Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of Angiogenesis and Pro-Angiogenic Exosomes in Regenerative Dentistry

Dental surgeries can result in traumatic wounds that provoke major discomfort and have a high risk of infection. In recent years, density research has taken a keen interest in finding answers to this problem by looking at the latest results made in regenerative medicine and adapting them to the specificities of oral tissue. One of the undertaken directions is the study of angiogenesis as an integrative part of oral tissue regeneration. The stimulation of this process is intended to enhance the local availability of stem cells, oxygen levels, nutrient supply, and evacuation of toxic waste. For a successful stimulation of local angiogenesis, two major cellular components must be considered: the stem cells and the vascular endothelial cells. The exosomes are extracellular vesicles, which mediate the communication between two cell types. In regenerative dentistry, the analysis of exosome miRNA content taps into the extended communication between these cell types with the purpose of improving the regenerative potential of oral tissue. This review analyzes the stem cells available for the dentistry, the molecular cargo of their exosomes, and the possible implications these may have for a future therapeutic induction of angiogenesis in the oral wounds.
Application of Prostate Cancer Models for Preclinical Study: Advantages and Limitations of Cell Lines, Patient-Derived Xenografts, and Three-Dimensional Culture of Patient-Derived Cells

Various preclinical models have been developed to clarify the pathophysiology of prostate cancer (PCa). Traditional PCa cell lines from clinical metastatic lesions, as exemplified by DU-145, PC-3, and LNCaP cells, are useful tools to define mechanisms underlying tumorigenesis and drug resistance. Cell line-based experiments, however, have limitations for preclinical studies because those cells are basically adapted to 2-dimensional monolayer culture conditions, in which the majority of primary PCa cells cannot survive. Recent tissue engineering enables generation of PCa patient-derived xenografts (PDXs) from both primary and metastatic lesions. Compared with fresh PCa tissue transplantation in athymic mice, co-injection of PCa tissues with extracellular matrix in highly immunodeficient mice has remarkably improved the success rate of PDX generation. PDX models have advantages to appropriately recapitulate the molecular diversity, cellular heterogeneity, and histology of original patient tumors. In contrast to PDX models, patient-derived organoid and spheroid PCa models in 3-dimensional culture are more feasible tools for in vitro studies for retaining the characteristics of patient tumors. In this article, we review PCa preclinical model cell lines and their sublines, PDXs, and patient-derived organoid and spheroid models. These PCa models will be applied to the development of new strategies for cancer precision medicine.
Signature Inspired Home Environments Monitoring System Using IR-UWB Technology

Home monitoring and remote care systems aim to ultimately provide independent living care scenarios through non-intrusive, privacy-protecting means. Their main aim is to provide care through appreciating normal habits, remotely recognizing changes and acting upon those changes either through informing the person themselves, care providers, family members, medical practitioners, or emergency services, depending on need. Care giving can be required at any age, encompassing young to the globally growing aging population. A non-wearable and unobtrusive architecture has been developed and tested here to provide a fruitful health and wellbeing-monitoring framework without interfering in a user’s regular daily habits and maintaining privacy. This work focuses on tracking locations in an unobtrusive way, recognizing daily activities, which are part of maintaining a healthy/regular lifestyle. This study shows an intelligent and locally based edge care system (ECS) solution to identify the location of an occupant’s movement from daily activities using impulse radio-ultra wide band (IR-UWB) radar. A new method is proposed calculating the azimuth angle of a movement from the received pulse and employing radar principles to determine the range of that movement. Moreover, short-term fourier transform (STFT) has been performed to determine the frequency distribution of the occupant’s action. Therefore, STFT, azimuth angle, and range calculation together provide the information to understand how occupants engage with their environment. An experiment has been carried out for an occupant at different times of the day during daily household activities and recorded with time and room position. Subsequently, these time-frequency outcomes, along with the range and azimuth information, have been employed to train a support vector machine (SVM) learning algorithm for recognizing indoor locations when the person is moving around the house, where little or no movement indicates the occurrence of abnormalities. The implemented framework is connected with a cloud server architecture, which enables to act against any abnormality remotely. The proposed methodology shows very promising results through statistical validation and achieved over 90% testing accuracy in a real-time scenario.
Bactericidal and Cytotoxic Properties of Silver Nanoparticles

