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1.
Proc Natl Acad Sci U S A ; 121(18): e2310283121, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38669183

ABSTRACT

Congenital scoliosis (CS), affecting approximately 0.5 to 1 in 1,000 live births, is commonly caused by congenital vertebral malformations (CVMs) arising from aberrant somitogenesis or somite differentiation. While Wnt/ß-catenin signaling has been implicated in somite development, the function of Wnt/planar cell polarity (Wnt/PCP) signaling in this process remains unclear. Here, we investigated the role of Vangl1 and Vangl2 in vertebral development and found that their deletion causes vertebral anomalies resembling human CVMs. Analysis of exome sequencing data from multiethnic CS patients revealed a number of rare and deleterious variants in VANGL1 and VANGL2, many of which exhibited loss-of-function and dominant-negative effects. Zebrafish models confirmed the pathogenicity of these variants. Furthermore, we found that Vangl1 knock-in (p.R258H) mice exhibited vertebral malformations in a Vangl gene dose- and environment-dependent manner. Our findings highlight critical roles for PCP signaling in vertebral development and predisposition to CVMs in CS patients, providing insights into the molecular mechanisms underlying this disorder.


Subject(s)
Carrier Proteins , Cell Polarity , Membrane Proteins , Spine , Zebrafish , Animals , Zebrafish/genetics , Zebrafish/embryology , Humans , Mice , Cell Polarity/genetics , Membrane Proteins/genetics , Membrane Proteins/metabolism , Spine/abnormalities , Spine/metabolism , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolism , Scoliosis/genetics , Scoliosis/congenital , Scoliosis/metabolism , Wnt Signaling Pathway/genetics , Genetic Predisposition to Disease , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Female
2.
Proc Natl Acad Sci U S A ; 119(22): e2121406119, 2022 05 31.
Article in English | MEDLINE | ID: mdl-35622890

ABSTRACT

In eukaryotes, the origin recognition complex (ORC) is required for the initiation of DNA replication. The smallest subunit of ORC, Orc6, is essential for prereplication complex (pre-RC) assembly and cell viability in yeast and for cytokinesis in metazoans. However, unlike other ORC components, the role of human Orc6 in replication remains to be resolved. Here, we identify an unexpected role for hOrc6, which is to promote S-phase progression after pre-RC assembly and DNA damage response. Orc6 localizes at the replication fork and is an accessory factor of the mismatch repair (MMR) complex. In response to oxidative damage during S phase, often repaired by MMR, Orc6 facilitates MMR complex assembly and activity, without which the checkpoint signaling is abrogated. Mechanistically, Orc6 directly binds to MutSα and enhances the chromatin-association of MutLα, thus enabling efficient MMR. Based on this, we conclude that hOrc6 plays a fundamental role in genome surveillance during S phase.


Subject(s)
DNA Mismatch Repair , Origin Recognition Complex , S Phase , DNA-Binding Proteins/metabolism , Humans , MutL Proteins/metabolism , Origin Recognition Complex/genetics , Origin Recognition Complex/metabolism , Protein Binding
3.
Chemphyschem ; : e202400297, 2024 May 26.
Article in English | MEDLINE | ID: mdl-38797706

ABSTRACT

Materials that integrate magnetism, electricity and luminescence can not only improve the operational efficiency of devices, but also potentially generate new functions through their coupling. Therefore, multifunctional synergistic effects have broad application prospects in fields such as optoelectronic devices, information storage and processing, and quantum computing. However, in the research field of molecular materials, there are few reports on the synergistic multifunctional properties. The main reason is that there is insufficient awareness of how to obtain such material. In this brief review, we summarized the molecular materials with this characteristic. The structural phase transition of substances will cause changes in their physical properties, as the electronic configurations of the active unit in different structural phases are different. Therefore, we will classify and describe the multifunctional synergistic complexes based on the structural factors that cause the first-order phase transition of the complexes. This enables us to quickly screen complexes with synergistic responses to these properties through structural phase transitions, providing ideas for studying the synergistic response of physical properties in molecular materials.

