Combining stereotactic body radiotherapy with immunotherapy in stage IV non-small cell lung cancer

Immunotherapy has revolutionized the treatment of metastatic non-small cell lung cancer (NSCLC). Oligometastasis has been associated with better prognosis than widespread metastatic disease and may be curable by stereotactic body radiotherapy (SBRT). SBRT can stimulate immunogenic anti-tumor activity, which can be further augmented when combined with immunotherapy, such as immune checkpoint inhibitors (ICIs). Thus, its combination with immunotherapy was recognized as a promising treatment option, especially in the metastatic setting. However, the most optimal approach to combine SBRT with immunotherapy remains controversial with early clinical evidence emerging. Here, we review the current clinical evidence supporting the combination of SBRT with immunotherapy in the treatment of metastatic NSCLC. Also, we discuss the current controversies and areas for further exploration associated with this treatment strategy

Interprofessional Collaboration in Addressing Diet as a Common Risk Factor: A Qualitative Study

Background: Unhealthy diet is a common risk factor threatening dental and general health. Conflicting dietary advice persists among different healthcare professions, despite some shared goals, causing mystification to patients and the public. This qualitative study aimed to understand the perspectives of dentists, physicians, and dietitians in targeting unhealthy diet as a common risk factor, their experiences and barriers in addressing conflicting dietary advice, and possible ways for improving cross-professional coordination.Methods and Findings: A purposive sample of 40 dentists, physicians, and dieticians was recruited from different service sectors and joined in semi-structured interviews, which were subjected to thematic content analysis. Participants supported the common risk factor approach and suggested improving cross-professional cooperation by maximizing potentials of multidisciplinary care, engaging auxiliary/allied staff, refining electronic systems, and incorporating cutting-edge communication technologies. Inconsistent dietary advice stemmed from different treatment focuses and lack of mutual understanding and well-followed guidelines. Inconsistencies can be resolved by striking a balance for the patient’s best interest, well-informing patients, respecting patients’ autonomy, acquiring cross-professional knowledge, and conforming to shared guidelines.Conclusions: Views solicited from three healthcare professions endorsed the importance of cross-professional partnership in preventing/managing dietrelated health problems. Educators, professional bodies, and administrators share the responsibility to dispel conflicting health messages and promote better practice in dietary counselling

Activation of the hedgehog pathway in advanced prostate cancer

BACKGROUND: The hedgehog pathway plays a critical role in the development of prostate. However, the role of the hedgehog pathway in prostate cancer is not clear. Prostate cancer is the second most prevalent cause of cancer death in American men. Therefore, identification of novel therapeutic targets for prostate cancer has significant clinical implications. RESULTS: Here we report that activation of the hedgehog pathway occurs frequently in advanced human prostate cancer. We find that high levels of hedgehog target genes, PTCH1 and hedgehog-interacting protein (HIP), are detected in over 70% of prostate tumors with Gleason scores 8–10, but in only 22% of tumors with Gleason scores 3–6. Furthermore, four available metastatic tumors all have high expression of PTCH1 and HIP. To identify the mechanism of the hedgehog signaling activation, we examine expression of Su(Fu) protein, a negative regulator of the hedgehog pathway. We find that Su(Fu) protein is undetectable in 11 of 27 PTCH1 positive tumors, two of them contain somatic loss-of-function mutations of Su(Fu). Furthermore, expression of sonic hedgehog protein is detected in majority of PTCH1 positive tumors (24 out of 27). High levels of hedgehog target genes are also detected in four prostate cancer cell lines (TSU, DU145, LN-Cap and PC3). We demonstrate that inhibition of hedgehog signaling by smoothened antagonist, cyclopamine, suppresses hedgehog signaling, down-regulates cell invasiveness and induces apoptosis. In addition, cancer cells expressing Gli1 under the CMV promoter are resistant to cyclopamine-mediated apoptosis. All these data suggest a significant role of the hedgehog pathway for cellular functions of prostate cancer cells. CONCLUSION: Our data indicate that activation of the hedgehog pathway, through loss of Su(Fu) or overexpression of sonic hedgehog, may involve tumor progression and metastases of prostate cancer. Thus, targeted inhibition of hedgehog signaling may have significant implications of prostate cancer therapeutics

