Development and validation of the newly developed Preschool Theory of Mind Assessment (ToMA-P).

Introduction: Theory of mind (ToM) refers to the ability to understand and attribute mental states to oneself and others. A ToM measure is warranted for preschool children to assess their ToM development from a multidimensional perspective (i.e., cognitive and affective dimensions). This study aimed to develop the Preschool Theory of Mind Assessment (ToMA-P) and to evaluate its construct validity and applicability. Methods: The ToMA-P was developed based on comprehensive literature review and revised with expert panel feedback. Its psychometric properties were evaluated in 205 typically developing preschoolers with Rasch analysis for its dimensionality, item difficulties, and convergent validity. Results: The results indicated that all ToMA-P items, except for one, fit the hypothesized two-dimensional construct. The item difficulties in the cognitive and affective dimensions followed developmental sequences. The ToMA-P scores exhibited good convergent validity, as evidenced by its significant correlations with age, verbal comprehension, adaptive functions, and daily ToM performance (p < 0.05). Children's responses and behaviors also showed that the ToMA-P has good applicability. Discussion: This study provides empirical evidence that the ToMA-P measures cognitive and affective ToM following developmental sequences, and that it has potential as a clinical tool for assessing ToM in preschool children.

Hyaluronic acid-based injectable formulation developed to mitigate metastasis and radiation-induced skin fibrosis in breast cancer treatment.

The standard treatment for early-stage breast cancer involves breast-conserving surgery followed by adjuvant radiotherapy. However, approximately 20 % of patients experience distant metastasis, and adjuvant radiotherapy often leads to radiation-induced skin fibrosis (RISF). In this study, we develop an on-site injectable formulation composed of selenocystamine (SeCA) and hyaluronic acid (HyA), referred to as SeCA cross-linked HyA (SCH) agent, and investigate its potential to mitigate metastasis and prevent RISF associated with breast cancer therapy. SCH agents are synthesized using the nanoprecipitation method to modulate cell-cell tight junctions and tissue inflammation. The toxicity assessments reveal that SCH agents with a higher Se content (Se payload 17.4 µg/mL) are well tolerated by L929 cells compared to SeCA (Se payload 3.2 µg/mL). In vitro, SCH agents significantly enhance cell-cell tight junctions and effectively mitigate migration and invasion of breast cancer cells (4T1). In vivo, SCH agents mitigate distant lung metastasis. Furthermore, in animal models, SCH agents reduce RISF and promote wound repair. These findings highlight the potential of SCH agents as a novel therapeutic formulation for effectively mitigating metastasis and reducing RISF. This holds great promise for improving clinical outcomes in breast cancer patients undergoing adjuvant radiotherapy.

Rice straw-derived chitosan-enhanced plasticizers as biologically and environmentally friendly alternatives for sustainable materials.

Plasticizers like Bis(2-ethylhexyl)phthalate (DEHP) are commonly used to enhance plastic properties but pose environmental and health risks. This study successfully derived plasticizers X and Y from rice straws, demonstrating efficacy in chitosan polymer coatings. Chitosan-based polymers exhibit exceptional hardness, with a value of 300 MPa, due to their enriched structure and robust chitosan bonding. This surpasses the hardness of DEHP. Zebrafish exposure over 5 days revealed that X and Y had no significant behavioral impact, while DEHP caused noticeable toxic effects. Maternal DEHP exposure reduced placental cell growth, unlike X and Y, which had no adverse effects on uterine differentiation or placenta formation, suggesting their safety in human pregnancy. The successful development of X and Y represents a crucial step towards greener plasticizers, addressing environmental concerns and promoting safer alternatives in various industries.

Histone Trimethylations and HDAC5 Regulate Spheroid Subpopulation and Differentiation Signaling of Human Adipose-Derived Stem Cells.

