Intonation words in initial intentional communication of Mandarin-speaking children.

Intonation words play a very important role in early childhood language development and serve as a crucial entry point for studying children's language acquisition. Utilizing a natural conversation corpus, this paper thoroughly examines the intentional communication scenes of five Mandarin-speaking children before the age of 1;05 (17 months). We found that children produced a limited yet high-frequency set of intonation words such as " [a], [æ], [ε], [ən], [ə], eng [əŋ], [o], and [i]." These intonation words do not express the children's emotional attitudes toward propositions or events; rather, they are utilized within the frameworks of imperative, declarative, and interrogative intents. The children employ non-verbal, multimodal means such as pointing, gesturing, and facial expressions to actively convey or receive commands, provide or receive information, and inquire or respond. The data suggests that the function of intonation words is essentially equivalent to holophrases, indicating the initial stage of syntactic acquisition, which is a milestone in early syntactic development. Based on the cross-linguistic universality of intonation word acquisition and its inherited relationship with pre-linguistic intentional vocalizations, this paper proposes that children's syntax is initiated by the prosodic features of intonation. The paper also contends that intonation words, as the initial form of human vocal language in individual development, naturally extend from early babbling, emotional vocalizations, or sound expressions for changing intentions. They do not originate from spontaneous gesturing, which seems to have no necessary evolutionary relationship with the body postures that chimpanzees use to change intentions, as suggested by existing research. Human vocal language and non-verbal multimodal means are two parallel and non-contradictory forms of communication, with no apparent evidence of the former inheriting from the latter.

Development and evaluation of multimodal AI for diagnosis and triage of ophthalmic diseases using ChatGPT and anterior segment images: protocol for a two-stage cross-sectional study.

Introduction: Artificial intelligence (AI) technology has made rapid progress for disease diagnosis and triage. In the field of ophthalmic diseases, image-based diagnosis has achieved high accuracy but still encounters limitations due to the lack of medical history. The emergence of ChatGPT enables human-computer interaction, allowing for the development of a multimodal AI system that integrates interactive text and image information. Objective: To develop a multimodal AI system using ChatGPT and anterior segment images for diagnosing and triaging ophthalmic diseases. To assess the AI system's performance through a two-stage cross-sectional study, starting with silent evaluation and followed by early clinical evaluation in outpatient clinics. Methods and analysis: Our study will be conducted across three distinct centers in Shanghai, Nanjing, and Suqian. The development of the smartphone-based multimodal AI system will take place in Shanghai with the goal of achieving ≥90% sensitivity and ≥95% specificity for diagnosing and triaging ophthalmic diseases. The first stage of the cross-sectional study will explore the system's performance in Shanghai's outpatient clinics. Medical histories will be collected without patient interaction, and anterior segment images will be captured using slit lamp equipment. This stage aims for ≥85% sensitivity and ≥95% specificity with a sample size of 100 patients. The second stage will take place at three locations, with Shanghai serving as the internal validation dataset, and Nanjing and Suqian as the external validation dataset. Medical history will be collected through patient interviews, and anterior segment images will be captured via smartphone devices. An expert panel will establish reference standards and assess AI accuracy for diagnosis and triage throughout all stages. A one-vs.-rest strategy will be used for data analysis, and a post-hoc power calculation will be performed to evaluate the impact of disease types on AI performance. Discussion: Our study may provide a user-friendly smartphone-based multimodal AI system for diagnosis and triage of ophthalmic diseases. This innovative system may support early detection of ocular abnormalities, facilitate establishment of a tiered healthcare system, and reduce the burdens on tertiary facilities. Trial registration: The study was registered in ClinicalTrials.gov on June 25th, 2023 (NCT05930444).

Designing a doctor evaluation index system for an online medical platform based on the information system success model in China.

