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BackgroundSerous ovarian carcinoma (SOC) is considered the most lethal gynecological malignancy. The current lack of reliable prognostic biomarkers for SOC reduces the efficacy of predictive, preventive, and personalized medicine (PPPM/3PM) in patients with SOC, leading to unsatisfactory therapeutic outcomes. N6-methyladenosine (m6A) modification-associated long noncoding RNAs (lncRNAs) are effective predictors of SOC. In this study, an effective risk prediction model for SOC was constructed based on m6A modification-associated lncRNAs.MethodsTranscriptomic data and clinical information of patients with SOC were downloaded from The Cancer Genome Atlas. Candidate lncRNAs were identified using univariate and multivariate and least absolute shrinkage and selection operator-penalized Cox regression analyses. The molecular mechanisms of m6A effector-related lncRNAs were explored via Gene Ontology, pathway analysis, gene set enrichment analysis, and gene set variation analysis (GSVA). The extent of immune cell infiltration was assessed using various algorithms, including CIBERSORT, Microenvironment Cell Populations counter, xCell, European Prospective Investigation into Cancer and Nutrition, and GSVA. The calcPhenotype algorithm was used to predict responses to the drugs commonly used in ovarian carcinoma therapy. In vitro experiments, such as migration and invasion Transwell assays, wound healing assays, and dot blot assays, were conducted to elucidate the functional roles of candidate lncRNAs.ResultsSix m6A effector-related lncRNAs that were markedly associated with prognosis were used to establish an m6A effector-related lncRNA risk model (m6A-LRM) for SOC. Immune microenvironment analysis suggested that the high-risk group exhibited a proinflammatory state and displayed increased sensitivity to immunotherapy. A nomogram was constructed with the m6A effector-related lncRNAs to assess the prognostic value of the model. Sixteen drugs potentially targeting m6A effector-related lncRNAs were identified. Furthermore, we developed an online web application for clinicians and researchers (https://leley.shinyapps.io/OC_m6A_lnc/). Overexpression of the lncRNA RP11-508M8.1 promoted SOC cell migration and invasion. METTL3 is an upstream regulator of RP11-508M8.1. The preliminary regulatory axis METTL3/m6A/RP11-508M8.1/hsa-miR-1270/ARSD underlying SOC was identified via a combination of in vitro and bioinformatic analyses.ConclusionIn this study, we propose an innovative prognostic risk model and provide novel insights into the mechanism underlying the role of m6A-related lncRNAs in SOC. Incorporating the m6A-LRM into PPPM may help identify high-risk patients and personalize treatment as early as possible.

A porous structure is essential for bone implants because it increases the bone ingrowth space and improves mechanical and biological properties. The biomimetically designed porous Voronoi scaffold can reconstruct the structure and function of cancellous bone; however, its comprehensive properties need to be investigated further. In this study, algorithms based on scaling factors were used to design the Voronoi scaffolds. Classic approaches, such as computer-aided design and the implicit surface method, have been used to design Diamond, Gyroid, and I-WP scaffolds as controls. All scaffolds were prepared by selective laser melting of titanium alloys and three-dimensional printing. Mechanical tests, finite element analysis, and in vitro and in vivo experiments were performed to investigate the biomechanical, cytologic, and osteogenic performance of the scaffolds, while computational fluid dynamics simulations were used to explore the underlying mechanisms. Diamond scaffolds have a better loading capacity, and the mechanical behaviors and fluid flow of Voronoi scaffolds are similar to those of the human trabecular bone. Cells showed more proliferation and distribution on the Diamond and Voronoi scaffolds and exhibited evident differentiation on Gyroid and Voronoi scaffolds. Bone formation was apparent on the inner part of the Gyroid, the outer part of the I-WP, and the entire Diamond and Voronoi scaffolds. The hydrodynamic properties and stimulus response of cells influenced by the porous structure account for the varied biological performance of the scaffolds. The Voronoi scaffolds with bionic mechanical behavior and an appropriate hydrodynamic response exhibit evident cell growth and osteogenesis, making them preferable for porous structural bone implants.

