Region Of Segment Research Articles

Genotype-phenotype correlation of transthyretin cardiomyopathy in patients with stage C/D heart failure: atrial and myocardial mechanics and fibrosis

Abstract Objectives We sought to investigate: (1) the relationship between transthyretin (TTR) pathogenic variants and their corresponding echocardiographic atrial and ventricular strains in patients with TTR cardiomyopathy (TTR-CM) and clinical evidence of heart failure (HF), and (2) the relationship between TTR pathogenic variants and atrial fibrosis assessed by cardiac MRI. Methods and results Fifty Asian patients with biopsy or scintigraphy proven TTR-CM and stage C or D (C/D) HF were identified from an advanced HF clinic in a tertiary-care university hospital. Genetic testing for the pathogenic variants in the TTR genes associated with hereditary TTR-CM (hTTR-CM) was available in 22 patients (67 ±13 years; 77% were male). Of these, 3 different mutations were identified. The most prevalent pathogenic variant was Ala97Ser (67%) followed by Val30Met (27%), and Gly67Glu (6%). Wild-type TTR-CM was diagnosed in 32% of the cohort. Strain analysis was performed using the TomTec Arena 2D-cardiac performance analysis (CPA) software. Atrial and left ventricular (LV) late gadolinium enhancement (LGE) was quantified using a 9-segment and a 17-segment model, respectively. Patients with hTTR-CM had less impaired longitudinal strain (LS) (more negative strain values) than those with wild-type TTR-CM in the regional basal right ventricular free wall (RV-FW) (-21 ± -8.3 % vs.-12.6 ± -8.1%, p = 0.048) and LV basal inferoseptum (-7.3 ± -4.1 % vs.-3.1 ± -3.0 %, p = 0.045). In univariate analysis, more negative LS values in the basal LV inferoseptum and basal RV-FW were significant predictors of hTTR-CM (OR 5.1 and 2.3; p <0.05, respectively). However, MRI findings revealed similar regional LGE extent involving basal inferolateral segments between hTTR-CM and wild-type TTR-CM (38.3 ± 7.9 vs. 52.5 ± 34.5%, p =0.314). Left atrial (LA) and right atrial (RA) LGE was present in 90% and 81% of patients, respectively. Patients with hTTR-CM had reduced RA LGE when compared to those with wild-type TTR-CM (41% vs 67%, p =0.039). Conclusions In patients with TTR-CM and stage C/D HF, a reduced RA LGE extent and/or more preserved myocardial deformation in specific regions of basal LV and RV segments (basal LV inferoseptum and basal RV free wall) assessed by 2-D speckle tracking echocardiography were significantly more prevalent in patients with hTTR-CM than in wild-type TTR-CM. These echocardiographic and/or MRI findings may facilitate genotype testing in patients with TTR-CM, particularly in resource-limited settings. Further validation of these novel findings in patients with TTR-CM with HF is needed.

Spatiotemporal control of transgene expression using an infrared laser in the crustacean Daphnia magna

The crustacean Daphnia magna is an emerging model for ecological and toxicological genomics. However, the lack of methods for spatial and temporal control of gene expression has impaired the elucidation of molecular mechanisms underlying responses to environments in vivo. Here we report local activation of the hsp70 promoter-driven gene cassette in D. magna by the infrared laser-evoked gene operator (IR-LEGO), a method for heating the target cells with infrared irradiation. We identified the heat-inducible promoter upstream of the D. magna hsp70-A gene. Using this promoter, we generated a transgenic Daphnia harboring the heat-shock responsive GFP reporter gene and confirmed that the GFP gene responds to heat treatment not only in juveniles and adults but also in embryos. We collected embryos from the reporter line and irradiated four different regions of interest in the embryos: a proximal region of the third thoracic segment, a part of the midline, a second maxilla, and a distal region of the endopodite of the second antenna, all of which increased GFP fluorescence with an infrared laser. Our results suggest that the IR-LEGO method is useful for spatial and temporal control of gene expression and would advance the functional genomics in D. magna.