Objective: In the context of "internet + medical health" and emphasis on evaluation mechanism for medical and health talents in China, we design an evaluation index system for doctors on online medical platforms by synthesizing two patterns of existing online medical platforms, which is the first step to enhance the capabilities of doctors on online medical platforms. Methods: Based on the doctor evaluation model integrating information systems success model (ISS-DE model) and grounded theory, the evaluation indicators were obtained through expert interviews, offline medical institutions investigation, online platforms investigation, and literature research, and were assigned weights using the analytic hierarchy process (AHP) method. A working group composed of 23 experts was set up to review and determine the competency standards of doctors on the online medical platforms. Results: A new indicator framework covering 3 dimensions of system quality, service quality and information quality was constructed in this study. The index system included 3 first-level indicators, 8 s-level indicators and 60 third-level indicators, and each indicator was given different weightage. Conclusion: The complete index system constructed by the Delphi method in this study is suitable for China's online medical platforms, which will help to improve the quality of platforms and the ability of doctors, thus promoting the process of internet medical integration.

Low-temperature molten-salt synthesis of Co3O4 nanoparticles grown on MXene can rapidly remove ornidazole via peroxymonosulfate activation.

We further developed previous work on MXene materials prepared using molten salt methodology. We substituted single, with mixed salts, and reduced the melting point from >724 °C to <360 °C. Cobalt (Co) compounds were simultaneously etched and doped while the MXene material was created using various techniques in which Co compounds occur as Co3O4. The synthesized Co3O4/MXene compound was used as a peroxymonosulfate (PMS) activator that would generate free radicals to degrade antibiotic ornidazole (ONZ). Under optimal conditions, almost 100% of ONZ (30 mg/L) was degraded within 10 min. The Co3O4/MXene + PMS system efficiently degraded ONZ in natural water bodies, and had a broad pH adaptation range (4-11), and strong anion anti-interference. We investigated how the four active substances were generated using radical quenching and electron paramagnetic resonance (EPR) spectroscopy. We identified 12 ONZ intermediates by liquid chromatography-mass spectrometry and propose a plausible degradative mechanism.

Ultrasmall nitrogen-doped Cu0·92Co2·08O4 nanocrystal-decorated cerium dioxide nanoparticles for fast and complete degradation of ranitidine via permonosulfate activation.

A simple and efficient coagulation method was used for the rapid preparation of nitrogen-doped copper-cobalt oxide (N-Cu0.92Co2·08O4) supported on cerium dioxide (CeO2), that is, N-Cu0.92Co2·08O4@CeO2. A low concentration of N-Cu0.92Co2·08O4@CeO2 (0.15 g L-1) was shown to rapidly activate permonosulfate (PMS) (0.15 g L-1) to achieve 100% degradation of ranitidine within 10 min. A 100% degradation of ranitidine enabled by the catalyst was achieved over a wide range of pH (5.5-9.0), which could be completed within 8 min in the presence of anionic H2PO4-. Moreover, the N-Cu0.92Co2·08O4@CeO2 catalyst enabled more than 90% degradation of various typical antibiotics within 30 min, including tetracycline, sulfaixoxazole, and chloramphenicol, with degradation rates of 100%, 93.51%, and 90.01%, respectively. Even after four catalytic cycles, N-Cu0.92Co2·08O4@CeO2 could be regenerated to achieve 100% degradation of ranitidine. Electrochemical analysis demonstrated that the combination of N-Cu0.92Co2·08O4@CeO2 and PMS immediately produced a strong current density, thereby rapidly producing reactive oxygen species (ROS) with high performance for the degradation of the target pollutant. Combined ion quenching and electron paramagnetic resonance analyses indicated that the main ROS was the non-free radical 1O2. Finally, a plausible ranitidine degradation pathway was deduced based on liquid chromatography-mass spectrometry (LC-MS) analysis, wherein the toxic substance N-nitrosodimethylamine was not produced during the degradation process. In short, this study provides a new perspective for preparing ternary metal catalysts for advanced oxidation processes with practical application significance.

Stalled oligodendrocyte differentiation in IDH-mutant gliomas.