4.
Gut ; 72(8): 1568-1580, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36450387

ABSTRACT

OBJECTIVE: Immune checkpoint blockade (ICB) has improved cancer treatment, yet why most hepatocellular carcinoma (HCC) patients are resistant to PD-1 ICB remains elusive. Here, we elucidated the role of a programmed cell death protein 1 (PD-1) isoform, Δ42PD-1, in HCC progression and resistance to nivolumab ICB. DESIGN: We investigated 74 HCC patients in three cohorts, including 41 untreated, 28 treated with nivolumab and 5 treated with pembrolizumab. Peripheral blood mononuclear cells from blood samples and tumour infiltrating lymphocytes from tumour tissues were isolated for immunophenotyping. The functional significance of Δ42PD-1 was explored by single-cell RNA sequencing analysis and validated by functional and mechanistic studies. The immunotherapeutic efficacy of Δ42PD-1 monoclonal antibody was determined in HCC humanised mouse models. RESULTS: We found distinct T cell subsets, which did not express PD-1 but expressed its isoform Δ42PD-1, accounting for up to 71% of cytotoxic T lymphocytes in untreated HCC patients. Δ42PD-1+ T cells were tumour-infiltrating and correlated positively with HCC severity. Moreover, they were more exhausted than PD-1+ T cells by single T cell and functional analysis. HCC patients treated with anti-PD-1 ICB showed effective PD-1 blockade but increased frequencies of Δ42PD-1+ T cells over time especially in patients with progressive disease. Tumour-infiltrated Δ42PD-1+ T cells likely sustained HCC through toll-like receptors-4-signalling for tumourigenesis. Anti-Δ42PD-1 antibody, but not nivolumab, inhibited tumour growth in three murine HCC models. CONCLUSION: Our findings not only revealed a mechanism underlying resistance to PD-1 ICB but also identified anti-Δ42PD-1 antibody for HCC immunotherapy.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Mice , Animals , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Leukocytes, Mononuclear , Immunosuppression Therapy , Immune Tolerance , Immunotherapy , Nivolumab/therapeutic use , CD8-Positive T-Lymphocytes
5.
Chemistry ; 29(66): e202301771, 2023 Nov 24.
Article in English | MEDLINE | ID: mdl-37665775

ABSTRACT

Qubits are the basic unit of quantum information and computation. To realize quantum computing and information processing, the decoherence times of qubits must be long enough. Among the studies of molecule-based electron spin qubits, most of the work focused on the ions with the spin S=1/2, where only single-bit gates can be constructed. However, quantum operations require the qubits to interact with each other, so people gradually carry out relevant research in ions or systems with S>1/2 and multilevel states. In this work, a two-dimensional (2D) oxygen-coordinated GdIII NaI -based oxamato supramolecular coordination framework, Na[Gd(4-HOpa)4 (H2 O)] ⋅ 2H2 O (1, 4-HOpa=N-4-hydroxyphenyloxamate), was selected as a possible carrier of qubit. The field-induced slow magnetic relaxation shows this system has phonon bottleneck (PB) effect at low temperatures with a very weak magnetic anisotropy. The pulse electron paramagnetic resonance studies show the spin-lattice and spin-spin relaxation times are T1 =1.66 ms at 4 K and Tm =4.25 µs at 8 K for its diamagnetically diluted sample (1Gd0.12 %). It suggested that the relatively long decoherence time is mainly ascribed to its near isotropic and the PB effect from resonance phonon trapped for pure sample, while the dilution further improves its qubit performance.

6.
Chemistry ; 29(38): e202300598, 2023 Jul 06.
Article in English | MEDLINE | ID: mdl-37062699

ABSTRACT

Multifunctional materials with working temperatures near room temperature are crucial for practical applications. Until now, it is still a great challenge to obtain such materials. In this paper, a complex of (C5 NH13 Cl)2 MnBr4 (1) with a structural phase transition near room temperature is reported. The phase transition induces switchable magnetic properties, dielectric anomalies and luminescent response over the same range of temperatures. It is the first time the synergetic effect of magnetism, dielectricity and luminescence near room temperature have been observed in the same molecular complex.


Subject(s)
Luminescence , Magnetics , Temperature , Phase Transition
7.
EMBO Rep ; 22(5): e52141, 2021 05 05.
Article in English | MEDLINE | ID: mdl-33764618

ABSTRACT

Tyrosine phosphorylation of secretion machinery proteins is a crucial regulatory mechanism for exocytosis. However, the participation of protein tyrosine phosphatases (PTPs) in different exocytosis stages has not been defined. Here we demonstrate that PTP-MEG2 controls multiple steps of catecholamine secretion. Biochemical and crystallographic analyses reveal key residues that govern the interaction between PTP-MEG2 and its substrate, a peptide containing the phosphorylated NSF-pY83 site, specify PTP-MEG2 substrate selectivity, and modulate the fusion of catecholamine-containing vesicles. Unexpectedly, delineation of PTP-MEG2 mutants along with the NSF binding interface reveals that PTP-MEG2 controls the fusion pore opening through NSF independent mechanisms. Utilizing bioinformatics search and biochemical and electrochemical screening approaches, we uncover that PTP-MEG2 regulates the opening and extension of the fusion pore by dephosphorylating the DYNAMIN2-pY125 and MUNC18-1-pY145 sites. Further structural and biochemical analyses confirmed the interaction of PTP-MEG2 with MUNC18-1-pY145 or DYNAMIN2-pY125 through a distinct structural basis compared with that of the NSF-pY83 site. Our studies thus provide mechanistic insights in complex exocytosis processes.


