Miracle-dz/UniFAR-FTUs huggingface dataset:
To Find Your Location: Secure and Practical Point Location Scheme

With the ubiquitous mobile devices and the advanced wireless communication, location-based service (LBS) helps people to enjoy a convenient lifestyle and has attracted numerous research interests. As a basic query process in LBS system, point location requires to find a region containing the query point. Since location belongs to sensitive information and also leads other private information leaked, it is urgent to design a secure and efficient point location scheme. In this paper, we propose a point location scheme named SecPL to protect sensitive information while supporting high efficient location query. Specifically, we introduce a LineTest scheme from asymmetric scalar-product-preserving encryption (ASPE) to facilitate the checking of whether a point lies above or below a line. Furthermore, the SecPL scheme is designed by leveraging LineTest and order-preserving encryption (OPE) scheme. Through detailed security analysis, we demonstrate that SecPL scheme achieves data privacy and query privacy at the same time. Finally, the performance evaluation demonstrates the high efficiency of the proposed SecPL scheme.
Chronic psychosocial stress compromises the immune response and endochondral ossification during bone fracture healing via β-AR signaling

Significance Our results show that one single systemic administration of the β-adrenoreceptor blocker propranolol prior to femur osteotomy in psychosocially stressed mice prevents stress-induced bone marrow mobilization of neutrophils and their immigration into the early fracture hematoma, as well as the decrease in bending stiffness and bony bridging of the fracture callus, which indicated a compromised fracture healing in stressed mice. These findings offer possibilities for clinical translation in patients suffering from posttraumatic stress disorder and fracture. Chronic psychosocial stress/trauma represents an increasing burden in our modern society and a risk factor for the development of mental disorders, including posttraumatic stress disorder (PTSD). PTSD, in turn, is highly comorbid with a plethora of inflammatory disorders and has been associated with increased bone fracture risk. Since a balanced inflammatory response after fracture is crucial for successful bone healing, we hypothesize that stress/trauma alters the inflammatory response after fracture and, consequently, compromises fracture healing. Here we show, employing the chronic subordinate colony housing (CSC) paradigm as a clinically relevant mouse model for PTSD, that mice subjected to CSC displayed increased numbers of neutrophils in the early fracture hematoma, whereas T lymphocytes and markers for cartilage-to-bone transition and angiogenesis were reduced. At late stages of fracture healing, CSC mice were characterized by decreased bending stiffness and bony bridging of the fracture callus. Strikingly, a single systemic administration of the β-adrenoreceptor (AR) blocker propranolol before femur osteotomy prevented bone marrow mobilization of neutrophils and invasion of neutrophils into the fracture hematoma, both seen in the early phase after fracture, as well as a compromised fracture healing in CSC mice. We conclude that chronic psychosocial stress leads to an imbalanced immune response after fracture via β-AR signaling, accompanied by disturbed fracture healing. These findings offer possibilities for clinical translation in patients suffering from PTSD and fracture.
Genome-wide Analysis of Common Copy Number Variation and Epithelial Ovarian Cancer Risk

