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Significance Diffusion-weighted MRI (DWI) tractography is widely used to map structural connections of the human brain in vivo and has been adopted by large-scale initiatives such as the human connectome project. Our results indicate that, even with high-quality data, DWI tractography alone is unlikely to provide an anatomically accurate map of the brain connectome. It is crucial to complement tractography results with a combination of histological or neurophysiological methods to map structural connectivity accurately. Our findings, however, do not diminish the importance of diffusion MRI as a noninvasive tool that offers important quantitative measures related to brain tissue microstructure and white matter architecture. Tractography based on diffusion-weighted MRI (DWI) is widely used for mapping the structural connections of the human brain. Its accuracy is known to be limited by technical factors affecting in vivo data acquisition, such as noise, artifacts, and data undersampling resulting from scan time constraints. It generally is assumed that improvements in data quality and implementation of sophisticated tractography methods will lead to increasingly accurate maps of human anatomical connections. However, assessing the anatomical accuracy of DWI tractography is difficult because of the lack of independent knowledge of the true anatomical connections in humans. Here we investigate the future prospects of DWI-based connectional imaging by applying advanced tractography methods to an ex vivo DWI dataset of the macaque brain. The results of different tractography methods were compared with maps of known axonal projections from previous tracer studies in the macaque. Despite the exceptional quality of the DWI data, none of the methods demonstrated high anatomical accuracy. The methods that showed the highest sensitivity showed the lowest specificity, and vice versa. Additionally, anatomical accuracy was highly dependent upon parameters of the tractography algorithm, with different optimal values for mapping different pathways. These results suggest that there is an inherent limitation in determining long-range anatomical projections based on voxel-averaged estimates of local fiber orientation obtained from DWI data that is unlikely to be overcome by improvements in data acquisition and analysis alone.

We propose an echo planar imaging (EPI) distortion correction method (DR-BUDDI), specialized for diffusion MRI, which uses data acquired twice with reversed phase encoding directions, often referred to as blip-up blip-down acquisitions. DR-BUDDI can incorporate information from an undistorted structural MRI and also use diffusion-weighted images (DWI) to guide the registration, improving the quality of the registration in the presence of large deformations and in white matter regions. DR-BUDDI does not require the transformations for correcting blip-up and blip-down images to be the exact inverse of each other. Imposing the theoretical “blip-up blip-down distortion symmetry” may not be appropriate in the presence of common clinical scanning artifacts such as motion, ghosting, Gibbs ringing, vibrations, and low signal-to-noise. The performance of DR-BUDDI is evaluated with several data sets and compared to other existing blip-up blip-down correction approaches. The proposed method is robust and generally outperforms existing approaches. The inclusion of the DWIs in the correction process proves to be important to obtain a reliable correction of distortions in the brain stem. Methods that do not use DWIs may produce a visually appealing correction of the non-diffusion weighted images, but the directionally encoded color maps computed from the tensor reveal an abnormal anatomy of the white matter pathways. •The proposed EPI distortion correction method, DR-BUDDI, outperforms existing ones.•Blip-up blip-down symmetry principle does not always hold in practice.•Using a structural image and DWIs significantly improves correction quality.•Color and anisotropy maps should also be used to assess the quality of correction.•Artifacts from Gibbs ringing and flow voids may significantly affect correction.

Background Community-associated S. aureus skin and soft-tissue infections are common and recur in 20 to >50% of cases. Decolonization trials have been disappointing for unclear reasons, but may be related to untreated reservoirs. Given recent data that oropharyngeal (OP) S. aureus colonization is common with a prevalence comparable to nasal colonization, we performed a double-blind, placebo controlled trial of the efficacy of oral chlorhexidine gluconate (CHG) for OP S. aureus colonization. Methods We enrolled healthy outpatient children from ages 5 to 17 who were tested for OP S. aureus colonization. Colonized subjects were randomized to 0.12% CHG or placebo gargle twice daily × 7 days. Primary endpoint was OP colonization at the End of Therapy (EOT) visit using an intention to treat (ITT) model. We also measured OP colonization at 28 days and nasal S. aureus colonization at all study visits. Results Among 189 consented subjects, 120 (63%) had OP colonization; 81/120 (66%) were randomized and 67 were analyzable (CHG: N = 33; Placebo: N = 34). Fourteen subjects were not analyzable due to product error or loss to follow-up prior to study drug receipt (figure). In the ITT analysis, EOT OP S. aureus colonization was 45% (15/33) in the CHG group and 79% (27/34) in the placebo group (P = 0.004). In the as treated analysis, OP colonization was 40% (11/29) and 77% (23/30) in the CHG group and placebo groups (P = 0.003). At Day 28 in the ITT model, OP colonization was 61% (20/33) vs. 85% (29/34) in the CHG and placebo groups (P = 0.03). At EOT nasal colonization in those without OP colonization was 11/25 (44%) vs. 15/34 (44%) in those still OP colonized. At Day 28, nasal colonization was 0/18 (0%) in those without OP colonization vs. 19/38 (50%) in those with OP colonization. Conclusion One week of 0.12% oral CHG gargle was more effective than the placebo at eradicating S. aureus OP colonization in S. aureus colonized children. Significant differences persisted at Day 28. Persistent OP colonization at Day 28 was associated with nasal S. aureus colonization, suggesting that nasal colonization may contribute to persistence and relapse of OP S. aureus colonization. Our findings support decolonization trials that include OP S. aureus decolonization as part of a more aggressive S. aureus decolonization strategy. Disclosures All authors: No reported disclosures.