Subject(s)
Protein Tyrosine Phosphatases, Non-Receptor , Protein Tyrosine Phosphatases , Peptides , Phosphorylation , Protein Tyrosine Phosphatases/metabolism , Protein Tyrosine Phosphatases, Non-Receptor/metabolism
8.
Environ Sci Technol ; 57(8): 3198-3205, 2023 02 28.
Article in English | MEDLINE | ID: mdl-36799527

ABSTRACT

While adverse biological effects of acute high-dose ionizing radiation have been extensively investigated, knowledge on chronic low-dose effects is scarce. The aims of the present study were to identify hazards of low-dose ionizing radiation to Daphnia magna using multiomics dose-response modeling and to demonstrate the use of omics data to support an adverse outcome pathway (AOP) network development for ionizing radiation. Neonatal D. magna were exposed to γ radiation for 8 days. Transcriptomic analysis was performed after 4 and 8 days of exposure, whereas metabolomics and confirmative bioassays to support the omics analyses were conducted after 8 days of exposure. Benchmark doses (BMDs, 10% benchmark response) as points of departure (PODs) were estimated for both dose-responsive genes/metabolites and the enriched KEGG pathways. Relevant pathways derived using the BMD modeling and additional functional end points measured by the bioassays were overlaid with a previously published AOP network. The results showed that several molecular pathways were highly relevant to the known modes of action of γ radiation, including oxidative stress, DNA damage, mitochondrial dysfunction, protein degradation, and apoptosis. The functional assays showed increased oxidative stress and decreased mitochondrial membrane potential and ATP pool. Ranking of PODs at the pathway and functional levels showed that oxidative damage related functions had relatively low PODs, followed by DNA damage, energy metabolism, and apoptosis. These were supportive of causal events in the proposed AOP network. This approach yielded promising results and can potentially provide additional empirical evidence to support further AOP development for ionizing radiation.


Subject(s)
Adverse Outcome Pathways , Multiomics , Radiation, Ionizing , Gamma Rays , Oxidative Stress
9.
Beijing Da Xue Xue Bao Yi Xue Ban ; 55(6): 1111-1117, 2023 Dec 18.
Article in Zh | MEDLINE | ID: mdl-38101797

