Artificial intelligence in gastroenterology: A state-of-the-art review

The development of artificial intelligence (AI) has increased dramatically in the last 20 years, with clinical applications progressively being explored for most of the medical specialties. The field of gastroenterology and hepatology, substantially reliant on vast amounts of imaging studies, is not an exception. The clinical applications of AI systems in this field include the identification of premalignant or malignant lesions (e.g., identification of dysplasia or esophageal adenocarcinoma in Barrett’s esophagus, pancreatic malignancies), detection of lesions (e.g., polyp identification and classification, small-bowel bleeding lesion on capsule endoscopy, pancreatic cystic lesions), development of objective scoring systems for risk stratification, predicting disease prognosis or treatment response [e.g., determining survival in patients post-resection of hepatocellular carcinoma), determining which patients with inflammatory bowel disease (IBD) will benefit from biologic therapy], or evaluation of metrics such as bowel preparation score or quality of endoscopic examination. The objective of this comprehensive review is to analyze the available AI-related studies pertaining to the entirety of the gastrointestinal tract, including the upper, middle and lower tracts; IBD; the hepatobiliary system; and the pancreas, discussing the findings and clinical applications, as well as outlining the current limitations and future directions in this field.     

The biological diagnosis of leishmaniasis in HIV-infected patients

This review emphasises the particular difficulties encountered in confirming a suspected case of cutaneous or visceral leishmaniasis when that case is co-infected with HIV. HIV infection appears to have a more profound impact on the development of visceral leishmaniasis than on the evolution of the purely cutaneous disease. The various techniques available for immunological, parasitological and molecular diagnosis are presented and evaluated. The value of serodiagnosis for the detection of antileishmanial antibodies is in part dependent on the antigens used. Western blots may have a use not only in diagnosis but also in predicting the cases of HIV infection that are at most risk of developing symptomatic leishmaniasis. The presence of leishmanial parasites may still only be demonstrated incontrovertibly by the microscopical examination of smears or the culture of blood or biopsy samples. The use of cultures not only permits diagnosis but also detailed study of the parasites. The potential use of PCR in diagnosis is explored and related to other possible tests. A recommended, standardized procedure for the diagnosis of leishmaniasis in HIV-infected patients is presented.     

Elastic distortion determining conduction in BiFeO3 phase boundaries

It is now well-established that boundaries separating tetragonal-like (T) and rhombohedral-like (R) phases in BiFeO₃ thin films can show enhanced electrical conductivity. However, the origin of this conductivity remains elusive. Here, we study mixed-phase BiFeO₃ thin films, where local populations of T and R can be readily altered using stress and electric fields. We observe that phase boundary electrical conductivity in regions which have undergone stress-writing is significantly greater than in the virgin microstructure. We use high-end electron microscopy techniques to identify key differences between the R–T boundaries present in stress-written and as-grown microstructures, to gain a better understanding of the mechanism responsible for electrical conduction. We find that point defects (and associated mixed valence states) are present in both electrically conducting and non-conducting regions; crucially, in both cases, the spatial distribution of defects is relatively homogeneous: there is no evidence of phase boundary defect aggregation. Atomic resolution imaging reveals that the only significant difference between non-conducting and conducting boundaries is the elastic distortion evident – detailed analysis of localised crystallography shows that the strain accommodation across the R–T boundaries is much more extensive in stress-written than in as-grown microstructures; this has a substantial effect on the straightening of local bonds within regions seen to electrically conduct. This work therefore offers distinct evidence that the elastic distortion is more important than point defect accumulation in determining the phase boundary conduction properties in mixed-phase BiFeO₃.

The localized crystallography of conducting and non-conducting phase boundaries in mixed-phase BiFeO₃ is directly compared using scanning transmission electron microscopy techniques.