BACKGROUND: Roughly 50% of adult gliomas harbor isocitrate dehydrogenase (IDH) mutations. According to the 2021 WHO classification guideline, these gliomas are diagnosed as astrocytomas, harboring no 1p19q co-deletion, or oligodendrogliomas, harboring 1p19q co-deletion. Recent studies report that IDH-mutant gliomas share a common developmental hierarchy. However, the neural lineages and differentiation stages in IDH-mutant gliomas remain inadequately characterized. METHODS: Using bulk transcriptomes and single-cell transcriptomes, we identified genes enriched in IDH-mutant gliomas with or without 1p19q co-deletion, we also assessed the expression pattern of stage-specific signatures and key regulators of oligodendrocyte lineage differentiation. We compared the expression of oligodendrocyte lineage stage-specific markers between quiescent and proliferating malignant single cells. The gene expression profiles were validated using RNAscope analysis and myelin staining and were further substantiated using data of DNA methylation and single-cell ATAC-seq. As a control, we assessed the expression pattern of astrocyte lineage markers. RESULTS: Genes concordantly enriched in both subtypes of IDH-mutant gliomas are upregulated in oligodendrocyte progenitor cells (OPC). Signatures of early stages of oligodendrocyte lineage and key regulators of OPC specification and maintenance are enriched in all IDH-mutant gliomas. In contrast, signature of myelin-forming oligodendrocytes, myelination regulators, and myelin components are significantly down-regulated or absent in IDH-mutant gliomas. Further, single-cell transcriptomes of IDH-mutant gliomas are similar to OPC and differentiation-committed oligodendrocyte progenitors, but not to myelinating oligodendrocyte. Most IDH-mutant glioma cells are quiescent; quiescent cells and proliferating cells resemble the same differentiation stage of oligodendrocyte lineage. Mirroring the gene expression profiles along the oligodendrocyte lineage, analyses of DNA methylation and single-cell ATAC-seq data demonstrate that genes of myelination regulators and myelin components are hypermethylated and show inaccessible chromatin status, whereas regulators of OPC specification and maintenance are hypomethylated and show open chromatin status. Markers of astrocyte precursors are not enriched in IDH-mutant gliomas. CONCLUSIONS: Our studies show that despite differences in clinical manifestation and genomic alterations, all IDH-mutant gliomas resemble early stages of oligodendrocyte lineage and are stalled in oligodendrocyte differentiation due to blocked myelination program. These findings provide a framework to accommodate biological features and therapy development for IDH-mutant gliomas.

Temporal and spatial stability of the EM/PM molecular subtypes in adult diffuse glioma.

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.

Nanomanganese cobaltate-decorated halloysite nanotubes for the complete degradation of ornidazole via peroxymonosulfate activation.

Peroxymonosulfate (PMS) driven by halloysite nanotubes (HNTs) modified with nanomanganese cobaltate (MnCo2O4) generates reactive oxygen species (ROS) that offer high degradation efficiency and mineralization rates for many typical antibiotic pollutants, such as ornidazole (ONZ). The experimental results show that halloysite nanotubes (HNTs) modified with nanomanganese cobaltate (MnCo2O4@HNTs denoted as MCO@HNTs) can degrade ONZ completely over a wide pH range (6.08-11.00) with little influence of the pH value. MCO@HNTs + PMS exhibited higher catalytic activity and lower Co- and Mn-ion leaching rates. It also showed a strong anti-interference effect on natural lake water and anions. Additionally, PMS can be quickly activated and consumed in natural lakes to avoid secondary pollution. The roasting of MCO@HNTs showed good catalytic activity and stability after degrading ONZ. The combination of ion quenching and electron paramagnetic resonance (EPR) analysis illustrated that the MCO@HNTs + PMS system had a strong oxidation capacity, and the produced singlet oxygen (1O2) was the main ROS for ONZ degradation. The degradation pathway of ONZ via the MCO@HNTs + PMS system was proposed based on the types of intermediates determined via liquid chromatography-mass spectrometry (LC-MS). This comprehensive study shows the preparation of a simple, environmentally friendly, and cheap PMS activation catalyst that has practical application value in the treatment of antibiotic wastewater and provides a focus on actual water testing with residual amount of PMS.

