ABSTRACT
Gallbladder cancer (GBC) is the most common malignant tumor of the biliary system, with poor response to current treatments. Abnormal alternative splicing has been associated with the development of a variety of tumors. Combining the GEO database and GBC mRNA-seq analysis, it is found high expression of the splicing factor polypyrimidine region- binding protein 3 (PTBP3) in GBC. Multi-omics analysis revealed that PTBP3 promoted exon skipping of interleukin-18 (IL-18), resulting in the expression of ΔIL-18, an isoform specifically expressed in tumors. That ΔIL-18 promotes GBC immune escape by down-regulating FBXO38 transcription levels in CD8+T cells to reduce PD-1 ubiquitin-mediated degradation is revealed. Using a HuPBMC mouse model, the role of PTBP3 and ΔIL-18 in promoting GBC growth is confirmed, and showed that an antisense oligonucleotide that blocked ΔIL-18 production displayed anti-tumor activity. Furthermore, that the H3K36me3 promotes exon skipping of IL-18 by recruiting PTBP3 via MRG15 is demonstrated, thereby coupling the processes of IL-18 transcription and alternative splicing. Interestingly, it is also found that the H3K36 methyltransferase SETD2 binds to hnRNPL, thereby interfering with PTBP3 binding to IL-18 pre-mRNA. Overall, this study provides new insights into how aberrant alternative splicing mechanisms affect immune escape, and provides potential new perspectives for improving GBC immunotherapy.
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Mycoplasma pneumoniae pneumonia (MPP) is a common respiratory tract infection disease in children. To date, there have been few studies on the relationship between cytological changes in bronchoalveolar lavage fluid (BALF) and clinical features. The objective of this study is to investigate the correlation between changes in the proportion of cell classifications in BALF and the clinical features in children with severe MPP (SMPP). In total, the study included 64 children with SMPP requiring bronchoalveolar lavage who were admitted to our hospital between March and September 2022 (study group) and 11 children with bronchial foreign bodies without co-infection (control group), who were admitted during the same period. The proportion of cell classifications in BALF was determined by microscopic examination after performing Wright-Giemsa staining. Patients were grouped according to different clinical characteristics, and between-group comparisons were made regarding the variations in the proportion of cell classifications in BALF. The levels of blood routine neutrophil percentage (GRA%), C-reactive protein, D-dimer and lactate dehydrogenase in the study group were higher than those in the control group (P < 0.05). There were differences in the GRA% and macrophage percentage in the BALF between the two groups (P < 0.05). The GRA% and blood lymphocyte percentage were associated with pleural effusion. Multiple indicators correlated with extrapulmonary manifestations (P < 0.05). Moreover, the percentage of lymphocytes in the BALF correlated with pleural effusion, extrapulmonary manifestations and refractory MPP (RMPP) (P < 0.05). Logistic regression showed that BALF lymphocytes were protective factors for RMPP, while serum amyloid A and extrapulmonary manifestations were risk factors (P < 0.05). CONCLUSION: The BALF of children with SMPP is predominantly neutrophilic. A lower percentage of lymphocytes is related to a higher incidence of pleural effusion, extrapulmonary manifestations and progression to RMPP, as well as a longer length of hospitalisation. WHAT IS KNOWN: ⢠Mycoplasma pneumonia in children is relatively common in clinical practice. Bronchoalveolar lavage (BAL) is a routine clinical procedure. WHAT IS NEW: However, there are relatively few studies focusing on the cytomorphological analysis of cells in BAL fluid.
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Additive manufacturing (AM) is a technology that builds parts layer by layer. Over the past decade, metal additive manufacturing (AM) technology has developed rapidly to form a complete industry chain. AM metal parts are employed in a multitude of industries, including biomedical, aerospace, automotive, marine, and offshore. The design of components can be improved to a greater extent than is possible with existing manufacturing processes, which can result in a significant enhancement of performance. Studies on the anisotropy of additively manufactured metallic materials have been reported, and they describe the advantages and disadvantages of preparing different metallic materials using additive manufacturing processes; however, there are few in-depth and comprehensive studies that summarize the microstructural and mechanical properties of different types of additively manufactured metallic materials in the same article. This paper begins by outlining the intricate relationship between the additive manufacturing process, microstructure, and metal properties. It then explains the fundamental principles of powder bed fusion (PBF) and directed energy deposition (DED). It goes on to describe the molten pool and heat-affected zone in the additive manufacturing process and analyzes their effects on the microstructure of the formed parts. Subsequently, the mechanical properties and typical microstructures of additively manufactured titanium alloys, stainless steel, magnesium-aluminum alloys, and high-temperature alloys, along with their anisotropy, are summarized and presented. The summary indicates that the factors leading to the anisotropy of the mechanical properties of metallic AM parts are either their unique microstructural features or manufacturing defects. This anisotropy can be improved by post-heat treatment. Finally, the most recent research on the subject of metal AM anisotropy is presented.