The complexity of electrical conductivity in domain walls in BiFeO₃ (and in ferroics in general) is as multifaceted as ever. Various influences such as point defect accumulation, octahedral rotations, magnetic interactions and electrostatic discontinuities are thought to be possible mechanisms at play,^1–8 either alone or in combination. The research area of domain wall conductivity is currently flourishing and the view that domain walls offer exciting prospects in terms of engineering systems in which the domain walls act as distinct identities to the domains which they separate is now widely accepted. We believe that it is pertinent timing to address a lack of experimental investigations providing meaningful direct comparison of the localised crystallography and defect structure responsible for observed enhanced electrical conductivity. This study is stimulated by the interesting discoveries of conductive phase boundaries, specifically, in mixed-phase BiFeO₃.^9,10 By tuning the local populations of the tetragonal-like (T) and rhombohedral-like (R) phases in BiFeO₃ thin films via electric and stress fields, we demonstrate that electrical conductivity along phase boundaries is significantly greater after stress-writing. We probe the key crystallographic differences between the R–T boundaries created via stress, compared to those already present in the as-grown microstructures, to disentangle the mechanism determining electrical conduction in mixed-phase BiFeO₃.The growth of BiFeO₃ on substrates enforcing a large in-plane compressive strain drives the formation of monoclinic phases that are approximately rhombohedral (R) and tetragonal (T). Similar to materials such as PbZr_0.53Ti_0.47O₃ that straddle a morphotropic phase boundary, highly strained BiFeO₃ can readily undergo phase transitions between the R and T phases (and vice versa). The high-strain T phase exhibits a tetragonal-like symmetry (almost P4mm) with a c/a ratio of ∼1.2; the Fe displacement towards one of the apical oxygens along [001]_pc results in fivefold oxygen coordinated Fe, and an enhanced polarisation roughly 1.5 times that of the bulk single crystal.^7,11 The R phase, on the other hand, resembles the rhombohedral bulk phase (almost R3c), where the Fe is octahedrally coordinated, with a ferroelectric distortion along the pseudocubic [111]_pc axis, and antiferrodistortive rotations of the FeO₆ octahedra around [111]_pc occur. The crystal structure and misfit strain associated with the native (as-grown) R and T phases is reported elsewhere, both theoretically^12–15 and experimentally,^6,7,16–21 making it well-known that the ferroelectric and the antiferrodistortive degrees of freedom in mixed-phase BiFeO₃ set it apart from other typical perovskites. Notably, despite the ample evidence provided on phase reversal and characterisation of the as-grown phases, most of the literature (especially regarding electric field cycling of the mixed-phase state) has been primarily concerned with X-ray diffraction (XRD) i.e. global measurements that will not necessarily pick up on the more subtle, atomic-scale aspects of structure local to the phase boundaries. The importance of the study described herein resides in the uniqueness of creating microstructures such that both the as-grown and stress-induced R–T phase boundaries can be included within one single cross-sectional transmission electron microscopy (TEM) lamella; this gives the best possible scenario to allow meaningful direct comparison of the localised crystallography and defect structure responsible for the observed enhanced electrical conductivity found at stress-induced phase boundaries.     

Effects on the buoyant density of rabbit platelets of ADP and agents that increase the concentration of cyclic AMP

Rabbit platelets were aggregated by adenosine diphosphate (ADP), allowed to deaggregate and then separated into density subpopulations by centrifugation through discontinuous Stractan density gradients. Although ADP causes little or no release of the contents of the amine storage granules of rabbit platelets, ADP caused a decrease in platelet density as compared with control platelets subjected to the same procedures except for exposure to ADP. The density change persisted for at least four hours. The apparent size of platelets stimulated with ADP increased initially, but returned to control values during a one-hour period. A similar decrease in platelet density was observed with an albumin density gradient. Under conditions in which aggregation did not occur in response to ADP with ethylenediaminetetraacetic acid (EDTA) in the medium, little or no decrease in platelet density was observed. Agglutination with polylysine did not change platelet density. Thus, not only agents such as thrombin and plasmin that cause the release of the contents of the platelet granules decrease platelet density, but ADP also has this effect. Platelets would be exposed to all of these stimuli during thromboembolic processes, and their effect on platelets may account for the decrease in platelet density observed previously in experiments with rabbits with indwelling aortic catheters. Agents that increase the concentration of cyclic AMP (cAMP) in platelets (PGE1, adenosine, dibutyryl cAMP, forskolin, and papaverine) also decreased platelet density. This effect persisted when the platelets were washed and resuspended in fresh medium and was also demonstrable in plasma. Platelet size was gradually increased by prostaglandin E1 (PGE1) which maintains platelets in a disc shape and does not cause the release of granule contents, indicating that the decrease in platelet density caused by PGE1 may be attributable to platelet swelling.     

