Opening the black box of AI‐Medicine Poon, Aaron I F; Sung, Joseph J Y
Journal of gastroenterology and hepatology,
March 2021, 2021-Mar, 2021-03-00, 20210301, Letnik:
36, Številka:
3
Journal Article
Recenzirano
One of the biggest challenges of utilizing artificial intelligence (AI) in medicine is that physicians are reluctant to trust and adopt something that they do not fully understand and regarded as a ...“black box.” Machine Learning (ML) can assist in reading radiological, endoscopic and histological pictures, suggesting diagnosis and predict disease outcome, and even recommending therapy and surgical decisions. However, clinical adoption of these AI tools has been slow because of a lack of trust. Besides clinician's doubt, patients lacking confidence with AI‐powered technologies also hamper development. While they may accept the reality that human errors can occur, little tolerance of machine error is anticipated. In order to implement AI medicine successfully, interpretability of ML algorithm needs to improve. Opening the black box in AI medicine needs to take a stepwise approach. Small steps of biological explanation and clinical experience in ML algorithm can help to build trust and acceptance. AI software developers will have to clearly demonstrate that when the ML technologies are integrated into the clinical decision‐making process, they can actually help to improve clinical outcome. Enhancing interpretability of ML algorithm is a crucial step in adopting AI in medicine.
Host immune peptides, including cathelicidins, have been reported to possess anticancer properties. We previously reported that LL-37, the only cathelicidin in humans, suppresses the development of ...colon cancer. In this study, the potential anticancer effect of FK-16, a fragment of LL-37 corresponding to residues 17 to 32, on cultured colon cancer cells was evaluated. FK-16 induced a unique pattern of cell death, marked by concurrent activation of caspase-independent apoptosis and autophagy. The former was mediated by the nuclear translocation of AIF and EndoG whereas the latter was characterized by enhanced expression of LC3-I/II, Atg5 and Atg7 and increased formation of LC3-positive autophagosomes. Knockdown of Atg5 or Atg7 attenuated the cytotoxicity of FK-16, indicating FK-16-induced autophagy was pro-death in nature. Mechanistically, FK-16 activated nuclear p53 to upregulate Bax and downregulate Bcl-2. Knockdown of p53, genetic ablation of Bax, or overexpression of Bcl-2 reversed FK-16-induced apoptosis and autophagy. Importantly, abolition of AIF/EndoG-dependent apoptosis enhanced FK-16-induced autophagy while abolition of autophagy augmented FK-16-induced AIF-/EndoG-dependent apoptosis. Collectively, FK-16 induces caspase-independent apoptosis and autophagy through the common p53-Bcl-2/Bax cascade in colon cancer cells. Our study also uncovered previously unknown reciprocal regulation between these two cell death pathways.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
TGF-β/Smad3 signaling promotes fibrosis, but the development of therapeutic interventions involving this pathway will require the identification and ultimate targeting of downstream fibrosis-specific ...genes. In this study, using a microRNA microarray and real-time PCR, wild-type mice had reduced expression of miR-29 along with the development of progressive renal fibrosis in obstructive nephropathy. In contrast, Smad3 knockout mice had increased expression of miR-29 along with the absence of renal fibrosis in the same model of obstruction. In cultured fibroblasts and tubular epithelial cells, Smad3 mediated TGF-β(1)-induced downregulation of miR-29 by binding to the promoter of miR-29. Furthermore, miR-29 acted as a downstream inhibitor and therapeutic microRNA for TGF-β/Smad3-mediated fibrosis. In vitro, overexpression of miR-29b inhibited, but knockdown of miR-29 enhanced, TGF-β(1)-induced expression of collagens I and III by renal tubular cells. Ultrasound-mediated gene delivery of miR-29b either before or after established obstructive nephropathy blocked progressive renal fibrosis. In conclusion, miR-29 is a downstream inhibitor of TGF-β/Smad3-mediated fibrosis and may have therapeutic potential for diseases involving fibrosis.
Altered gut microbiota is implicated in development of colorectal cancer (CRC). Some intestinal bacteria have been reported to potentiate intestinal carcinogenesis by producing genotoxins, altering ...the immune response and intestinal microenvironment, and activating oncogenic signaling pathways. We investigated whether stool from patients with CRC could directly induce colorectal carcinogenesis in mice.