Apical Sparing of Longitudinal Strain as a Specific Pattern of Myocardial Fibrosis in Patients with Severe Left Ventricular Hypertrophy: A Comparison between Deformation Imaging and Histological Findings.

Objectives: This study aimed to investigate the correlation between apical sparing of longitudinal strain (LS), as measured by speckle-tracking echocardiography (STE), and the histological presence of myocardial fibrosis (MF), in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods: Twenty-seven HOCM patients who underwent elective Morrow procedures +/- aortic valve replacement (AVR) were included. All patients had standard echocardiography, with STE pre- and post-operatively. Intraoperative probes of the interventricular septum were sent for histological analysis. Correlation of different regional LS patterns with the histological findings of MF and with clinical outcome were analyzed. In addition, a logistic regression and ROC analysis were performed. Results: All patients underwent the Morrow procedure for HOCM, with 33.3% also undergoing AVR. A total of 74.1% showed evidence of MF in the histological analysis. Patients with MF had significantly lower GLS than patients without MF (-12.7 ± 2.7% vs. -23.0 ± 5.7%, p < 0.001). The LS in patients with MF was significantly lower at the basal regions of the LV segments and increased significantly towards the apex as compared to the patients without MF (mean basal-strain %: -10.6 ± 2.6 vs. -17.3 ± 4.6, p < 0.001; mean apical strain %: -21.8 ± 4.8 vs. -16.7 ± 5.6, p = 0.032). In the logistic regression, only the GLS remained as an independent predictor of MF with an Odds ratio of 1.07 (95%-CI: 1.05-1.09, p < 0.001). Conclusions: Our study highlights the significant correlation between GLS and MF in HOCM patients. These findings contribute to the growing understanding of MF in HOCM and may inform future approaches to patient management and risk stratification.

Evaluation of pathogenic variants detected in high homology regions of the PMS2 gene. How effective is long-range PCR?

Lynch syndrome (LS) is an inherited cancer predisposition syndrome characterized by a high risk of colorectal and extracolonic tumors. Germline pathogenic variants (GPV) in the PMS2 gene are associated with <15% of all cases. The PMS2CL pseudogene presents high homology with PMS2, challenging molecular diagnosis by next-generation sequencing (NGS). Due to the high methodological complexity required to distinguish variants between PMS2 and PMS2CL, most laboratories do not clearly report the origin of this molecular finding. The aim of this study was to confirm the GPVs detected by NGS in regions of high homology segments of the PMS2 gene in a Brazilian sample. An orthogonal and gold standard long-range PCR (LR-PCR) methodology to separate variants detected in the PMS2 gene from those detected in the pseudogene. A total of 74 samples with a PMS2 GPV detected by NGS in exons with high homology with PMS2CL pseudogene were evaluated. The most common was NM_000535.6:c.2182_2184delinsG, which was previously described as deleterious mutation in a study of African-American patients with LS and has been widely reported by laboratories as a pathogenic variant associated with the LS phenotype. Of all GPVs identified, only 6.8% were confirmed by LR-PCR. Conversely, more than 90% of GPV were not confirmed after LR-PCR, and the diagnosis of LS was ruled out by molecular mechanisms associated with PMS2. In conclusion, the use of LR-PCR was demonstrated to be a reliable approach for accurate molecular analysis of PMS2 variants in segments with high homology with PMS2CL. We highlight that our laboratory is a pioneer in routine diagnostic complementation of the PMS2 gene in Brazil, directly contributing to a more assertive molecular diagnosis and adequate genetic counseling for these patients and their families.

