Miracle-dz/UniFAR-FTUs huggingface dataset:
INTRApersonal Synchrony as Constituent of INTERpersonal Synchrony and Its Relevance for Autism Spectrum Disorder

INTERpersonal synchrony leads to increased empathy, rapport and understanding, enabling successful human-human interactions and reciprocal bonding. Research shows that individuals with Autism Spectrum Disorder (ASD) exhibit difficulties to INTERpersonally synchronize but underlying causes are yet unknown. In order to successfully synchronize with others, INTRApersonal synchronization of communicative signals appears to be a necessary prerequisite. We understand INTRApersonal synchrony as an implicit factor of INTERpersonal synchrony and therefore hypothesize that atypicalities of INTRApersonal synchrony may add to INTERpersonal synchrony problems in ASD and their interaction partners. In this perspective article, we first review evidence for INTERpersonal dissynchrony in ASD, with respect to different approaches and assessment methods. Second, we draft a theoretical conceptualization of INTRApersonal dissynchrony in ASD based on a temporal model of human interaction. We will outline literature indicating INTRApersonal dissynchrony in ASD, therefore highlighting findings of atypical timing functions and findings from clinical and behavioral studies that indicate peculiar motion patterns and communicative signal production in ASD. Third, we hypothesize that findings from these domains suggest an assessment and investigation of temporal parameters of social behavior in individuals with ASD. We will further propose specific goals of empirical approaches on INTRApersonal dissynchrony. Finally we present implications of research on INTRApersonal timing in ASD for diagnostic and therapeutic purposes, what in our opinion warrants the increase of research efforts in this domain.
Host Genetic Determinants of Hepatitis B Virus Infection

Chronic hepatitis B virus (HBV) infection is still a major health problem worldwide. Recently, a great number of genetic studies based on single nucleotide polymorphisms (SNPs) and genome-wide association studies have been performed to search for host determinants of the development of chronic HBV infection, clinical outcomes, therapeutic efficacy, and responses to hepatitis B vaccines, with a focus on human leukocyte antigens (HLA), cytokine genes, and toll-like receptors. In addition to SNPs, gene insertions/deletions and copy number variants are associated with infection. However, conflicting results have been obtained. In the present review, we summarize the current state of research on host genetic factors and chronic HBV infection, its clinical type, therapies, and hepatitis B vaccine responses and classify published results according to their reliability. The potential roles of host genetic determinants of chronic HBV infection identified in these studies and their clinical significance are discussed. In particular, HLAs were relevant for HBV infection and pathogenesis. Finally, we highlight the need for additional studies with large sample sizes, well-matched study designs, appropriate statistical methods, and validation in multiple populations to improve the treatment of HBV infection.
Strong anion exchange‐mediated phosphoproteomics reveals extensive human non‐canonical phosphorylation

Phosphorylation is a key regulator of protein function under (patho)physiological conditions, and defining site‐specific phosphorylation is essential to understand basic and disease biology. In vertebrates, the investigative focus has primarily been on serine, threonine and tyrosine phosphorylation, but mounting evidence suggests that phosphorylation of other “non‐canonical” amino acids also regulates critical aspects of cell biology. However, standard methods of phosphoprotein characterisation are largely unsuitable for the analysis of non‐canonical phosphorylation due to their relative instability under acidic conditions and/or elevated temperature. Consequently, the complete landscape of phosphorylation remains unexplored. Here, we report an unbiased phosphopeptide enrichment strategy based on strong anion exchange (SAX) chromatography (UPAX), which permits identification of histidine (His), arginine (Arg), lysine (Lys), aspartate (Asp), glutamate (Glu) and cysteine (Cys) phosphorylation sites on human proteins by mass spectrometry‐based phosphoproteomics. Remarkably, under basal conditions, and having accounted for false site localisation probabilities, the number of unique non‐canonical phosphosites is approximately one‐third of the number of observed canonical phosphosites. Our resource reveals the previously unappreciated diversity of protein phosphorylation in human cells, and opens up avenues for high‐throughput exploration of non‐canonical phosphorylation in all organisms.
Generalized Representation of Stereoscopic Surface Shape and Orientation in the Human Visual Cortex