ABSTRACT

Systemic lupus erythematosus (SLE) associated macrophage activation syndrome (MAS) is clinically severe, with a high mortality rate and rare neuropsychiatric symptoms. In the course of diagnosis and treatment, it is necessary to actively determine whether the neuropsychiatric symptoms in patients are caused by neuropsychiatric systemic lupus erythematosus (NPSLE) or macrophage activation syndrome. This paper retrospectively analyzed the clinical data of 2 cases of SLE associated MAS with neuropsychiatric lesions, Case 1: A 30-year-old female had obvious alopecia in 2019, accompanied by emaciation, fatigue and dry mouth. In March 2021, she felt weak legs and fell down, followed by fever and chills without obvious causes. After completing relevant examinations, she was diagnosed with SLE and given symptomatic treatments such as hormones and anti-infection, but the patient still had fever. The relevant examinations showed moderate anemia, elevated ferritin, elevated triglycerides, decreased NK cell activity, and a perforin positivity rate of 4.27%, which led to the diagnosis of "pre-hemophagocytic syndrome (HPS)". In May 2021, the patient showed mental trance and babble, and was diagnosed with "SLE-associated MAS"after completing relevant examinations. After treatment with methylprednisolone, anti-infection and psychotropic drugs, the patient's temperature was normal and mental symptoms improved. Case 2: A 30-year-old female patient developed butterfly erythema on both sides of the nose on her face and several erythema on her neck in June 2019, accompanied by alopecia, oral ulcers, and fever. She was diagnosed with "SLE" after completing relevant examinations, and her condition was relieved after treatment with methylprednisolone and human immunoglobulin. In October 2019, the patient showed apathy, no lethargy, and fever again, accompanied by dizziness and vomiting. The relevant examination indicated moderate anemia, decreased NK cell activity, elevated triglycerides, and elevated ferritin. The patient was considered to be diagnosed with "SLE, NPSLE, and SLE-associated MAS". After treatment with hormones, human immunoglobulin, anti-infection, rituximab (Mabthera), the patient's condition improved and was discharged from the hospital. After discharge, the patient regularly took methylprednisolone tablets (Medrol), and her psychiatric symptoms were still intermittent. In November 2019, she developed symptoms of fever, mania, and delirium, and later turned to an apathetic state, and was given methylprednisolone intravenous drip and olanzapine tablets (Zyprexa) orally. After the mental symptoms improved, she was treated with rituximab (Mabthera). Later, due to repeated infections, she was replaced with Belizumab (Benlysta), and she was recovered from her psychiatric anomalies in March 2021. Through the analysis of clinical symptoms, imaging examination, laboratory examination, treatment course and effect, it is speculated that the neuropsychiatric symptoms of case 1 are more likely to be caused by MAS, and that of case 2 is more likely to be caused by SLE. At present, there is no direct laboratory basis for the identification of the two neuropsychiatric symptoms. The etiology of neuropsychiatric symptoms can be determined by clinical manifestations, imaging manifestations, cerebrospinal fluid detection, and the patient's response to treatment. Early diagnosis is of great significance for guiding clinical treatment, monitoring the condition and judging the prognosis. The good prognosis of the two cases in this paper is closely related to the early diagnosis, treatment and intervention of the disease.


Subject(s)
Anemia , Lupus Erythematosus, Systemic , Lupus Vasculitis, Central Nervous System , Macrophage Activation Syndrome , Humans , Female , Adult , Rituximab/therapeutic use , Macrophage Activation Syndrome/diagnosis , Macrophage Activation Syndrome/drug therapy , Macrophage Activation Syndrome/etiology , Retrospective Studies , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/drug therapy , Methylprednisolone/therapeutic use , Fever/drug therapy , Erythema/complications , Erythema/drug therapy , Hormones/therapeutic use , Alopecia/complications , Alopecia/drug therapy , Triglycerides/therapeutic use , Ferritins/therapeutic use
10.
Angew Chem Int Ed Engl ; 62(42): e202309852, 2023 Oct 16.
Article in English | MEDLINE | ID: mdl-37635684

ABSTRACT

Conventional solid electrolyte frameworks typically consist of anions such as sulphur, oxygen, chlorine, and others, leading to inherent limitations in their properties. Despite the emergence of sulphide, oxide, and halide-based solid electrolytes for all-solid-state batteries, their utilization is hampered by issues, including the evolution of H2 S gas, the need for expensive elements, and poor contact. Here, we first introduce Prussian Blue analogue (PBA) open-framework structures as a solid electrolyte that demonstrates appreciable Na+ conductivity (>10-2 mS cm-1 ). We delve into the relationship between Na+ conductivity and the lattice parameter of N-coordinated transition metal, which is attributed to the reduced interaction between Na+ and the framework, corroborated by the distribution of relaxation times and density functional theory calculations. Among the five PBAs studied, Mn-PBA have exhibited the highest Na+ conductivity of 9.1×10-2 mS cm-1 . Feasibility tests have revealed that Mn-PBA have maintained a cycle retention of 95.1 % after 80cycles at 30 °C and a C-rate of 0.2C. Our investigation into the underlying mechanisms that play a significant role in governing the conductivity and kinetics of these materials contributes valuable insights for the development of alternative strategies to realize all-solid-state batteries.