Silver nanoparticles (AgNPs) can be synthesized from a variety of techniques including physical, chemical and biological routes. They have been widely used as nanomaterials for manufacturing cosmetic and healthcare products, antimicrobial textiles, wound dressings, antitumor drug carriers, etc. due to their excellent antimicrobial properties. Accordingly, AgNPs have gained access into our daily life, and the inevitable human exposure to these nanoparticles has raised concerns about their potential hazards to the environment, health, and safety in recent years. From in vitro cell cultivation tests, AgNPs have been reported to be toxic to several human cell lines including human bronchial epithelial cells, human umbilical vein endothelial cells, red blood cells, human peripheral blood mononuclear cells, immortal human keratinocytes, liver cells, etc. AgNPs induce a dose-, size- and time-dependent cytotoxicity, particularly for those with sizes ≤10 nm. Furthermore, AgNPs can cross the brain blood barrier of mice through the circulation system on the basis of in vivo animal tests. AgNPs tend to accumulate in mice organs such as liver, spleen, kidney and brain following intravenous, intraperitoneal, and intratracheal routes of administration. In this respect, AgNPs are considered a double-edged sword that can eliminate microorganisms but induce cytotoxicity in mammalian cells. This article provides a state-of-the-art review on the synthesis of AgNPs, and their applications in antimicrobial textile fabrics, food packaging films, and wound dressings. Particular attention is paid to the bactericidal activity and cytotoxic effect in mammalian cells.
Intratumor DNA methylation heterogeneity in glioblastoma: implications for DNA methylation-based classification

Abstract Background A feature of glioblastoma (GBM) is cellular and molecular heterogeneity, both within and between tumors. This variability causes a risk for sampling bias and potential tumor escape from future targeted therapy. Heterogeneous intratumor gene expression in GBM is well documented, but little is known regarding the epigenetic heterogeneity. Variability in DNA methylation within tumors would have implications for diagnostics, as methylation can be used for tumor classification, subtyping, and determination of the clinically used biomarker O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. We therefore aimed to profile the intratumor DNA methylation heterogeneity in GBM and its effect on diagnostic properties. Methods Three to 4 spatially separated biopsies per tumor were collected from 12 GBM patients. We performed genome-wide DNA methylation analysis and investigated intratumor variation. Results All samples were classified as GBM isocitrate dehydrogenase (IDH) wild type (wt)/mutated by methylation profiling, but the subclass differed within 5 tumors. Some GBM samples exhibited higher DNA methylation differences within tumors than between, and many cytosine-phosphate-guanine (CpG) sites (mean: 17 000) had different methylation levels within the tumors. MGMT methylation status differed in IDH mutated patients (1/1). Conclusions We demonstrated that intratumor DNA methylation heterogeneity is a feature of GBM. Although all biopsies were classified as GBM IDH wt/mutated by methylation analysis, the assigned subclass differed in samples from the same patient. The observed heterogeneity within tumors is important to consider for methylation-based biomarkers and future improvements in stratification of GBM patients.
It takes a village - asthma networks utilized by parents when managing childhood asthma medications