Control of moisture is critical for retention of sealants, which can reduce the incidence of caries in high-risk groups. Objectives: We investigated the safety and efficacy of the novel SS-suction device in the laboratory and a small clinical trial in children aged 6 to 8-years-old. Methods: First, a laboratory test of 52 SS-suction devices was conducted to determine the pressure generated by the chin plate to maintain suction at different intervals and to determine the pressure resistance of the spring to maintain suction in a child's mouth. Second, 12 healthy children with sound lower molars participated in a clinical trial of the use of SS-suction during sealant application. Results: The laboratory test showed that when pressed to the maximum distance of 25 mm, the chin plate produced a pressure of 247.5 ± 116.6 mmHg. At this pressure, the SS-suction could be used safely for up to 120 min without damaging the soft tissues. In the clinical study, the dentists inserted and removed the SS-suction in 7.80 ± 2.48 s. The range by which the chin plate was pressed down varied between 0 and 13 mm. The highest pressure on the skin was 120 mmHg (at 13 mm) and the device effectively maintained suction and effectively removed water and saliva. The time required to apply sealant was 7.01 ± 2.26 min. Conclusions: The SS-suction is a safe, effective device for two-handed application of sealants in children, with no negative side effects. Clinical significance: We demonstrate the unique SS-suction device can quickly drain water and saliva to help dentists treat young patients using a two-handed approach; this device provides good control of moisture during sealant application. The device prevents the tongue and cheeks from interfering with the operation area, reduces tension, and does not require a dental assistant.

Yong Fang Zhu,1,2 Peter Kan,3 Gurmit Singh1,2 1Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, ON, Canada; 2Department of Pathology & Molecular Medicine, McMaster University, Hamilton, ON, Canada; 3Health Sciences, McMaster University, Hamilton, ON, CanadaCorrespondence: Gurmit Singh, Email Singhg@mcmaster.caBackground: Clinical data on cancer-induced pain (CIP) demonstrate widespread changes in sensory function. It is characterized in humans not only by stimulus-invoked pain, but also by spontaneous pain. In our previous studies in an animal model of CIP, we observed changes in intrinsic membrane properties and excitability of dorsal root ganglion (DRG) sensory neurons corresponding to mechanical allodynia and hyperalgesia, of which abnormal activities of Aβ-fiber sensory neurons are consistent in a rat model of peripheral neuropathic pain (NEP).Objective: To investigate whether there are related peripheral neural mechanisms between the CIP and NEP models of spontaneous pain, we compared the electrophysiological properties of DRG sensory neurons at 2– 3 weeks after CIP and NEP model induction.Methods: CIP models were induced with metastasis tumour-1 rat breast cancer cells implanted into the distal epiphysis of the femur. NEP models were induced with a polyethylene cuff implanted around the sciatic nerve. Spontaneous pain in animals is measured by spontaneous foot lifting (SFL). After measurement of SFL, the animals were prepared for electrophysiological recordings of spontaneous activity (SA) in DRG neurons in vivo.Results: Our data showed that SFL and SA occurred in both models. The proportion of SFL and SA of C-fiber sensory neurons in CIP was more significantly increased than in NEP models. There was no difference in duration of SFL and the rate of SA between the two models. The duration of SFL is related to the rate of SA in C-fiber in both models.Conclusion: Thus, SFL may result from SA activity in C-fiber neurons in CIP and NEP rats. The differences and similarities in spontaneous pain between CIP and NEP rats is related to the proportion and rate of SA in C-fibers, respectively.Keywords: electrophysiology recording, spontaneous pain, sensory neuron, cancer-induced pain, neuropathic pain

Sanusi Umar,1– 3 Petrina Kan,4 Marissa J Carter,5 Paul Shitabata1,2,6 1Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA; 2Division of Dermatology, Department of Medicine, Harbor-UCLA Medical Center, Torrance, CA, USA; 3Dr. U Hair and Skin Clinic, Manhattan Beach, CA, USA; 4Department of Molecular Biology, University of California at Los Angeles, Los Angeles, CA, USA; 5Strategic Solutions, Inc, Bozeman, MT, USA; 6Dermatopathology Institute, Torrance, CA, USACorrespondence: Sanusi Umar, Dr. U Hair and Skin Clinic, 2121 N. Sepulveda Avenue, Suite 200, Manhattan Beach, CA, 90266, USA, Tel +1 (310) 318-1500, Fax +1 (310) 318-1590, Email drumar@dru.comPurpose: Central centrifugal cicatricial alopecia (CCCA) is the most common cause of scarring alopecia in women of African descent. However, current treatments for CCCA, such as immunosuppressants and immunomodulatory pharmaceutical agents, have suboptimal efficacy and undesirable side effects. This case series reports the therapeutic effect of a new botanical formulation (Dr. UGro Gashee) in four patients with histologically supported diagnoses of CCCA. The formulations contain at least three phytoactive ingredients that affect multiple targets in the cascade of pathophysiologic events contributing to CCCA. Possible mechanisms of action include anti-inflammatory effects, inhibiting proinflammatory cytokines, and the net antifibrotic effect of inhibiting transforming growth factor-beta while upregulating AMP-activated protein kinase and peroxisome proliferator-associated receptor-gamma activity.Patients and Methods: Four African American women with treatment-refractory CCCA were treated with a new topical botanical formula (cosmeceutical) alone or in combination with its oral formulation (nutraceutical) for 8 weeks to 1 year. The cosmeceutical and nutraceutical treatments contain similar phytoactive ingredient profiles. Treatment outcomes were collected using documented patient reports and images and by direct observation.Results: In all patients, scalp pruritus cessation occurred within 2 weeks of treatment, and significant hair regrowth was observed within 2 months. All patients reported a high satisfaction level without adverse effects.Conclusion: Patients with treatment-refractory CCCA responded to the novel botanical treatment reported in this study. Further evaluations in a controlled trial with more patients are warranted.Keywords: scarring alopecia, follicular degeneration syndrome, hot comb alopecia, African American women, hair loss, cosmeceutical, nutraceutical, phytoactive