The brain’s ability to extract three-dimensional (3D) shape and orientation information from viewed objects is vital in daily life. Stereoscopic 3D surface perception relies on binocular disparity. Neurons selective to binocular disparity are widely distributed among visual areas, but the manner in these areas are involved in stereoscopic 3D surface representation is unclear. To address this, participants were instructed to observe random dot stereograms (RDS) depicting convex and concave curved surfaces and the blood oxygenation level-dependent (BOLD) signal of visual cortices was recorded. Two surface types were: (i) horizontally positioned surfaces defined by shear disparity; and (ii) vertically positioned surfaces defined by compression disparity. The surfaces were presented at different depth positions per trial. Functional magnetic resonance imaging (fMRI) data were classified from early visual areas to higher visual areas. We determined whether cortical areas were selective to shape and orientation by assessing same-type stimuli classification accuracies based on multi-voxel activity patterns per area. To identify whether some areas were related to a more generalized sign of curvature or orientation representation, transfer classification was used by training classifiers on one dataset type and testing classifiers on another type. Same-type stimuli classification results showed that most selected visual areas were selective to shape and all were selective to the orientation of disparity-defined 3D surfaces. Transfer classification results showed that in the dorsal visual area V3A, classification accuracies for the discriminate sign of surface curvature were higher than the baseline of statistical significance for all types of classifications, demonstrating that V3A is related to generalized shape representation. Classification accuracies for discriminating horizontal–vertical surfaces in higher dorsal areas V3A and V7 and ventral area lateral occipital complex (LOC) as well as in some areas of intraparietal sulcus (IPS) were higher than the baseline of statistical significance, indicating their relation to the generalized representation of 3D surface orientation.
Neutrophil Maturity in Cancer

Neutrophils are implicated in almost every stage of oncogenesis and paradoxically display anti- and pro-tumor properties. Accumulating evidence indicates that neutrophils display diversity in their phenotype resulting from functional plasticity and/or changes to granulopoiesis. In cancer, neutrophils at a range of maturation stages can be identified in the blood and tissues (i.e., outside of their developmental niche). The functional capacity of neutrophils at different states of maturation is poorly understood resulting from challenges in their isolation, identification, and investigation. Thus, the impact of neutrophil maturity on cancer progression and therapy remains enigmatic. In this review, we discuss the identification, prevalence, and function of immature and mature neutrophils in cancer and the potential impact of this on tumor progression and cancer therapy.
Targeting IL-6 Is a Potential Treatment for Primary Cystic Craniopharyngioma

Adamantinomatous craniopharyngioma (ACP) makes up between 6 and 8% of pediatric brain tumors and is the most common pediatric tumor arising in the sellar/suprasellar region of the brain. The 10-year survival for patients diagnosed with craniopharyngioma ranges between 64 and 92%, but complicating factors such as location, common cyst formation, and potential hypothalamic infiltration cause significant morbidity in this population. There are a number of therapeutic options for children with ACP, including surgery, radiation, and cyst directed therapies such as interferon and bleomycin. Research has raised concerns regarding the efficacy and side effects associated with these conventional therapies, as well as with the difficulty in treating recurrent cystic ACP. Evidence from our group and others has shown that the cystic and solid tumor components of craniopharyngioma have high levels of IL-6R and IL-6, providing a potential target for therapy. Tocilizumab, a humanized monoclonal antibody, acts against soluble and membrane bound IL-6R, and has been widely utilized in pediatric patients. Two patients with recurrent cystic ACP were offered systemically administered tocilizumab or a combination of tocilizumab and bevacizumab on a compassionate use basis. Both patients' tumors had a significant response, with decreased cyst burden, supporting the assertion that tocilizumab with or without bevacizumab may be an option for patients suffering from cystic ACP.
Comparative analysis of the NAL-NL2 and DSL v5.0a prescription procedures in the adaptation of hearing aids in the elderly.

PURPOSE To comparatively analyze the NAL-NL2 and DSL v5.0a prescriptive methods according to the hearing aids individualized programming for the elderly with hearing loss. METHODS The study included 60 elderly individuals with hearing loss, who underwent RECD (Real Ear to Coupler Difference) measurement and hearing aids individualized programming by NAL-NL2 and DSL v5.0a prescriptive methods. The performance verification for each prescription was performed using REAR measurements (Real Ear Aided Response), SII calculation (Speech Intelligibility Index) and HINT (Hearing In Noise Test). The comparative statistical analysis was performed using the paired t-test. RESULTS The NAL-NL2 method presented a better performance in the REAR evaluation in low and high frequency bands for medium and loud intensity input sounds, in the high frequency range for low intensity input sounds, and in the SII calculation for soft input sounds. The DSL v5.0a presented better results in the REAR evaluation in medium frequencies for medium input sounds, in low and medium frequencies for soft input sounds, in the SII calculation for medium and loud input sound, and in the HINT test in silent and noisy situations. CONCLUSION The findings of this study point to an equivalent performance between the DSL v5.0a and NAL-NL2 procedures in the adaptation of hearing aids in the elderly with hearing loss. The amplification calculated by DSL v5.0a provided better speech perception in silence.
Usefulness and Usability of a Personal Health Record and Survivorship Care Plan for Colorectal Cancer Survivors: Survey Study

