Miracle-dz/UniFAR-FTUs huggingface dataset:
Narrative recall in relapsing-remitting multiple sclerosis: A potentially useful speech task for detecting subtle cognitive changes

ABSTRACT Our research studied relapsing-remitting multiple sclerosis (RRMS). In half of the RRMS cases, mild cognitive difficulties are present, but often remain undetected despite their adverse effects on individuals’ daily life. Detecting subtle cognitive alterations using speech analysis have rarely been implemented in MS research. We applied automatic speech recognition technology to devise a speech task with potential diagnostic value. Therefore, we used two narrative tasks adjusted for the neural and cognitive characteristics of RRMS; namely narrative recall and personal narrative. In addition to speech analysis, we examined the information processing speed, working memory, verbal fluency, and naming skills. Twenty-one participants with RRMS and 21 gender-, age-, and education-matched healthy controls took part in the study. All the participants with RRMS achieved a normal performance on Addenbrooke’s Cognitive Examination. The following parameters of speech were measured: articulation and speech rate, the proportion, duration, frequency, and average length of silent and filled pauses. We found significant differences in the temporal parameters between groups and speech tasks. ROC analysis produced high classification accuracy for the narrative recall task (0.877 and 0.866), but low accuracy for the personal narrative task (0.617 and 0.592). The information processing speed affected the speech of the RRMS group but not that of the control group. The higher cognitive load of the narrative recall task may be the cause of significant changes in the speech of the RRMS group relative to the controls. Results suggest that narrative recall task may be effective for detecting subtle cognitive changes in RRMS.
Compact molecular gas structure in the interacting galaxy pair Arp 299 (IC 694-NGC 3690)

High-resolution (about 5-arcsec) CO observations of the interacting galaxy pair Arp 299 (IC 694-NGC 3690) show that about 40 percent of the total molecular gas content is concentrated in two compact regions each of mass 1.4 x 10 to the 9th solar mass. One component lies at the nucleus of IC 694, while the other spans the region of overlap between the two galaxies. The properties of the latter component are consistent with its being a region of greatly enhanced star formation. However, the unusually high L(FIR)/M(H2) ration for IC 694, together with the presence of a flat-spectrum radio source, suggest that its remarkable luminosity may be largely produced by nonthermal processes. 22 references.
Integrated versus non-integrated peripheral intravenous catheters: a cross-sectional survey of nurse experiences.

BACKGROUND Integrated peripheral intravenous catheters (PIVCs) demonstrate clinical efficacy, however, device complexity and design differences may be a potential barrier to implementation. AIMS To assess nurse acceptability of integrated PIVC systems. METHODS A cross-sectional survey was nested within a multicentre randomised controlled trial. One hundred nurses caring for patients with integrated and non-integrated PIVCs completed a 17-item survey about key differences between devices (eg function and appearance, perceived patient comfort and skin injuries). FINDINGS Most nurses reported the integrated PIVC wings prevented device movement (80%), achieved patient comfort in areas of flexion (78%), and no patients developed skin injuries (100%). Nurses rated the ease of accessing and overall confidence using the integrated PIVC as significantly higher than the non-integrated design (P<0.001). CONCLUSION The integrated PIVC received positive feedback from nurses and had few barriers to implementation.
Global dynamics of a piece-wise epidemic model with switching vaccination strategy

A piece-wise epidemic model of a switching vaccination program, implemented once the number of people exposed to a disease-causing virus reaches a critical level, is proposed. In addition, variation or uncertainties in interventions are examined with a perturbed system version of the model. We also analyzed the global dynamic behaviors of both the original piece-wise system and the perturbed version theoretically, using generalized Jacobian theory, Lyapunov constants for a non-smooth vector field and a generalization of Dulac's criterion. The main results show that, as the critical value varies, there are three possibilities for stabilization of the piece-wise system: (i) at the disease-free equilibrium; (ii) at the endemic states for the two subsystems or (iii) at a generalized equilibrium which is a novel global attractor for non-smooth systems. The perturbed system exhibits new global attractors including a pseudo-focus of parabolic-parabolic (PP) type, a pseudo-equilibrium and a crossing cycle surrounding a sliding mode region. Our findings demonstrate that an infectious disease can be eradicated either by increasing the vaccination rate or by stabilizing the number of infected individuals at a previously given level, conditional upon a suitable critical level and the parameter values.
Lipin1 plays complementary roles in myofibre stability and regeneration in dystrophic muscles