Developmental stage dependent effects of posterior and germline regeneration on sexual maturation in Platynereis dumerilii

Regeneration, regrowing lost and injured body parts, is an ability that generally declines with age or developmental transitions (i.e. metamorphosis, sexual maturation). Regeneration is also an energetically costly process, and trade-offs occur between regeneration and other costly processes such as growth, or sexual reproduction. Here we investigate the interplay of regeneration, reproduction, and developmental stage in the segmented worm Platynereis dumerilii. P. dumerilii can regenerate its whole posterior body axis, along with its reproductive cells, thereby having to carry out the two costly processes (somatic and germ cell regeneration) after injury. We specifically examine how developmental stage affects the success of germ cell regeneration and sexual maturation in developmentally young versus developmentally old organisms. We hypothesized that developmentally younger individuals (i.e. with gametes in early mitotic stages) will have higher regeneration success than the individuals at developmentally older stages (i.e. with gametes undergoing meiosis and maturation). Surprisingly, older amputated worms grew faster and matured earlier than younger amputees. To analyze germ cell regeneration during and after posterior regeneration, we used Hybridization Chain Reaction for the germline marker vasa. We found that regenerated worms start repopulating new segments with germ cell clusters as early as 14 days post amputation. In addition, vasa expression is observed in a wide region of newly-regenerated segments, which appears different from expression patterns during normal growth or regeneration in worms before gonial cluster expansion.

Loop-Mediated Isothermal Amplification and Lateral Flow Immunochromatography Technology for Rapid Diagnosis of Influenza A/B.

Influenza viruses cause highly contagious respiratory diseases that cause millions of deaths worldwide. Rapid detection of influenza viruses is essential for accurate diagnosis and the initiation of appropriate treatment. We developed a loop-mediated isothermal amplification and lateral flow assay (LAMP-LFA) capable of simultaneously detecting influenza A and influenza B. Primer sets for influenza A and influenza B were designed to target conserved regions of segment 7 and the nucleoprotein gene, respectively. Optimized through various primer set ratios, the assay operated at 62 °C for 30 min. For a total of 243 (85 influenza A positive, 58 influenza B positive and 100 negative) nasopharyngeal swab samples, the performance of the influenza A/B multiplex LAMP-LFA was compared with that of the commercial AllplexTM Respiratory Panel 1 assay (Seegene, Seoul, Korea). The influenza A/B multiplex LAMP-LFA demonstrated a specificity of 98% for the non-infected clinical samples, along with sensitivities of 94.1% for the influenza A clinical samples and 96.6% for the influenza B clinical samples, respectively. The influenza A/B multiplex LAMP-LFA showed high sensitivity and specificity, indicating that it is reliable for use in a low-resource environment.

Annotator bias and its effect on deep learning segmentation of uncured composite micrographs

This study demonstrated substantial agreement between groups of experts and non-experts in labelling image regions required for semantic segmentation of X-ray micrographs of uncured composite prepregs. Twelve participants, six experts and six non-experts, were given a 1-h training session covering the three different image regions that are present in an uncured composite micrograph: voids, dry fibre areas, and filled fibre areas. High consensus was observed in the centre of objects, but disagreement in labelling between the groups was observed at the interphase regions where the grey level intensity becomes ambiguous in these low-contrast images, such as at the edges of the dry fibre areas and voids. Also, labelling small interlaminar voids caused disagreement. The participants highlighted the role of software by reporting a preference to defining the vertices of a polygon over colouring-in regions of image segments. The resulting Deep Learning segmentation with expert and non-expert group labels were in almost perfect agreement, as measured by the Fleiss Kappa coefficient, and was able to segment voids and dry fibre areas better than thresholding.

Digital spatial profiling of segmental outflow regions in trabecular meshwork reveals a role for ADAM15.