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BACKGROUND: The effect of neoadjuvant chemotherapy (NACT) in gallbladder cancer (GBC) patients remains controversial. The aim of this study was to assess the impact of NACT on overall survival (OS) and cancer specific survival (CSS) in patients with localized or locoregionally advanced GBC, and to explore possible protective predictors for prognosis. METHODS: Data for patients with localized or locoregionally advanced GBC (i.e., categories cTx-cT4, cN0-2, and cM0) from 2004 to 2020 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients in the NACT and non-NACT groups were propensity score matched (PSM) 1:3, and the Kaplan-Meier method and log-rank test were performed to analyze the impact of NACT on OS and CSS. Univariable and multivariable Cox regression models were applied to identify the possible prognostic factors. Subgroup analysis was conducted to identify patients who would benefit from NACT. RESULTS: Of the 2676 cases included, 78 NACT and 234 non-NACT patients remained after PSM. In localized or locoregionally advanced GBC patients, the median OS of the NACT and non-NACT was 31 and 16 months (log-rank P < 0.01), and the median CSS of NACT and non-NACT was 32 and 17 months (log-rank P < 0.01), respectively. Longer median OS (31 vs 17 months, log-rank P < 0.01) and CSS (32 vs 20 months, log-rank P < 0.01) was associated with NACT compared with surgery alone. Multivariable Cox regression analysis showed that NACT, stage, and surgery type were prognostic factors for OS and CSS in GBC patients. Subgroup analysis revealed that the survival hazard ratios (HRs) of NACT vs non-NACT for localized or locoregionally advanced GBC patients were significant in most subgroups. CONCLUSIONS: NACT may provide therapeutic benefits for localized or locoregionally advanced GBC patients, especially for those with advanced stage, node-positive, poorly differentiated or undifferentiated disease. NACT combined with radical surgery was associated with a survival advantage. Therefore, NACT combined with surgery may provide a better treatment option for resectable GBC patients.
Subject(s)
Gallbladder Neoplasms , Neoadjuvant Therapy , Propensity Score , SEER Program , Humans , Gallbladder Neoplasms/pathology , Gallbladder Neoplasms/mortality , Gallbladder Neoplasms/drug therapy , Gallbladder Neoplasms/therapy , Female , Male , Neoadjuvant Therapy/methods , Neoadjuvant Therapy/statistics & numerical data , Middle Aged , Prognosis , Aged , Chemotherapy, Adjuvant/statistics & numerical data , Chemotherapy, Adjuvant/methods , Neoplasm Staging , Kaplan-Meier EstimateABSTRACT
Hepatocellular Carcinoma (HCC), the most common primary liver cancer, ranks as the third most common cause of cancer-related deaths globally. A deeper understanding of the cell death mechanisms in HCC is essential for developing more effective treatment strategies. This review explores programmed cell death (PCD) pathways involved in HCC, including apoptosis, necroptosis, pyroptosis, ferroptosis, and immunogenic cell death (ICD). These mechanisms trigger specific cell death cascades that influence the development and progression of HCC. Although multiple PCD pathways are involved in HCC, shared cellular factors suggest a possible interplay between the different forms of cell death. However, the exact roles of different cell death pathways in HCC and which cell death pathway plays a major role remain unclear. This review also highlights how disruptions in cell death pathways are related to drug resistance in cancer therapy, promoting a combined approach of cell death induction and anti-tumor treatment to enhance therapeutic efficacy. Further research is required to unravel the complex interplay between cell death modalities in HCC, which may lead to innovative therapeutic breakthroughs.