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disorder caused by dystrophin mutations, leading to the loss of sarcolemmal integrity, and resulting in progressive myofibre necrosis and impaired muscle function. Our previous studies suggest that lipin1 is important for skeletal muscle regeneration and myofibre integrity. Additionally, we discovered that mRNA expression levels of lipin1 were significantly reduced in skeletal muscle of DMD patients and the mdx mouse model. To understand the role of lipin1 in dystrophic muscle, we generated dystrophin/lipin1 double knockout (DKO) mice, and compared the limb muscle pathology and function of wild‐type B10, muscle‐specific lipin1 deficient (lipin1Myf5cKO), mdx and DKO mice. We found that further knockout of lipin1 in dystrophic muscle exhibited a more severe phenotype characterized by increased necroptosis, fibrosis and exacerbated membrane damage in DKO compared to mdx mice. In barium chloride‐induced muscle injury, both lipin1Myf5cKO and DKO showed prolonged regeneration at day 14 post‐injection, suggesting that lipin1 is critical for muscle regeneration. In situ contractile function assays showed that lipin1 deficiency in dystrophic muscle led to reduced specific force production. Using a cell culture system, we found that lipin1 deficiency led to elevated expression levels of necroptotic markers and medium creatine kinase, which could be a result of sarcolemmal damage. Most importantly, restoration of lipin1 inhibited the elevation of necroptotic markers in differentiated primary lipin1‐deficient myoblasts. Overall, our data suggests that lipin1 plays complementary roles in myofibre stability and muscle function in dystrophic muscles, and overexpression of lipin1 may serve as a potential therapeutic strategy for dystrophic muscles.
Thirty Years of Continuum and Emission-Line Variability in NGC 5548

We analyze a total of 827 optical spectra of NGC 5548 obtained over the 30 year period 1972-2001 for the purpose of studying the long-term behavior of the broad Hβ line profile. The variability characteristics, such as mean continuum and emission-line fluxes, rms variability amplitude, autocorrelation functions, and cross-correlation results, are found to be similar for CCD spectra obtained during the period 1989-2001 and for archival pre-CCD spectra from 1972 to 1988. The only significant difference between these two sets of data is that the mean Hβ flux is higher for 1972-1988. While the Hβ profile can vary dramatically on timescales of months to years, the mean profiles for these two periods are similar, but not identical. We searched for correlations among Hβ profile parameters (such as line width, line centroid, blue-to-red ratio of the line wing fluxes) and investigated their relationship to the continuum flux. Only trivial correlations were found, specifically the correlation between continuum and line fluxes and the anticorrelation between line width and line flux, the latter following from the former and from the inverse correlation between line time lag and line width expected for gravitationally dominated motion.
Prediagnostic serum glyceraldehyde‐derived advanced glycation end products and mortality among colorectal cancer patients

Glyceraldehyde‐derived advanced glycation end products (glycer‐AGEs) could contribute to colorectal cancer development and progression due to their pro‐oxidative and pro‐inflammatory properties. However, the association of glycer‐AGEs with mortality after colorectal cancer diagnosis has not been previously investigated. Circulating glycer‐AGEs were measured by competitive ELISA. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for associations of circulating glycer‐AGEs concentrations with CRC‐specific and all‐cause mortality among 1034 colorectal cancer (CRC) cases identified within the European Prospective Investigation into Cancer and Nutrition (EPIC) study between 1993 and 2013. During a mean of 48 months of follow‐up, 529 participants died (409 from CRC). Glycer‐AGEs were statistically significantly positively associated with CRC‐specific (HRQ5 vs Q1 = 1.53, 95% CI: 1.04‐2.25, Ptrend = .002) and all‐cause (HRQ5 vs Q1 = 1.62, 95% CI: 1.16‐2.26, Ptrend < .001) mortality among individuals with CRC. There was suggestion of a stronger association between glycer‐AGEs and CRC‐specific mortality among patients with distal colon cancer (per SD increment: HRproximal colon = 1.02, 95% CI: 0.74‐1.42; HRdistal colon = 1.51, 95% CI: 1.20‐1.91; Peffect modification = .02). The highest HR was observed among CRC cases in the highest body mass index (BMI) and glycer‐AGEs category relative to lowest BMI and glycer‐AGEs category for both CRC‐specific (HR = 1.78, 95% CI: 1.02‐3.01) and all‐cause mortality (HR = 2.15, 95% CI: 1.33‐3.47), although no statistically significant effect modification was observed. Our study found that prediagnostic circulating glycer‐AGEs are positively associated with CRC‐specific and all‐cause mortality among individuals with CRC. Further investigations in other populations and stratifying by tumor location and BMI are warranted.
Comparative molecular docking analysis for analyzing the inhibitory effect of Anakinra and Ustekinumab against IL17F