Human adipose-derived stem cells (ASCs) have shown immense potential for regenerative medicine. Our previous work demonstrated that chitosan nano-deposited surfaces induce spheroid formation and differentiation of ASCs for treating sciatic nerve injuries. However, the underlying cell fate and differentiation mechanisms of ASC-derived spheroids remain unknown. Here, we investigate the epigenetic regulation and signaling coordination of these therapeutic spheroids. During spheroid formation, we observed significant increases in histone 3 trimethylation at lysine 4 (H3K4me3), lysine 9 (H3K9me3), and lysine 27 (H3K27me3), accompanied by increased histone deacetylase (HDAC) activities and decreased histone acetyltransferase activities. Additionally, HDAC5 translocated from the cytoplasm to the nucleus, along with increased nuclear HDAC5 activities. Utilizing single-cell RNA sequencing (scRNA-seq), we analyzed the chitosan-induced ASC spheroids and discovered distinct cluster subpopulations, cell fate trajectories, differentiation traits, and signaling networks using the 10x Genomics platform, R studio/language, and the Ingenuity Pathway Analysis (IPA) tool. Specific subpopulations were identified within the spheroids that corresponded to a transient reprogramming state (Cluster 6) and the endpoint cell state (Cluster 3). H3K4me3 and H3K9me3 were discovered as key epigenetic regulators by IPA to initiate stem cell differentiation in Cluster 6 cells, and confirmed by qPCR and their respective histone methyltransferase inhibitors: SNDX-5613 (a KMT2A inhibitor for H3K4me3) and SUVi (an SUV39H1 inhibitor for H3K9me3). Moreover, H3K9me3 and HDAC5 were involved in regulating downstream signaling and neuronal markers during differentiation in Cluster 3 cells. These findings emphasize the critical role of epigenetic regulation, particularly H3K4me3, H3K9me3, and HDAC5, in shaping stem cell fate and directing lineage-specific differentiation.

Interpreting the results of explicit and applied theory of mind collectively in autistic children: A solution from Rasch analysis.

LAY ABSTRACT: Theory of mind is an ability to infer others' mental states, which is a foundation for generating appropriate social responses. Theory of mind can be conceptually divided into two related but distinguishable constructs: explicit theory of mind (conceptual knowledge/information about others' mental states) and applied theory of mind (the ability to use theory of mind skills in real-life contexts). Although these two theory of mind scores can be described by the percentages of children in the early, basic, and advanced developmental stages, the resulting information may not be sufficient to determine the corresponding relationships between these two theory of mind constructs or identify children with mismatched theory of mind abilities (e.g. children who have difficulty in effectively applying their theory of mind knowledge in real-life contexts). To resolve these limitations, methods for simultaneously interpreting the relationships between the two theory of mind scores are proposed. Based on the findings, each applied theory of mind score can reflect multiple scores of explicit theory of mind. In particular, the results do not take measurement error into consideration, which would make them more ambiguous. Therefore, the scores of applied theory of mind should be interpreted carefully, given that children who have the same applied theory of mind score may actually have high or low explicit theory of mind. Regarding the method for joint interpretation, cutoff scores were selected to identify children who have mismatched theory of mind abilities (high explicit theory of mind with low applied theory of mind or low explicit theory of mind with high applied theory of mind) and determine the priority for interventions.

Synergistically Enhancing Immunotherapy Efficacy in Glioblastoma with Gold-Core Silica-Shell Nanoparticles and Radiation.