Background As a result of improvements in cancer screening, treatment, and supportive care, nearly two-thirds of individuals diagnosed with colorectal cancer (CRC) live for 5 years after diagnosis. An ever-increasing population of CRC survivors creates a need for effective survivorship care to help manage and mitigate the impact of CRC and its treatment. Personal health records (PHRs) and survivorship care plans provide a means of supporting the long-term care of cancer survivors. Objective The purpose of this study is to characterize the usefulness of a CRC PHR and survivorship care plan and to describe the usability of these technologies in a population of CRC survivors. To our knowledge, this is the first study to assess a PHR and survivorship care plan specifically targeting CRC survivors. Methods Twenty-two patients with CRC were recruited from surgery clinics of an academic medical center and Veterans Affairs hospital in Indianapolis and provided access to an online Colorectal Cancer Survivor’s Personal Health Record (CRCS-PHR). Survey data were collected to characterize the usefulness of the CRCS-PHR and describe its usability in a population of CRC survivors. CRC survivors were surveyed 6 months after being provided online access. Means and proportions were used to describe the usefulness and ease of using the CRC website. Open-ended questions were qualitatively coded using the constant comparative method. Results CRC survivors perceived features related to their health care (ie, summary of cancer treatment history, follow-up care schedule, description of side effects, and list of community resources) to be more useful than communication features (ie, creating online relationships with family members or caregivers, communicating with doctor, and secure messages). CRC survivors typically described utilizing traditional channels (eg, via telephone or in person) to communicate with their health care provider. Participants had overall positive perceptions with respect to ease of use and overall satisfaction. Major challenges experienced by participants included barriers to system log-in, lack of computer literacy or experience, and difficulty entering their patient information. Conclusions For CRC, survivors may find the greater value in a PHR’s medical content than the communication functions, which they have available elsewhere. These findings regarding the usefulness and usability of a PHR for the management of CRC survivorship provide valuable insights into how best to tailor these technologies to patients’ needs. These findings can inform future design and development of PHRs for purposes of both cancer and chronic disease management.
Parcellation of the Hippocampus Using Resting Functional Connectivity in Temporal Lobe Epilepsy

We have previously shown that the connectivity of the hippocampus to other regions of the default mode network (DMN) is a strong indicator of memory ability in people with temporal lobe epilepsy (TLE). Recent work in the cognitive neuroscience literature has suggested that the anterior and posterior aspects of the hippocampus have distinct connections to the rest of the DMN and may support different memory operations. Further, structural analysis of epileptogenic hippocampi has found greater atrophy, characterized by mesial temporal sclerosis, in the anterior region of the hippocampus. Here, we used resting state FMRI data to parcellate the hippocampus according to its functional connectivity to the rest of the brain in people with left lateralized TLE (LTLE) and right lateralized TLE (RTLE), and in a group of neurologically healthy controls. We found similar anterior and posterior compartments in all groups. However, there was weaker connectivity of the epileptogenic hippocampus to multiple regions of the DMN. Both TLE groups showed reduced connectivity of the posterior hippocampus to key hubs of the DMN, the posterior cingulate cortex (PCC) and the medial pre-frontal cortex (mPFC). In the LTLE group, the anterior hippocampus also showed reduced connectivity to the DMN, and this effect was influenced by the presence of mesial temporal sclerosis. When we explored brain-behavior relationships, we found that reduced connectivity of the left anterior hippocampus to the DMN hubs related to poorer verbal memory ability in people with LTLE, and reduced connectivity of the right posterior hippocampus to the PCC related to poorer visual memory ability in those with RTLE. These findings may inform models regarding functional distinctions of the hippocampal anteroposterior axis.
The Cdk2-c-Myc-miR-571 Axis Regulates DNA Replication and Genomic Stability by Targeting Geminin.

DNA re-replication leads to genomic instability and has been implicated in the pathology of a variety of human cancers. Eukaryotic DNA replication is tightly controlled to ensure it occurs only once during each cell cycle. Geminin is a critical component of this control, it prevents DNA re-replication from occurring during S, G2 and early M phases by preventing MCM helicases from forming pre-replication complexes. Geminin is targeted for degradation by the anaphase promoting complex (APC/C) from anaphase through G1 phase, however, accumulating evidence indicates that Geminin is downregulated in late S phase due to an unknown mechanism. Here, we used a high throughput screen (HTS) to identify microRNAs that can induce excess DNA replication and found that miR-571 could reduce the protein level of Geminin in late S phase independent of the APC/C. Furthermore, miR-571 regulated efficient DNA replication and S phase cell cycle progression. Strikingly, c-Myc suppressed miR-571 expression by binding directly to the miR-571 promoter. At the beginning of S phase, Cdk2 phosphorylated c-Myc at Serine 62, promoting its association with the miR-571 promoter region. Collectively, we identify miR-571 as the first miRNA that prevents aberrant DNA replication, and the Cdk2-c-Myc-miR-571 axis as a new pathway for regulating DNA replication, cell cycle and genomic stability in cancer cells.
Expanding the Toolbox of Upconversion Nanoparticles for In Vivo Optogenetics and Neuromodulation