In this study we used a spatial transcriptomics approach to identify genes specifically associated with either high or low outflow regions in the trabecular meshwork (TM) that could potentially affect aqueous humor outflow in vivo. High and low outflow regions were identified and isolated from organ cultured human anterior segments perfused with fluorescently-labeled 200 nm FluoSpheres. The NanoString GeoMx Digital Spatial Profiler (DSP) platform was then used to identified genes in the paraffin embedded tissue sections from within those regions. These transcriptome analyses revealed that 16 genes were statistically upregulated in high outflow regions and 57 genes were statistically downregulated in high outflow regions when compared to low outflow regions. Gene ontology enrichment analysis indicated that the top three biological categories of these differentially expressed genes were ECM/cell adhesion, signal transduction, and transcription. The ECM/cell adhesion genes that showed the largest differential expression (Log2FC ±1.5) were ADAM15, BGN, LDB3, and CRKL. ADAM15, which is a metalloproteinase that can bind integrins, was upregulated in high outflow regions, while the proteoglycan BGN and two genes associated with integrin signaling (LDB3, and CRKL) were downregulated. Immunolabeling studies supported the differential expression of ADAM15 and showed that it was specifically upregulated in high outflow regions along the inner wall of Schlemm's canal and in the juxtacanalicular (JCT) region of the TM. In addition to these genes, the studies showed that genes for decorin, a small leucine-rich proteoglycan, and the α8 integrin subunit were enriched in high outflow regions. These studies identify several novel genes that could be involved in segmental outflow, thus demonstrating that digital spatial profiling could be a useful approach for understanding segmental flow through the TM. Furthermore, this study suggests that changes in the expression of genes involved in regulating the activity and/or organization of the ECM and integrins in the TM are likely to be key players in segmental outflow.

Global domain adaptation attention with data-dependent regulator for scene segmentation.

Most semantic segmentation works have obtained accurate segmentation results through exploring the contextual dependencies. However, there are several major limitations that need further investigation. For example, most approaches rarely distinguish different types of contextual dependencies, which may pollute the scene understanding. Moreover, local convolutions are commonly used in deep learning models to learn attention and capture local patterns in the data. These convolutions operate on a small neighborhood of the input, focusing on nearby information and disregarding global structural patterns. To address these concerns, we propose a Global Domain Adaptation Attention with Data-Dependent Regulator (GDAAR) method to explore the contextual dependencies. Specifically, to effectively capture both the global distribution information and local appearance details, we suggest using a stacked relation approach. This involves incorporating the feature node itself and its pairwise affinities with all other feature nodes within the network, arranged in raster scan order. By doing so, we can learn a global domain adaptation attention mechanism. Meanwhile, to improve the features similarity belonging to the same segment region while keeping the discriminative power of features belonging to different segments, we design a data-dependent regulator to adjust the global domain adaptation attention on the feature map during inference. Extensive ablation studies demonstrate that our GDAAR better captures the global distribution information for the contextual dependencies and achieves the state-of-the-art performance on several popular benchmarks.

Correlation between acupoint sensitization of body surface and pituitary adenylate cyclase activating polypeptide expression in myocardial ischemia mice