Abstract Objective: We are yet to understand how widely parents seek asthma medication management information for their children, how they are used for health information, how parents engage with them and their influence on parent’s decision-making. This study aimed to gauge the current level of asthma knowledge and skills of parents of children with asthma and gain insight into who and what influences their child’s asthma medication management decisions. Method: Social network theory was used to map parents’ asthma networks and identify the level of influence of each individual/resource nominated. Parents of children with asthma (aged 4–18 years) were interviewed, completed an asthma network map, questionnaires and an inhaler technique assessment. Results: Twenty-six parents participated and had significant gaps in asthma knowledge and inhaler technique skills. The asthma networks of participants ranged from two to ten individuals/resources, with an average number of five. The most commonly nominated individual/resource was general practitioners followed by family members and the internet. Professional connections represented 44% of individuals/resources in networks, personal connections 42% and impersonal connections 14%. When parents were asked about how influential individuals/resources were, professional connections represented 53% of parents influences, personal connections 36% and impersonal connections 11%. Conclusion: This study highlights the priority and co-influence of non-medical sources of information/support on parent’s behaviors and decision-making with regards to their child’s asthma medicine taking. In further understanding the complexities surrounding these connections and relationships, HCPs are better positioned to assist parents in addressing their needs and better supporting them in the management of their child’s asthma.
Cord-Blood Lipidome in Progression to Islet Autoimmunity and Type 1 Diabetes

Previous studies suggest that children who progress to type 1 diabetes (T1D) later in life already have an altered serum lipid molecular profile at birth. Here, we compared cord blood lipidome across the three study groups: children who progressed to T1D (PT1D; n = 30), children who developed at least one islet autoantibody but did not progress to T1D during the follow-up (P1Ab; n = 33), and their age-matched controls (CTR; n = 38). We found that phospholipids, specifically sphingomyelins, were lower in T1D progressors when compared to P1Ab and the CTR. Cholesterol esters remained higher in PT1D when compared to other groups. A signature comprising five lipids was predictive of the risk of progression to T1D, with an area under the receiver operating characteristic curve (AUROC) of 0.83. Our findings provide further evidence that the lipidomic profiles of newborn infants who progress to T1D later in life are different from lipidomic profiles in P1Ab and CTR.
Nonclinical Exon Skipping Studies with 2′-O-Methyl Phosphorothioate Antisense Oligonucleotides in mdx and mdx-utrn−/− Mice Inspired by Clinical Trial Results

Duchenne muscular dystrophy is a severe, progressive muscle-wasting disease that is caused by mutations that abolish the production of functional dystrophin protein. The exon skipping approach aims to restore the disrupted dystrophin reading frame, to allow the production of partially functional dystrophins, such as found in the less severe Becker muscular dystrophy. Exon skipping is achieved by antisense oligonucleotides (AONs). Several chemical modifications have been tested in nonclinical and clinical trials. The morpholino phosphorodiamidate oligomer eteplirsen has been approved by the Food and Drug Administration, whereas clinical development with the 2′-O-methyl phosphorothioate (2OMePS) AON drisapersen was recently stopped. In this study, we aimed to study various aspects of 2OMePS AONs in nonclinical animal studies. We show that while efficiency of exon skipping restoration is comparable in young and older C57BL/10ScSn-Dmdmdx/J (mdx/BL10) mice, functional improvement was only observed for younger treated mice. Muscle quality did not affect exon skipping efficiency as exon skip and dystrophin levels were similar between mdx/BL10 and more severely affected, age-matched D2-mdx mice. We further report that treadmill running increases AON uptake and dystrophin levels in mdx/BL10 mice. Finally, we show that even low levels of exon skipping and dystrophin restoration are sufficient to significantly increase the survival of mdx-utrn−/− mice from 70 to 97 days.
[Long-term efficacy and safety of electroacupuncture on improving MMSE in patients with Alzheimer's disease].

