Miracle-dz/UniFAR-FTUs huggingface dataset:
The Longitudinal Trajectory of Default Mode Network Connectivity in Healthy Older Adults Varies As a Function of Age and Is Associated with Changes in Episodic Memory and Processing Speed

The default mode network (DMN) supports memory functioning and may be sensitive to preclinical Alzheimer's pathology. Little is known, however, about the longitudinal trajectory of this network's intrinsic functional connectivity (FC). In this study, we evaluated longitudinal FC in 111 cognitively normal older human adults (ages 49–87, 46 women/65 men), 92 of whom had at least three task-free fMRI scans (n = 353 total scans). Whole-brain FC and three DMN subnetworks were assessed: (1) within-DMN, (2) between anterior and posterior DMN, and (3) between medial temporal lobe network and posterior DMN. Linear mixed-effects models demonstrated significant baseline age × time interactions, indicating a nonlinear trajectory. There was a trend toward increasing FC between ages 50–66 and significantly accelerating declines after age 74. A similar interaction was observed for whole-brain FC. APOE status did not predict baseline connectivity or change in connectivity. After adjusting for network volume, changes in within-DMN connectivity were specifically associated with changes in episodic memory and processing speed but not working memory or executive functions. The relationship with processing speed was attenuated after covarying for white matter hyperintensities (WMH) and whole-brain FC, whereas within-DMN connectivity remained associated with memory above and beyond WMH and whole-brain FC. Whole-brain and DMN FC exhibit a nonlinear trajectory, with more rapid declines in older age and possibly increases in connectivity early in the aging process. Within-DMN connectivity is a marker of episodic memory performance even among cognitively healthy older adults. SIGNIFICANCE STATEMENT Default mode network and whole-brain connectivity, measured using task-free fMRI, changed nonlinearly as a function of age, with some suggestion of early increases in connectivity. For the first time, longitudinal changes in DMN connectivity were shown to correlate with changes in episodic memory, whereas volume changes in relevant brain regions did not. This relationship was not accounted for by white matter hyperintensities or mean whole-brain connectivity. Functional connectivity may be an early biomarker of changes in aging but should be used with caution given its nonmonotonic nature, which could complicate interpretation. Future studies investigating longitudinal network changes should consider whole-brain changes in connectivity.
A Security Architecture for the Internet of Things

This paper demonstrates a case for an end-to-end pure Application Security Layer for reliable and confidential communications within an Internet of Things (IoT) constrained environment. To provide a secure key exchange and to setup a secure data connection, Transport Layer Security (TLS) is used, which provides native protection against replay attacks. TLS along with digital signature can be used to achieve non-repudiation within app-to-app communications. This paper studies the use of TLS over the JavaScript Object Notation (JSON) via a The Constrained Application Protocol (CoAP) RESTful service to verify the hypothesis that in this way one can provide end-to-end communication flexibility and potentially retain identity information for repudiation. As a proof of concept, a prototype has been developed to simulate an IoT software client with the capability of hosting a CoAP RESTful service. The prototype studies data requests via a network client establishing a TLS over JSON session using a hosted CoAP RESTful service. To prove reputability and integrity of TLS JSON messages, JSON messages was intercepted and verified against simulated MITM attacks. The experimental results confirm that TLS over JSON works as hypothesised.
Abnormal functional integration across core brain networks in migraine without aura

Background As a complex subjective experience, pain processing may be related to functional integration among intrinsic connectivity networks of migraine patients without aura. However, few study focused on the pattern alterations in the intrinsic connectivity networks of migraine patients without aura. Results Thirty-one migraine patients without aura and 31 age- and education-matched healthy controls participated in this study. After identifying the default mode network, central executive network and salience network as core intrinsic connectivity networks by using independent component analysis, functional connectivity, and effective connectivity during the resting state were used to investigate the abnormalities in intrinsic connectivity network interactions. Migraine patients without aura showed decreased functional connectivity among intrinsic connectivity networks compared with healthy controls. The strength of causal influences from the right frontoinsular cortex to the right anterior cingulate cortex became weaker, and the right frontoinsular cortex to the right medial prefrontal cortex became stronger in migraine patients without aura. Conclusions These changes suggested that the salience network may play a major role in the pathophysiological features of migraine patients without aura and helped us to synthesize previous findings into an aberrant network dynamical framework.
Next-Generation Sequencing Approaches in Genome-Wide Discovery of Single Nucleotide Polymorphism Markers Associated with Pungency and Disease Resistance in Pepper