To explore the relationship between sensitization points of the body surface and the expression of pituitary adenylate cyclase activating polypeptides (PACAP) in myocardial ischemia (MI) mice, so as to reveal the underlying mechanisms of acupoint sensitization from the perspective of molecular biology. Male C57BL/6J mice were randomly divided into control and model groups (28 mice/group). The MI-induced visceral pain model was established by intraperitoneal injection of isoprenaline (ISO, 160 mg/kg). The mice of the control group received intraperitoneal injection of the same dose of normal saline. Six days after modeling, the Evans blue (EB) dye was injected into the tail vein of mice to observe the distribution and quantity of the plasma extravasated EB points at the body surface. Meanwhile, the mechanical pain threshold (MPT) was measured to evaluate the level of pain sensitivity in the activated area on their body surface and left forelimb and hindlimb, respectively. Hematoxylin-eosin (H.E.) staining was used to evaluate the morphologic and pathological changes of the heart tissue in the two groups. Then, the expressions of PACAP in the thoracic (T)1-T5 dorsal root ganglia (DRGs), spinal cord and skin in the dominant area of body surface were detected by Western blot and immunofluorescence staining, respectively. Compared with the control group, the heart tissue of the model group was hypertrophic and the myocardial tissue showed obvious inflammatory cell infiltration and fibrosis. In addition to these pathologic changes, the number of EB exudation points on the body surface was significantly increased (P<0.01), and was mainly distributed in the innervated region of T1-T5 segments of the spinal cord, and the MPT of these EB exudation points was lower than that of non-exudation points (P<0.01). At the same time, the MPTs of left forelimb and hindlimb were significantly decreased in the model group (P<0.001). More importantly, the level of protein and positive expression of PACAP were significantly higher in the model group than those in the control group, which was observed in the innervated body surface, spinal cord and its DRG neurons of T1-T5 segments (P<0.01, P<0.001, P<0.05). ISO injection resulted in histological lesions and cardiogenic referred pain on the body surface after the formation of MI in mice. The expression of PACAP in the body surface of the sensitization points, the corresponding T1-T5 segments of spinal cord and DRG neurons were significantly increased, which may partly explain the reason for acupoint sensitization in the animal model of visceral pain.

Intrinsic signal optoretinography of dark adaptation abnormality due to rod photoreceptor degeneration.

This research aims to investigate the potential of using intrinsic optical signal (IOS) optoretinography (ORG) to objectively detect dark adaptation (DA) abnormalities related to rod photoreceptor degeneration. Functional optical coherence tomography (OCT) was employed in both wild-type (WT) and retinal degeneration 10 (rd10) mice to conduct this assessment. Dynamic OCT measurements captured the changes in retinal thickness and reflectance from light-to-dark transition. Comparative analysis revealed significant IOS alterations within the outer retina. Specifically, a reduction in thickness from external limiting membrane (ELM) peak to retinal pigment epithelium (RPE) peak was observed (WT: 1.13 ± 0.69µm, 30min DA; rd10: 2.64 ± 0.86µm, 30min DA), as well as a decrease in the intensity of the inner segment ellipsoid zone (EZ) in 30min DA compared to light adaptation (LA). The reduction of relative EZ intensity was notable in rd10 after 5min DA and in WT after 15min DA, with a distinguishable difference between rd10 and WT after 10min DA. Furthermore, our findings indicated a significant decrease in the relative intensity of the hypo-reflective band between EZ and RPE in rd10 retinas during DA, which primarily corresponds to the outer segment (OS) region. In conclusion, the observed DA-IOS abnormalities, including changes in ELM-RPE thickness, EZ, and OS intensity, hold promise as differentiators between WT and rd10 mice before noticeable morphological abnormalities occur. These findings suggest the potential of this non-invasive imaging technique for the early detection of dysfunction in retinal photoreceptors.

Data-driven models for the prediction of coronary atherosclerotic plaque progression/regression