DLKN-MLC: A Disease Prediction Model via Multi-Label Learning.

With the increasingly available electronic health records (EHR), disease prediction has recently gained immense research attention, where an accurate classifier needs to be trained to map the input prediction signals (e.g., symptoms, auxiliary examination results, etc.) to the estimated diseases for each patient. However, most of the current disease prediction models focus on the prediction of a single disease; in the medical field, a patient often suffers from multiple diseases (especially multiple chronic diseases) at the same time. Therefore, multi-disease prediction is of greater significance for patients' early intervention and treatment, but there is no doubt that multi-disease prediction has higher requirements for data extraction ability and greater complexity of classification. In this paper, we propose a novel disease prediction model DLKN-MLC. The model extracts the information in EHR through deep learning combined with a disease knowledge network, quantifies the correlation between diseases through NodeRank, and completes multi-disease prediction. in addition, we distinguished the importance of common disease symptoms, occasional disease symptoms and auxiliary examination results in the process of disease diagnosis. In empirical and comparative experiments on real EHR datasets, the Hamming loss, one-error rate, ranking loss, average precision, and micro-F1 values of the DLKN-MLC model were 0.2624, 0.2136, 0.2190, 88.21%, and 87.86%, respectively, which were better compared with those from previous methods. Extensive experiments on a real-world EHR dataset have demonstrated the state-of-the-art performance of our proposed model.

Amorphous Co@TiO2 heterojunctions: A high-performance and stable catalyst for the efficient degradation of sulfamethazine via peroxymonosulfate activation.

Persulfate-based advanced oxidation processes (AOPs) cannot easily achieve the efficient degradation of persistent organic pollutants (POPs) with high stability. In this study, a simple in situ precipitation method was used to prepare an amorphous Co@TiO2 heterojunction catalyst. The deposition of Co oxide on TiO2, which is relatively nontoxic, efficiently activated peroxymonosulfate (PMS) to degrade sulfamethazine (SMT) and reduce the leaching of Co ions (0.915%). A catalytic system prepared using 0.3 g L-1 Co@TiO2 and 0.5 g L-1 PMS could degrade SMT within 30 min with a degradation rate of 95.8%. Co@TiO2 could activate PMS over a wide pH range (5.00-9.00) to efficiently degrade other antibiotics and dyes. Radical-capture experiments and electron paramagnetic resonance analysis suggested that SMT degradation occurs through a combination of the free radical and non-radical pathways, in which singlet 1O2 played a major role. Owing to the novelty of the proposed composite materials, the degradation path of SMT, which was determined through liquid chromatography-mass spectrometry, differed from that reported previously. This study provides not only an advanced and renewable catalyst for SMT degradation but also a feasible strategy for designing materials for AOPs.

Nutrition Literacy Measurement Tool With Multiple Features for Chinese Adults.

BACKGROUND: Nutrition literacy is an emerging term which is increasingly used in policy and research. Progression is limited by the lack of an accepted method to measure nutrition literacy in Chinese adults, even as research in this area is growing. OBJECTIVE: The objective of this study is to develop a valid instrument to assess nutrition literacy in Chinese adults. METHODS: The process involved 2 steps: constructed nutrition literacy conceptual framework, and developed potential items of scale based on literature review; and conducted 2 rounds of Delphi consultation to select items of the preliminary questionnaire. RESULTS: In the Delphi survey, the content validity index for each domain, level, and dimension of nutrition literacy was 1.0, coefficient of variation was less than 0.10, and Kendall's coefficient of concordance was greater than 0.83. All of the 2 domains, 3 levels, and 6 dimensions initially formulated by our research team were reserved in the conceptual framework of nutrition literacy. Furthermore, a 43-item nutrition literacy measurement scale was established. Each item kept in the final scale reaches a high degree of concentration and a high degree of coordination, with the mean of importance ranging from 4.38 to 5.00. CONCLUSIONS: A nutrition literacy measurement scale with multiple features was established for Chinese adults, providing an operationalized tool to assess comprehensively nutrition literacy for research and practice in the field of nutrition, diet, and health.

