Miracle-dz/UniFAR-FTUs huggingface dataset:
Visfatin Induces Senescence of Human Dental Pulp Cells

Dental pulp plays an important role in the health of teeth. The aging of teeth is strongly related to the senescence of dental pulp cells. A novel adipokine, visfatin, is closely associated with cellular senescence. However, little is known about the effect of visfatin on the senescence of human dental pulp cells (hDPCs). Here, it was found that in vivo visfatin levels in human dental pulp tissues increase with age and are upregulated in vitro in hDPCs during premature senescence activated by H2O2, suggesting a correlation between visfatin and senescence. In addition, visfatin knockdown by small interfering RNA led to the reduction in hDPC senescence; however, treatment with exogenous visfatin protein induced the senescence of hDPCs along with increased NADPH consumption, which was reversed by FK866, a chemical inhibitor of visfatin. Furthermore, visfatin-induced senescence was associated with both the induction of telomere damage and the upregulation of senescence-associated secretory phenotype (SASP) factors as well as NF-κB activation, which were all inhibited by FK866. Taken together, these results demonstrate, for the first time, that visfatin plays a pivotal role in hDPC senescence in association with telomere dysfunction and the induction of SASP factors.
THE EXPRESSION PATTERN OF DEATH ASSOCIATED PROTEIN KINASE1 IN NORMAL DORSAL ROOT GANGLION NEURONS AND FOLLOWING PERIPHERAL NERVE INJURY

Death-associated protein kinase1 (DAPK1) is a calcium/calmodulin (Ca2+/CaM) regulated serine/threonine kinase. An increasing body of evidence supports the significance of DAPK1 protein in cancer and CNS diseases. The role of DAPK in peripheral nerve regeneration and neuropathic pain remains completely unexplored. The aim of this study is to investigate the expression pattern of DAPK1 along with key proand anti-apoptotic cell signaling molecules (p53, Bax, Akt, ERK5, p38) and to verify the possibilities of DAPK1-NMDA NR2B relationship in dorsal root ganglion neurons (DRG) after 2 hours, 7 days and 14 days following a sciatic nerve injury. Gene expression analysis and immunohistochemistry were used to assess the effects of nerve injury. ATF3 was used as a neuronal injury marker. The results showed that DAPK1 mRNA was expressed and translated to functional protein in normal DRG neurons. Soon after a sciatic nerve injury (2 hours), DAPK1 was significantly up-regulated (p<0.05, 2.2 fold) in the injured L4 and L5 DRG compared with the contralateral uninjured side. However, 7 days after axotomy a profound decrease was observed in the DAPK1 level, with a further reduction that reached its minimum level at 14 days postoperatively. In addition, 7 days after injury, most of the DAPK1 positive injured neurons (76.11%) were ATF3 positive, while after 14 days DAPK1 immunoreactivity significantly decreased (53.89%) in injured ATF3 positive neurons. Interestingly, DAPK1, p53 and Bax exhibited a similar expression pattern in axotomized lumbar DRG. The results also revealed that a sciatic nerve injury had no effects on the gene expression of ERK5, p38 and Akt at every time point. Moreover, NMDA NR2B mRNA expression increased after 7 days and continued to up-regulate significantly until 14 days postoperatively (p<0.05, 3.6 fold). In contrast, our immunofluorescence results showed a decrease in the protein level in DRG neurons during this time period; but a strong positive NMDA NR2B immunoreactivety appeared in the satellite cells that surround the injured large-sized neurons in L4 and L5 DRG neurons. In addition, immunofluorescence double labelling revealed that DAPK1 and NMDA NR2B are co-localized in normal and injured DRG neurons. In conclusion, the down-regulations of DAPK1 following sciatic nerve injury,
Deep learning-based automated speech detection as a marker of social functioning in late-life depression