Coronary artery disease is defined by the existence of atherosclerotic plaque on the arterial wall, which can cause blood flow impairment, or plaque rupture, and ultimately lead to myocardial ischemia. Intravascular ultrasound (IVUS) imaging can provide a detailed characterization of lumen and vessel features, and so plaque burden, in coronary vessels. Prediction of the regions in a vascular segment where plaque burden can either increase (progression) or decrease (regression) following a certain therapy, has remained an elusive major milestone in cardiology. Studies like IBIS-4 showed an association between plaque burden regression and high-intensity rosuvastatin therapy over 13 months. Nevertheless, it has not been possible to predict if a patient would respond in a favorable/adverse fashion to such a treatment. This work aims to (i) Develop a framework that processes lumen and vessel cross-sectional contours and extracts geometric descriptors from baseline and follow-up IVUS pullbacks; and to (ii) Develop, train, and validate a machine learning model based on baseline/follow-up IVUS datasets that predicts future percent of atheroma volume changes in coronary vascular segments using only baseline information, i.e. geometric features and clinical data. This is a post hoc analysis, revisiting the IBIS-4 study. We employed 140 arteries, from 81 patients, for which expert delineation of lumen and vessel contours were available at baseline and 13-month follow-up. Contour data from baseline and follow-up pullbacks were co-registered and then processed to extract several frame-wise features, e.g. areas, plaque burden, eccentricity, etc. Each pullback was divided into regions of interest (ROIs), following different criteria. Frame-wise features were condensed into region-wise markers using tools from statistics, signal processing, and information theory. Finally, a stratified 5-fold cross-validation strategy (20 repetitions) was used to train/validate an XGBoost regression models. A feature selection method before the model training was also applied. When the models were trained/validated on ROI defined by the difference between follow-up and baseline plaque burden, the average accuracy and Mathews correlation coefficient were 0.70 and 0.41 respectively. Using a ROI partition criterion based only on the baseline’s plaque burden resulted in averages of 0.60 accuracy and 0.23 Mathews correlation coefficient. An XGBoost model was capable of predicting plaque progression/regression changes in coronary vascular segments of patients treated with rosuvastatin therapy in 13 months. The proposed method, first of its kind, successfully managed to address the problem of stratification of patients at risk of coronary plaque progression, using IVUS images and standard patient clinical data.

A GFP-expressing minigenome of a chrysovirus replicating in fungi

The Fusarium graminearum virus China 9 (FgV-ch9) is a member of the genus Betachrysovirus in the Chrysoviridae family and causes hypovirulence in its host, Fusarium graminearum, the causal agent of Fusarium head blight. Although insights into viral biology of FgV-ch9 have expanded in recent years, questions regarding the function of virus-encoded proteins, cis-acting elements, and virus transmission are yet to be answered. Therefore, we developed a tool for the establishment of an artificial 6th segment of FgV-ch9, which encodes a GFP gene flanked by the non-translated regions of FgV-ch9 segment 1. Subsequently, we have proved successful encapsidation of this artificial segment into virus particles as well as its horizontal transmission. Expression of GFP was further verified via immunoassay and life cell imaging. Thus far, we were able to establish for the first time a mini-replicon system for segmented dsRNA viruses replicating in fungi.

Real-Time RT-PCR for the Diagnosis of Epizootic Hemorrhagic Disease Virus.

Real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) has become an essential tool in rapid and reliable detection of animal diseases such as epizootic hemorrhagic disease (EHD). Here we provide a protocol for the detection of epizootic hemorrhagic disease virus (EHDV) genetic material in blood and tissue samples, using a real-time RT-PCR that targets a conserved region in segment 9 of the EHDV genome. This protocol can be used to detect up to approximately 90 samples in a single run and can be completed in less than 4h.

Nitric oxide transport in carotid bifurcation after different stent interventions: a numerical study

Stent restenosis and late thrombosis compromise endovascular stent implantation clinical benefit, and the mechanism is unclear. Since nitric oxide (NO) plays a pivotal role in maintaining vascular homeostasis, we believe that stenting can affect NO concentration in the host artery, thereby contributing to postoperative adverse events. We numerically investigated NO concentration after stenting based on the patient-specific carotid to verify this hypothesis. The simulation revealed that stent implantation caused blood flow disturbance, a low wall shear stress, and a significant decrease in NO on the luminal surface, especially in the region of the stented segment. Moreover, severe damage to the artery wall or low blood flow, leading to a low NO generation rate, would induce relatively low NO level in the stented segment. Additionally, we demonstrated that NO distribution might be affected by the combination of stent struts and carotid bifurcation geometry, while the host arterial configuration might play a leading role in the distribution of NO concentration. In conclusion, the carotid artery had a relatively low NO concentration level near stent struts, especially at the severely injured artery, low blood flow, long stenting, and complex host artery which might lead to a genesis/development of adverse events after that intervention.

AASeg: Artery-aware Global-to-Local Framework for Aneurysm Segmentation in Head and Neck CTA Images.