Abstract Interleukin 17 F is a member of IL-17 cytokine family with a 50% structural homology to IL-17A and plays a significant role either alone or in combination with IL-17A towards inflammation in Rheumatoid arthritis (RA). A growing number of drugs targeting IL-17 pathway are being tested against population specific disease markers. The major objective of this research was to investigate the anti-inflammatory effect of Anakinra (an IL-1 R1 inhibitor) and Ustekinumab (an IL-12 and IL-23 inhibitor) by targeting IL17F. The three dimensional structures of IL17F was taken from PDB while structures of drugs were taken from PubChem database. Docking was performed using MOE and Schrodinger ligand docking software and binding energies, including s-score using London-dG fitness function and glide score using glide internal energy function, between drug and targets were compared. Furthermore, Protein-Drug complex were subjected to 150 ns Molecular Dynamics (MD) Simulations using Schrodinger’s Desmond Module. Docking and MD simulation results suggest anakinra as a more potent IL17F inhibitor and forming a more structurally stable complex. Communicated by Ramaswamy H. Sarma
The potential implication of MDR1 and NAC1 genetic polymorphisms on resistance to antiepileptic drugs among a Jordanian epileptic population: a cross-sectional study

Abstract Background Resistance to antiepileptic drugs (AEDs) remains one of the main challenges to neurologists. Polymorphisms of drug efflux transporters such as multidrug resistance (MDR1) gene and target sites such as the nucleus accumbens–associated 1 (NAC1) gene have been suggested to influence the responsiveness to treatment. Aim Evaluation of the association of MDR1 and NAC1 polymorphisms with AEDs resistance among Jordanian epileptic patients. Subjects and methods 86 Jordanian epileptics were included in the study. DNA was extracted and genotyping was conducted by polymerase chain reaction followed by sequencing. Nine single nucleotide polymorphisms (SNPs) on the MDR1 gene and six SNPs on the NAC1 gene were investigated. Results MDR1 and NAC1 polymorphisms don’t seem to influence the resistance to AEDs at the genotype or allele level. However, a strong association was found between MDR1 rs2032588 (OR = 5; 95%CI = [1.3–18.8], p = 0.01) and AEDs resistance among males at the allele level. Also, data revealed an association between MDR1 rs1128503 and AEDs resistance among females at the allele level. Conclusion The data suggest that MDR1 and NAC1 polymorphisms do not influence the AEDs resistance among Jordanian epileptics. However, there is a gender-dependent association between MDR1 polymorphisms and resistance to AEDs at two SNPs (rs2032588 and rs1128503).
Conclusions of the SIGNAL study in Huntington and implications for treatment of other slowly progressive neurodegenerative diseases

Astrogliosis is associated with slowly progressive neurodegenerative/neuroinflammatory diseases, including Huntington’s (HD) and Alzheimer’s (AD). In their normal homeostatic state, astrocytes extend numerous specialised cytoplasmic projections that fully cover brain capillaries and facilitate glucose uptake while also extending projections to synapses that recycle 80% of released excitatory transmitters.1 However, under conditions of diseaserelated stress, they undergo a dramatic transformation in which their actin cytoskeleton collapses, they retract cytoplasmic projections, build up secretory machinery, and switch to synthesis and secretion of soluble biological effectors some ofwhichhave neurotoxic activity and others recruit and activate other inflammatory cells.2 In two recent publications,3.4 we investigated the signals that trigger the striking morphological transformation of astrocytes. Based on the previouswork of our own and others, wewere aware of the important role of the semaphorin 4D:plexin-B1/B2 pathway in triggering collapse of the actin cytoskeleton. Binding of Semaphorin 4D (SEMA4D) ligand to the extracellular domain of plexin-B receptors triggers activation of their cytoplasmic Rho-GTPase activating domain. This leads to the inactivation of Rho kinase which is normally required to initiate a chain of events that prevents cofilin-driven depolymerisation of actin filaments.5 We, therefore, investigated expression of SEMA4D and
Bromodomain-containing protein 4 (BRD4): a key player in inflammatory bowel disease and potential to inspire epigenetic therapeutics