Abstract Background Late-life depression (LLD) is associated with poor social functioning. However, previous research uses bias-prone self-report scales to measure social functioning and a more objective measure is lacking. We tested a novel wearable device to measure speech that participants encounter as an indicator of social interaction. Methods Twenty nine participants with LLD and 29 age-matched controls wore a wrist-worn device continuously for seven days, which recorded their acoustic environment. Acoustic data were automatically analysed using deep learning models that had been developed and validated on an independent speech dataset. Total speech activity and the proportion of speech produced by the device wearer were both detected whilst maintaining participants' privacy. Participants underwent a neuropsychological test battery and clinical and self-report scales to measure severity of depression, general and social functioning. Results Compared to controls, participants with LLD showed poorer self-reported social and general functioning. Total speech activity was much lower for participants with LLD than controls, with no overlap between groups. The proportion of speech produced by the participants was smaller for LLD than controls. In LLD, both speech measures correlated with attention and psychomotor speed performance but not with depression severity or self-reported social functioning. Conclusions Using this device, LLD was associated with lower levels of speech than controls and speech activity was related to psychomotor retardation. We have demonstrated that speech activity measured by wearable technology differentiated LLD from controls with high precision and, in this study, provided an objective measure of an aspect of real-world social functioning in LLD.
Experience with antiretroviral electronic adherence monitoring among young African American men who have sex with men living with HIV: findings to inform a triaged real-time alert intervention

ABSTRACT We performed a pilot study among young African-American men who have sex with men (AAMSM) of real-time electronic adherence monitoring (EAM) in Chicago to explore acceptability and feasibility of EAM and to inform intervention development. We recruited 40 young AAMSM living with HIV on ART to participate in up to 3 months of monitoring with the Wisepill device. Participants were interviewed at baseline, in response to the first true adjudicated 1-dose, 3-day, and 7-day misses, and at the end of monitoring. Reasons for missing doses and the acceptability and feasibility of electronic monitoring were assessed using mixed methods. The median participant observation time was 90 days (N = 40). For 21 participants with 90 days of follow-up, <90% and <80% adherence occurred in 82% and 79%, respectively in at least one of their monitored months (n = 63 monitored months). The participants generally found the proposed intervention acceptable and useful. Although seven participants said the device attracted attention, none said it led to disclosure of their HIV status. This study found real-time EAM to be generally acceptable and feasible among YAAMSM living with HIV in Chicago. Future work will develop a triaged real-time EAM intervention including text alerts following detection of nonadherence.
Assessment of neovascularization during bone healing using contrast-enhanced ultrasonography in a canine tibial osteotomy model: a preliminary study

Blood perfusion of skeletal muscle and callus was evaluated using contrast-enhanced ultrasonography (CEUS) in a canine osteotomy model to determine the applicability of CEUS in the assessment of neovascularization during fracture healing and to compare the vascular signals on CEUS between external skeletal fixation and cast-applied dogs. In 6 Beagle dogs, a simple transverse osteotomy was performed at the left tibial shaft and external skeletal fixation (n = 3) or a cast (n = 3) was applied. Radiography, power Doppler ultrasonography (power Doppler), and CEUS were performed until complete union was achieved. On CEUS, vascular changes were quantitatively evaluated by measuring peak intensity (PI) and time to PI in the soft tissue and callus and by counting the vascular signals. Vascular signals from the soft tissue were detected on power Doppler and CEUS on day 2. Significantly more vascular signals were detected by CEUS than by power Doppler. On CEUS, PI in the surrounding soft tissue was markedly increased after the fracture line appeared indistinctively changed on radiography in all dogs. In the cast-applied dogs, vascular signals from the periosteal and endosteal callus were detected on CEUS before mineralized callus was observed on radiography. CEUS was useful in assessing the vascularity of soft tissue and callus, particularly in indirect fracture healing, and provided indications of a normally healing fracture.
Cholinergic White Matter Lesions, AD-Signature Cortical Thickness, and Change in Cognition: The Northern Manhattan Study.