11.
RNA ; 26(11): 1603-1620, 2020 11.
Article in English | MEDLINE | ID: mdl-32675111

ABSTRACT

Cellular quiescence and cell cycle reentry regulate vital biological processes such as cellular development and tissue homeostasis and are controlled by precise regulation of gene expression. The roles of long noncoding RNAs (lncRNAs) during these processes remain to be elucidated. By performing genome-wide transcriptome analyses, we identify differential expression of several hundreds of lncRNAs, including a significant number of the less-characterized class of microRNA-host-gene (MIRHG) lncRNAs or lnc-MIRHGs, during cellular quiescence and cell cycle reentry in human diploid fibroblasts. We observe that MIR222HG lncRNA displays serum-stimulated RNA processing due to enhanced splicing of the host nascent pri-MIR222HG transcript. The pre-mRNA splicing factor SRSF1 negatively regulates the microprocessor-catalyzed cleavage of pri-miR-222, thereby increasing the cellular pool of the mature MIR222HG Association of SRSF1 to pri-MIR222HG, including to a mini-exon, which partially overlaps with the primary miR-222 precursor, promotes serum-stimulated splicing over microRNA processing of MIR222HG Further, we observe that the increased levels of spliced MIR222HG in serum-stimulated cells promote the cell cycle reentry post quiescence in a microRNA-independent manner. MIR222HG interacts with DNM3OS, another lncRNA whose expression is elevated upon serum-stimulation, and promotes cell cycle reentry. The double-stranded RNA binding protein ILF3/2 complex facilitates MIR222HG:DNM3OS RNP complex assembly, thereby promoting DNM3OS RNA stability. Our study identifies a novel mechanism whereby competition between the splicing and microprocessor machinery modulates the serum-induced RNA processing of MIR222HG, which dictates cell cycle reentry.


Subject(s)
Gene Expression Profiling/methods , Lung/cytology , RNA, Long Noncoding/genetics , Serine-Arginine Splicing Factors/metabolism , Serum/chemistry , Cell Cycle , Cell Line , Fibroblasts/chemistry , Fibroblasts/cytology , HEK293 Cells , Humans , Lung/chemistry , Nuclear Factor 45 Protein/metabolism , Nuclear Factor 90 Proteins/metabolism , RNA Processing, Post-Transcriptional , RNA Splicing , Sequence Analysis, RNA , Single Molecule Imaging , Up-Regulation , Exome Sequencing
12.
J Exp Bot ; 73(7): 1910-1925, 2022 04 05.
Article in English | MEDLINE | ID: mdl-35104311

ABSTRACT

It has been increasingly recognized that CWIN (cell wall invertase) and sugar transporters including STP (sugar transport protein) and SWEET (sugar will eventually be exported transporters) play important roles in plant-pathogen interactions. However, the information available in the literature comes from diverse systems and often yields contradictory findings and conclusions. To solve this puzzle, we provide here a comprehensive assessment of the topic. Our analyses revealed that the regulation of plant-microbe interactions by CWIN, SWEET, and STP is conditioned by the specific pathosystems involved. The roles of CWINs in plant resistance are largely determined by the lifestyle of pathogens (biotrophs versus necrotrophs or hemibiotrophs), possibly through CWIN-mediated salicylic acid or jasmonic acid signaling and programmed cell death pathways. The up-regulation of SWEETs and STPs may enhance or reduce plant resistance, depending on the cellular sites from which pathogens acquire sugars from the host cells. Finally, plants employ unique mechanisms to defend against viral infection, in part through a sugar-based regulation of plasmodesmatal development or aperture. Our appraisal further calls for attention to be paid to the involvement of microbial sugar metabolism and transport in plant-pathogen interactions, which is an integrated but overlooked component of such interactions.


Subject(s)
Sugars , beta-Fructofuranosidase , Biological Transport , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism , Plants/metabolism , Sugars/metabolism , beta-Fructofuranosidase/metabolism
13.
Inorg Chem ; 61(51): 20923-20930, 2022 Dec 26.
Article in English | MEDLINE | ID: mdl-36510686

ABSTRACT

We designed and synthesized a strong fluorescent tetradentate pyridine ligand, 3,6,11,12-tetra(pyridin-4-yl)dibenzo[a,c]phenazine (TPDP), by covalently grafting pyridyl to fluorescent dye dbpz, which can react with the Fe(NCX)2 (X = S and Se) unit, obtaining two new 2D [4 × 4] square-grid compounds, namely, {FeII(TPDP)2(SCN)2·CHCl3·4CH3OH}n (1) and {[FeII(TPDP)2(SeCN)2]·CH2Cl2·4CH3OH}n (2). Both of them show expected one-step spin-crossover (SCO) properties, and complex 2vacuum exhibits a combination of the SCO phenomenon and fluorescence in a synergetic way. The energy transfer mechanism of 2vacuum is verified by the theoretical calculations and experimental results. This study provides an effective strategy to synthesize large conjugated fluorescent ligands using dyes to further form SCO-luminescent bifunctional materials.