ABSTRACT Introduction Inflammatory bowel diseases (IBDs) are debilitating chronic inflammatory disorders with increasing prevalence worldwide. Epigenetic regulator bromodomain-containing protein 4 (BRD4) is critical in controlling gene expression of IBD-associated inflammatory cytokine networks. BRD4 as a promising therapeutic target is also tightly associated with many other diseases, such as airway inflammation and fibrosis, cancers, infectious diseases and central nervous system disorders. Areas covered This review briefly summarized the critical role of BRD4 in the pathogenesis of IBDs and the current clinical landscape of developing bromodomain and extra terminal domain (BET) inhibitors. The challenges and opportunities as well as future directions of targeting BRD4 inhibition for potential IBD medications were also discussed. Expert opinion Targeting BRD4 with potent and specific inhibitors may offer novel effective therapeutics for IBD patients, particularly those who are refractory to anti-TNFα therapy and IBD-related profibrotic. Developing highly specific BRD4 inhibitors for IBD medications may help erase the drawbacks of most current pan-BET/BRD4 inhibitors, such as off-target effects, poor oral bioavailability, and low gut mucosal absorbance. Novel strategies such as combinatorial therapy, BRD4-based dual inhibitors and proteolysis targeting chimeras (PROTACs) may also have great potential to mitigate side effects and overcome drug resistance during IBD treatment.
The structural mechanism for transcription activation by Caulobacter crescentus GcrA

Abstract Canonical bacterial transcription activators bind to their cognate cis elements at the upstream of transcription start site (TSS) in a form of dimer. Caulobacter crescentus GcrA, a non-canonical transcription activator, can activate transcription from promoters harboring its cis element at the upstream or downstream of TSS in a form of monomer. We determined two cryo-EM structures of C. crescentus GcrA-bound transcription activation complexes, GcrA TACU and GcrA TACD, which comprise GcrA, RNAP, σ70 and promoter DNA with GcrA cis elements at either the upstream or downstream of TSS at 3.6 and 3.8 Å, respectively. In the GcrA-TACU structure, GcrA makes bipartite interactions with both σ70 domain 2 (σ702) and its cis element, while in the GcrA-TACD structure, GcrA retains interaction with σ702 but loses the interaction with its cis element. Our results suggest that GcrA likely forms a functionally specialized GcrA-RNAP-σA holoenzyme, in which GcrA first locates its cis element and then facilitates RNAP to load on core promoter at its proximal region. The sequence-specific interaction of GcrA and DNA is disrupted either at the stage of RPo formation or promoter escape depending on the location of GcrA cis elements relative to TSS.
Factors that affect the outcomes of root canal treatment and retreatment - a reframing of the principles.