BACKGROUND How cerebrovascular disease and neurodegeneration affect each other to impact cognition is not yet known. We aimed to test whether Alzheimer's disease-signature (AD) cortical thickness mediates the association between cholinergic white matter lesion load and change in domain-specific cognition. METHODS Clinically stroke-free participants from the Northern Manhattan Study with both regional white matter hyperintensity volume (WMHV) and gray matter measurements were included (N = 894). Tract-specific WMHVs were quantified through FSL using the Johns Hopkins University white matter tract atlas. We used Freesurfer 5.1 to estimate regional cortical thickness. We fit structural equation models, including multiple indicator latent change score models, to examine associations between white matter hyperintensity volume (WMHV) in cholinergic tracts, AD-signature region cortical thickness (CT), and domain-specific cognition. RESULTS Our sample (N = 894) had a mean (SD) age = 70 (9) years, years of education = 10 (5), 63% women, and 67% Hispanics/Latinos. Greater cholinergic WMHV was significantly related to worse processing speed at baseline (standardized β = -0.17, SE = 0.05, p = .001) and over time (standardized β = -0.28, SE = 0.09, p = .003), with a significant indirect effect of AD-signature region CT (baseline: standardized β = -0.02, SE = 0.01, p = .023; change: standardized β = -0.03, SE = 0.02, p = .040). CONCLUSIONS Cholinergic tract WMHV is associated with worse processing speed, both directly and indirectly through its effect on AD-signature region CT.
The constitutive high affinity Met binding site in the kringle domain is dispensable for the signaling activity of hepatocyte growth factor.

Activation of a tyrosine kinase receptor Met by hepatocyte growth factor (HGF) requires binding of proteolytically activated, two-chain (tc) HGF, but the biochemical detail of this ligand-receptor interaction specificity remains elusive because biologically inactive single-chain (sc) HGF can also bind to Met with high affinity. We found that this proteolysis-independent Met binding can be eliminated by mutagenesis introduced in the kringle domain without losing the ability to bind and activate cellular Met receptor after proteolytic activation, arguing against this site's involvement in the physiological signaling. This non-signal producing Met-HGF interaction can also be eliminated by addition of a heparin mimetic sucrose octasulfate (SOS). By including SOS in the running buffer, we succeeded in detecting cleavage-dependent tcHGF-Met complex formation by size exclusion chromatography.
Subfoveal Choroidal Thickness and Its Intereye Differences in Fuchs Uveitis Syndrome Evaluated Using Optical Coherent Tomography

ABSTRACT Purpose: To measure the subfoveal choroidal thickness (SFCT) and assess intereye subfoveal choroidal thickness difference (ISFCTD) in patients with unilateral Fuchs Uveitis Syndrome (FUS) compared with healthy controls. Methods: Forty-two patients with unilateral FUS were included in this observational retrospective study. SFCT in both eyes was measured in patients and controls using optical coherent tomography. The measurements were analyzed and compared as follows: for SFTC-affected eye vs fellow eye (FUS); affected eye (FUS) vs right control eye; fellow eye (FUS) vs left control eye; for ISFCTD – FUS patients vs controls. In addition, measurement error analysis was performed. Results: No significant differences in SFCT between the compared eyes were found (p > .05). The mean ISFCTD was 57.24 ± 40.8 µm in FUS patients and 30.33 ± 25.48 µm in controls (p < .,001). Conclusion: The ISFCTD was higher in FUS patients than in controls. There were no statistically significant differences in SFCT between the compared eyes.
Transgenic expression of GFP-LC3 perturbs autophagy in exocrine pancreas and acute pancreatitis responses in mice