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Using the novel inflammatory biomarker lymphocyte-to-monocyte ratio (LMR), this work aimed to look into any potential connections between LMR and prostate cancer (PCa). A cross-sectional research investigation was conducted on 7706 male participants involved in the National Health and Nutrition Examination Survey from 2001 to 2010. Multivariate logistic regression modeling investigated the relationship between LMR levels and PCa risk. Furthermore, threshold analysis, subgroup analysis, interaction testing, and smoothed curve fitting were carried out. A significant negative correlation was seen between LMR and PCa risk (ORâ =â 0.79, 95% CI: 0.65-0.97, Pâ =â .0002), even after controlling for potential confounding factors. A significant nonlinear negative correlation with a threshold effect and a breakpoint of 4.86 was found by smooth curve fitting between LMR and PCa. Subgroup analysis revealed a significant interaction (P for interactionâ =â 0.0448) between the negative correlation between PCa and LMR about hypertension. Moreover, additional stratified smoothed curve fitting demonstrated a statistically significant inverse relationship between PCa risk and LMR. According to our findings, there is a substantial inverse relationship between PCa risk and LMR level. The inflammatory response-related index is quick, easy to use, and offers some clinical references. However, more extensive prospective investigations are required to confirm the involvement of LMR levels in PCa.
Subject(s)
Lymphocytes , Monocytes , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/blood , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/diagnosis , Cross-Sectional Studies , Middle Aged , Aged , Nutrition Surveys , Lymphocyte Count , Risk Factors , Adult , Leukocyte Count , Logistic ModelsABSTRACT
Toxoplasma gondii( T. gondii or Tg), is an obligatory intracellular parasite with humans as its intermediate hosts. In recent years, significant correlations between T. gondii infection and schizophrenia have been reported, including the possible mediating mechanisms. Currently, mechanisms and hypotheses focus on central neurotransmitters, immunity, neuroinflammation, and epigenetics; however, the exact underlying mechanisms remain unclear. In this article, we review the studies related to T. gondii infection and schizophrenia, particularly the latest research progress. Research on dopamine (DA) and other neurotransmitters, the blood-brain barrier, inflammatory factors, disease heterogeneity, and other confounders is also discussed. In addition, we also summarized the results of some new epidemiological investigations.
Subject(s)
Schizophrenia , Toxoplasma , Toxoplasmosis , Schizophrenia/parasitology , Schizophrenia/etiology , Humans , Toxoplasmosis/complications , Toxoplasmosis/epidemiology , Toxoplasmosis/parasitology , AnimalsABSTRACT
BACKGROUND: Amputation of the wrist or distal forearm after high-energy trauma due to a crushing mechanism is associated with complex tissue defects, making repair, and reconstruction challenging. Given the difficulty of this type of salvage, patients unfortunately experience a high revision amputation rate. However, a higher quality of life has been reported in patients with successful reconstructions. Herein, we described a protocolized approach for revascularization and reconstruction for functional hand salvage after traumatic amputation from a crushing mechanism using an anterolateral thigh flap (ALT). METHODS: A retrospective review was performed between October 2016 and October 2023 for all patients who underwent single-stage emergent debridement, revascularization, and soft tissue coverage using the ALT after amputation at the level of the wrist or distal forearm secondary to high-energy crush injury. Charts were reviewed for the preoperative Mangled Extremity Salvage Score, intraoperative details including what structures were injured and the reconstructive method performed, and postoperative data such as follow-up duration, outcomes, and complications. RESULTS: Eleven patients met the inclusion criteria with an average age of 35.5 (21-49) years old. The average size of the skin soft tissue defects was 17.3 × 8 cm (range, length: 13-25 cm, width: 6-13 cm), and all cases had associated injury to the underlying bone, nerves, and blood vessels. The average size of the ALT flap used for reconstruction was 19.2 × 9.8 cm (range, length: 14-27 cm, width: 7-15 cm). All patients had survival of the replanted limb. One patient experienced partial flap necrosis that required secondary debridement and skin graft. Nine patients healed without requiring any additional debridement procedures. Patient follow-up averaged 24.6 (12-38) months. All patients achieved satisfactory functional recovery with Grade II to III of Chen's criteria. CONCLUSIONS: For patients with traumatic crush amputation to the wrist with surrounding soft tissue injury, thorough debridement, revascularization, and reconstruction of amputated limbs can be performed in a single stage using the ALT. A protocolized approach from two institutions is presented, demonstrating improved survival and reduced complications of the traumatized limb with improved long-term patient outcomes.