RNA binding proteins: Linking mechanotransduction and tumor metastasis.

Mechanotransduction is the leading cellular process that mammalian cells adopted to receive and respond to various mechanical cues from their local microenvironment. Increasing evidence suggests that mechano-transduction is involved in many physiological and disease conditions, ranging from early embryonic development, organogenesis, to a variety of human diseases including cancer. Mechanotransduction is mediated through several classes of senor proteins on the cell surface, intracellular signaling mediators, and core transcriptional regulation networks. Dissecting the molecular mechanisms regulating mechanotransduction and their association with cancer metastasis has received much attention in recent years. RNA binding proteins (RBPs) are a special group of nucleic acid interacting factors that participate in many important cellular processes. In this review, we would like to summarize recent research progresses in understanding the role of RBPs-mediated regulation in mechanotransduction and cancer metastasis. Those intriguing findings will provide novel insights for the disease and guide the potential development of new therapeutic approaches.

Comparison of allelopathic effects of two typical invasive plants: Mikania micrantha and Ipomoea cairica in Hainan island.

Mikania micrantha and Ipomoea cairica are two invasive plants widely distribute and seriously damage in Hainan island. In this study, the leaves extracts of two weeds were collected and determined for their allelopathic potentials on Chrysanthemum coronarium. The phytotoxicity bioassay showed that when the extract concentration was 50 and 100 mg/ml, the inhibited effects of M. micrantha on growth of C. coronarium were greater than by I. cairica. However, when the extract concertation at 400 mg/ml, the opposite inhibited effects were observed. We speculated this phenomenon was caused by different allelopathic compounds. Therefore, using gas chromatography-mass spectrometry, 19 and 23 compounds were identified respectively, benzoic acid and cinnamic acid were the main components in the two leaves extracts, which were selected to carry out the further bioassays. Subsequent bioassay results showed the effects of two allelochemicals on morphological index and chlorophyll content and POD activity were all negative to C. coronarium, whereas the content of MDA and activity of SOD, CAT represented adverse changes. Moreover, the inhibitions by cinnamic acid were generally greater than those by benzoic acid. Thus, the phenolic acids played the most crucial roles in the allelopathic effccts of M. micrantha and I. cairica leaves extracts.

Validation of the Chinese version of the memory binding test for distinguishing amnestic mild cognitive impairment from cognitively normal elderly individuals.

BACKGROUND: Episodic memory starts to decline very early in the development of Alzheimer's disease (AD). Subtle impairments in memory binding may be detected in mild cognitive impairment (MCI). This study aims to examine the psychometric properties of the Chinese version of the memory binding test (MBT). METHODS: One hundred and sixty-four subjects (26 individuals with AD, 67 individuals with amnestic MCI (aMCI), 30 individuals with subjective cognitive impairment (SCI), and 41 cognitively normal elderly individuals (NC)) participated in the study. Twenty-two subjects repeated the assessment of the MBT within 6 weeks (± 2 weeks). Pearson correlation was used to calculate the convergent validity. The test--retest reliability was determined by the calculation of the intraclass correlation coefficient (ICC). Discriminative validity was calculated to evaluate the receiver-operating characteristic curves. The optimal index was chosen by comparing the area under the curve for specificity and sensitivity ≥ 0.80. The optimal cutoff score of the index was chosen to maximize the sum of sensitivity and specificity. RESULTS: The absolute value of the convergent validity of the direct indexes of MBT ranged from 0.443 to 0.684. The ICC for each of direct indexes was 0.887-0.958. Total delayed paired recall (TDPR) was the optimal index for discriminating aMCI from NC. The cutoff score for TDPR was ≤25 to distinguish aMCI from NC (sensitivity = 0.896, specificity = 0.707). CONCLUSION: The Chinese version of MBT is a valid and reliable instrument to detect MCI.

Individual Assignment of Adult Diffuse Gliomas into the EM/PM Molecular Subtypes Using a TaqMan Low-Density Array.