14.
Brain ; 144(9): 2759-2770, 2021 10 22.
Article in English | MEDLINE | ID: mdl-34428276

ABSTRACT

The molecular link between amyloid-ß plaques and neurofibrillary tangles, the two pathological hallmarks of Alzheimer's disease, is still unclear. Increasing evidence suggests that amyloid-ß peptide activates multiple regulators of cell cycle pathways, including transcription factors CDKs and E2F1, leading to hyperphosphorylation of tau protein. However, the exact pathways downstream of amyloid-ß-induced cell cycle imbalance are unknown. Here, we show that PAX6, a transcription factor essential for eye and brain development which is quiescent in adults, is increased in the brains of patients with Alzheimer's disease and in APP transgenic mice, and plays a key role between amyloid-ß and tau hyperphosphorylation. Downregulation of PAX6 protects against amyloid-ß peptide-induced neuronal death, suggesting that PAX6 is a key executor of the amyloid-ß toxicity pathway. Mechanistically, amyloid-ß upregulates E2F1, followed by the induction of PAX6 and c-Myb, while Pax6 is a direct target for both E2F1 and its downstream target c-Myb. Furthermore, PAX6 directly regulates transcription of GSK-3ß, a kinase involved in tau hyperphosphorylation and neurofibrillary tangles formation, and its phosphorylation of tau at Ser356, Ser396 and Ser404. In conclusion, we show that signalling pathways that include CDK/pRB/E2F1 modulate neuronal death signals by activating downstream transcription factors c-Myb and PAX6, leading to GSK-3ß activation and tau pathology, providing novel potential targets for pharmaceutical intervention.


Subject(s)
Alzheimer Disease/metabolism , Amyloid beta-Peptides/toxicity , PAX6 Transcription Factor/metabolism , Peptide Fragments/toxicity , tau Proteins/metabolism , Alzheimer Disease/pathology , Animals , Brain/drug effects , Brain/metabolism , Brain/pathology , Cells, Cultured , HEK293 Cells , Humans , Mice , Mice, Inbred C57BL , Mice, Transgenic , Phosphorylation/drug effects , Phosphorylation/physiology , Signal Transduction/drug effects , Signal Transduction/physiology
15.
Acta Radiol ; 63(8): 1086-1092, 2022 Aug.
Article in English | MEDLINE | ID: mdl-34260321

ABSTRACT

BACKGROUND: Even though radiologic diagnosis of bone tumors and tumor-like lesions is usually based on radiographs, radiographically faint imaging features sometimes remain challenging due to overlapping anatomical structures. PURPOSE: To compare tomosynthesis with radiography for the evaluation of bone tumors and tumor-like lesions. MATERIAL AND METHODS: Forty-seven bone tumors and tumor-like lesions were assessed with radiographs and tomosynthesis images. Two radiologists independently analyzed imaging features of lesions, including margin, periosteal reaction, cortical thinning, matrix mineralization, cortical destruction (such as pathologic fracture), and extraosseous soft-tissue extension. Computed tomography (CT) imaging was used as a reference method. Diagnostic performances of radiography and tomosynthesis were analyzed and compared based on sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. Effective radiation dose was compared among the three imaging modalities by phantom studies. RESULTS: Inter-observer variability (kappa value) for imaging features was slight to moderate on radiography (0.167-0.588), whereas it was nearly perfect on tomosynthesis (0.898-1.000) except for extraosseous soft-tissue extension (0.647 vs. 0.647). Tomosynthesis showed significantly higher sensitivity than radiography in evaluating the margin for bone tumors or tumor-like lesions (1.00 vs. 0.85; P = 0.016), and significantly higher accuracy than radiography in evaluating the margin and matrix mineralization for those (1.00 vs. 0.85; P = 0.016 and 0.91 vs.0.77; P = 0.023, respectively). In phantom studies, mean effective radiation doses were highest in order of CT, tomography, and radiography. CONCLUSION: Tomosynthesis increases sensitivity and accuracy of the margin as well as accuracy of the matrix mineralization of bone tumors and tumor-like lesions compared to radiography.


Subject(s)
Bone Neoplasms , Tomography, X-Ray Computed , Bone Neoplasms/diagnostic imaging , Humans , Phantoms, Imaging , Predictive Value of Tests , Radiography , Tomography, X-Ray Computed/methods
16.
Skeletal Radiol ; 51(11): 2223-2227, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35366096