A new reading curriculum incorporating the principles of concept-based instruction and reading strategy instruction was designed and implemented for a previous study. Concept-based instruction was compared with reading strategy instruction to determine the impact of the new curriculum on language learners' reading and reflective thinking skills. The data revealed that the concept-based group performed better in reflective reading and thinking skills. The new curriculum involves the creation of a Schema of a Complete Orienting Basis of an Action (SCOBA) during reflection sessions. To explore the necessity of SCOBA creation, an experimental study with two groups was conducted, where only one group created a SCOBA. Both groups received concept-based reading instruction and were compared based on their reading, reflective reading, and reflective thinking skills. The data revealed that the groups performed similarly in reading and reflective reading skills, but the SCOBA group performed better in reflective thinking skills. The study sheds light on the importance of incorporating reflective thinking activities, such as SCOBA creation, in concept-based reading instruction.

5-methylcytosine (m5C) post-transcriptional modifications affect the maturation, stability, and translation of the mRNA molecule. These modifications play an important role in many physiological and pathological processes, including stress response, tumorigenesis, tumor cell migration, embryogenesis, and viral replication. Recently, there has been a better understanding of the biological implications of m5C modification owing to the rapid development and optimization of detection technologies, including liquid chromatography-tandem mass spectrometry (LC-MS/MS) and RNA-BisSeq. Further, predictive models (such as PEA-m5C, m5C-PseDNC, and DeepMRMP) for the identification of potential m5C modification sites have also emerged. In this review, we summarize the current experimental detection methods and predictive models for mRNA m5C modifications, focusing on their advantages and limitations. We systematically surveyed the latest research on the effectors related to mRNA m5C modifications and their biological functions in multiple species. Finally, we discuss the physiological effects and pathological significance of m5C modifications in multiple diseases, as well as their therapeutic potential, thereby providing new perspectives for disease treatment and prognosis.

The osteoblast cell growth and cancer cell inhibition of titanium (Ti) metal implant coated with polyvinyl alcohol (PVA) reinforced hydroxyapatite (HAP) composite were investigated. The fibrous composite of PVA/HAP/folic acid (FA)/Methotrexate (MTX) was coated on the surface of a titanium plate and observed with microscopy. During the PVA/HAP/FA/MTX composite's preparation, the functional changes and crystalline phases were observed through Fourier-transform infrared spectroscopy and X-ray diffraction analysis, respectively. The fiber composite had an average diameter of 19 nm and a greater mechanical strength (9660 Pa) than that of pure HAP (4965 Pa), critical to the fibrous scaffold under load-bearing applications. Biocompatibility, cell growth, and proliferation capability of the PVA/HAP/FA/MTX composite were studied in human bone marrow-derived stem cells (hBMSCs). The fiber composite was found to have excellent biocompatibility with significant cell growth, while the MTX-loaded PVA/HAP/FA composite showed cytotoxicity against A459 cells. The prepared fibrous composites will serve as a superior biomaterial for osteosarcoma-diseased bone repair after evidencing of in-vivo and clinical trials.

Serous ovarian carcinoma (SOC) is a gynecological malignancy with high mortality rates. Currently, there is a lack of reliable biomarkers for accurate SOC patient prognosis. Here, we analyzed SOC RNA-Seq data from The Cancer Genome Atlas (TCGA) to identify prognostic biomarkers. Through the pearson correlation analysis, univariate Cox regression analysis, and LASSO-penalized Cox regression analysis, we identified nine lncRNAs significantly associated with four types of RNA modification writers (m6A, m1A, APA, and A-I) and with the prognosis of SOC patients (P

As a significant tool to integrate information technology and education, dynamic mathematical software (DMS) has been widely concerned in recent years. However, how to better apply it to instruction practice deserves further exploration. Thus, we adopted the meta-analysis method to analyze the DMS-based experiments published between 2000 and 2020. A three-level meta-analysis of data from 107 studies involving 10,507 participants and 138 effect sizes revealed a moderate effect size (d = 0.632, 95% CI = [0.550, 0.713]). Moreover, moderator analyses showed that: (1) cultural background had significant moderating effects; (2) students performed better on near-transfer tests than far-transfer tests; (3) DMS used by students independently had better effects; (4) intervention duration had significant moderating effects; (5) some of the above significant moderating effects were unique after controlling for others. Overall, our findings suggest that DMS has positive effects on students' performance and teachers should be meticulous in designing their teaching plans.