Aneurysm segmentation in computed tomography angiography (CTA) images is essential for medical intervention aimed at preventing subarachnoid hemorrhages. However, most existing studies tend to overlook the topological characteristics of arteries related to aneurysms, often resulting in suboptimal performance in aneurysm segmentation. To address this challenge, we propose an arteryaware global-to-local framework for aneurysm segmentation (AASeg) using CTA images of head and neck. This framework consists of two key components: 1) a centerline graph network (CG-Net) for aneurysm global localization, and 2) a point cloud network (PC-Net) for local aneurysm segmentation. The centerline graph is generated by extracting artery centerline structures from vessel masks obtained through a pre-trained model for head and neck vessel segmentation. This representation serves as a high-level representation of the artery structure, allowing for analysis of aneurysms along the entire arteries. It facilitates aneurysm localization via aneurysm-segment graph classification along the arteries. Then, local region of aneurysm segment can be sampled from the vessel mask according to the aneurysm-segment graph. Subsequently, aneurysm segmentation is performed on the point cloud constructed from the aneurysm segment through the PC-Net. Extensive experiments show that the proposed framework achieves state-of-the-art performance in aneurysm localization on a main dataset and an external testing dataset, with Recall of 84.1% and 80.7%, false positives per case of 1.72 and 1.69, and segmentation DSC of 66.1% and 60.2%, respectively.

MRI tractographic validation of drug-enhanced hepatic clearance of amyloid-beta and the therapeutic potential for Alzheimer's Disease: A pilot study

Alzheimer's disease (AD) may require alternative therapeutic perspectives as current interventions may sometimes be sub-optimal. Amyloid-beta 42 (Aβ42) is mainly eliminated by hepatic clearance which diminishes in AD, hence hepatomodulatory drugs enhancing this clearance may have potentiality for therapeutic implication. Here, we clinically substantiate our systems-biology investigation on repurposed hepatomodulating drugs (metformin, cilostazol and rifampicin) which enhance brain insoluble Aβ42 clearance through liver-bile-faeces route. Through MRI-tractographic analysis, we now formulate a three-segmental basis of brain Aβ42 spread: fronto-thalamic region (segment-1), temporo-occipital region (segment-2), and dorso-cingulate region (segment-3). This segmental pattern is corroborated histopathologically by Braak's stages A, B and C. We further observed that the aforesaid three pharmaceuticals respectively acted on those three segmental regions differentially. We analysed MRI and DTI images of 15 healthy controls (CDR: 0; MMSE: 24–20), and 15 AD patients (CDR: 0.5–1.0; MMSE: 20–26). We found that, tractographically, there is a significant reduction in neuronal integrity in the three aforesaid regions in untreated AD compared to controls. Nevertheless, the three drugs increased neural activation of AD patients in the three corresponding areas. These three drugs act by regulating respectively the genes ABCB11, ABCA1 and MDR1. These genes were correspondingly downregulated in the above-mentioned anatomical segments 1, 2 and 3 of Alzheimer's disease. Thus personalized patient-specific hepatomodulative drugs for AD intervention may be explored, as corroborated by the neuroanatomical involvement in AD.

MEDICINAL BIOMAGNETISM FOR ANALGESIA IN MUSCULOSKELETAL DISORDERS OF THE SPINE – APPLICATION OF STATIC MAGNETIC FIELDS USING THE SPINE PROTOCOL