Subject(s)
Amputation, Traumatic , Crush Injuries , Forearm Injuries , Plastic Surgery Procedures , Wrist Injuries , Humans , Retrospective Studies , Adult , Male , Middle Aged , Forearm Injuries/surgery , Plastic Surgery Procedures/methods , Crush Injuries/surgery , Female , Wrist Injuries/surgery , Amputation, Traumatic/surgery , Young Adult , Limb Salvage/methods , Clinical Protocols , Free Tissue Flaps/transplantation , Free Tissue Flaps/blood supply , Surgical Flaps/blood supply , Surgical Flaps/transplantation , Treatment Outcome , Debridement/methodsABSTRACT
OBJECTIVES: To investigate whether negative remodeling (NR) detected by intravascular ultrasound (IVUS) of the side branch ostium (SBO) would affect in-stent neointimal hyperplasia (NIH) at the one-year follow-up and the clinical outcome of target lesion failure (TLF) at the long-term follow-up for patients with left main bifurcation (LMb) lesions treated with a two-stent strategy. METHODS: A total of 328 patients with de novo true complex LMb lesions who underwent a 2-stent strategy of percutaneous coronary intervention (PCI) treatment guided by IVUS were enrolled in this study. We divided the study into two phases. Of all the patients, 48 patients who had complete IVUS detection pre- and post-PCI and at the 1-year follow-up were enrolled in phase I analysis, which aimed to analyze the correlation between NR and in-stent NIH at SBO at the 1-year follow-up. If the correlation was confirmed, the cutoff value of the remodeling index (RI) for predicting NIH ≥ 50% was analyzed next. The phase II analysis focused on the incidence of TLF as the primary endpoint at the 1- to 5-year follow-up for all 328 patients by grouping based on the cutoff value of RI. RESULTS: In phase I: according to the results of a binary logistic regression analysis and receiver operating characteristic (ROC) analysis, the RI cutoff value predicting percent NIH ≥ 50% was 0.85 based on the ROC curve analysis, with a sensitivity of 85.7%, a specificity of 88.3%, and an AUC of 0.893 (0.778, 1.000), P = 0.002. In phase II: the TLR rate (35.8% vs. 5.3%, P < 0.0001) was significantly higher in the several NR (sNR, defined as RI ≤ 0.85) group than in the non-sNR group. CONCLUSION: The NR of LCxO is associated with more in-stent NIH post-PCI for distal LMb lesions with a 2-stent strategy, and NR with RI ≤ 0.85 is linked to percent NIH area ≥ 50% at the 1-year follow-up and more TLF at the 5-year follow-up.
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BACKGROUND: Treatment and prevention of intracranial hypertension (IH) to minimize secondary brain injury are central to the neurocritical care management of traumatic brain injury (TBI). Predicting the onset of IH in advance allows for a more aggressive prophylactic treatment. This study aimed to develop random forest (RF) models for predicting IH events in TBI patients. METHODS: We analyzed prospectively collected data from patients admitted to the intensive care unit with invasive intracranial pressure (ICP) monitoring. Patients with persistent ICP > 22 mmHg in the early postoperative period (first 6 h) were excluded to focus on IH events that had not yet occurred. ICP-related data from the initial 6 h were used to extract linear (ICP, cerebral perfusion pressure, pressure reactivity index, and cerebrospinal fluid compensatory reserve index) and nonlinear features (complexity of ICP and cerebral perfusion pressure). IH was defined as ICP > 22 mmHg for > 5 min, and severe IH (SIH) as ICP > 22 mmHg for > 1 h during the subsequent ICP monitoring period. RF models were then developed using baseline characteristics (age, sex, and initial Glasgow Coma Scale score) along with linear and nonlinear features. Fivefold cross-validation was performed to avoid overfitting. RESULTS: The study included 69 patients. Forty-three patients (62.3%) experienced an IH event, of whom 30 (43%) progressed to SIH. The median time to IH events was 9.83 h, and to SIH events, it was 11.22 h. The RF model showed acceptable performance in predicting IH with an area under the curve (AUC) of 0.76 and excellent performance in predicting SIH (AUC = 0.84). Cross-validation analysis confirmed the stability of the results. CONCLUSIONS: The presented RF model can forecast subsequent IH events, particularly severe ones, in TBI patients using ICP data from the early postoperative period. It provides researchers and clinicians with a potentially predictive pathway and framework that could help triage patients requiring more intensive neurological treatment at an early stage.