Background: Germline DNA copy number variation (CNV) is a ubiquitous source of genetic variation and remains largely unexplored in association with epithelial ovarian cancer (EOC) risk. Methods: CNV was quantified in the DNA of approximately 3,500 cases and controls genotyped with the Illumina 610k and HumanOmni2.5M arrays. We performed a genome-wide association study of common (>1%) CNV regions (CNVRs) with EOC and high-grade serous (HGSOC) risk and, using The Cancer Genome Atlas (TCGA), performed in silico analyses of tumor-gene expression. Results: Three CNVRs were associated (P < 0.01) with EOC risk: two large (∼100 kb) regions within the 610k set and one small (<5 kb) region with the higher resolution 2.5M data. Large CNVRs included a duplication at LILRA6 (OR = 2.57; P = 0.001) and a deletion at CYP2A7 (OR = 1.90; P = 0.007) that were strongly associated with HGSOC risk (OR = 3.02; P = 8.98 × 10−5). Somatic CYP2A7 alterations correlated with EGLN2 expression in tumors (P = 2.94 × 10−47). An intronic ERBB4/HER4 deletion was associated with reduced EOC risk (OR = 0.33; P = 9.5 × 10−2), and somatic deletions correlated with ERBB4 downregulation (P = 7.05 × 10−5). Five CNVRs were associated with HGSOC, including two reduced-risk deletions: one at 1p36.33 (OR = 0.28; P = 0.001) that correlated with lower CDKIIA expression in TCGA tumors (P = 2.7 × 10−7), and another at 8p21.2 (OR = 0.52; P = 0.002) that was present somatically where it correlated with lower GNRH1 expression (P = 5.9 × 10−5). Conclusions: Though CNV appears to not contribute largely to EOC susceptibility, a number of low-to-common frequency variants may influence the risk of EOC and tumor-gene expression. Impact: Further research on CNV and EOC susceptibility is warranted, particularly with CNVs estimated from high-density arrays.
HER3-Targeted Affibodies with Optimized Formats Reduce Ovarian Cancer Progression in a Mouse Xenograft Model

Expression of the receptor tyrosine kinase HER3 is negatively correlated with survival in ovarian cancer, and HER3 overexpression is associated with cancer progression and therapeutic resistance. Thus, improvements in HER3-targeted therapy could lead to significant clinical impact for ovarian cancer patients. Previous work from our group established multivalency as a potential strategy to improve the therapeutic efficacy of HER3-targeted ligands, including affibodies. Others have established HER3 affibodies as viable and potentially superior alternatives to monoclonal antibodies for cancer therapy. Here, bivalent HER3 affibodies were engineered for optimized production, specificity, and function as evaluated in an ovarian cancer xenograft model. Enhanced inhibition of HER3-mediated signaling and increased HER3 downregulation associated with multivalency could be achieved with a simplified construct, potentially increasing translational potential. Additionally, functional effects of affibodies due to multivalency were found to be specific to HER3 targeting, suggesting a unique molecular mechanism. Further, HER3 affibodies demonstrated efficacy in ovarian cancer xenograft mouse models, both as single agents and in combination with carboplatin. Overall, these results reinforce the potential of HER3-targeted affibodies for cancer therapy and establish treatment of ovarian cancer as an application where multivalent HER3 ligands may be useful. Further, this work introduces the potential of HER3 affibodies to be utilized as part of clinically relevant combination therapies (e.g., with carboplatin).
Hematological and Biochemical Parameters of Cattle Declared Healthy for Slaughter at the Municipal Slaughterhouse of Korhogo (Côte d’Ivoire)

1 Department of Animal Biology, Training and Research Unity of Biological Sciences, Peleforo Gon Coulibaly, University of Korhogo (UPGCK), Bp 1328 Korhogo, Côte d'Ivoire 2 Laboratory of Biotechnology Agriculture and Valorization of the Biological Resources (LBAVRB), Department of Biosciences, Félix Houphouët-Boigny University (UFHB), Cocody Abidjan, 22 BP 582 Abidjan 22, Côte d'Ivoire 3 Department of Physiology Pharmacology and Pharmacopoeia, Nangui Abrogoua University, Abidjan, 02 BP 801 Abidjan 02, Côte d'Ivoire
The dyslexia susceptibility KIAA0319 gene shows a specific expression pattern during zebrafish development supporting a role beyond neuronal migration