PURPOSE: We aimed to develop a diagnostic platform to capture the transcriptomic resemblance of individual adult diffuse gliomas of WHO grades II to IV to neural development and the genomic signature associated with glioma progression. EXPERIMENTAL DESIGN: Based on the EM/PM classification scheme, we designed a RT-PCR-based TaqMan low-density array (TLDA) containing 44 classifier and 4 reference genes. Samples of a training dataset (GSE48865), characterized by RNA-sequencing, were utilized to optimize the TLDA design and to develop a support vector machine (SVM)-based prediction model. Complemented with Sanger sequencing for IDH1/2, and low coverage whole genome sequencing (WGS), the TLDA and SVM prediction model were tested in a validation (31 gliomas) and a test (121 gliomas) dataset. RESULTS: Independent of morphologically defined subtypes and grades, gliomas can be individually assigned into the EM and PM glioma subtypes with the respective areas under ROC curves at 0.86 and 0.85 in the validation dataset. The EM gliomas showed a medium overall survival (OS) of 15.6 months, whereas the medium OS for PM gliomas was not reached (HR = 3.55; 95% confidence interval, 1.96-6.45). The EM and PM gliomas showed distinct patterns of genomic alterations, with IDH mutation and 1p19q codeletion in the PM gliomas and gain of chromosome 7/loss of chromosome 10 in the EM gliomas. Extensive chromosomal abnormalities marked the progression of PM gliomas. CONCLUSIONS: The integration of EM/PM subtyping, IDH sequencing, and low coverage WGS may improve the risk stratification and selection of treatment regimens for patients with glioma.

CTAB Enhances Chemo-Sensitivity Through Activation of AMPK Signaling Cascades in Breast Cancer.

Metabolic reprogramming is thought to be one of the initiators in cancer drug resistance. It has been shown that CTAB is capable of interfering the efficiency of cancer therapy by regulation of cell metabolic reprogramming. In this study, we hypothesized that AMPK as a key metabolic regulator plays a crucial role in regulation of breast cancer drug resistance, which could be alleviated by treatment of CTAB. We observed that CTAB can improve the DOX sensitivity of the breast cancer cells by inhibition of the ATP-dependent drug-efflux pump P-gp complex through activation of the AMPK-HIF-1α-P-gp cascades. The CTAB effect was also confirmed in vivo showing low systemic toxicity. Taken together, our results showed that CTAB sensitized drug resistance of breast cancer to DOX chemotherapy by activating AMPK signaling cascades both in vitro and in vivo, suggested that CTAB may be developed as a promising and novel chemosensitizer and chemotherapeutic candidate for breast cancer treatment.

Elevated signature of a gene module coexpressed with CDC20 marks genomic instability in glioma.

Genomic instability (GI) drives tumor heterogeneity and promotes tumor progression and therapy resistance. However, causative factors underlying GI and means for clinical detection of GI in glioma are inadequately identified. We describe here that elevated expression of a gene module coexpressed with CDC20 (CDC20-M), the activator of the anaphase-promoting complex in the cell cycle, marks GI in glioma. The CDC20-M, containing 139 members involved in cell proliferation, DNA damage response, and chromosome segregation, was found to be consistently coexpressed in glioma transcriptomes. The coexpression of these genes was conserved across multiple species and organ systems, particularly in human neural stem and progenitor cells. CDC20-M expression was not correlated with the morphological subtypes, nor with the recently defined molecular subtypes of glioma. CDC20-M signature was an independent and robust predictor for poorer prognosis in over 1,000 patients from four large databases. Elevated CDC20-M signature enabled the identification of individual glioma samples with severe chromosome instability and mutation burden and of primary glioma cell lines with extensive mitotic errors leading to chromosome mis-segregation. AURKA, a core member of CDC20-M, was amplified in one-third of CDC20-M-high gliomas with gene-dosage-dependent expression. MLN8237, a Food and Drug Administration-approved AURKA inhibitor, selectively killed temozolomide-resistant primary glioma cells in vitro and prolonged the survival of a patient-derived xenograft mouse model with a high-CDC20-M signature. Our findings suggest that application of the CDC20-M signature may permit more selective use of adjuvant therapies for glioma patients and that dysregulated CDC20-M members may provide a therapeutic vulnerability in glioma.