Purpose: Glioblastoma is a highly aggressive brain tumor with universally poor outcomes. Recent progress in immune checkpoint inhibitors has led to increased interest in their application in glioblastoma. Nonetheless, the unique immune milieu in the brain has posed remarkable challenges to the efficacy of immunotherapy. We aimed to leverage the radiation-induced immunogenic cell death to overcome the immunosuppressive network in glioblastoma. Methods: We developed a novel approach using the gold-core silica-shell nanoparticles (Au@SiO2 NPs) in combination with low-dose radiation to enhance the therapeutic efficacy of the immune checkpoint inhibitor (atezolizumab) in brain tumors. The biocompatibility, immune cell recruitment, and antitumor ability of the combinatorial strategy were determined using in vitro assays and in vivo models. Results: Our approach successfully induced the migration of macrophages towards brain tumors and promoted cancer cell apoptosis. Subcutaneous tumor models demonstrated favorable safety profiles and significantly enhanced anticancer effects. In orthotopic brain tumor models, the multimodal therapy yielded substantial prognostic benefits over any individual modalities, achieving an impressive 40% survival rate. Conclusion: In summary, the combination of Au@SiO2 NPs and low-dose radiation holds the potential to improve the clinical efficacy of immune checkpoint inhibitors. The synergetic strategy modulates tumor microenvironments and enhances systemic antitumor immunity, paving a novel way for glioblastoma treatment.

Generational effects and abnormalities in craniofacial chondrogenesis in zebrafish (Danio rerio) embryos upon maternal exposure to estrogen endocrine disrupting chemicals.

Bisphenol A (BPA) and diethyl phthalate (DEP) are estrogenic endocrine disrupting chemicals (EEDCs). The present study reconfirmed that the angle of the ceratohyal cartilage (CH) in embryos were larger from maternal BPA and E2, but smaller from DEP compared to the control. However, it is still unknown whether both the BPA and DEP chemicals disrupted the action of E2 and thereby influence the estrogen signaling pathways. Additionally, it remains unclear whether they also disrupted certain related genes in the migratory pathways of neural crest cells (NCCs) in their offspring. The present data showed that nuclear estrogen receptors and membrane estrogen receptors have different disrupted profiles among female zebrafish exposed to BPA (F-BPA), and DEP (F-DEP), and external E2 (F-E2). However, certain related genes in the migratory pathways of NCCs in embryos from F-BPA and F-E2 such as the sox10, chm1, and tgfbr1a mRNA expressions showed a positive relationship compared with CH angles; the gene expressions of sox9a, smad3, and col2a1a and the CH angles of embryos exhibited an opposite relationship upon F-DEP treatments. Thus, we suggested that the genes involved in NCCs migration were potentially induced by the residual maternal DEP contents. Two sets of genes, chm1/tgfb3 and chm1/gper1, exhibited an identical profile in the ovary and its offspring at 2 h of post fertilization upon F-E2 and F-BPA treatments, respectively. We suggested that the maternal mRNA from female to embryos were transferred before the maternal-to-zygotic transition stage.

Adipose-derived stem cells modulate neuroinflammation and improve functional recovery in chronic constriction injury of the rat sciatic nerve.

Introduction: Compressive neuropathy, a common chronic traumatic injury of peripheral nerves, leads to variable impairment in sensory and motor function. Clinical symptoms persist in a significant portion of patients despite decompression, with muscle atrophy and persistent neuropathic pain affecting 10%-25% of cases. Excessive inflammation and immune cell infiltration in the injured nerve hinder axon regeneration and functional recovery. Although adipose-derived stem cells (ASCs) have demonstrated neural regeneration and immunomodulatory potential, their specific effects on compressive neuropathy are still unclear. Methods: We conducted modified CCI models on adult male Sprague-Dawley rats to induce irreversible neuropathic pain and muscle atrophy in the sciatic nerve. Intraneural ASC injection and nerve decompression were performed. Behavioral analysis, muscle examination, electrophysiological evaluation, and immunofluorescent examination of the injured nerve and associated DRG were conducted to explore axon regeneration, neuroinflammation, and the modulation of inflammatory gene expression. Transplanted ASCs were tracked to investigate potential beneficial mechanisms on the local nerve and DRG. Results: Persistent neuropathic pain was induced by chronic constriction of the rat sciatic nerve. Local ASC treatment has demonstrated robust beneficial outcomes, including the alleviation of mechanical allodynia, improvement of gait, regeneration of muscle fibers, and electrophysiological recovery. In addition, locally transplanted ASCs facilitated axon remyelination, alleviated neuroinflammation, and reduced inflammatory cell infiltration of the injured nerve and associated dorsal root ganglion (DRG). Trafficking of the transplanted ASC preserved viability and phenotype less than 7 days but contributed to robust immunomodulatory regulation of inflammatory gene expression in both the injured nerve and DRG. Discussion: Locally transplanted ASC on compressed nerve improve sensory and motor recoveries from irreversible chronic constriction injury of rat sciatic nerve via alleviation of both local and remote neuroinflammation, suggesting the promising role of adjuvant ASC therapies for clinical compressive neuropathy.