The aim of this study is to develop a measurement tool that can determine the attitudes of social studies teachers and classroom teachers towards the use of current events in the social studies course. The scale consists of 23 five-point Likert-type items. The scale form consisting of 40 items prepared by the researchers was administered to a total of 394 teachers, including 303 classroom teachers and 91 social studies teachers working in different provinces of Turkey. As a result of the EFA, it was determined that the scale consists of 23 items and 2 sub-dimensions. The first sub-factor consisting of 14 items explains 40.44% of the variance of the related attitude variable, while the second sub-factor consisting of 9 items explains 12.99% of the variance of the related attitude variable. This two-factor structure explains 53.43% of the total variance. According to CFA analysis, values of X[superscript 2] / df = 2.73 (p = 0.000); RMSEA = 0.098; NFI = 0.90; CFI = 0.94; GFI = 0.77; NNFI = 0.97; and IFI = 0.94 were found. These findings reveal that the scale is a valid and reliable measurement tool to measure attitudes towards the use of current events in the social studies course. The original form of the scale is in Turkish.

Purpose: This study examined the impact of bilingualism on affective theory of mind (ToM) and social prioritization (SP) among autistic adults compared to neurotypical comparison participants. Method: Fifty-two (25 autistic, 27 neurotypical) adult participants (ages 21-35 years) with varying second language (L2) experience, ranging from monolingual to bilingual, completed an affective ToM task. A subset of this sample also completed a dynamic eye-tracking task designed to capture differences in time spent looking at social aspects of a scene (SP). Four language groups were compared on task performance (monolingual autism and neurotypical, bilingual autism and neurotypical), followed by analyses examining the contribution of L2 experience, autism characteristics, and social face prioritization on affective ToM, controlling for verbal IQ. Finally, we conducted an analysis to identify the contribution of SP on affective ToM when moderated by autism status and L2 experience, controlling for verbal IQ. Results: The monolingual autism group performed significantly worse than the other three groups (bilingual autism, monolingual neurotypical, and bilingual neurotypical) on the affective ToM task; however, there were no significant differences between the bilingual autism group compared to the monolingual and bilingual neurotypical groups. For autistic individuals, affective ToM capabilities were positively associated with both verbal IQ and L2 experience but did not relate to autism characteristics or SP during eye tracking. Neurotypical participants showed greater SP during the eye-tracking task, and SP did not relate to L2 or autism characteristics for autistic individuals. SP and verbal IQ predicted affective ToM performance across autism and neurotypical groups, but this relationship was moderated by L2 experience; SP more strongly predicted affective ToM performance among participants with lower L2 experience (e.g., monolingual) and had less of an impact for those with higher L2 experience. Conclusion: This study provides support for a bilingual advantage in affective ToM for autistic individuals.

Purpose: Nonword repetition (NWR) has been described as a clinical marker of developmental language disorder (DLD), as NWR tasks consistently discriminate between DLD and typical development (TD) cross-linguistically, with Cantonese as the only reported exception. This study reexamines whether NWR is able to generate TD/DLD group differences in Cantonese-speaking children by reporting on a novel set of NWR stimuli that take into account factors known to affect NWR performance and group differentiation, including lexicality, sublexicality, length, and syllable complexity. Method: Sixteen Cantonese-speaking children with DLD and 16 age-matched children with TD repeated two sets of high-lexicality nonwords, where all constituent syllables are morphemic in Cantonese but meaningless when combined, and one set of low-lexicality nonwords, where all constituent syllables are nonmorphemic. Low-lexicality nonwords were further classified on sublexicality in terms of consonant-vowel (CV) combination attestedness (whether or not CV combinations in nonword syllables occur in real Cantonese words). Results: Children with DLD scored significantly below their peers with TD. Effect sizes showed that high-lexicality nonwords and nonword syllables with attested CV combinations offered the greatest TD/DLD group differentiation. Nonword length and syllable complexity did not affect TD/DLD group differentiation. Conclusions: NWR can capture TD/DLD group differences in Cantonese-speaking children. Lexicality and sublexicality effects must be considered in designing NWR stimuli for TD/DLD group differentiation. Future studies should replicate the present study on a larger sample size and a younger population as well as examine the diagnostic accuracy of this NWR test.