Pepper is an economically important horticultural plant that has been widely used for its pungency and spicy taste in worldwide cuisines. Therefore, the domestication of pepper has been carried out since antiquity. Owing to meet the growing demand for pepper with high quality, organoleptic property, nutraceutical contents, and disease tolerance, genomics assisted breeding techniques can be incorporated to develop novel pepper varieties with desired traits. The application of next-generation sequencing (NGS) approaches has reformed the plant breeding technology especially in the area of molecular marker assisted breeding. The availability of genomic information aids in the deeper understanding of several molecular mechanisms behind the vital physiological processes. In addition, the NGS methods facilitate the genome-wide discovery of DNA based markers linked to key genes involved in important biological phenomenon. Among the molecular markers, single nucleotide polymorphism (SNP) indulges various benefits in comparison with other existing DNA based markers. The present review concentrates on the impact of NGS approaches in the discovery of useful SNP markers associated with pungency and disease resistance in pepper. The information provided in the current endeavor can be utilized for the betterment of pepper breeding in future.
Reconfiguration of Cortical Networks in MDD Uncovered by Multiscale Community Detection with fMRI

Abstract Major depressive disorder (MDD) is known to be associated with altered interactions between distributed brain regions. How these regional changes relate to the reorganization of cortical functional systems, and their modulation by antidepressant medication, is relatively unexplored. To identify changes in the community structure of cortical functional networks in MDD, we performed a multiscale community detection algorithm on resting-state functional connectivity networks of unmedicated MDD (uMDD) patients (n = 46), medicated MDD (mMDD) patients (n = 38), and healthy controls (n = 50), which yielded a spectrum of multiscale community partitions. we selected an optimal resolution level by identifying the most stable community partition for each group. uMDD and mMDD groups exhibited a similar reconfiguration of the community structure of the visual association and the default mode systems but showed different reconfiguration profiles in the frontoparietal control (FPC) subsystems. Furthermore, the central system (somatomotor/salience) and 3 frontoparietal subsystems showed strengthened connectivity with other communities in uMDD but, with the exception of 1 frontoparietal subsystem, returned to control levels in mMDD. These findings provide evidence for reconfiguration of specific cortical functional systems associated with MDD, as well as potential effects of medication in restoring disease-related network alterations, especially those of the FPC system.
Type 2 diabetes mellitus: distribution of genetic markers in Kazakh population

Background Ethnic differences exist in the frequencies of genetic variations that contribute to the risk of common disease. This study aimed to analyse the distribution of several genes, previously associated with susceptibility to type 2 diabetes and obesity-related phenotypes, in a Kazakh population. Methods A total of 966 individuals belonging to the Kazakh ethnicity were recruited from an outpatient clinic. We genotyped 41 common single nucleotide polymorphisms (SNPs) previously associated with type 2 diabetes in other ethnic groups and 31 of these were in Hardy–Weinberg equilibrium. The obtained allele frequencies were further compared to publicly available data from other ethnic populations. Allele frequencies for other (compared) populations were pooled from the haplotype map (HapMap) database. Principal component analysis (PCA), cluster analysis, and multidimensional scaling (MDS) were used for the analysis of genetic relationship between the populations. Results Comparative analysis of allele frequencies of the studied SNPs showed significant differentiation among the studied populations. The Kazakh population was grouped with Asian populations according to the cluster analysis and with the Caucasian populations according to PCA. According to MDS, results of the current study show that the Kazakh population holds an intermediate position between Caucasian and Asian populations. Conclusion A high percentage of population differentiation was observed between Kazakh and world populations. The Kazakh population was clustered with Caucasian populations, and this result may indicate a significant Caucasian component in the Kazakh gene pool.
The Diagnostic Value of Nuclear Matrix Proteins in Bladder Cancer in the Aspect of Environmental Risk from Carcinogens

Background The interaction of environmental factors with genetic susceptibility and detoxification level seems to be an important causative factor in bladder cancer (BC). The aim of this study was to look for a BC marker panel which reflects the environmental risk. The nuclear matrix protein 22 (NMP22), bladder cancer-4 (BLCA-4), and total level proteins NMP22 and BLCA-4 (NMBL) in BC patients with genetic predisposition NAT2 (classified as slow acetylators, SA), DNA damage (8-OHdG), and detoxification by isoenzyme GSTπ activity were measured. Materials and Methods The urine and blood from 91 BC patients and controls were examined, also according to tumor stage (T) and grade (G). The participants completed a questionnaire in order to evaluate environmental risk. Results Most patients (75.3%) were previous or actual smokers. The levels of 8-OHdG, NMP22, BLCA-4, NMBL, and GSTπ were significantly higher in BC (p ≤ 0.001). The majority of patients (59.3%) were slow acetylators (SA). The highest BLCA-4/8-OHdG correlation was observed in total BC and SA smokers. Conclusions The total pool of nuclear matrix proteins in the urine (NMBL) has a higher diagnostic value in bladder cancer than single proteins. The particular value of BLCA-4 and GSTπ in the aspect of environmental risk was noted.
Feasibility trial for primary stroke prevention in children with sickle cell anemia in Nigeria (SPIN trial)