A spatiotemporal barrier formed by Follistatin is required for left-right patterning.

How left-right (LR) asymmetry emerges in a patterning field along the anterior-posterior axis remains an unresolved problem in developmental biology. Left-biased Nodal emanating from the LR organizer propagates from posterior to anterior (PA) and establishes the LR pattern of the whole embryo. However, little is known about the regulatory mechanism of the PA spread of Nodal and its asymmetric activation in the forebrain. Here, we identify bilaterally expressed Follistatin (Fst) as a regulator blocking the propagation of the zebrafish Nodal ortholog Southpaw (Spaw) in the right lateral plate mesoderm (LPM), and restricting Spaw transmission in the left LPM to facilitate the establishment of a robust LR asymmetric Nodal patterning. In addition, Fst inhibits the Activin-Nodal signaling pathway in the forebrain thus preventing Nodal activation prior to the arrival, at a later time, of Spaw emanating from the left LPM. This contributes to the orderly propagation of asymmetric Nodal activation along the PA axis. The LR regulation function of Fst is further confirmed in chick and frog embryos. Overall, our results suggest that a robust LR patterning emerges by counteracting a Fst barrier formed along the PA axis.

Hybrid optimization algorithm for thermal displacement compensation of computer numerical control machine tool using regression analysis and fuzzy inference.

During the machining process, the computer numerical control machine is susceptible to variations in ambient temperature, cutting heat, and friction within the transmission parts, which generate different heat sources. These heat sources affect the machine structure in different ways, causing deformation of the machine and displacement of the tooltip and workpiece position, ultimately resulting in deviations in machining accuracy. The amount of thermal drift depends on several factors, including the material of the machine components, the cutting conditions, the duration of the machining process, and the environment. This study proposes a hybrid optimization algorithm to optimize the thermal variables of computer numerical control machine tool spindles. The proposed approach combines regression analysis and fuzzy inference to model the thermal behavior of the spindle. Spindle speed and 16 temperature measurement points distributed on the machine are input factors, while the spindle's axial thermal error is considered an output factor. This study develops a regression equation for each speed to account for the different temperature rise slopes and spindle thermal variations at different speeds. The experimental results show that the hybrid thermal displacement compensation framework proposed in this study effectively reduces the thermal displacement error caused by spindle temperature variation. Furthermore, the study finds that the model can be adapted to significant variations in environmental conditions by limiting the machining speed range, which significantly reduces the amount of data needed for model adaptation and shortens the adaptation time of the thermal displacement compensation model. As a result, this framework can indirectly improve product yield. The effects observed in this study are remarkable.

Therapeutic potential of nanoceria pretreatment in preventing the development of urological chronic pelvic pain syndrome: Immunomodulation via reactive oxygen species scavenging and SerpinB2 downregulation.