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Designing high-performance binder-free electrochemical electrodes is crucially important toward supercapacitors. In this paper, a Zn/N-doped porous carbon film coating on flexible carbon nanotubes (ZIF-8@CT-800) derived from the epitaxial Zn-MOF film growth on cotton textile was successfully fabricated via a combination of the liquid-phase epitaxial (LPE) method and calcination treatments. The ZIF-8@CT-800 serves directly as a self-supported electrode for supercapacitors and exhibits a high areal capacitance of 930 mF·cm-2 at a current density of 1 mA·cm-2 and a good recyclability of 86% after 2000 cycles. The excellent supercapacitor property is ascribed to the unique structural design of ZIF-8@CT-800, which provides appropriate channels for enhanced electronic and ionic transport as well as increased surface area for accessing more electrolyte ions. This work will provide significant guidance for designing MOF-derived porous carbon to construct flexible binder-free electrode materials with high electrochemical performance.
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OBJECTIVES: The study aims to investigate genes associated with endometrial cancer (EC) progression to identify new biomarkers for early detection. METHODS: Differentially expressed genes (DEGs), Series test of cluster (STC) and protein-protein interaction analyses identified hub genes in EC. Clinical samples were utilized to examine the expression pattern of ECT2, assess its prognostic value, and evaluate its diagnostic potential. RESULTS: Upregulated DEGs were significantly enriched in cancer-related processes and pathways. Validations across databases identified ASPM, ATAD2, BUB1B, ECT2, KIF14, NUF2, NCAPG, and SPAG5 as potential hub genes, with ECT2 exhibiting the highest diagnostic efficacy. The expression levels of ECT2 varied significantly across different clinical stages, pathological grades, and metastasis statuses in UCEC. Furthermore, ECT2 mRNA was upregulated in the p53abn group, indicating a poorer prognosis, and downregulated in the MMRd and NSMP groups, suggesting a moderate prognosis. In clinical samples, ECT2 expression increased from normal endometria and endometrial hyperplasia without atypia (EH) to atypical endometrial hyperplasia (AH) and EC, effectively distinguishing between benign and malignant endometria. High ECT2 expression was associated with an unfavourable prognosis. CONCLUSIONS: ECT2 expression significantly rises in AH and EC, showing high accuracy in distinguishing between benign and malignant endometria. ECT2 emerges as a promising biomarker for diagnosing endometrial neoplasia and as a prognostic indicator in EC.
Subject(s)
Biomarkers, Tumor , Endometrial Neoplasms , Gene Expression Regulation, Neoplastic , Proto-Oncogene Proteins , Humans , Female , Endometrial Neoplasms/genetics , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/pathology , Endometrial Neoplasms/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Prognosis , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , Protein Interaction Maps/genetics , Up-Regulation , Gene Expression ProfilingABSTRACT
BACKGROUND: Traumatic brain injury (TBI) among elderly individuals poses a significant global health concern due to the increasing ageing population. METHODS: We searched PubMed, Cochrane Library, and Embase from database inception to Feb 1, 2024. Studies performed in inpatient settings reporting in-hospital mortality of elderly people (≥60 years) with TBI and/or identifying risk factors predictive of such outcomes, were included. Data were extracted from published reports, in-hospital mortality as our main outcome was synthesized in the form of rates, and risk factors predicting in-hospital mortality was synthesized in the form of odds ratios. Subgroup analyses, meta-regression and dose-response meta-analysis were used in our analyses. FINDINGS: We included 105 studies covering 2217,964 patients from 30 countries/regions. The overall in-hospital mortality of elderly patients with TBI was 16â¯% (95â¯% CI 15â¯%-17â¯%) from 70 studies. In-hospital mortality was 5â¯% (95â¯% CI, 3â¯%-7â¯%), 18â¯% (95â¯% CI, 12â¯%-24â¯%), 65â¯% (95â¯% CI, 59â¯%-70â¯%) for mild, moderate and severe subgroups from 10, 7, and 23 studies, respectively. A decrease in in-hospital mortality over years was observed in overall (1981-2022) and in severe (1986-2022) elderly patients with TBI. Older age 1.69 (95â¯% CI, 1.58-1.82, P < 0.001), male gender 1.34 (95â¯% CI, 1.25-1.42, P < 0.001), clinical conditions including traffic-related cause of injury 1.22 (95â¯% CI, 1.02-1.45, P = 0.029), GCS moderate (GCS 9-12 compared to GCS 13-15) 4.33 (95â¯% CI, 3.13-5.99, P < 0.001), GCS severe (GCS 3-8 compared to GCS 13-15) 23.09 (95â¯% CI, 13.80-38.63, P < 0.001), abnormal pupillary light reflex 3.22 (95â¯% CI, 2.09-4.96, P < 0.001), hypotension after injury 2.88 (95â¯% CI, 1.06-7.81, P = 0.038), polytrauma 2.31 (95â¯% CI, 2.03-2.62, P < 0.001), surgical intervention 2.21 (95â¯% CI, 