The polyomavirus puzzle: is host immune response beneficial in controlling BK virus after adult hematopoietic cell transplantion?

BK virus (BKV), a ubiquitous human polyomavirus, usually does not cause disease in healthy individuals. BKV reactivation and disease can occur in immunosuppressed individuals, such as those who have undergone renal transplantation or hematopoietic cell transplantation (HCT). Clinical manifestations of BKV disease include graft dysfunction and failure in renal transplant recipients; HCT recipients frequently experience hematuria, cystitis, hemorrhagic cystitis (HC), and renal dysfunction. Studies of HCT patients have identified several risk factors for the development of BKV disease including myeloablative conditioning, acute graft‐versus‐host disease, and undergoing an umbilical cord blood (uCB) HCT. Although these risk factors indicate that alterations in the immune system are necessary for BKV pathogenesis in HCT patients, few studies have examined the interactions between host immune responses and viral reactivation in BKV disease. Specifically, having BKV immunoglobulin‐G before HCT does not protect against BKV infection and disease after HCT. A limited number of studies have demonstrated BKV‐specific cytotoxic T cells in healthy adults as well as in post‐HCT patients who had experienced HC. New areas of research are required for a better understanding of this emerging infectious disease post HCT, including prospective studies examining BK viruria, viremia, and their relationship with clinical disease, a detailed analysis of urothelial histopathology, and laboratory evaluation of systemic and local cellular and humoral immune responses to BKV in patients receiving HCT from different sources, including uCB and haploidentical donors.     

Inter- and Intra-Subject Variability of Neuromagnetic Resting State Networks

Functional connectivity studies conducted at the group level using magnetoencephalography (MEG) suggest that resting state networks (RSNs) emerge from the large-scale envelope correlation structure within spontaneous oscillatory brain activity. However, little is known about the consistency of MEG RSNs at the individual level. This paper investigates the inter- and intra-subject variability of three MEG RSNs (sensorimotor, auditory and visual) using seed-based source space envelope correlation analysis applied to 5 min of resting state MEG data acquired from a 306-channel whole-scalp neuromagnetometer (Elekta Oy, Helsinki, Finland) and source projected with minimum norm estimation. The main finding is that these three MEG RSNs exhibit substantial variability at the single-subject level across and within individuals, which depends on the RSN type, but can be reduced after averaging over subjects or sessions. Over- and under-estimations of true RSNs variability are respectively obtained using template seeds, which are potentially mislocated due to inter-subject variations, and a seed optimization method minimizing variability. In particular, bounds on the minimal number of subjects or sessions required to obtain highly consistent between- or within-subject averages of MEG RSNs are derived. Furthermore, MEG RSN topography positively correlates with their mean connectivity at the inter-subject level. These results indicate that MEG RSNs associated with primary cortices can be robustly extracted from seed-based envelope correlation and adequate averaging. MEG thus appears to be a valid technique to compare RSNs across subjects or conditions, at least when using the current methods.     

Colonic manifestations of PTEN hamartoma tumor syndrome: Case series and systematic review