Urological chronic pelvic pain syndrome (UCPPS) manifests as pelvic pain with frequent urination and has a 10% prevalence rate without effective therapy. Nanoceria (cerium oxide nanoparticles [CNPs]) were synthesized in this study to achieve potential long-term pain relief, using a commonly used UCPPS mouse model with cyclophosphamide-induced cystitis. Transcriptome sequencing analysis revealed that serpin family B member 2 (SerpinB2) was the most upregulated marker in mouse bladder, and SerpinB2 was downregulated with CNP pretreatment. The transcriptome sequencing analysis results agreed with quantitative polymerase chain reaction and western blot analysis results for the expression of related mRNAs and proteins. Analysis of Gene Expression Omnibus (GEO) datasets revealed that SerpinB2 was a differentially upregulated gene in human UCPPS. In vitro SerpinB2 knockdown downregulated proinflammatory chemokine expression (chemokine receptor CXCR3 and C-X-C motif chemokine ligand 10) upon treatment with 4-hydroperoxycyclophosphamide. In conclusion, CNP pretreatment may prevent the development of UCPPS, and reactive oxygen species (ROS) scavenging and SerpinB2 downregulation may modulate the immune response in UCPPS.

Factorial Validity of the Theory of Mind Inventory-2 in Typically Developing Children.

The Theory of Mind Inventory-2 (ToMI-2) is a promising measure for assessing theory of mind (ToM) and social-related functions. However, limited evidence on its factorial validity hampers score interpretation. To examine the factorial validity, confirmatory factor analysis for two currently-available structures was performed in 420 typically developing children aged three to seven years. One, the development-based structure, contains three stages of ToM development: the early, basic, and advanced ToM stages. The other, the social-related structure, comprises three social-related ToM functions: emotion recognition, mental state term comprehension, and pragmatics. The results showed that these structures and the unidimensionality of each domain were not supported even after modifications. Thus, further revisions and examinations of the underlying structures of the ToMI-2 are needed.

Autologous Platelet-Rich Growth Factor Reduces M1 Macrophages and Modulates Inflammatory Microenvironments to Promote Sciatic Nerve Regeneration.

The failure of peripheral nerve regeneration is often associated with the inability to generate a permissive molecular and cellular microenvironment for nerve repair. Autologous therapies, such as platelet-rich plasma (PRP) or its derivative platelet-rich growth factors (PRGF), may improve peripheral nerve regeneration via unknown mechanistic roles and actions in macrophage polarization. In the current study, we hypothesize that excessive and prolonged inflammation might result in the failure of pro-inflammatory M1 macrophage transit to anti-inflammatory M2 macrophages in large nerve defects. PRGF was used in vitro at the time the unpolarized macrophages (M0) macrophages were induced to M1 macrophages to observe if PRGF altered the secretion of cytokines and resulted in a phenotypic change. PRGF was also employed in the nerve conduit of a rat sciatic nerve transection model to identify alterations in macrophages that might influence excessive inflammation and nerve regeneration. PRGF administration reduced the mRNA expression of tumor necrosis factor-α (TNFα), interleukin-1ß (IL-1ß), and IL-6 in M0 macrophages. Increased CD206 substantiated the shift of pro-inflammatory cytokines to the M2 regenerative macrophage. Administration of PRGF in the nerve conduit after rat sciatic nerve transection promoted nerve regeneration by improving nerve gross morphology and its targeted gastrocnemius muscle mass. The regenerative markers were increased for regrown axons (protein gene product, PGP9.5), Schwann cells (S100ß), and myelin basic protein (MBP) after 6 weeks of injury. The decreased expression of TNFα, IL-1ß, IL-6, and CD68+ M1 macrophages indicated that the inflammatory microenvironments were reduced in the PRGF-treated nerve tissue. The increase in RECA-positive cells suggested the PRGF also promoted angiogenesis during nerve regeneration. Taken together, these results indicate the potential role and clinical implication of autologous PRGF in regulating inflammatory microenvironments via macrophage polarization after nerve transection.

Identification of Novel Vascular Genes Downstream of Islet2 and Nr2f1b Transcription Factors.