MCL1 gene co-expression module stratifies multiple myeloma and predicts response to proteasome inhibitor-based therapy.

Multiple myeloma (MM) is the second most common hematologic cancer, characterized by abnormal accumulation of plasma cells in the bone marrow. The extensive biological and clinical heterogeneity of MM hinders effective treatment and etiology research. Several molecular classification systems of prognostic impact have been proposed, but they do not predict the response to treatment nor do they correlate to plasma cell development pathways. Here we describe the classification of MM into two distinct subtypes based on the expression levels of a gene module coexpressed with MCL1 (MCL1-M), a regulator of plasma cell survival. The classification system enabled prediction of the prognosis and the response to bortezomib-based therapy. Moreover, the two MM subtypes were associated with two different plasma cell differentiation pathways (enrichment of a preplasmablast signature versus aberrant expression of B cell genes). 1q gain, harboring 63 of the 87 MCL1-M members including MCL1, was found in about 80% of the MM with upregulated MCL1-M expression. Clonal analysis showed that 1q gain tended to occur as an early clonal event. Members of MCL1-M captured both MM cell-intrinsically acting signals and the signals regulating the interaction between MM cells with bone marrow microenvironment. MCL1-M members were co-expressed in mouse germinal center B cells. Together, these findings indicate that MCL1-M may play previously inadequately recognized, initiating role in the pathogenesis of MM. Our findings suggest that MCL1-M signature-based molecular clustering of MM constitutes a solid framework toward understanding the etiology of this disease and establishing personalized care. Article Summary: A pathogenic mechanism-guided molecular classification would facilitate treatment decision and etiology research of multiple myeloma. On the basis of the expression levels of a gene module coexpressed with MCL1, we have established a classification scheme assigning multiple myeloma into two subtypes with distinct prognosis, treatment responses and pathogenic backgrounds.

Finite element analysis of impact loads on the femur.

OBJECTIVE: To investigate the stress distribution and fracture mechanism of proximal femur under impact loads. METHODS: The image data of one male's femur were collected by the Lightspeed multi-lay spiral computed tomography. A 3D finite element model of the femur was established by employing the finite element software ANSYS, which mainly concentrated on the effects of the directions of the impact loads arising from intense movements and the parenchyma on the hip joint as well as those of the femur material properties on the distribution of the Mises equivalent stress in the femur after impact. RESULTS: The numerical results about the effects of the angle sigma of the impact loads to the anterior direction and the angle gamma of the impact loads to the femur shaft on the bone fracture were given. The angle sigma had larger effect on the stress distribution than the angle gamma, which mainly represented the fracture of the upper femur including the femoral neck fracture when the posterolateral femur was impacted. This result was consistent with the clinical one. The parenchyma on the hip joint has relatively large relaxation effect on the impact loads. CONCLUSIONS: A 3D finite element analysis model of the femoral hip joint under dynamic loads is successfully established by using the impact dynamic theory.

Cerebral perfusion SPECT imaging for assessment of the effect of hyperbaric oxygen therapy on patients with postbrain injury neural status.

OBJECTIVE: To evaluate the effects of hyperbaric oxygen (HBO) therapy on patients with postbrain injury neural status. METHODS: Two to 4 courses of HBO therapy and/or medications were used to treat 320 patients who were randomly divided into two groups. Assessment was made with (99m)Tc-ethyl cysteinate dimer ( (99m)Tc-ECD) single photon emission computed tomography (SPECT) before and after treatment. RESULTS: There was a significant difference between the HBO therapy group and the non-HBO therapy group. HBO therapy was superior to medication treatment alone in the recovery of clinical symptoms, control of epilepsy, and resolution of hydrocephalus (P<0.01). CONCLUSIONS: HBO therapy has specific curative effects on patients with postbrain injury neural status, and (99m)Tc-ECD SPECT could play an important role in diagnosing postbrain injury neural status and monitoring the therapeutic effects of HBO.