ABSTRACT Pancreatitis is a common, sometimes fatal, disease of exocrine pancreas, initiated by damaged acinar cells. Recent studies implicate disordered macroautophagy/autophagy in pancreatitis pathogenesis. ATG8/LC3 protein is critical for autophagosome formation and a widely used marker of autophagic vacuoles. Transgenic GFP-LC3 mice are a valuable tool to investigate autophagy ; however, comparison of homeostatic and disease responses between GFP-LC3 and wild-type (WT) mice has not been done. We examined the effects of GFP-LC3 expression on autophagy, acinar cell function, and experimental pancreatitis. Unexpectedly, GFP-LC3 expression markedly increased endogenous LC3-II level in pancreas, caused by downregulation of ATG4B, the protease that deconjugates/delipidates LC3-II. By contrast, GFP-LC3 expression had lesser or no effect on autophagy in liver, lung and spleen. Autophagic flux analysis showed that autophagosome formation in GFP-LC3 acinar cells increased 3-fold but was not fully counterbalanced by increased autophagic degradation. Acinar cell (ex vivo) pancreatitis inhibited autophagic flux in WT and essentially blocked it in GFP-LC3 cells. In vivo pancreatitis caused autophagy impairment in WT mice, manifest by upregulation of LC3-II and SQSTM1/p62, increased number and size of autophagic vacuoles, and decreased level of TFEB, all of which were exacerbated in GFP-LC3 mice. GFP-LC3 expression affected key pancreatitis responses; most dramatically, it worsened increases in serum AMY (amylase), a diagnostic marker of acute pancreatitis, in several mouse models. The results emphasize physiological importance of autophagy for acinar cell function, demonstrate organ-specific effects of GFP-LC3 expression, and indicate that application of GFP-LC3 mice in disease models should be done with caution.Abbreviations: AP: acute pancreatitis; Arg-AP: L-arginine-induced acute pancreatitis; ATG: autophagy-related (protein); AVs: autophagic vacuoles; CCK: cholecystokinin-8; CDE: choline-deficient, D,L-ethionine supplemented diet; CER: caerulein (ortholog of CCK); CTSB: cathepsin B; CTSD: cathepsin D; CTSL: cathepsin L; ER: endoplasmic reticulum; LAMP: lysosomal-associated membrane protein; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; TEM: transmission electron microscopy; TFEB: transcription factor EB; ZG: zymogen granule(s).
Contribution of CSF biomarkers to early‐onset Alzheimer's disease and frontotemporal dementia neuroimaging signatures

Prior studies have described distinct patterns of brain gray matter and white matter alterations in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), as well as differences in their cerebrospinal fluid (CSF) biomarkers profiles. We aim to investigate the relationship between early‐onset AD (EOAD) and FTLD structural alterations and CSF biomarker levels. We included 138 subjects (64 EOAD, 26 FTLD, and 48 controls), all of them with a 3T MRI brain scan and CSF biomarkers available (the 42 amino acid‐long form of the amyloid‐beta protein [Aβ42], total‐tau protein [T‐tau], neurofilament light chain [NfL], neurogranin [Ng], and 14‐3‐3 levels). We used FreeSurfer and FSL to obtain cortical thickness (CTh) and fraction anisotropy (FA) maps. We studied group differences in CTh and FA and described the “AD signature” and “FTLD signature. ” We tested multiple regression models to find which CSF‐biomarkers better explained each disease neuroimaging signature. CTh and FA maps corresponding to the AD and FTLD signatures were in accordance with previous literature. Multiple regression analyses showed that the biomarkers that better explained CTh values within the AD signature were Aβ and 14‐3‐3; whereas NfL and 14‐3‐3 levels explained CTh values within the FTLD signature. Similarly, NfL levels explained FA values in the FTLD signature. Ng levels were not predictive in any of the models. Biochemical markers contribute differently to structural (CTh and FA) changes typical of AD and FTLD.
End Points, Collection, Processing, and Time: Four Key Elements to Consider When Planning for Use of Handheld Devices in a Drug Development Setting

Digital technology is rapidly enhancing the ability of electronic data capture. In drug development, use of handheld devices in clinical trials is part of this digital revolution. When implementing these new technologies, it is imperative that the data quality remains uncompromised. Therefore, attention to data collection details, including setting appropriate hierarchical relationships, standardization of data collection procedures, and appropriate data processing for quality control, should be rigorously planned.
Evolution Strategy-Based Many-Objective Evolutionary Algorithm Through Vector Equilibrium

In recent years, numerous many-objective evolutionary algorithms (MaOEAs) have been developed to search for well-diversified and well-converged Pareto optimal solutions for high-dimensional many-objective optimization problems (MaOPs). However, existing MaOEAs have to tackle some daunting challenges, including the emergence of dominance resistance solutions, effective diversity preservation scheme, management of a large population size, extremely high computational complexity, sensitivity to the shape of Pareto front (PF), and overly relying on high-quality reference points. In this article, we present an evolution strategy (ES) for solving MaOPs, called MaOES, which can solve these challenges efficiently and effectively. Inspired by the Vector Equilibrium phenomenon in magnetic fields, isotropic magnetic particles would automatically repel from each other, keep the uniform distance from the nearest neighbors, and extend the entire magnetic fields as far as possible, all at the same time. In the proposed algorithm, an efficient self-adaptive Precision-Controllable Mutation operator is designed for individuals to explore and exploit the decision space. In addition, the Maximum Extension Distance strategy, which emulates the isotropic magnetic particle behavior in a magnetic field, is developed to guide individuals to keep uniform distance and extension to approximate the entire PF. As a result, the MaOES can obtain a well-converged and well-diversified PF with much less population size and far lower computational complexity. The larger the number of individuals, the sharper the contour the resulting approximate PF will be. Finally, the proposed algorithm is evaluated by the scalable MaOPs test suites on DTLZ and WFG. The experimental results have been demonstrated to provide a competitive and oftentimes better performance when compared against some chosen state-of-the-art MaOEAs.
Laboratory‐based interventions targeting food craving: A systematic review and meta‐analysis