The genetic regulation of vascular development is not elucidated completely. We previously characterized the transcription factors Islet2 (Isl2) and Nr2f1b as being critical for vascular growth. In this study, we further performed combinatorial microarrays to identify genes that are potentially regulated by these factors. We verified the changed expression of several targets in isl2/nr2f1b morphants. Those genes expressed in vessels during embryogenesis suggested their functions in vascular development. We selectively assayed a potential target follistatin a (fsta). Follistatin is known to inhibit BMP, and BMP signaling has been shown to be important for angiogenesis. However, the fsta's role in vascular development has not been well studied. Here, we showed the vascular defects in ISV growth and CVP patterning while overexpressing fsta in the embryo, which mimics the phenotype of isl2/nr2f1b morphants. The vascular abnormalities are likely caused by defects in migration and proliferation. We further observed the altered expression of vessel markers consistent with the vascular defects in (fli:fsta) embryos. We showed that the knockdown of fsta can rescue the vascular defects in (fli:fsta) fish, suggesting the functional specificity of fsta. Moreover, the decreased expression of fsta rescues abnormal vessel growth in isl2 and nr2f1b morphants, indicating that fsta functions downstream of isl2/nr2f1b. Lastly, we showed that Isl2/Nr2f1b control vascular development, via Fsta-BMP signaling in part. Collectively, our microarray data identify many interesting genes regulated by isl2/nr2f1b, which likely function in the vasculature. Our research provides useful information on the genetic control of vascular development.

Interpreting the Evidence of Body Mass Index in Relation to Mental Health Status in Community-Dwelling Older Adults.

INTRODUCTION: Maintaining a better physical and mental health status is an important issue for older adults in their later life. Thus, the study's purpose was to evaluate the association between body mass index (BMI) and mental health status in older adults aged 65 years old or above residing in communities of Taipei City, Taiwan. METHODS: We carried out secondary data analysis with data from a volunteer-based health examination project for older adults >65 years old residing in Taipei City from 2006 to 2010 with a retrospective study design. BMI, calculated by standardized measuring procedures for height and weight, and mental health status, evaluated by 5-item Brief Symptom Rating Scale (BSRS-5), were collected at their first visits of health examination. A BSRS-5 score ≥6 was considered an inferior mental health status for the outcome. In statistical analysis, univariable and multivariable logistic regressions were adopted to estimate the relative risk of inferior mental health status, treating BMI as the major exposure of interest. RESULTS: A total of 90,576 subjects were involved, with a mean age of 73.38 years old (SD = 6.64 years) and 49.21% females. With confounders controlled, compared to normal or overweight (23 ≤ BMI <30), an adjusted OR of 1.23 (95% CI: 1.18, 1.29) on inferior mental health status was detected for the underweight group (BMI <23) significantly. Adjusted OR for those obese (BMI ≧30) was 0.87 (95% CI: 0.79, 0.96). Significantly elevated ORs of underweight were found for both genders, but the significantly protective effect of obese was only detected for females. CONCLUSION: Keeping an appropriate weight or even being overweighted might be beneficial for older adults dwelling in the community, especially for males.

ProDisc-C versus anterior cervical discectomy and fusion for the surgical treatment of symptomatic cervical disc disease: two-year outcomes of Asian prospective randomized controlled multicentre study.