Dyslexia is a common neurodevelopmental disorder caused by a significant genetic component. The KIAA0319 gene is one of the most robust dyslexia susceptibility factors but its function remains poorly understood. Initial RNA‐interference studies in rats suggested a role in neuronal migration whereas subsequent work with double knock‐out mouse models for both Kiaa0319 and its paralogue Kiaa0319‐like reported effects in the auditory system but not in neuronal migration. To further understand the role of KIAA0319 during neurodevelopment, we carried out an expression study of its zebrafish orthologue at different embryonic stages. We used different approaches including RNAscope in situ hybridization combined with light‐sheet microscopy. The results show particularly high expression during the first few hours of development. Later, expression becomes localized in well‐defined structures. In addition to high expression in the brain, we report for the first time expression in the eyes and the notochord. Surprisingly, kiaa0319‐like, which generally shows a similar expression pattern to kiaa0319, was not expressed in the notochord suggesting a distinct role for kiaa0319 in this structure. This observation was supported by the identification of notochord enhancers enriched upstream of the KIAA0319 transcription start site, in both zebrafish and humans. This study supports a developmental role for KIAA0319 in the brain as well as in other developing structures, particularly in the notochord which, is key for establishing body patterning in vertebrates.
IntronDB: a database for eukaryotic intron features

SUMMARY The rate and extent of unbalanced eukaryotic intron changes exhibit dynamic patterns for different lineages of species or certain functional groups of genes with varied spatio-temporal expression modes affected by selective pressure. To date, only a few key conserved splicing signals or regulatory elements have been identified in introns and little is known about the remaining intronic regions. To trace the evolutionary trajectory of spliceosomal introns from available genomes under a unified framework, we present IntronDB, which catalogues approximately 50000000 introns from over 1000 genomes spanning the major eukaryotic clades in the tree of life. Based on the position of introns relative to coding regions, it categorizes introns into three groups such as 5'UTR, CDS and 3'UTR and subsequently divides CDS introns into three categories such as phase 0, phase 1 and phase 2. It provides the quality evaluation for each sequence entry and characterizes the intronic parameters including number, size, sequence composition and positioning information as well as the features for exons and genes, making possible the comparisons between introns and exons. It reports the dinucleotides around the intron boundary and displays the consensus sequence features for all introns, small introns and large introns for each genome. By incorporating the taxonomic assignment of genomes, it performs high-level or genome-wide statistical analysis for single feature and coupled features both in a single genome and across multiple genomes. It offers functionalities to browse the data from representative protein-coding transcripts and download the data from all transcripts from protein-coding genes. AVAILABILITY http://www.nextgenbioinformatics. org/IntronDB. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Nebulin and titin modulate cross-bridge cycling and length-dependent calcium sensitivity

Various mutations in the structural proteins nebulin and titin that are present in human disease are known to affect the contractility of striated muscle. Loss of nebulin is associated with reduced actin filament length and impairment of myosin binding to actin, whereas titin is thought to regulate muscle passive elasticity and is likely involved in length-dependent activation. Here, we sought to assess the modulation of muscle function by these sarcomeric proteins by using the computational platform muscle simulation code (MUSICO) to quantitatively separate the effects of structural changes, kinetics of cross-bridge cycling, and calcium sensitivity of the thin filaments. The simulations show that variation in thin filament length cannot by itself account for experimental observations of the contractility in nebulin-deficient muscle, but instead must be accompanied by a decreased myosin binding rate. Additionally, to match the observed calcium sensitivity, the rate of TnI detachment from actin needed to be increased. Simulations for cardiac muscle provided quantitative estimates of the effects of different titin-based passive elasticities on muscle force and activation in response to changes in sarcomere length and interfilament lattice spacing. Predicted force–pCa relations showed a decrease in both active tension and sensitivity to calcium with a decrease in passive tension and sarcomere length. We conclude that this behavior is caused by partial redistribution of the muscle load between active muscle force and titin-dependent passive force, and also by redistribution of stretch along the thin filament, which together modulate the release of TnI from actin. These data help advance understanding of how nebulin and titin mutations affect muscle function.
Comparison of the Efficacies of Dry Needling and Botox Methods in the Treatment of Myofascial Pain Syndrome Affecting the Temporomandibular Joint.

