative mammography.

Results

The histologic findings were benign, borderline and malignant PTs in 16.7% (4/24), 45.8% (11/24) and 37.5% (9/24) of cases, respectively. The tumor size (p = 0.001), irregular shape on sonographic imaging (p = 0.039), internal non-enhanced septations (p = 0.009), silt-like changes in enhanced images (p = 0.006) and signal changes from T2-weighted to enhanced images on MRI (p = 0.001) correlated significantly with the histologic grade; the BI-RADS category of the MRI could reflect the PT's histologic grade with a correlation coefficient of 0.440 (p = 0.031). If the category BI-RADS ≥4a was considered to be a suspicious malignant lesion, the diagnostic accuracy of mammography, US and MRI would be 70% (7/10), 62.5% (15/24) and 95.8% (23/24), respectively.

Conclusion

The tumor size and several US and MRI findings can be used to help preoperatively determine the histologic grade of breast PTs. When a patient presents with a progressively enlarging, painless breast mass, MRI should be recommended first.     

Mortality in a Chinese chrysotile miner cohort

Background  

Few data were available to address cause-specific mortality in asbestos miners in China. This study observed a cohort of workers from the largest chrysotile asbestos mine to evaluate the association between asbestos exposure and cause-specific mortality.     

Relaxivity enhancement of aquated Tris(β‐diketonate)gadolinium(III) chelates by confinement within ultrashort single‐walled carbon nanotubes

Ultrashort single‐walled carbon nanotubes loaded with gadolinium ions (gadonanotubes) have been previously shown to exhibit extremely high T₁‐weighted relaxivities (>100 mm ^?1 s^?1). To further examine the effect of nanoconfinement on the relaxivity of gadolinium‐based contrast agents for magnetic resonance imaging, a series of ultrashort single‐walled carbon nanotube (US‐tube) materials internally loaded with gadolinium chelates have been prepared and studied. US‐tubes were loaded with Gd(acac)₃ · 2H₂O, Gd(hfac)₃ · 2H₂O, and Gd(thd)₃ (acac = acetylacetone, hfac = hexafluoroacetylacetone, thd = tetramethylheptanedione). The longitudinal relaxivities of the prepared materials determined at 25°C in a 1.5 T field were 103 mm ^?1 s^?1 for Gd(acac)₃ · 2H₂O@US‐tubes, 105 mm ^?1 s^?1 for Gd(hfac)₃ · 2H₂O@US‐tubes and 26 mm ^?1 s^?1 for Gd(thd)₃@US‐tubes. Compared with the relaxivities obtained for the unloaded chelates (<10 mm ^?1 s^?1) as well as accounting for the T₁ reduction observed for the empty US‐tubes, the boost in relaxivity for chelate‐loaded US‐tubes is attributed to confinement within the nanotube and depends on the number of coordinated water molecules. Copyright © 2014 John Wiley & Sons, Ltd.     

Cognitive deficits 3 to 6 years before dementia onset in a population sample: the Honolulu-Asia aging study

OBJECTIVE: To determine the type of cognitive deficits occurring 3 to 6 years before onset of dementia in a population sample. DESIGN: A prospective study in which cognitive deficits in participants who had incident dementia at the 6-year follow-up were examined at baseline and 3 years. SETTING: Honolulu, Hawaii. PARTICIPANTS: Three thousand seven hundred thirty-four Japanese-American men aged 71 to 93 at baseline. At the 6-year follow-up, there were 52 incident cases of dementia, and 1,559 controls. MEASUREMENTS: The Cognitive Abilities Screening Instrument (CASI) and a questionnaire on subjective memory problems were administered at baseline. Dementia was assessed at baseline and at 3-year and 6-year follow-ups. RESULTS: Subjects who had incident dementia at 6-year follow-up, had showed deficits 3 to 6 years earlier in the CASI domain of episodic memory and in the questionnaire covering subjective memory problems. Up to 3 years before onset, there was worsening of the episodic memory deficit from baseline and new deficits in language, verbal fluency, and orientation. CONCLUSION: Cognitive deficits and awareness of memory problems are frequently present several years before dementia onset. The predictive value of these deficits is not large enough to allow earlier diagnosis of dementia, but information about such deficits may be useful as criteria for mild cognitive impairment.     

Deep resequencing unveils genetic architecture of ADIPOQ and identifies a novel low-frequency variant strongly associated with adiponectin variation

Increased adiponectin levels have been shown to be associated with a lower risk of type 2 diabetes. To understand the relations between genetic variation at the adiponectin-encoding gene, ADIPOQ, and adiponectin levels, and subsequently its role in disease, we conducted a deep resequencing experiment of ADIPOQ in 14,002 subjects, including 12,514 Europeans, 594 African Americans, and 567 Indian Asians. We identified 296 single nucleotide polymorphisms (SNPs), including 30 amino acid changes, and carried out association analyses in a subset of 3,665 subjects from two independent studies. We confirmed multiple genome-wide association study findings and identified a novel association between a low-frequency SNP (rs17366653) and adiponectin levels (P = 2.2E-17). We show that seven SNPs exert independent effects on adiponectin levels. Together, they explained 6% of adiponectin variation in our samples. We subsequently assessed association between these SNPs and type 2 diabetes in the Genetics of Diabetes Audit and Research in Tayside Scotland (GO-DARTS) study, comprised of 5,145 case and 6,374 control subjects. No evidence of association with type 2 diabetes was found, but we were also unable to exclude the possibility of substantial effects (e.g., odds ratio 95% CI for rs7366653 [0.91-1.58]). Further investigation by large-scale and well-powered Mendelian randomization studies is warranted.     

Acute epiglottitis: A review of 50 patients

We reviewed 50 patients admitted to the department of Otorhinolaryngology and Head & Neck Surgery of Govt Medical College Srinagar from September 19% to September 2002 diagnosed with acute epiglottitis. Male were more commonly involved than females in the ratio of 2.8:1 with only 6 cases younger than 10 years of age. The highest incidence was in the month of January (22%). The common symptoms of acute epiglottitis were sorethroat(92%) and odynophagia(88%). Any patient with sudden onset of these symptoms should be suspected of having acute epiglottitis and should have an indirect laryngoscopy. Blood culture was obtained in 20 cases Cultures were positive only in 5 cases, out of which 4 were positive for Hemophilus influenzae type B. Throat cultures were not obtamed The primary treatment of acute epiglottitis is intravenous antibiotics, steriods, and humidified air. Treacheostomy was needed only in 4 patients. There were no deaths.