1.22-4.01, P = 0.009), pre-injury health conditions including pre-injury comorbidity 1.52 (95â¯% CI, 1.24-1.86, P = 0.0020), and pre-injury anti-thrombotic therapy 1.51 (95â¯% CI, 1.23-1.84, P < 0.001) were related to higher in-hospital mortality in elderly patients with TBI. Subgroup analyses according to multiple types of anti-thrombotic drugs with at least two included studies showed that anticoagulant therapy 1.70 (95â¯% CI, 1.04-2.76, P = 0.032), Warfarin 2.26 (95â¯% CI, 2.05-2.51, P < 0.001), DOACs 1.99 (95â¯% CI, 1.43-2.76, P < 0.001) were related to elevated mortality. Dose-response meta-analysis of age found an odds ratio of 1.029 (95â¯% CI, 1.024-1.034, P < 0.001) for every 1-year increase in age on in-hospital mortality. CONCLUSIONS: In the field of elderly patients with TBI, the overall in-hospital mortality and its temporal-spatial feature, the subgroup in-hospital mortalities according to injury severity, and dose-response meta-analysis of age were firstly comprehensively summarized. Substantial key risk factors, including the ones previously not elucidated, were identified. Our study is thus of help in underlining the importance of treating elderly TBI, providing useful information for healthcare providers, and initiating future management guidelines. This work underscores the necessity of integrating elderly TBI treatment and management into broader health strategies to address the challenges posed by the aging global population. REVIEW REGISTRATION: PROSPERO CRD42022323231.
Subject(s)
Brain Injuries, Traumatic , Hospital Mortality , Humans , Brain Injuries, Traumatic/mortality , Brain Injuries, Traumatic/epidemiology , Aged , Risk Factors , Aged, 80 and over , Male , Female , Middle Aged , Age FactorsABSTRACT
BACKGROUND: Lithium carbonate is used to manage various mood disorders, but it can cause thyroid abnormalities, including goiter, hypothyroidism, and hyperthyroidism. In rare cases, it can lead to giant goiter and subclinical hyperthyroidism, which may require surgical intervention in severe cases. CASE SUMMARY: This case represents a rare development of giant goiter and subclinical hyperthyroidism in a schizophrenia patient who was subjected to prolonged lithium carbonate treatment. The enlarged thyroid gland caused pressure on the airway and recurrent laryngeal nerve, which led to respiratory distress, hoarseness, and dysphagia. The immediate danger of suffocation required urgent surgical intervention. In this report, we describe the case of a 41-year-old Chinese woman. This sheds light on the etiology and challenges associated with managing a giant goiter. The patient underwent a subtotal thyroidectomy to relieve airway compression and facilitate airway expansion. Prior to the procedure, the patient was given iodine to prepare. Concurrently, changes were made to the psychiatric medication regimen. Following surgery, the patient's respiratory function and vocal cord functionality improved significantly, and her mental state remained stable. CONCLUSION: It is essential to monitor thyroid function, test thyroid antibody levels, and perform thyroid ultrasounds consistently in all patients undergoing long-term lithium carbonate treatment. This vigilance helps prevent severe and potentially life-threatening thyroid enlargement.
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Rice bacterial leaf blight and rice bacterial leaf streak have induced tremendous damage to production of rice worldwide. To discover an effective novel antibacterial agent, a series of novel trans-resveratrol (RSV) derivatives containing 1,3,4-oxadiazole and amide moieties were designed and synthesized for the first time. Most of them showed excellent antibacterial activities against Xanthomonas oryzae pv oryzicola and Xanthomonas oryzae pv oryzae. Especially, compound J12 had the best inhibitory with the half-maximal effective concentration values of 4.2 and 5.0 mg/L, respectively, which were better than that of RSV (63.7 and 75.4 mg/L), bismerthiazol (79.5 and 89.6 mg/L), and thiodiazole copper (105.4 and 112.8 mg/L). Furthermore, compound J12 had an excellent control effect against rice bacterial leaf streak and rice bacterial leaf blight, with protective activities of 46.2 and 42.1% and curative activities of 44.5 and 41.7%, respectively. Preliminary mechanisms indicated that compound J12 could not only remarkably decrease biofilm formation, extracellular polysaccharide production, and the synthesis of extracellular enzymes but also destroy bacterial cell surface morphology, thereby reducing the pathogenicity of bacteria. In addition, compound J12 could increase the activity of defense-related enzymes and affect the expression of multiple pathogenic-related genes including plant-pathogen interaction, the MAPK signaling pathway, and phenylpropanoid biosynthesis, and this could improve the defense of rice against rice bacterial leaf streak infection. The present work indicates that the RSV derivatives can be used as promising candidates for the development of antibacterial agents.