The human immune system is very complex. Understanding it traditionally required specialized knowledge and expertise along with years of study. However, in recent times, the introduction of technologies such as AIoMT (Artificial Intelligence of Medical Things), genetic intelligence algorithms, smart immunological methodologies, etc., has made this process easier. These technologies can observe relations and patterns that humans do and recognize patterns that are unobservable by humans. Furthermore, these technologies have also enabled us to understand better the different types of cells in the immune system, their structures, their importance, and their impact on our immunity, particularly in the case of debilitating diseases such as cancer. The undertaken study explores the AI methodologies currently in the field of immunology. The initial part of this study explains the integration of AI in healthcare and how it has changed the face of the medical industry. It also details the current applications of AI in the different healthcare domains and the key challenges faced when trying to integrate AI with healthcare, along with the recent developments and contributions in this field by other researchers. The core part of this study is focused on exploring the most common classifications of health diseases, immunology, and its key subdomains. The later part of the study presents a statistical analysis of the contributions in AI in the different domains of immunology and an in-depth review of the machine learning and deep learning methodologies and algorithms that can and have been applied in the field of immunology. We have also analyzed a list of machine learning and deep learning datasets about the different subdomains of immunology. Finally, in the end, the presented study discusses the future research directions in the field of AI in immunology and provides some possible solutions for the same.

The electronic properties studied using the X-ray absorption near-edge structure (XANES) spectroscopy performed in the vicinity of O K -, Ca L 3,2 -, Fe L 3,2 -, and Cu L 3,2 -edges demonstrate the reversal of orbital symmetry in CaCu 3 Ti 4 O 12 on Fe 3+ ions substitution. The study of Cu L 3,2 - and Fe L 3,2 -edges confirms that the valence states to be +2 and +3 for Cu and Fe ions, respectively. The O K -edge XANES spectra show a very systematic change leading to a reversal of relative intensities of the spectral features assigned to 3 d (t 2g ) and 3 d (e g ) peaks. This implies that Fe substitution induces the tilted octahedral to the square planar symmetry transformation. This is well supported by the cation distribution and also indicates that there is a strong hybridization of Cu-Fe 3 d and O-2 p orbitals and a weakening of the hybridization of Ti 3 d , Fe 3 d, and O-2 p orbitals.

The current research project was undertaken to explore the therapeutic potential of two potent probiotic Lactobacillus fermentum strains, i.e., PD2 and PH5 in a hyperlipemic healthy adult Wistar rat model, with a particular focus as biotherapeutics for the management of high cholesterol in Indian population. Rats fed on cholesterol-enriched diet supplemented with potential probiotics strain Lactobacillus fermentum PH5 significantly affected serum lipid profile by reducing serum cholesterol (67.21%), triglycerides level (66.21%), and LDL cholesterol level (63.25%) in comparison to rats that received cholesterol-enriched diet (Model) only. Both the strains decreased the cholesterol levels in liver compared with Model group, but PH5 was found to be more effective (30.65% reduction) in liver total cholesterol (TC) lowering action. In addition, the fecal coliforms were significantly reduced besides increased LAB in feces of rats receiving probiotic curd having Lactobacillus fermentum PH5. Our results demonstrated that supplementation with either of the two strains was efficient in reducing serum cholesterol, LDL-cholesterol and TG concentrations in rats compared to those fed the same high-cholesterol diet but without LAB supplementation.