This systematic review and meta‐analysis aimed to quantify the effects of laboratory‐based interventions targeting specific mechanisms of food craving, to identify moderators of effects, and to qualitatively summarize findings. The study was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Sixty‐nine studies were included in the quantitative synthesis, and separate meta‐analyses were conducted for the outcomes self‐reported craving and objective food intake. Results show small to medium positive effects across specific craving interventions on both outcomes. Effect sizes were partly moderated by intervention type. The most effective intervention regarding food intake was in sensu cue exposure. For subjective craving, the most robust evidence was found for beneficial effects of cognitive regulation strategies (ie, reappraisal, suppression, and distraction). Results further indicate that training inhibitory control through behavioral inhibition might be more effective than approach‐avoidance training when considering its effect on subjective craving and food intake. People with external eating habits, overeating, or loss‐of‐control eating might benefit from these types of specific craving interventions. Future research should focus on long‐term effects, transferability, and effectiveness in clinical samples.
A Recurrent Neural Network for Particle Tracking in Microscopy Images Using Future Information, Track Hypotheses, and Multiple Detections

Automatic tracking of particles in time-lapse fluorescence microscopy images is essential for quantifying the dynamic behavior of subcellular structures and virus structures. We introduce a novel particle tracking approach based on a deep recurrent neural network architecture that exploits past and future information in both forward and backward direction. Assignment probabilities are determined jointly across multiple detections, and the probability of missing detections is computed. In addition, existence probabilities are determined by the network to handle track initiation and termination. For correspondence finding, track hypotheses are propagated to future time points so that information at later time points can be used to resolve ambiguities. A handcrafted similarity measure and handcrafted motion features are not necessary. Manually labeled data is not required for network training. We evaluated the performance of our approach using image data of the Particle Tracking Challenge as well as real fluorescence microscopy image sequences of virus structures. It turned out that the proposed approach outperforms previous methods.
Is physical exercise and dietary therapy a feasible alternative to cognitive behavior therapy in treatment of eating disorders? A randomized controlled trial of two group therapies

Abstract Objective To compare effects of physical exercise and dietary therapy (PED‐t) to cognitive behavioral therapy (CBT) in treatment of bulimia nervosa (BN) and binge‐eating disorder (BED). Method The active sample (18–40 years of age) consisted of 76 women in the PED‐t condition and 73 in the CBT condition. Participants who chose not to initiate treatment immediately (n = 23) were put on a waiting list. Outcome measures were the eating disorder examination questionnaire (EDE‐Q), Clinical Impairment Assessment (CIA), Satisfaction with Life Scale (SWLS), Beck Depression Inventory (BDI), and numbers in remission at posttreatment, and at 6‐, 12‐, and 24‐months follow‐up. Results Both treatment conditions produced medium to strong significant improvements on all outcomes with long‐term effect. The PED‐t produced a faster improvement in EDE‐Q and CIA, but these differences vanished at follow‐ups. Only PED‐t provided improvements in BDI, still with no between‐group difference. Totally, 30–50% of participants responded favorable to treatments, with no statistical between‐group difference. Discussion Both treatments shared a focus on normalizing eating patterns, correcting basic self‐regulatory processes and reducing idealized aesthetic evaluations of self‐worth. The results point to the PED‐t as an alternative to CBT for BN and BED, although results are limited due to compliance and dropout rates. Replications are needed by independent research groups as well as in more clinical settings.