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1.
Many environmental risk factors for hepatobiliary cancers are known but whether they are associated with specific cancer types is unclear. We present here a novel approach of assessing standardized incidence ratios (SIRs) of previously diagnosed comorbidities for hepatocellular carcinoma (HCC), gallbladder cancer (GBC), cholangiocarcinoma (CCA) and ampullary cancer. The 13 comorbidities included alcohol and nonalcohol related liver disease, chronic obstructive pulmonary disease, gallstone disease, viral and other kinds of hepatitis, infection of bile ducts, hepatic and other autoimmune diseases, obesity and diabetes. Patients were identified from the Swedish Inpatient Register from 1987 to 2018, and their cancers were followed from 1997 onwards. SIRs for HCC were 80 to 100 in men and women diagnosed with hepatitis C virus and they were also >10 in patients diagnosed with hepatitis B virus, other kind of hepatitis, hepatic autoimmune disease and nonalcohol related liver disease. Many of these risks, as well as alcohol related liver disease, were either specific to HCC or were shared with intrahepatic CCA. For GBC, CCA and ampullary cancer infection of bile ducts was the main risk factor. Gallstone disease, nonhepatic autoimmune diseases and diabetes were associated with all hepatobiliary cancers. The limitations of the study include inability to cover some rare risk factors and limited follow-up time. Many of the considered comorbidities are characterized by chronic inflammation and/or overt immune disturbance in autoimmune diseases. The results suggest that local chronic inflammation and a related immune disturbance is the carcinogenic trigger for all these cancers.  相似文献   
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Numerous studies showed that postural balance improves through light touch on a stable surface highlighting the importance of haptic information, seemingly downplaying the mechanical contributions of the support. The present study examined the mechanical effects of canes for assisting balance in healthy individuals challenged by standing on a beam. Sixteen participants supported themselves with two canes, one in each hand, and applied minimal, preferred, or maximum force onto the canes. They positioned the canes in the frontal plane or in a tripod configuration. Statistical analysis used a linear mixed model to evaluate the effects on the center of pressure and the center of mass. The canes significantly reduced the variability of the center of pressure and the center of mass to the same level as when standing on the ground. Increasing the exerted force beyond the preferred level yielded no further benefits, although in the preferred force condition, participants exploited the altered mechanics by resting their arms on the canes. The tripod configuration allowed for larger variability of the center of pressure in the task-irrelevant anterior–posterior dimension. High forces had a destabilizing effect on the canes: the displacement of the hand on the cane handle increased with the force. Given this static instability, these results show that using canes can provide not only mechanical benefits but also challenges. From a control perspective, effort can be reduced by resting the arms on the canes and by channeling noise in the task-irrelevant dimensions. However, larger forces exerted onto the canes can also have destabilizing effects and the instability of the canes needs to be counteracted, possibly by arm and shoulder stiffness. Insights into the variety of mechanical effects is important for the design of canes and the instructions of how to use them.  相似文献   
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Kinase alterations are increasingly recognised as oncogenic drivers in mesenchymal tumours. Infantile fibrosarcoma and the related renal tumour, congenital mesoblastic nephroma, were among the first solid tumours shown to harbour recurrent tyrosine kinase fusions, with the canonical ETV6::NTRK3 fusion identified more than 20 years ago. Although targeted testing has long been used in diagnosis, the advent of more robust sequencing techniques has driven the discovery of kinase alterations in an array of mesenchymal tumours. As our ability to identify these genetic alterations has improved, as has our recognition and understanding of the tumours that harbour these alterations. Specifically, this study will focus upon mesenchymal tumours harbouring NTRK or other kinase alterations, including tumours with an infantile fibrosarcoma-like appearance, spindle cell tumours resembling lipofibromatosis or peripheral nerve sheath tumours and those occurring in adults with a fibrosarcoma-like appearance. As publications describing the histology of these tumours increase so, too, do the variety kinase alterations reported, now including NTRK1/2/3, RET, MET, RAF1, BRAF, ALK, EGFR and ABL1 fusions or alterations. To date, these tumours appear locally aggressive and rarely metastatic, without a clear link between traditional features used in histological grading (e.g. mitotic activity, necrosis) and outcome. However, most of these tumours are amenable to new targeted therapies, making their recognition of both diagnostic and therapeutic import. The goal of this study is to review the clinicopathological features of tumours with NTRK and other tyrosine kinase alterations, discuss the most common differential diagnoses and provide recommendations for molecular confirmation with associated treatment implications.  相似文献   
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