Distributed denial-of-service (DDoS) attacks are significant threats to the cyber world because of their potential to quickly bring down victims. Memcached vulnerabilities have been targeted by attackers using DDoS amplification attacks. GitHub and Arbor Networks were the victims of Memcached DDoS attacks with 1.3 Tbps and 1.8 Tbps attack strengths, respectively. The bandwidth amplification factor of nearly 50,000 makes Memcached the deadliest DDoS attack vector to date. In recent times, fellow researchers have made specific efforts to analyze and evaluate Memcached vulnerabilities; however, the solutions provided for security are based on best practices by users and service providers. This study is the first attempt at modifying the architecture of Memcached servers in the context of improving security against DDoS attacks. This study discusses the Memcached protocol, the vulnerabilities associated with it, the future challenges for different IoT applications associated with caches, and the solutions for detecting Memcached DDoS attacks. The proposed solution is a novel identification-pattern mechanism using a threshold scheme for detecting volume-based DDoS attacks. In the undertaken study, the solution acts as a pre-emptive measure for detecting DDoS attacks while maintaining low latency and high throughput.

Background There is an urgent need for novel and effective treatment options for acute myeloid leukemia (AML). Triptolide, a diterpenoid tri-epoxide compound isolated from the herb Tripterygium wilfordii and its water-soluble pro-drug-Minnelide have shown promising anti-cancer activity. A recent clinical trial for patients with solid tumors confirmed the safety and efficacy at biologically equivalent doses of 0.2 mg/kg/day and lower. Methods Cell viability of multiple AML cell lines as well as patient apheresis samples were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) based assay. Apoptosis was evaluated by estimating the amount of cleaved caspase. AML cell line (THP1-Luc) was implanted in immunocompromised mice and treated with indicated doses of Minnelide. Leukemic burden before and after treatment was evaluated by imaging in an In Vivo Imaging System (IVIS). Results In the current study, we show that Minnelide, at doses below maximum tolerated dose (MTD) demonstrates leukemic clearance of both primary AML blasts and luciferase expressing THP-1 cells in mice. In vitro, multiple primary AML apheresis samples and AML cell lines (THP-1, KG1, Kasumi-1, HL-60) were sensitive to triptolide mediated cell death and apoptosis in low doses. Treatment with triptolide led to a significant decrease in the colony forming ability of AML cell lines as well as in the expression of stem cell markers. Additionally, it resulted in the cell cycle arrest in the G1/S phase with significant downregulation of c-Myc, a major transcriptional regulator mediating cancer cell growth and stemness. Conclusion Our results suggest that Minnelide, with confirmed safety and activity in the clinic, exerts a potent anti-leukemic effect in multiple models of AML at doses easily achievable in patients.

Background of the study To assess the prenatal development of the human liver between 12-36 weeks of gestational age by measuring morphometric parameters using conventional autopsy and to evaluate the morphometric parameters of the human fetus and its liver and their correlation to predict the gestation age. Materials & methods The present study was conducted in the Department of Anatomy, All India Institute of Medical Sciences, Rishikesh, India, on 33 normal fetuses of gestational age 12-36 weeks collected from the Department of Obstetrics and Gynecology of the same institute. which were classified into five groups: A (12-16 weeks), B (17-21 weeks), C (22-26 weeks), D (27-31 weeks), and E (32-36 weeks). The parameters measured were liver weight, liver volume, transverse diameter, sagittal diameter, vertical length, length, and width of all four lobes of the liver, i.e., right, left, caudate and quadrate lobe. Also, general morphometric parameters of the fetuses were measured like fetal body weight, crown-rump length, crown-heel length, biparietal diameter, head circumference, chest circumference, abdominal circumference, hand length, foot length, inner inter-canthal distance, outer inter-canthal distance. The obtained data were statistically analyzed using ANOVA, and Pearson's correlation was assessed. Results There was a statistically significant increase amongst all the fetal general parameters and parameters of liver except bi-parietal diameter, p-value <0.001. The bi-parietal diameter was weakly statistically significant correlated with all other parameters except with chest circumference, crown-heel length, length and width of caudate lobe, and the width of the quadrate lobe and left lobe where it was statistically non-significant. Conclusion Bi-parietal diameter is a statistically non-significant parameter to calculate gestation age. The knowledge of morphological features and normal limits of dimensions of the liver with respect to gestational age is a reliable reference to help to prevent misdiagnosis of various pathological conditions of the liver like cirrhosis, hepatomegaly, fetal anemia, intrauterine growth retardation, congenital anomalies like Down's Syndrome, etc.