Subject(s)
Anti-Bacterial Agents , Oryza , Plant Diseases , Resveratrol , Xanthomonas , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Xanthomonas/drug effects , Resveratrol/pharmacology , Resveratrol/chemistry , Plant Diseases/microbiology , Oryza/microbiology , Structure-Activity Relationship , Drug Design , Microbial Sensitivity Tests , Biofilms/drug effectsABSTRACT
The surging popularity of virtual reality (VR) technology raises concerns about VR-induced motion sickness, linked to discomfort and nausea in simulated environments. Our method involves in-depth analysis of EEG data and user feedback to train a sophisticated deep learning model, utilizing an enhanced GRU network for identifying motion sickness patterns. Following comprehensive data pre-processing and feature engineering to ensure input accuracy, a deep learning model is trained using supervised and unsupervised techniques for classifying and predicting motion sickness severity. Rigorous training and validation procedures confirm the model's robustness across diverse scenarios. Research results affirm our deep learning model's 84.9% accuracy in classifying and predicting VR-induced motion sickness, surpassing existing models. This information is vital for improving the VR experience and advancing VR technology.
Subject(s)
Deep Learning , Electroencephalography , Motion Sickness , Virtual Reality , Humans , Motion Sickness/physiopathology , Electroencephalography/methods , Adult , Male , Female , Wavelet Analysis , Young AdultABSTRACT
Medical adhesives play an important role in clinical medicine because of their flexibility and convenient operation. However, they are still limited to laparoscopic surgeries, which have demonstrated urgent demand for liver retraction with minimal damage to the human body. Here, inspired by the suction cup structure of octopus, an adhesive patch with excellent mechanical properties, robust and switchable adhesiveness, and biocompatibility is proposed. The adhesive patch is combined by the attachment body mainly made of poly(acrylic acid) grafted with N-hydroxysuccinimide ester, crosslinked biodegradable gelatin methacrylate and biodegradable biopolymer gelatin to mimic the adhesive sucker rim, and the temperature-sensitive telescopic layer of microgel-crosslinked poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate) to shrink and form internal cavity with reduced pressure. Through mechanical tests, adhesion evaluation, and biocompatibility analysis, the bioinspired adhesive patch has demonstrated its capacity not only in adhesion to tissues but also in potential treatment for medical applications, especially laparoscopic technology. The bioinspired adhesive patch can break through the limitations of traditional retraction methods, and become an ideal candidate for liver retraction in laparoscopic surgery and related clinical medicine.
ABSTRACT
Ligand-to-metal charge transfer (LMCT) is conceived as a universal theory to account for voltage hysteresis in oxygen-redox battery electrodes. However, the influence of oxygen anionic species on mediating LMCT and its reflection to voltage hysteresis remain poorly understood. Herein, we demonstrate a close interplay between the chemical states of oxidized oxygen species, the cationic species, and the kinetics of LMCT and forcefully identify their influence on the magnitude of voltage hysteresis. Combining electrochemical/spectroscopic evidence and first-principles calculations, we clarify two distinct kinds of dynamic LMCT processesâthat is, the formation of trapped molecular O2 accompanied by the reduction of Ni4+/Ni3+ to Ni2+ (fast LMCT) during relaxation in Li-rich cation-disordered rock-salt (DRX) Li1.3Ni0.27Ta0.43O2 with extremely large voltage hysteresis, the formation of O-O dimers, and the partial reduction of Mn4+ to Mn3+ (slow LMCT) in DRX-Li1.3Mn0.4Ta0.3O2 with medium hysteresis. We further validate the maintenance of both cationic (Mn4+) and anionic (O-â¢) species during relaxation in Na2Mn3O7, reconciling its nonhysteretic behavior to the absence of LMCT. This study highlights the critical role of intermediate anionic species in mediating LMCT and provides a causal explanation of various voltage hysteresis signatures of oxygen-redox materials.