BACKGROUND To compare the efficacies of botulinum toxin-A injection and dry needling methods in the treatment of patients with myofascial pain syndrome (MPS) in the temporomandibular joint (TMJ). METHODS In this prospective study, 40 MPS patients (29 women, 11 men) were randomly assigned to abobotulinum toxin-A injection (Group 1, n = 20) or dry needling (Group 2, n = 20) groups. Pain, crepitation, functional limitation, maximum mouth opening, jaw strength were evaluated at baseline and 6 weeks, and the results in both groups were compared. RESULTS The average age of the authors' patients was 33.8±8.1. There was a remarkable difference between 2 groups regarding visual analog scale for TMJ pain at rest (P = 0.048). The pain at rest was relieved more effectively in Group 2 at the end of 6 weeks. Improvement in jaw protrusion angles on the right (P = 0.009) and left (P = 0.002) sides was more evident in Group 2 after 6 weeks. There were significant pain relief and functional improvement after treatment in both groups. In Group 2, recovery of the TMJ function was more obvious in 6 weeks following dry needling (P = 0.002). CONCLUSION The authors suggest that abobotulinum toxin-A injection and dry needling yield satisfactory therapeutic outcomes regarding pain relief and restoration of function in patients with MPS involving TMJ. Further multicentric, randomized, controlled trials on larger series are warranted to obtain more accurate and reliable information.
Parallels between lumbosacral radiculopathy and complex regional pain syndrome: α1-adrenoceptor upregulation, reduced dermal nerve fibre density and hemi-sensory disturbances in post-surgical sciatica.

Residual lower limb pain after low back surgery (post-surgical sciatica) and complex regional pain syndrome involving a lower limb (CRPS) are separate conditions, but may share some mechanisms (e.g., tissue inflammation, neuro-immune disturbances and central neuro-plasticity). As adrenergically-evoked pain contributes, in part, to CRPS, whether an adrenergic mechanism also contributes to post-surgical sciatica was investigated in this study. Immunohistochemistry was used to identify α1-adrenoceptors (α1-AR) on nerve fibres and other targets in the affected and contralateral skin of 25 patients with post-surgical sciatica, and α1-AR expression was investigated in relation to pain and pinprick hyperalgesia after intradermal injection of the α1-AR agonist phenylephrine. In addition, quantitative sensory testing was performed on all four limbs and on each side of the forehead. α1-AR expression was greater in keratinocytes (but not blood vessels or nerve fibres) in the symptomatic than contralateral leg, and dermal nerve fibre density was reduced in both legs. However, distal adrenergic involvement in pain in post-surgical sciatica seems unlikely, as neither heightened α1-AR expression in keratinocytes nor reduced dermal nerve fibre density were associated with pain or hyperalgesia to intradermal phenylephrine injection. Sensitivity to pressure-pain, pinprick and cold-pain was greater in the ipsilateral than contralateral forehead of the entire cohort, but sensory disturbances were most pronounced in patients with additional CRPS-like features. Together, these findings suggest that bilateral distal neuropathy and central neuro-plastic changes are involved not only in the pathophysiology of CRPS but also in post-surgical sciatica. This may have treatment implications for patients with post-surgical sciatica.
Circadian misalignment and weekend alcohol use in late adolescent drinkers: preliminary evidence