The vast majority of children with sickle cell anemia (SCA) live in Africa, where evidence‐based guidelines for primary stroke prevention are lacking. In Kano, Nigeria, we conducted a feasibility trial to determine the acceptability of hydroxyurea therapy for primary stroke prevention in children with abnormal transcranial Doppler (TCD) measurements. Children with SCA and abnormal non‐imaging TCD measurements (≥200 cm/s) received moderate fixed‐dose hydroxyurea therapy (∼20 mg/kg/day). A comparison group of children with TCD measurements <200 cm/s was followed prospectively. Approximately 88% (330 of 375) of families agreed to be screened, while 87% (29 of 33) of those with abnormal TCD measurements, enrolled in the trial. No participant elected to withdraw from the trial. The average mean corpuscular volume increased from 85.7 fl at baseline to 95.5 fl at 24 months (not all of the children who crossed over had a 24 month visit), demonstrating adherence to hydroxyurea. The comparison group consisted of initially 210 children, of which four developed abnormal TCD measurements, and were started on hydroxyurea. None of the monthly research visits were missed (n = total 603 visits). Two and 10 deaths occurred in the treatment and comparison groups, with mortality rates of 2.69 and 1.81 per 100 patient‐years, respectively (P = .67). Our results provide strong evidence, for high family recruitment, retention, and adherence rates, to undertake the first randomized controlled trial with hydroxyurea therapy for primary stroke prevention in children with SCA living in Africa.
Culm Form Structure and Physico-mechanical Properties of Neosinocalamus affinisin Growth Process

Culm form structure and main physico-mechanical properties of Neosinocalamus affinis in growth process planted in Lushan,Sichuan were determined and analyzed.The results showed that the internode length and culm diameter increased rapidly with the bamboo forest age before 3 years,then the internode lengh increased slowly and the culm diameter remained relatively stable with the bamboo forest age from 3 to 5 years.When the bamboo forest age was 3-year-old,the average internode length,culm diameter and bamboo wall thickness all reached the utilized level(37.99 cm,32.94 mm,3.46 mm respectively). The values of the basic density,compression strength parallel to grain,shear strength parallel to grain were maximum at the age of 3 years,and they were 0.570 g/cm3,69.475 Mpa,18.833 Mpa respectively,while the maximum value of the radial and tangential shrinking ratio were at age of 1 year,0.339 and 0.330 respectively.The values of physico-mechanical properties were minimum at the bamboo culm age of 2 years.When the bamboo culm was 3-year-old,the physical-mechanical properties satisfied the demand of structural material.
Primary systemic therapy in resectable pancreatic ductal adenocarcinoma using mFOLFIRINOX: A pilot study

Surgery followed by gemcitabine and/or a fluoropyrimidine is standard therapy for resectable PDAC. mFOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2 Day 1, 5‐FU 2400 mg/m2 × 48 h IV, peg‐filgrastim 6 mg SQ day 3, every 14 days) has substantial activity in metastatic PDAC. We wished to determine the tolerability/efficacy of peri‐operative mFOLFIRINOX in resectable PDAC.
The empirical correlations for natural convection heat transfer Al2O3 and ZrO2 nanofluid in vertical sub-channel

Study on convection heat transfer using water-Al2O3 nanofluid as the working fluid in the vertical sub-channel has been conducted. The results of the study have been compared with the water-ZrO2 nanofluid and pure-water as the working fluid. The equipment used in this experiment is a vertical triangular sub-channel, equipped by primary cooling system, heat exchanger and a secondary cooling system. As a heating source used three vertical cylinders that have a uniform heat flux with a pitch to diameter ratio (P/D) 01:16. Cooling is used is water-Al2O3 colloid at 0.05 wt. %. Heat transfer from heating to cooling would occur in natural or forced convection. However, in this study will be discussed only natural convection heat transfer. The results showed that the natural convection heat transfer of water-Al2O3 nanofluid in a triangular sub-channels depending on the position. The results of the correlation as follows,
Upregulation of P2Y1 in neonatal nociceptors regulates heat and mechanical sensitization during cutaneous inflammation