ABSTRACT

Recently, many attempts have been made to use injectable materials in the subcutaneous fat layer anywhere in the body, including the breast and face, for cosmetic purposes. A 56-year-old woman presented with multiple palpable lumps without tenderness or skin color changes on the anterior and lateral chest and the abdominal walls. Magnetic resonance imaging showed fluid-like collections without surrounding soft tissue inflammatory changes in the chest wall, abdominal wall, and deeper within the abdomen. The lesions penetrated the peritoneum and were observed adjacent to the liver dome. Ultrasonography also showed hypoechogenicity suggestive of fluid collection in the left axilla and trunk. The differential diagnosis based on radiologic findings included parasite manifestation, non-specific inflammatory conditions, and chronic granulomatous infections such as tuberculosis or non-tuberculous mycobacterial infections. However, these conditions are usually accompanied by changes in the adjacent subcutaneous fat layers, but our patient did not show any other abnormalities in the adjacent soft tissue. After biopsy and aspiration analysis, the patient was found to have a history of filler injection for breast augmentation approximately 17 years prior. It is often difficult to make a differential diagnosis without detailed knowledge of the patient's medical history. Here we describe a rare case of distant migration of the filler to the axilla, chest wall, abdominal wall, and peritoneum following breast augmentation with filler injection. Knowledge of the radiologic characteristics and migration patterns of gel fillers and their related complications is useful for making an accurate diagnosis.


Subject(s)
Mammaplasty , Chronic Disease , Female , Humans , Injections , Magnetic Resonance Imaging , Mammaplasty/methods , Middle Aged , Ultrasonography
17.
Medicina (Kaunas) ; 58(10)2022 Oct 14.
Article in English | MEDLINE | ID: mdl-36295612

ABSTRACT

Myositis ossificans (MO) is a benign heterotopic bone formation in muscle or soft tissue. It is a self-limiting disease that is usually initiated by trauma and often occurs in the extremities of the body. Here we report a rare case of traumatic myositis ossificans caused by unusual trauma (extracorporeal shock wave therapy) at thoracic paraspinal muscles. After a needle biopsy, the lesion increased in size, and the patient's symptoms worsened. Malignant soft tissue tumors such as osteosarcoma should be differentiated, so excision of the mass was performed. The final diagnosis was MO with aneurysmal bone cystic change. This case is a very rare form of MO that showed an unusual cause, location, clinical course, and pathologic result on follow-up. This can be an instructive case for radiologists as it is a common disease entity with unusual manifestations.


Subject(s)
Myositis Ossificans , Myositis , Humans , Myositis Ossificans/diagnosis , Myositis Ossificans/etiology , Myositis Ossificans/pathology , Thorax , Muscle, Skeletal/pathology
18.
Medicina (Kaunas) ; 58(7)2022 Jul 15.
Article in English | MEDLINE | ID: mdl-35888658

ABSTRACT

Background and Objectives: Although reducing the radiation dose level is important during diagnostic computed tomography (CT) applications, effective image quality enhancement strategies are crucial to compensate for the degradation that is caused by a dose reduction. We performed this prospective study to quantify emphysema on ultra-low-dose CT images that were reconstructed using deep learning-based image reconstruction (DLIR) algorithms, and compared and evaluated the accuracies of DLIR algorithms versus standard-dose CT. Materials and Methods: A total of 32 patients were prospectively enrolled, and all underwent standard-dose and ultra-low-dose (120 kVp; CTDIvol < 0.7 mGy) chest CT scans at the same time in a single examination. A total of six image datasets (filtered back projection (FBP) for standard-dose CT, and FBP, adaptive statistical iterative reconstruction (ASIR-V) 50%, DLIR-low, DLIR-medium, DLIR-high for ultra-low-dose CT) were reconstructed for each patient. Image noise values, emphysema indices, total lung volumes, and mean lung attenuations were measured in the six image datasets and compared (one-way repeated measures ANOVA). Results: The mean effective doses for standard-dose and ultra-low-dose CT scans were 3.43 ± 0.57 mSv and 0.39 ± 0.03 mSv, respectively (p < 0.001). The total lung volume and mean lung attenuation of five image datasets of ultra-low-dose CT scans, emphysema indices of ultra-low-dose CT scans reconstructed using ASIR-V 50 or DLIR-low, and the image noise of ultra-low-dose CT scans that were reconstructed using DLIR-low were not different from those of standard-dose CT scans. Conclusions: Ultra-low-dose CT images that were reconstructed using DLIR-low were found to be useful for emphysema quantification at a radiation dose of only 11% of that required for standard-dose CT.