AIM:To investigate our clinical experience with the colonic manifestations of phosphatase and tensin homolog on chromosome ten(PTEN)hamartoma tumor syndrome(PHTS)and to perform a systematic literature review regarding the same.METHODS:This study was approved by the appropriate institutional review board prior to initiation.A clinical genetics database was searched for patients with PHTS or a component syndrome that received gastrointestinal endoscopy or pathology interpretation at our center.These patient’s records were retrospectively reviewed for clinical characteristics(including family history and genetic testing),endoscopy results and pathology findings.We also performed a systematic review of the literature for case series of PHTS or component syndromes that reported gastrointestinal manifestations and investigations published after consensus diagnostic criteria were established in 1996.These results were compiled and reported.RESULTS:Eight patients from our institution met initial inclusion criteria.Of these,5 patients underwent4.2 colonoscopies at mean age 45.8±10.8 years.All were found to have colon polyps during their clinical course and polyp histology included adenoma,hyperplastic,ganglioneuroma and juvenile.No malignant lesions were identified.Two had multiple histologic types.One patient underwent colectomy due to innumerable polyps and concern for future malignant potential.Systematic literature review of PHTS patients undergoing endoscopy revealed 107 patients receiving colonoscopy at mean age 37.4 years.Colon polyps were noted in92.5%and multiple colon polyp histologies were reported in 53.6%.Common polyp histologies included hyperplastic(43.6%),adenoma(40.4%),hamartoma(38.3%),ganglioneuroma(33%)and inflammatory(24.5%)polyps.Twelve(11.2%)patients had colorectal cancer at mean age 46.7 years(range 35-62).Clinical outcomes secondary to colon polyposis and malignancy were not commonly reported.CONCLUSION:PHTS has a high prevalence of colon polyposis with multiple histologic types.It should be considered a mixed polyposis syndrome.Systematic review found an increased prevalence of colorectal cancer and we recommend initiating colonoscopy for colorectal cancer surveillance at age 35 years.     

Systematic comparison of adeno‐associated virus and biotinylated dextran amine reveals equivalent sensitivity between tracers and novel projection targets in the mouse brain

As an anterograde neuronal tracer, recombinant adeno‐associated virus (AAV) has distinct advantages over the widely used biotinylated dextran amine (BDA). However, the sensitivity and selectivity of AAV remain uncharacterized for many brain regions and species. To validate this tracing method further, AAV (serotype 1) was systematically compared with BDA as an anterograde tracer by injecting both tracers into three cortical and 15 subcortical regions in C57BL/6J mice. Identical parameters were used for our sequential iontophoretic injections, producing injections of AAV that were more robust in size and in density of neurons infected compared with those of BDA. However, these differences did not preclude further comparison between the tracers, because the pairs of injections were suitably colocalized and contained some percentage of double‐labeled neurons. A qualitative analysis of projection patterns showed that the two tracers behave very similarly when injection sites are well matched. Additionally, a quantitative analysis of relative projection intensity for cases targeting primary motor cortex (MOp), primary somatosensory cortex (SSp), and caudoputamen (CP) showed strong agreement in the ranked order of projection intensities between the two tracers. A detailed analysis of the projections of two brain regions (SSp and MOp) revealed many targets that have not previously been described in the mouse or rat. Minor retrograde labeling of neurons was observed in all cases examined, for both AAV and BDA. Our results show that AAV has actions equivalent to those of BDA as an anterograde tracer and is suitable for analysis of neural circuitry throughout the mouse brain. J. Comp. Neurol. 522:1989–2012, 2014. © 2014 Wiley Periodicals, Inc.     

Dementia in Down’s syndrome: an MRI comparison with Alzheimer’s disease in the general population

Background

Down’s syndrome (DS) is the most common genetic cause of intellectual disability. People with DS are at an increased risk of Alzheimer’s disease (AD) compared to the general population. Neuroimaging studies of AD have focused on medial temporal structures; however, to our knowledge, no in vivo case–control study exists comparing the anatomy of dementia in DS to people with AD in the general population. We therefore compared the in vivo brain anatomy of people with DS and dementia (DS+) to those with AD in the general population.

Method

Using MRI in 192 adults, we compared the volume of whole brain matter, lateral ventricles, temporal lobes and hippocampus in DS subjects with and without dementia (DS+, DS-), to each other and to three non-DS groups. These included one group of individuals with AD and two groups of controls (each age-matched for their respective DS and general population AD cohorts).

Results

AD and DS+ subjects showed significant reductions in the volume of the whole brain, hippocampus and temporal lobes and a significant elevation in the volume of the lateral ventricle, compared to their non-demented counterparts. People with DS+ had a smaller reduction in temporal lobe volume compared to individuals with AD.

Conclusions

DS+ and AD subjects have a significant reduction in volume of the same brain regions. We found preliminary evidence that DS individuals may be more sensitive to tissue loss than others and have less ‘cognitive reserve’.