This paper undertakes a broad and comprehensive synthesis of relevant clinical, biological, biomechanical, technical and healthcare services data to understand the factors affecting outcomes of periapical healing after root canal (re)treatment. The medical and dental evidence-based era (1980-present) is contextualised with the earlier evidence drive in endodontics (1911-present) triggered by the focal infection era. The current evidence-based approach has a sharper focus on evidence quality and derivation of practice guidelines. Contrary views question whether guideline-driven, or expertise-development-driven endeavours would best serve outcome improvement in society. The endodontic discipline functions in a broad healthcare framework and sustains industrial, economic and trend pressures that may be deemed to influence outcomes. The nature of root canal treatment and the challenges in determining the factors that affect its outcomes is discussed. The factors potentially affecting periapical healing after root canal treatment are classified into pre-operative, intra-operative and post-operative groups. These categories subsume multiple elements with interactive influences, creating a complex picture, further confounded by some apparently surprising, counter-intuitive and contradictory findings. The technical versus biological conundrum in root canal treatment continues to cause cognitive dissonance. However, due reflection and cross-discipline-synthesis resolve the apparent data conflicts into a very simple, consistent and plausible picture of how root canal treatment works and the key factors that affect periapical healing. Root canal retreatment is considered mainly in the context of its differences from primary treatment as the majority of factors influencing outcomes are common to both. The exceptional difference is that retreatments have a proportionately reduced probability of healing by virtue of compromised apical root canal ramification access or modified host/infection interactions. Root canal (re)treatment outcomes are dominantly influenced by the nature of prior dynamic host/infection interaction (pre-operative patient factors) and how the direction of this dynamic is influenced by two factors: 1) the active efficacy of the operators' root canal treatment protocol to sustain a microbial ecological shift (intra-operative treatment factors); and 2) the passive ability of the functional tooth (and its restoration margin) to maintain its integrity to resist infection reversal (post-operative restorative factors).
Isothermal equation of state for gold with a He-pressure medium

The isothermal equation of state (EOS) for gold has been determined by powder x-ray diffraction experiments up to 123 GPa at room temperature. We have performed experiments independently in two institutions to check the consistency of the results. A He-pressure medium was used to minimize the effect of uniaxial stress on the sample volume and ruby pressures. The stress state in the He-pressure medium gradually becomes nonhydrostatic above about 30 GPa, with the magnitude of the uniaxial stress largely depending on experiments. Since the measured lattice spacings deviate under different stress states, it is a likely cause of the disagreement of the EOS parameters found in the literature. The lattice spacing ${d}_{111}$ for the 111 reflection is least affected by the uniaxial stress in the case of gold. Hence we have calculated the sample volume from ${d}_{111}$ and fitted the obtained pressure-volume data to the Vinet form of EOS. The bulk modulus ${B}_{0}$ at atmospheric pressure was fixed to 167 GPa, a value well established by ultrasonic measurements. The fit gives the pressure derivative of the bulk modulus at atmospheric pressure as ${B}_{0}^{\ensuremath{'}}=5.5(1)$ for the current ruby pressure scale after Zha et al. [Proc. Natl. Acad. Sci. U.S.A. 97, 13494 (2000)]. Alternatively, if we use a different calibration of this standard [Phys. Rev. B 75, 024115 (2007)], we obtain ${B}_{0}^{\ensuremath{'}}=5.9(1)$, which is in excellent agreement with the ultrasonic measurements and first-principles calculations. Discussions are given to the use of gold as a pressure standard and the hydrostaticity of the He-pressure medium.
Salt-induced phosphoproteomic changes in the subfornical organ in rats with chronic kidney disease

Abstract Objectives Subfornical organ (SFO) is vital in chronic kidney disease (CKD) progression caused by high salt levels. The current study investigated the effects of high salt on phosphoproteomic changes in SFO in CKD rats. Methods 5/6 nephrectomized rats were fed a normal-salt diet (0.4%) (NC group) or a high-salt diet (4%) (HC group) for three weeks, while sham-operated rats were fed a normal-salt diet (0.4%) (NS group). For phosphoproteomic analysis of SFO in different groups, TiO2 enrichment, isobaric tags for relative and absolute quantification (iTRAQ) labeling, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used. Results There were 6808 distinct phosphopeptides found, which corresponded to 2661 phosphoproteins. NC group had 168 upregulated and 250 downregulated phosphopeptides compared to NS group. Comparison to NC group, HC group had 154 upregulated and 124 downregulated phosphopeptides. Growth associated protein 43 (GAP43) and heat shock protein 27 (Hsp27) were significantly upregulated phosphoproteins and may protect against high-salt damage. Differential phosphoproteins with tight functional connection were synapse proteins and microtubule-associated proteins, implying that high-salt diet disrupted brain’s structure and function. Furthermore, differential phosphoproteins in HC/NC comparison group were annotated to participate in GABAergic synapse signaling pathway and aldosterone synthesis and secretion, which attenuated inhibitory neurotransmitter effects and increased sympathetic nerve activity (SNA). Discussion This large scale phosphoproteomic profiling of SFO sheds light on how salt aggravates CKD via the central nervous system.