Introduction: Spinal pain affects approximately 80% of the population at some point of their lives. It’s the second biggest cause of absenteeism in professional or academic environments, directly impinging upon reduced productivity, psychological states and quality of life. Allopathy is the most widely used treatment, however its adverse effects are recurrent. Medicinal Biomagnetism (MB) is a therapy that uses static magnetic fields (SMF) provided from magnets, which have minimal side effects, assisting in the restoration of health, yielding an analgesic effect. Goal: Evaluate the effect of SMF usage by means of the Spine Protocol (SP) from MB applied onto pain deriving from musculoskeletal disorders of the vertebral column. Methodology: Longitudinal study with clinical trials of 15 participants assessed using the Visual Analogue Scale (VAS) and Brief Pain Inventory, followed up after treatment for 30 days. Result: A reduction in pain perception was observed in 91% of the sample, representing 21 treatments of spinal segments, from just 15 minutes of exposure to the SP procedure, with a significative difference for the VAS variables (p=0.0000014). Most participants were female and the most common pain was located around the lumbar segment region. Conclusion: The SP procedure has therapeutic potential in both short and long term for the treatment of acute and chronic pain of any intensity, and it can be considered as a primary or supporting intervention in musculoskeletal disorders of the spine. It has demonstrated a shorter initial time and a longer duration for its analgesic effect when compared with the drug action reported in the literature.

Automated deviation-aware landmark selection for freeform product accuracy qualification in 3D printing

Landmarks are essential in non-rigid shape registration for identifying the correspondence between designs and actual products. In 3D printing, manual selection of landmarks becomes labor-intensive, due to complex product geometries and their non-uniform shape deviations. Automatic selection, however, has to pinpoint landmarks indicative of geometric regions prone to deviations for accuracy qualification. Existing automatic landmarking methods often generate clustered and redundant landmarks for prominent features with high curvatures, compromising the balance between global and local registration errors. To address these issues, we propose an automatic landmark selection method through deviation-aware segmentation and landmarking. As opposed to segmentation for semantic feature identification, deviation-aware segmentation partitions a freeform product for high-curvature region identification. Prone to deviation, these regions are generated through curvature-sensitive remeshing to extract vertices of high curvature and automatic clustering of vertices based on vertex density. Within each segment or high-curvature region, a curvature-weighted function is tailored for the Gaussian process landmarking to sequentially select landmarks with the highest local curvatures. Furthermore, we propose a new evaluation criterion to assess the effectiveness of selected landmarks through registration. The proposed approach is tested through automatic landmarking of printed dental models.

Increase in ENHANCER OF SHOOT REGENERATION2 expression by treatment with strigolactone-related inhibitors and kinetin during adventitious shoot formation in ipecac.

Increase of ENHANCER OF SHOOT REGENERATION 2 expression was consistent to treatment with kinetin, TIS108, and KK094 in adventitious shoot formation of ipecac. Unlike many plant species, ipecac (Carapichea ipecacuanha (Brot.) L. Andersson) can form adventitious shoots in tissue culture without cytokinin (CK) treatment. Strigolactone (SL) biosynthesis and signaling inhibitors stimulate adventitious shoot formation in ipecac, suggesting their potential use as novel growth regulators in plant tissue culture, but the molecular mechanism of their action is unclear. In this study, we compared the effects of SL-related inhibitors (TIS108 and KK094) and CKs (2iP, tZ, and kinetin) on adventitious shoot formation in ipecac. Exogenously applied SL-related inhibitors and CKs stimulated adventitious shoot formation. Combinations of SL-related inhibitors and kinetin also promoted adventitious shoot formation, but without additive effects. We also analyzed the expression of CK biosynthesis genes in ipecac. TIS108 increased the expression of the ipecac homolog of ISOPENTENYL TRANSFERASE 3 (CiIPT3) but decreased that of LONELY GUY 7 homolog (CiLOG7), presumably resulting in no change in 2iP-type CK levels. KK094 and kinetin increased CiLOG7 expression, elevating 2iP-type CK levels. Among pluripotency- and meristem-related genes, TIS108, KK094, and kinetin consistently increased the expression of ENHANCER OF SHOOT REGENERATION 2 homolog (CiESR2), which has a key role in shoot regeneration, in the internodal segment region that formed adventitious shoots. We propose that CiESR2 might be a key stimulator of adventitious shoot formation in ipecac.