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BACKGROUND: Fleas are one of the most common and pervasive ectoparasites worldwide, comprising at least 2500 valid species. They are vectors of several disease-causing agents, such as Yersinia pestis. Despite their significance, however, the molecular genetics, biology, and phylogenetics of fleas remain poorly understood. METHODS: We sequenced, assembled, and annotated the complete mitochondrial (mt) genome of the rodent flea Nosopsyllus laeviceps using next-generation sequencing technology. Then we combined the new mitogenome generated here with mt genomic data available for 23 other flea species to perform comparative mitogenomics, nucleotide diversity, and evolutionary rate analysis. Subsequently, the phylogenetic relationship within the order Siphonaptera was explored using the Bayesian inference (BI) and maximum likelihood (ML) methods based on concentrated data for 13 mt protein-coding genes. RESULTS: The complete mt genome of the rodent flea N. laeviceps was 16,533 base pairs (bp) in a circular DNA molecule, containing 37 typical genes (13 protein-coding genes, 22 transfer RNA [tRNA] genes, and two ribosomal RNA [rRNA] genes) with one large non-coding region (NCR). Comparative analysis among the order Siphonaptera showed a stable gene order with no gene arrangement, and high AT content (76.71-83.21%) with an apparent negative AT and GC skew except in three fleas Aviostivalius klossi bispiniformis, Leptopsylla segnis, and Neopsylla specialis. Moreover, we found robust evidence that the cytochrome c oxidase subunit 1 (cox1) gene was the most conserved protein-coding gene (Pi = 0.15, non-synonymous/synonymous [Ka/Ks] ratio = 0.13) of fleas. Phylogenomic analysis conducted using two methods revealed different topologies, but both results strongly indicated that (i) the families Ceratophyllidae and Leptopsyllidae were paraphyletic and were the closest to each other, and (ii) the family Ctenophthalmidae was paraphyletic. CONCLUSIONS: In this study, we obtained a high-quality mt genome of the rodent flea N. laeviceps and performed comparative mitogenomics and phylogeny of the order Siphonaptera using the mt database. The results will enrich the mt genome data for fleas, lay a foundation for the phylogenetic analysis of fleas, and promote the evolutionary analysis of Siphonaptera.
Subject(s)
Genome, Mitochondrial , Phylogeny , Siphonaptera , Animals , Siphonaptera/genetics , Siphonaptera/classification , Genome, Mitochondrial/genetics , Rodentia , High-Throughput Nucleotide Sequencing , RNA, Transfer/geneticsABSTRACT
Background: Breast cancer remains a pressing global health concern, necessitating accurate diagnostics for effective interventions. Deep learning models (AlexNet, ResNet-50, VGG16, GoogLeNet) show remarkable microcalcification identification (>90%). However, distinct architectures and methodologies pose challenges. We propose an ensemble model, merging unique perspectives, enhancing precision, and understanding critical factors for breast cancer intervention. Evaluation favors GoogleNet and ResNet-50, driving their selection for combined functionalities, ensuring improved precision, and dependability in microcalcification detection in clinical settings. Methods: This study presents a comprehensive mammogram preprocessing framework using an optimized deep learning ensemble approach. The proposed framework begins with artifact removal using Otsu Segmentation and morphological operation. Subsequent steps include image resizing, adaptive median filtering, and deep convolutional neural network (D-CNN) development via transfer learning with ResNet-50 model. Hyperparameters are optimized, and ensemble optimization (AlexNet, GoogLeNet, VGG16, ResNet-50) are constructed to identify the localized area of microcalcification. Rigorous evaluation protocol validates the efficacy of individual models, culminating in the ensemble model demonstrating superior predictive accuracy. Results: Based on our analysis, the proposed ensemble model exhibited exceptional performance in the classification of microcalcifications. This was evidenced by the model's average confidence score, which indicated a high degree of dependability and certainty in differentiating these critical characteristics. The proposed model demonstrated a noteworthy average confidence level of 0.9305 in the classification of microcalcification, outperforming alternative models and providing substantial insights into the dependability of the model. The average confidence of the ensemble model in classifying normal cases was 0.8859, which strengthened the model's consistent and dependable predictions. In addition, the ensemble models attained remarkably high performances in terms of accuracy, precision, recall, F1-score, and area under the curve (AUC). Conclusion: The proposed model's thorough dataset integration and focus on average confidence ratings within classes improve clinical diagnosis accuracy and effectiveness for breast cancer. This study introduces a novel methodology that takes advantage of an ensemble model and rigorous evaluation standards to substantially improve the accuracy and dependability of breast cancer diagnostics, specifically in the detection of microcalcifications.