Subject(s)
Deep Learning , Emphysema , Pulmonary Emphysema , Humans , Image Processing, Computer-Assisted/methods , Prospective Studies , Pulmonary Emphysema/diagnostic imaging , Radiographic Image Interpretation, Computer-Assisted/methods , Tomography, X-Ray Computed/methods
19.
Medicina (Kaunas) ; 58(9)2022 Sep 19.
Article in English | MEDLINE | ID: mdl-36143984

ABSTRACT

Backgroundand Objectives: To date, imaging characterization of non-rheumatic retro-odontoid pseudotumors (NRROPs) has been lacking; therefore, NRROPs have been confused with atlantoaxial joint involvement of rheumatoid arthritis (RA). It is important to differentiate these two disease because the treatment strategies may differ. The purpose of this study is to characterize imaging findings of NRROPs and compare them with those of RA. Material and Methods: From January 2015 to December 2019, 27 patients (14 women and 13 men) with NRROPs and 19 patients (15 women and 4 men) with RA were enrolled in this study. We evaluated various imaging findings, including atlantoaxial instability (AAI), and measured the maximum diameter of preodontoid and retro-odontoid spaces with magnetic resonance imaging (MRI) and computed tomography (CT). Results: Statistical significance was considered for p < 0.05. AAI was detected in eight patients with NRROPs and in all patients with RA (p < 0.0001). Seventeen patients with NRROPs and six patients with RA showed spinal cord compression (p = 0.047). Compressive myelopathy was observed in 14 patients with NRROPs and in 4 patients with RA (p = 0.048). Subaxial degeneration was observed in 25 patients with NRROPs and in 9 patients with RA (p = 0.001). Moreover, C2-3 disc abnormalities were observed in 11 patients with NRROPs and in 2 patients with RA (p = 0.02). Axial and longitudinal diameter of retro-odontoid soft tissue and preodontoid and retro-odontoid spaces showed significant differences between NRROP and RA patients (p < 0.0001). Furthermore, CT AAI measurements were differed significantly between NRROP and RA patients (p < 0.05). Conclusions: NRROPs showed prominent retro-odontoid soft tissue thickening, causing compressive myelopathy and a high frequency of subaxial and C2-3 degeneration without AAI.


Subject(s)
Arthritis, Rheumatoid , Atlanto-Axial Joint , Joint Instability , Odontoid Process , Spinal Cord Compression , Spinal Diseases , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/diagnostic imaging , Atlanto-Axial Joint/diagnostic imaging , Atlanto-Axial Joint/pathology , Female , Humans , Joint Instability/diagnostic imaging , Joint Instability/etiology , Magnetic Resonance Imaging/methods , Male , Odontoid Process/diagnostic imaging , Odontoid Process/pathology , Spinal Cord Compression/etiology , Spinal Cord Compression/pathology , Spinal Diseases/complications
20.
Psychogeriatrics ; 22(1): 84-98, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34729865

ABSTRACT

BACKGROUND: Mild behavioural impairment (MBI) is a neurobehavioural syndrome characterised by later life emergence of persistent neuropsychiatric symptoms. Our previous meta-analysis showed that MBI is prevalent among cognitively normal (CN), subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) subjects. This study is to calculate the pooled prevalence of MBI domains among CN, SCI, and MCI subjects. METHODS: A search of relevant literature published between 1 January 2003 and 6 August 2021 was conducted. Meta-analysis using a random effects model and meta-regression was performed. RESULTS: Ten studies conducted among 12 067 subjects (9758 CN, 1057 SCI and 1252 MCI) with retrievable MBI domains data underwent meta-analysis, revealing pooled prevalence of affective dysregulation (AFD), impulse dyscontrol (IDS), decreased motivation (DMT), social inappropriateness (SIP) and abnormal perception/thought (APT) of 32.84% (95% CI 24.44-42.5%), 26.67% (95% CI 18.24-37.23%), 12.58% (95% CI 6.93-21.75%), 6.05% (95% CI 3.44-10.42%), and 2.81% (95% CI 1.67-4.69%) respectively. AFD and APT domains demonstrated ordinal increase in pooled prevalence from CN, SCI and MCI subgroups, but meta-regression demonstrated no significant difference in MBI domains prevalence among cognitive subgroups (in contrast to the significant increase in MBI prevalence from CN to SCI to MCI). The pooled prevalence of AFD and IDS are greater than that of DMT, SIP and APT among all cognitive subgroups. Several variables were found to explain the high heterogeneity. CONCLUSIONS: AFD and IDS are the two most prevalent MBI domains and remain the same with cognitive deterioration. This finding is potentially relevant to clinical practice.


Subject(s)
Cognition Disorders , Cognitive Dysfunction , Cognitive Dysfunction/epidemiology , Humans , Prevalence
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