We obtained stored stool samples from participants in a metagenome study performed in Hong Kong. Conventional (male C57BL/6) mice were given azoxymethane to induce colon neoplasia after receiving a course of antibiotics in drinking water. Mice were gavaged twice weekly with stool from 5 patients with CRC or 5 healthy individuals (controls) for 5 weeks. Germ-free C57BL/6 mice were gavaged once with stool from 5 patients with CRC or 5 controls. We collected intestinal tissues from mice and performed histology, immunohistochemistry, expression microarray, quantitative polymerase chain reaction, immunoblot, and flow cytometry analyses. We performed 16S ribosomal RNA gene sequencing analysis of feces from mice.
Significantly higher proportions of conventional mice fed with stool from individuals with CRC than control stool developed high-grade dysplasia (P < .05) and macroscopic polyps (P < .01). We observed a higher proportion of proliferating (Ki-67-positive) cells in colons of germ-free mice fed with stool from patients with CRC vs those fed with stool from controls (P < .05). Feces from germ-free and conventional mice fed with stool from patients with CRC vs controls contained different microbial compositions, with lower richness in mice fed with stool from patients with CRC. Intestines collected from conventional and germ-free mice fed with stool from patients with CRC had increased expression of cytokines that modulate inflammation, including C-X-C motif chemokine receptor 1, C-X-C motif chemokine receptor 2, interleukin 17A (IL17A), IL22, and IL23A. Intestines from conventional and germ-free mice fed with stool from patients with CRC contained higher proportions of T-helper 1 (Th1) cells (2.25% vs 0.44%) and Th17 cells (2.08% vs 0.31%) (P < .05 for each) than mice fed with stool from controls. Real-time polymerase chain reaction arrays revealed up-regulation of genes involved in cell proliferation, stemness, apoptosis, angiogenesis, invasiveness, and metastasis in mice fed with stool from patients with CRC.
We fed stool samples from patients with CRC and heathy individuals to germ-free mice and conventional mice with azoxymethane. We found stool from patients with CRC to increase the numbers of polyps, levels of intestinal dysplasia and proliferation, markers of inflammation, and proportions of Th1 and Th17 cells in colon, compared with stool from individuals without CRC. This study provides evidence that the fecal microbiota from patients with CRC can promote tumorigenesis in germ-free mice and mice given a carcinogen.
From its beginning in December 2019, the coronavirus disease 2019 outbreak has spread globally from Wuhan and is now declared a pandemic by the World Health Organization. The sheer scale and severity ...of this pandemic is unprecedented in the modern era. Although primarily a respiratory tract infection transmitted by direct contact and droplets, during aerosol‐generating procedures, there is a possibility of airborne transmission. In addition, emerging evidence suggests possible fecal–oral spread of the virus. Clinical departments that perform endoscopy are faced with daunting challenges during this pandemic. To date, multiple position statements and guidelines have been issued by various professional organizations to recommend practices in endoscopic procedures. This article aims to summarize and discuss available evidence for these practices, to provide guidance for endoscopy to enhance patient safety, avoid nosocomial outbreaks, protect healthcare personnel, and ensure rational use of personal protective equipment. Responses adapted to national recommendations and local infection control guidelines and tailored to the availability of medical resources are imminently needed to fight the coronavirus disease 2019 pandemic.
There is a need for early detection of colorectal cancer (CRC) at precancerous-stage adenoma. Here, we identified novel faecal bacterial markers for diagnosing adenoma.
This study included 1012 ...subjects (274 CRC, 353 adenoma and 385 controls) from two independent Asian groups. Candidate markers were identified by metagenomics and validated by targeted quantitative PCR.
Metagenomic analysis identified '
' from a
sp.,
(
) and
(
) to be significantly enriched in adenoma. Faecal
and
were significantly increased from normal to adenoma to CRC (p<0.0001, linear trend by one-way ANOVA) in group I (n=698), which was further confirmed in group II (n=313; p<0.0001). Faecal
may perform better than
in distinguishing adenoma from controls (areas under the receiver operating characteristic curve (AUROCs)
=0.675 vs
=0.620, p=0.09), while
performed better in diagnosing CRC (AUROCs
=0.862 vs
=0.741, p<0.0001). At 78.5% specificity,
and
showed sensitivities of 48.3% and 33.8% for adenoma, and 62.1% and 77.8% for CRC, respectively. In a subgroup tested with faecal immunochemical test (FIT; n=642),
performed better than FIT in detecting adenoma (sensitivities for non-advanced and advanced adenomas of 44.2% and 50.8% by
(specificity=79.6%) vs 0% and 16.1% by FIT (specificity=98.5%)). Combining with FIT improved sensitivity of
for advanced adenoma to 56.8%. The combination of
with
,
,
and FIT performed best for diagnosing CRC (specificity=81.2% and sensitivity=93.8%).