PURPOSE: Our study aimed to evaluate non-inferiority of ProDisc-C to anterior cervical discectomy and fusion (ACDF) in terms of clinical outcomes and incidence of adjacent segment disease (ASD) at 24-months post-surgery in Asian patients with symptomatic cervical disc disease (SCDD). METHODS: This multicentre, prospective, randomized controlled trial was initiated after ethics committee approval at nine centres (China/Hong Kong/Korea/Singapore/Taiwan). Patients with single-level SCDD involving C3-C7-vertebral segments were randomized (2:1) into: group-A treated with ProDisc-C and group-B with ACDF. Assessments were conducted at baseline, 6-weeks, 3/6/12/18/24-months post-surgery and annually thereafter till 84-months. Primary endpoint was overall success at 24-months, defined as composite of: (1) ≥ 20% improvement in neck disability index (NDI); (2) maintained/improved neurologic parameters; (3) no implant removal/revision/re-operation at index level; and (4) no adverse/severe/life-threatening events. RESULTS: Of 120 patients (80ProDisc-C,40ACDF), 76 and 37 were treated as per protocol (PP). Overall success (PP) was 76.5% in group-A and 81.8% in group-B at 24-months (p = 0.12), indicating no clear non-inferiority of ProDisc-C to ACDF. Secondary outcomes improved for both groups with no significant inter-group differences. Occurrence of ASD was higher in group-B with no significant between-group differences. Range of motion (ROM) was sustained with ProDisc-C but lost with ACDF at 24-months. CONCLUSION: Cervical TDR with ProDisc-C is feasible, safe, and effective for treatment of SCDD in Asians. No clear non-inferiority was demonstrated between ProDisc-C and ACDF. However, patients treated with ProDisc-C demonstrated significant improvement in NDI, neurologic success, pain scores, and 36-item-short-form survey, along with ROM preservation at 24-months. Enrolment difficulties resulted in inability to achieve pre-planned sample size to prove non-inferiority. Future Asian-focused, large-scale studies are needed to establish unbiased efficacy of ProDisc-C to ACDF.

Mineral Nanomedicine to Enhance the Efficacy of Adjuvant Radiotherapy for Treating Osteosarcoma.

It is vital to remove residual tumor cells after resection to avoid the recurrence and metastasis of osteosarcoma. In this study, a mineral nanomedicine, europium-doped calcium fluoride (CaF2:Eu) nanoparticles (NPs), is developed to enhance the efficacy of adjuvant radiotherapy (i.e., surgical resection followed by radiotherapy) for tumor cell growth and metastasis of osteosarcoma. In vitro studies show that CaF2:Eu NPs (200 µg/mL) exert osteosarcoma cell (143B)-selective toxicity and migration-inhibiting effects at a Eu dopant amount of 2.95 atomic weight percentage. These effects are further enhanced under X-ray irradiation (6 MeV, 4 Gy). Furthermore, in vivo tests show that intraosseous injection of CaF2:Eu NPs and X-ray irradiation have satisfactory therapeutic efficacy in controlling primary tumor size and inhibiting primary tumor metastasis. Overall, our results suggest that CaF2:Eu NPs with their osteosarcoma cell (143B)-selective toxicity and migration-inhibiting effects combined with radiotherapy might be nanomedicines for treating osteosarcoma after tumor resection.

Classifying microscopic images as acute lymphoblastic leukemia by Resnet ensemble model and Taguchi method.

BACKGROUND: Researchers have attempted to apply deep learning methods of artificial intelligence for rapidly and accurately detecting acute lymphoblastic leukemia (ALL) in microscopic images. RESULTS: A Resnet101-9 ensemble model was developed for classifying ALL in microscopic images. The proposed Resnet101-9 ensemble model combined the use of the nine trained Resnet-101 models with a majority voting strategy. Each trained Resnet-101 model integrated the well-known pre-trained Resnet-101 model and its algorithm hyperparameters by using transfer learning method to classify ALL in microscopic images. The best combination of algorithm hyperparameters for the pre-trained Resnet-101 model was determined by Taguchi experimental method. The microscopic images used for training of the pre-trained Resnet-101 model and for performance tests of the trained Resnet-101 model were obtained from the C-NMC dataset. In experimental tests of performance, the Resnet101-9 ensemble model achieved an accuracy of 85.11% and an F1-score of 88.94 in classifying ALL in microscopic images. The accuracy of the Resnet101-9 ensemble model was superior to that of the nine trained Resnet-101 individual models. All other performance measures (i.e., precision, recall, and specificity) for the Resnet101-9 ensemble model exceeded those for the nine trained Resnet-101 individual models. CONCLUSION: Compared to the nine trained Resnet-101 individual models, the Resnet101-9 ensemble model had superior accuracy in classifying ALL in microscopic images obtained from the C-NMC dataset.