The upregulation of various channels and receptors classically linked to sensory transduction from the periphery tightly correspond with changes in the responsiveness of specific subpopulations of primary afferents to mechanical and heat stimulation of the skin at different ages. Previous reports in adults have suggested that the purinergic adenosine diphosphate receptor, P2Y1 can specifically regulate sensory neuron responsiveness to heat stimuli in addition to neurochemical alterations in primary afferents during cutaneous inflammation. To determine if the upregulation of P2Y1 found in the dorsal root ganglia of neonatal mice with cutaneous inflammation initiated at postnatal day 7 (P7) was responsible for the specific alteration in heat sensitivity found in faster conducting (“A”-fiber) nociceptors, we assessed the response properties of cutaneous afferents using an ex vivo hairy hindpaw skin-saphenous nerve-dorsal root ganglion-spinal cord preparation in conjunction with nerve-targeted knockdown of P2Y1. We found that P2Y1 knockdown during neonatal cutaneous inflammation was sufficient to reduce the sensitization of “A”-fiber nociceptors to heat stimuli. Surprisingly, we also found that nerve-specific downregulation of P2Y1 could reduce the observed sensitization of these afferent subtypes to mechanical deformation of the skin. Immunocytochemical analysis of dorsal root ganglia showed that P2Y1 may mediate its effects through modulation of the injury-induced increase of transient receptor potential vanilloid type 1 receptor. This suggests that the upregulation of P2Y1 in cutaneous nociceptors during early life peripheral inflammation can regulate the sensitization of myelinated nociceptors to both mechanical and heat stimuli possibly through modulation of transient receptor potential vanilloid type 1 expression.
Time to onset of bisphosphonate-related osteonecrosis of the jaws: a multicentre retrospective cohort study.

OBJECTIVES Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to estimate the TTO and associated risk factors in BP-treated patients. SUBJECTS AND METHODS Retrospective analysis of data from 22 secondary care centres in seven countries relevant to 349 patients who developed BP-related ONJ between 2004 and 2012. RESULTS The median (95%CI) TTO was 6.0 years in patients treated with alendronate (n = 88) and 2.2 years in those treated with zoledronate (n = 218). Multivariable Cox regression showed that dentoalveolar surgery was inversely associated, and the use of antiangiogenics directly associated, with the TTO in patients with cancer treated with zoledronate. CONCLUSIONS The incidence of ONJ increases with the duration of BP therapy, with notable differences observed with respect to BP type and potency, route of administration and underlying disease. When data are stratified by BP type, a time of 6.0 and 2.2 years of oral alendronate and intravenous zoledronate therapy, respectively, is required for 50% of patients to develop ONJ. After stratification by disease, a time of 5.3 and 2.2 years of BP therapy is required for 50% of patients with osteoporosis and cancer, respectively, to develop ONJ. These findings have significant implications for the design of future clinical studies and the development of risk-reduction strategies aimed at either assessing or modulating the risk of ONJ associated with BP.
Characterization of Erbium Doped Photonic Crystal Fiber

Photonic crystal fibers (PCFs) which exhibit unique and tremendous optical properties have been undergoing quick growth in recent years. Studies on the characteristics of various types of PCFs have been reported. However, characterization on erbium-doped PCF has not previously been investigated. Therefore, in this paper, an erbium-doped core PCF having 7 rings of hexagonal air holes has been modeled. A perfectly matched layer (PML) is modeled within the PCF structure and simulated using Finite Element Method (FEM) using COMSOL software. The PML is optimized by varying the radius and thickness of the layer. Modal properties of the PCF have been investigated in terms of its effective index of the supported fundamental mode, confinement loss and thickness of the perfectly matched layer. This erbium-doped PCF has a confinement loss of 1.0E-6 at 1500 nm and a maximum effective refractive index of 1.476. This paper gathers useful data, which could be used for studying the characteristics of a PCF.
Parkin protein expression and its impact on survival of patients with advanced colorectal cancer

Objective: Features of colorectal cancer such as natural history, molecular, chromosomal, and epigenetic alterations have been well described. However, there is still a lack of accurate prognostic markers, which is evident by the lower overall survival rates of patients with advanced cancer. Although alterations in parkin protein expression have been described in colorectal cancer, the functional significance of this protein remains unknown. The present study aimed to investigate the involvement of parkin expression in colorectal adenocarcinoma development and progression by evaluating the association between its expression, clinicopathological parameters, and expression of known proteins involved in colorectal cancer. Methods: Tissue microarrays consisting of 73 tumor and 64 normal tissue samples were generated to examine parkin expression and localization by immunohistochemistry. Results: A positive correlation of parkin and APC expression was observed in the superficial, intermediate, and profound regions of all cases (ρ = 0.37; P = 0.001). Parkin expression was also significantly associated with tumors in men (P = 0.049), those of the mucinous subtype (P = 0.028), and of advanced stage (III + IV, P = 0.041). In addition, increased parkin expression was observed in the invasive front tumor region (P = 0.013). More importantly, a positive correlation was found between parkin expression and the overall survival of patients with advanced colorectal cancer (P = 0.019). Multivariate analysis showed that parkin expression was independent of any of the clinicopathological parameters evaluated in relation to patient survival. Conclusions: These results suggest that parkin expression status can be used as a potential independent prognostic marker of survival in advanced colorectal cancer.