ABSTRACT Alcohol use accelerates during late adolescence, predicting the development of alcohol use disorders (AUDs) and other negative outcomes. Identifying modifiable risk factors for alcohol use during this time could lead to novel prevention approaches. Burgeoning evidence suggests that sleep and circadian factors are cross-sectionally and longitudinally linked to alcohol use and problems, but more proximal relationships have been understudied. Circadian misalignment, in particular, is hypothesized to increase the risk for AUDs, but almost no published studies have included a biological measure of misalignment. In the present study, we aimed to extend existing research by assessing the relationship between adolescent circadian misalignment and alcohol use on a proximal timeframe (over two weeks) and by including three complementary measures of circadian alignment. We studied 36 healthy late (18–22 years old, 22 females) alcohol drinkers (reporting ≥1, standard drink per week over the past 30 days) over 14 days. Throughout the study, participants reported prior day’s alcohol use and prior night’s sleep each morning via smartphone and a secure, browser-based interface. Circadian phase was assessed via the dim light melatonin onset (DLMO) in the laboratory on two occasions (Thursday and Sunday nights) in counterbalanced order. The three measures of circadian alignment included DLMO-midsleep interval, “classic” social jet lag (weekday-weekend difference in midsleep), and “objective” social jet lag (weekday-weekend difference in DLMO). Multivariate imputation by chained equations was used to impute missing data, and Poisson regression models were used to assess associations between circadian alignment variables and weekend alcohol use. Covariates included sex, age, Thursday alcohol use, and Thursday sleep characteristics. As predicted, greater misalignment was associated with greater weekend alcohol use for two of the three alignment measures (shorter DLMO-midsleep intervals and larger weekday-weekend differences in midsleep), while larger weekday-weekend differences in DLMO were associated with less alcohol use. Notably, in contrast to expectations, the distribution of weekday-weekend differences in DLMO was nearly equally distributed between individuals advancing over the weekend and those delaying over the weekend. This unexpected finding plausibly reflects the fact that college students are not subject to the same systematically earlier weekday schedules observed in high school students and working adults. These preliminary findings support the need for larger, more definitive studies investigating the proximal relationships between circadian alignment and alcohol use among late adolescents.
An integrative method to predict signalling perturbations for cellular transitions

Abstract Induction of specific cellular transitions is of clinical importance, as it allows to revert disease cellular phenotype, or induce cellular reprogramming and differentiation for regenerative medicine. Signalling is a convenient way to accomplish such transitions without transfer of genetic material. Here we present the first general computational method that systematically predicts signalling molecules, whose perturbations induce desired cellular transitions. This probabilistic method integrates gene regulatory networks (GRNs) with manually-curated signalling pathways obtained from MetaCore from Clarivate Analytics, to model how signalling cues are received and processed in the GRN. The method was applied to 219 cellular transition examples, including cell type transitions, and overall correctly predicted experimentally validated signalling molecules, consistently outperforming other well-established approaches, such as differential gene expression and pathway enrichment analyses. Further, we validated our method predictions in the case of rat cirrhotic liver, and identified the activation of angiopoietins receptor Tie2 as a potential target for reverting the disease phenotype. Experimental results indicated that this perturbation induced desired changes in the gene expression of key TFs involved in fibrosis and angiogenesis. Importantly, this method only requires gene expression data of the initial and desired cell states, and therefore is suited for the discovery of signalling interventions for disease treatments and cellular therapies.
Practices, knowledge and inter‐professional relationships between speech pathologists and radiation therapists managing patients with head and neck cancer

This study examined knowledge and practices of speech pathologists (SPs) and radiation therapists (RTs) regarding plan optimisation for head and neck cancer (HNC) patients, and the potential impacts on swallowing function. The secondary aim was to explore the level of interaction occurring between these professional groups within cancer centres.
Glutamatergic signaling between neurons and oligodendrocyte lineage cells: Is it synaptic or non‐synaptic?

Fast chemical synaptic transmission is a major form of neuronal communication in the nervous system of mammals. Another important, but very different, form of intercellular communication is volume transmission, which is a slower non‐synaptic signaling. The amino acid glutamate is the most abundant excitatory neurotransmitter in the nervous system, which mediates both synaptic and non‐synaptic signaling via ionotropic and metabotropic glutamate receptors. Intriguingly, neurons establish glutamatergic synapses also with oligodendrocyte precursor cells (NG2+‐glia). Moreover, neuronal activity and glutamate receptors play an important role in the development and functionality of oligodendrocytes and their precursors in vivo. Yet, molecular characteristics and functional significance of neuron–glia synapses remain poorly understood, and it is unclear how glutamate receptors mediate the effects of neuronal activity on the oligodendrocyte lineage cells. In this review, we discuss what is known with regard to synaptic and non‐synaptic glutamatergic signaling between neurons and oligodendrocyte lineage cells, what can be suggested based on the current state of knowledge, and what is fully unknown and requires new research.