Molecular characterization of cathepsin B from Clonorchis sinensis excretory/secretory products and assessment of its potential for serodiagnosis of clonorchiasis

<p>Abstract</p> <p>Background</p> <p>Cathepsin cysteine proteases play multiple roles in the life cycle of parasites such as food uptake, immune invasion and pathogenesis, making them valuable targets for diagnostic assays, vaccines and drugs. The purpose of this study was to identify a cathepsin B of <it>Clonorchis sinensis </it>(<it>Cs</it>CB) and to investigate its diagnostic value for human helminthiases.</p> <p>Results</p> <p>The predicted amino acid sequence of the cathepsin B of <it>C. sinensis </it>shared 63%, 52%, 50% identity with that of <it>Schistosoma japonicum</it>, <it>Homo sapiens </it>and <it>Fasciola hepatica</it>, respectively. Sequence encoding proenzyme of <it>Cs</it>CB was overexpressed in <it>Escherichia coli</it>. Reverse transcription PCR experiments revealed that <it>Cs</it>CB transcribed in both adult worm and metacercaria of <it>C. sinensis</it>. <it>Cs</it>CB was identified as a <it>C. sinensis </it>excretory/secretory product by immunoblot assay, which was consistent with immunohistochemical localization showing that <it>Cs</it>CB was especially expressed in the intestine of <it>C. sinensis </it>adults. Both ELISA and western blotting analysis showed recombinant <it>Cs</it>CB could react with human sera from clonorchiasis and other helminthiases.</p> <p>Conclusions</p> <p>Our findings revealed that secreted CsCB may play an important role in the biology of C. sinensis and could be a diagnostic candidate for helminthiases.</p

Molecular identification of Clonorchis sinensis and discrimination with other opisthorchid liver fluke species using multiple Ligation-depended Probe Amplification (MLPA)

<p>Abstract</p> <p>Background</p> <p>Infections with the opisthorchid liver flukes <it>Clonorchis sinensis</it>, <it>Opisthorchis viverrini</it>, and <it>O. felineus </it>cause severe health problems globally, particularly in Southeast Asia. Early identification of the infection is essential to provide timely and appropriate chemotherapy to patients.</p> <p>Results</p> <p>In this study we evaluate a PCR-based molecular identification method, Multiplex Ligation-dependent Probe Amplification (MLPA), which allows rapid and specific detection of single nucleotide acid differences between <it>Clonorchis sinensis</it>, <it>Opisthorchis viverrini </it>and <it>O. felineus</it>. Three probe pairs were derived from the Internally Transcribed Spacer 1 (ITS1) of three opisthorchid liver flukes using a systematic phylogenetic analysis. Specific loci were detected in all three species, yielding three amplicons with 198,172 and 152 bp, respectively, while no cross reactions were observed. A panel of 66 <it>C. sinensis </it>isolates was screened using MLPA. All species were positively identified, and no inhibition was observed. The detection limit was 10³copies of the ITS gene for the three liver flukes, or about 60 pg genomic DNA for <it>Clonorchis sinensis</it>. Amplification products can be detected by electrophoresis on agarose gel or in a capillary sequencer. In addition, genomic DNA of <it>Clonorchis sinensis </it>in fecal samples of infected rats was positively amplified by MLPA.</p> <p>Conclusion</p> <p>The flexibility and specificity make MLPA a potential tool for specific identification of infections by opisthorchid liver flukes in endemic areas.</p

Navigating the Complexity of Describing Chinese Historical Places Using the Wikibase Platform

Chinese historical places, with their extensive history spanning thousands of years, serve as profound symbols of the nation's rich cultural legacy. Capturing their historical changes in a consistent data model for describing cultural heritage, however, poses significant challenges due to shifts in the places’ name, administrative boundaries, administrative units, and geographical locations. Various data models on platforms like Wikidata offer differing approaches: some separate place names and locations into distinct classes, while others consolidate them. This poster showcases the authors’ investigation into different data models for describing cultural heritage historical places and their chosen approach. By leveraging Wikibase as a testbed database, the authors delve into the merits and limitations of each data model, unveiling the techniques employed for bulk data creation, complexities encountered, and valuable insights derived from this exploration.</p