This study identifies a novel bacterial marker
for the non-invasive diagnosis of colorectal adenoma.
With the advancement of artificial intelligence (AI) technology, it comes in a big wave carrying possibly huge impact in the field of medicine. Gastroenterology and hepatology, being a specialty ...relying much on diagnostic imaging, endoscopy, and histopathology, AI technology has promised improving the quality and consistency of care to the patients. In this review, we will elucidate the development of machine learning methods, especially the visual representation mechanism in deep learning on recognition tasks. Various AI‐image analysis applications in endoscopy, radiology, and pathology are covered in gastroenterology and hepatology and reveal the enormous potentials for AI in assisting diagnosis, prognosis, and treatment. We also discuss the promises as well as pitfalls for AI in medical image analysis and pointing out future research directions.
The detection of molecular markers in stool samples is a potential strategy for colorectal cancer (CRC) screening. This study evaluated the feasibility of detecting miR-21 and miR-92a in stool ...samples of patients with CRC or polyps.
The reproducibility of detection and stability of stool-based microRNA were evaluated. Stool samples were collected from 88 patients with CRC, 57 patients with colorectal polyps and 101 healthy controls. MiRNA levels in CRC tissues and stool samples were detected by real-time quantitative reverse transcription PCR. Stool miR-21 and miR-92a levels were compared before and after the removal of tumour or advanced adenoma.
The study demonstrated that stool-based miRNA were stable with highly reproducible detection. The expression of miR-21 and miR-92a was significantly higher in CRC tissues compared with their adjacent normal tissues (p<0.0001). Patients with CRC had a significantly higher stool miR-21 level (p<0.01) and miR-92a level (p<0.0001) compared with normal controls. Stool miR-92a, but not miR-21, was significantly higher in patients with polyps than in controls (p<0.0001). At a cut-off value of 435 copies/ng of stool RNA, miR-92a had a sensitivity of 71.6% and 56.1% for CRC and polyp, respectively, and a specificity of 73.3%. In addition, the stool miR-92a level demonstrated a higher sensitivity for distal CRC than proximal CRC (p<0.05), and a higher sensitivity for advanced adenoma than minor polyps (p<0.05). Removal of tumour resulted in reduced stool miR-21 and miR-92a levels (p<0.01), and the removal of advanced adenoma resulted in a reduction of the stool miR-92a level (p<0.05).
Stool miRNA are useful for screening CRC and polyps.
miR-18a is one of the most up-regulated miRNAs in colorectal cancers (CRC) based on miRNA profiling. In this study, we examined the functional significance of miR-18a in CRC.
Expression of miR-18a ...was investigated in 45 CRC patients. Potential target genes of miR-18a were predicted by in silico search and confirmed by luciferase activity assay and Western blot. DNA damage was measured by comet assay. Gene function was measured by cell viability, colony formation and apoptosis assays.
The up-regulation of miR-18a was validated and confirmed in 45 primary CRC tumors compared with adjacent normal tissues (p<0.0001). Through in silico search, the 3'UTR of Ataxia telangiectasia mutated (ATM) contains a conserved miR-18a binding site. Expression of ATM was down-regulated in CRC tumors (p<0.0001) and inversely correlated with miR-18a expression (r = -0.4562, p<0.01). Over-expression of miR-18a in colon cancer cells significantly reduced the luciferase activity of the construct with wild-type ATM 3'UTR but not that with mutant ATM 3'UTR, inferring a direct interaction of miR-18a with ATM 3'UTR. This was further confirmed by the down-regulation of ATM protein by miR-18a. As ATM is a key enzyme in DNA damage repair, we evaluated the effect of miR-18a on DNA double-strand breaks. Ectopic expression of miR-18a significantly inhibited the repair of DNA damage induced by etoposide (p<0.001), leading to accumulation of DNA damage, increase in cell apoptosis and poor clonogenic survival.
miR-18a attenuates cellular repair of DNA double-strand breaks by directly suppressing ATM, a key enzyme in DNA damage repair.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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