OBJECTIVE To observe the efficacy and safety of electroacupuncture (EA) on improving mini-mental state examination (MMSE) in patients with Alzheimer's disease (AD), and to evaluate the efficacy during follow-up visit. METHODS Forty patients were randomly divided into a treatment group and a control group, 20 patients in each one (3 patients dropped off in the treatment group and 4 patients in the control group). The patients in the treatment group were treated with acupuncture at Baihui (GV 20), Fengfu (GV 16), Shenting (GV 24), Taiyang (EX-HN 5), Shangyintang (Extra 3) and Dazhong (KI 14); besides, EA was applied at Taiyang (EX-HN 5), Baihui (GV 20) and Shenting (GV 24) with dilatational wave, 10 Hz/50 Hz in frequency, 0.5 to 5.0 mA in intensity, once every two days, three treatments per week. The patients in the control group were treated with oral administration of donepezil hydrochloride tablets, once a day, taken before sleep. The treatment was given for 12 weeks in the two groups. The MMSE was evaluated before treatment, 12 weeks±3 days into treatment, and 24 weeks±7 days after treatment, respectively. RESULTS The difference of total score of MMSE before and 12 weeks±3 days into treatment was not significant between the two groups (P>0.05); the total score of MMSE after treatment was higher than that before treatment (both P<0.05); compared before treatment, the short-term memory score was increased in the treatment group (P<0.05), and the increasing range was superior to that in the control group (P<0.05). Compared before treatment, the total score of MMSE in the two groups were reduced 24 weeks ±7 days after treatment (both P<0.05), and the reduction in the treatment group was less than that in the control group (P<0.05); the differences of short-term memory score before and after treatment was significant between the two groups (P<0.05). No adverse reaction occurred in the two groups. CONCLUSION The effect of EA on improving MMSE in patients with AD is similar to donepezil supported by evidence-based medicine. The effect of EA may have a certain continuous effect, and may have advantages in instantaneous memory. In addition, the EA is safe.
Memory and Confusion Complaints in Visually Impaired Older Adults: An Understudied Aspect of Well-Being

Objective: To determine the prevalence of cognitive (memory or confusion) complaints in older adults with visual impairment (VI). Method: We assessed the relationship between VI (corrected visual acuity [VA] < 20/40) and self-reported confusion or problems with memory among participants aged 60 years to 85 years in the 1999-2006 cycles of National Health and Nutrition Examination Survey (n = 5,795). Prevalence estimates of cognitive complaints were calculated using Current Population Surveys. Results: Memory/confusion complaints were reported in 22% of the VI group and 11% of the no VI group (p < .001). In individuals aged ≥ 80 years, 30% of those with VI reported cognitive complaints, as compared with 19% with no VI (p = .003). In fully adjusted models, individuals with VI were more likely (OR = 1.3, p = .049) to report cognitive complaints as compared with those without VI. Conclusion: Subjective reports of memory or confusion are highly prevalent in older individuals with VI.
Mutagenesis of Snu114 domain IV identifies a developmental role in meiotic splicing

ABSTRACT Snu114, a component of the U5 snRNP, plays a key role in activation of the spliceosome. It controls the action of Brr2, an RNA-stimulated ATPase/RNA helicase that disrupts U4/U6 snRNA base-pairing prior to formation of the spliceosome’s catalytic centre. Snu114 has a highly conserved domain structure that resembles that of the GTPase EF-2/EF-G in the ribosome. It has been suggested that the regulatory function of Snu114 in activation of the spliceosome is mediated by its C-terminal region, however, there has been only limited characterisation of the interactions of the C-terminal domains. We show a direct interaction between protein phosphatase PP1 and Snu114 domain ‘IVa’ and identify sequence ‘YGVQYK’ as a PP1 binding motif. Interestingly, this motif is also required for Cwc21 binding. We provide evidence for mutually exclusive interaction of Cwc21 and PP1 with Snu114 and show that the affinity of Cwc21 and PP1 for Snu114 is influenced by the different nucleotide-bound states of Snu114. Moreover, we identify a novel mutation in domain IVa that, while not affecting vegetative growth of yeast cells, causes a defect in splicing transcripts of the meiotic genes, SPO22, AMA1 and MER2, thereby inhibiting an early stage of meiosis.
A Novel Wearable Device for Continuous Ambulatory ECG Recording: Proof of Concept and Assessment of Signal Quality