Repairing TALEN-mediated double-strand break by microhomology-mediated recombination in tobacco plastids generates abundant subgenomic DNA.

Transcription activator-like effector nuclease (TALEN) technology has been widely used to edit nuclear genomes in plants but rarely for editing organellar genomes. In addition, ciprofloxacin, commonly used to cause the double-strand break of organellar DNA for studying the repair mechanism in plants, confers no organellar selectivity and site-specificity. To demonstrate the feasibility of TALEN-mediated chloroplast DNA editing and to use it for studying the repair mechanism in plastids, we developed a TALEN-mediated editing technology fused with chloroplast transit peptide (cpTALEN) to site-specifically edit the rpoB gene via Agrobacteria-mediated transformation of tobacco leaf. Transgenic plants showed various degrees of chlorotic phenotype. Repairing damaged plastid DNA resulted in point mutation, large deletion and small inversion surrounding the rpoB gene by homologous recombination and/or microhomology-mediated recombination. In an albino line, microhomology-mediated recombination via a pair of 12-bp direct repeats between rpoC2 and ycf2 genes generated the chimeric ycf2-rpoC2 subgenome, with the level about 3- to 5-fold higher for subgenomic DNA than ycf2. Additionally, the expression of chimeric ycf2-rpoC2 transcripts versus ycf2 mRNA agreed well with the level of corresponding DNA. The ycf2-rpoC2 subgenomic DNA might independently and preferentially replicate in plastids.

Robust optimization of convolutional neural networks with a uniform experiment design method: a case of phonocardiogram testing in patients with heart diseases.

BACKGROUND: Heart sound measurement is crucial for analyzing and diagnosing patients with heart diseases. This study employed phonocardiogram signals as the input signal for heart disease analysis due to the accessibility of the respective method. This study referenced preprocessing techniques proposed by other researchers for the conversion of phonocardiogram signals into characteristic images composed using frequency subband. Image recognition was then conducted through the use of convolutional neural networks (CNNs), in order to classify the predicted of phonocardiogram signals as normal or abnormal. However, CNN requires the tuning of multiple hyperparameters, which entails an optimization problem for the hyperparameters in the model. To maximize CNN robustness, the uniform experiment design method and a science-based methodical experiment design were used to optimize CNN hyperparameters in this study. RESULTS: An artificial intelligence prediction model was constructed using CNN, and the uniform experiment design method was proposed to acquire hyperparameters for optimal CNN robustness. The results indicate Filters ([Formula: see text]), Stride ([Formula: see text]), Activation functions ([Formula: see text]), and Dropout ([Formula: see text]) to be significant factors considerably influencing the ability of CNN to distinguish among heart sound states. Finally, the confirmation experiment was conducted, and the hyperparameter combination for optimal model robustness was Filters ([Formula: see text]) = 32, Kernel Size ([Formula: see text] = 3 × 3, Stride ([Formula: see text]) = (1,1), Padding ([Formula: see text] as same, Optimizer ([Formula: see text] as the stochastic gradient descent, Activation functions ([Formula: see text]) as relu, and Dropout ([Formula: see text]) = 0.544. With this combination of parameters, the model had an average prediction accuracy rate of 0.787 and standard deviation of 0. CONCLUSION: In this study, phonocardiogram signals were used for the early prediction of heart diseases. The science-based and methodical uniform experiment design was used for the optimization of CNN hyperparameters to construct a CNN with optimal robustness. The results revealed that the constructed model exhibited robustness and an acceptable accuracy rate. Other literature has failed to address hyperparameter optimization problems in CNN; a method is subsequently proposed for robust CNN optimization, thereby solving this problem.