Optogenetics is an optical technique that exploits visible light for selective neuromodulation with spatio‐temporal precision. Despite enormous effort, the effective stimulation of targeted neurons, which are located in deeper structures of the nervous system, by visible light, remains a technical challenge. Compared to visible light, near‐infrared illumination offers a higher depth of tissue penetration owing to a lower degree of light attenuation. Herein, an overview of advances in developing new modalities for neural circuitry modulation utilizing upconversion‐nanoparticle‐mediated optogenetics is presented. These developments have led to minimally invasive optical stimulation and inhibition of neurons with substantially improved selectivity, sensitivity, and spatial resolution. The focus is to provide a comprehensive review of the mechanistic basis for evaluating upconversion parameters, which will be useful in designing, executing, and reporting optogenetic experiments.
RhoBTB1 interacts with ROCKs and inhibits invasion

RhoBTB1 is an atypical Rho GTPase with two BTB domains in addition to its Rho domain. Although most Rho GTPases regulate actin cytoskeletal dynamics, RhoBTB1 is not known to affect cell shape or motility. We report that RhoBTB1 depletion increases prostate cancer cell invasion and induces elongation in Matrigel, a phenotype similar to that induced by depletion of ROCK1 and ROCK2. We demonstrate that RhoBTB1 associates with ROCK1 and ROCK2 and its association with ROCK1 is via its Rho domain. The Rho domain binds to the coiled-coil region of ROCK1 close to its kinase domain. We identify two amino acids within the Rho domain that alter RhoBTB1 association with ROCK1. RhoBTB1 is a substrate for ROCK1, and mutation of putative phosphorylation sites reduces its association with Cullin3, a scaffold for ubiquitin ligases. We propose that RhoBTB1 suppresses cancer cell invasion through interacting with ROCKs, which in turn regulate its association with Cullin3. Via Cullin3, RhoBTB1 has the potential to affect protein degradation.
Application of Chitosan in Bone and Dental Engineering

Chitosan is a deacetylated polysaccharide from chitin, the natural biopolymer primarily found in shells of marine crustaceans and fungi cell walls. Upon deacetylation, the protonation of free amino groups of the d-glucosamine residues of chitosan turns it into a polycation, which can easily interact with DNA, proteins, lipids, or negatively charged synthetic polymers. This positive-charged characteristic of chitosan not only increases its solubility, biodegradability, and biocompatibility, but also directly contributes to the muco-adhesion, hemostasis, and antimicrobial properties of chitosan. Combined with its low-cost and economic nature, chitosan has been extensively studied and widely used in biopharmaceutical and biomedical applications for several decades. In this review, we summarize the current chitosan-based applications for bone and dental engineering. Combining chitosan-based scaffolds with other nature or synthetic polymers and biomaterials induces their mechanical properties and bioactivities, as well as promoting osteogenesis. Incorporating the bioactive molecules into these biocomposite scaffolds accelerates new bone regeneration and enhances neovascularization in vivo.
Interaction pattern and in vitro, in vivo release behavior of simvastatin-loaded chitosan nanoformulation

Abstract Objective and methods: This study predicted the nature of chitosan interactions and effects of this interaction on drug release mechanism in simvastatin-loaded chitosan nanoformulation using molecular docking, spectroscopic and thermal analysis. Significance: This work explains in depth the molecular mechanism of simvastatin and chitosan bond formation in nanoformulation. Results: The effective encapsulation and sustain release properties of chitosan were indicated by increase in melting endotherm of simvastatin. Intermolecular hydrogen bond between third hydroxyl group pyranone ring of simvastatin and amino group of chitosan represented the stability of active lactone moiety that was not cleaved during formulation which is prerequisite for biological activity. UV–vis spectroscopic characterization, shift in infrared vibration wavenumber of simvastatin and chitosan, ligand titration, 1HNMR and 13C-NMR analyses confirmed this interaction pattern. The pharmacokinetic evaluation in mouse model revealed the sustain release property of nanoformulation. Conclusion: Thus formation of intermolecular hydrogen bond in nanoformulation contributed to modified physicochemical properties and improved in vivo performance of simvastatin.