Diagnosis of arrhythmic disorders is challenging because of their short-lasting, intermittent character. Conventional technologies of noninvasive ambulatory rhythm monitoring are limited by modest sensitivity. We present a novel form of wearable electrocardiogram (ECG) sensors providing an alternative tool for long-term rhythm monitoring with the potential of increased sensitivity to detect intermittent or subclinical arrhythmia. The objective was to assess the signal quality and R-R coverage of a wearable ECG sensor system compared to a standard 3-lead Holter. In this phase-1 trial, healthy individuals underwent 24-h simultaneous rhythm monitoring using the OMsignal system together with a 3-lead Holter recording. The OMsignal system consists of a garment (bra or shirt) with integrated sensors recording a single-lead ECG and an acquisition module for data storage and processing. Head-to-head signal quality was assessed regarding adequate P-QRS-T distinction and was performed by three electrophysiologists blinded to the recording technology. The accuracy of signal coverage was assessed using Bland-Altman analysis. Fifteen individuals underwent simultaneous 24-h recording. Signal quality and accuracy of the OMgaments was equivalent to Holter-monitoring (84% vs. 93% electrophysiologists rating, p = 0.06). Signal coverage of R-R intervals showed a very close overlay between the OMsignal system and Holter signals, mean difference in heart rate of 2 ± 5 bpm. The noise level of OMgarments was comparable to Holter recording. OMgarments provide high signal quality for adequate rhythm analysis, representing a promising novel technology for long-term non-invasive ECG monitoring.
Genome-wide analysis of genomic alterations induced by oxidative DNA damage in yeast

Abstract Oxidative DNA damage is a threat to genome stability. Using a genetic system in yeast that allows detection of mitotic recombination, we found that the frequency of crossovers is greatly elevated when cells are treated with hydrogen peroxide (H2O2). Using a combination of microarray analysis and genomic sequencing, we mapped the breakpoints of mitotic recombination events and other chromosome rearrangements at a resolution of about 1 kb. Gene conversions and crossovers were the two most common types of events, but we also observed deletions, duplications, and chromosome aneuploidy. In addition, H2O2-treated cells had elevated rates of point mutations (particularly A to T/T to A and C to G/G to C transversions) and small insertions/deletions (in/dels). In cells that underwent multiple rounds of H2O2 treatments, we identified a genetic alteration that resulted in improved H2O2 tolerance by amplification of the CTT1 gene that encodes cytosolic catalase T. Lastly, we showed that cells grown in the absence of oxygen have reduced levels of recombination. This study provided multiple novel insights into how oxidative stress affects genomic instability and phenotypic evolution in aerobic cells.
The Forkhead box F1 transcription factor inhibits collagen deposition and accumulation of myofibroblasts during liver fibrosis

ABSTRACT Hepatic fibrosis is the common end stage to a variety of chronic liver injuries and is characterized by an excessive deposition of extracellular matrix (ECM), which disrupts the liver architecture and impairs liver function. The fibrous lesions are produced by myofibroblasts, which differentiate from hepatic stellate cells (HSC). The myofibroblast’s transcriptional networks remain poorly characterized. Previous studies have shown that the Forkhead box F1 (FOXF1) transcription factor is expressed in HSCs and stimulates their activation during acute liver injury; however, the role of FOXF1 in the progression of hepatic fibrosis is unknown. In the present study, we generated αSMACreER;Foxf1fl/fl mice to conditionally inactivate Foxf1 in myofibroblasts during carbon tetrachloride-mediated liver fibrosis. Foxf1 deletion increased collagen depositions and disrupted liver architecture. Timp2 expression was significantly increased in Foxf1-deficient mice while MMP9 activity was reduced. RNA sequencing of purified liver myofibroblasts demonstrated that FOXF1 inhibits expression of pro-fibrotic genes, Col1α2, Col5α2, and Mmp2 in fibrotic livers and binds to active repressors located in promotors and introns of these genes. Overexpression of FOXF1 inhibits Col1a2, Col5a2, and MMP2 in primary murine HSCs in vitro. Altogether, FOXF1 prevents aberrant ECM depositions during hepatic fibrosis by repressing pro-fibrotic gene transcription in myofibroblasts and HSCs. Summary: The transcription factor FOXF1 is expressed in liver fibroblasts and regulates fibrosis by repressing pro-fibrotic genes. FOXF1 prevents aberrant extracellular matrix depositions during hepatic fibrosis.