An automatic texture feature analysis framework of renal tumor: surgical, pathological, and molecular evaluation based on multi-phase abdominal CT.

OBJECTIVES: To determine whether the texture feature analysis of multi-phase abdominal CT can provide a robust prediction of benign and malignant, histological subtype, pathological stage, nephrectomy risk, pathological grade, and Ki67 index in renal tumor. METHODS: A total of 1051 participants with renal tumor were split into the internal cohort (850 patients from four different hospitals) and the external testing cohort (201 patients from another local hospital). The proposed framework comprised a 3D-kidney and tumor segmentation model by 3D-UNet, a feature extractor for the regions of interest based on radiomics and image dimension reduction, and the six classifiers by XGBoost. A quantitative model interpretation method called SHAP was used to explore the contribution of each feature. RESULTS: The proposed multi-phase abdominal CT model provides robust prediction for benign and malignant, histological subtype, pathological stage, nephrectomy risk, pathological grade, and Ki67 index in the internal validation set, with the AUROC values of 0.88 ± 0.1, 0.90 ± 0.1, 0.91 ± 0.1, 0.89 ± 0.1, 0.84 ± 0.1, and 0.88 ± 0.1, respectively. The external testing set also showed impressive results, with AUROC values of 0.83 ± 0.1, 0.83 ± 0.1, 0.85 ± 0.1, 0.81 ± 0.1, 0.79 ± 0.1, and 0.81 ± 0.1, respectively. The radiomics feature including the first-order statistics, the tumor size-related morphology, and the shape-related tumor features contributed most to the model predictions. CONCLUSIONS: Automatic texture feature analysis of abdominal multi-phase CT provides reliable predictions for multi-tasks, suggesting the potential usage of clinical application. CLINICAL RELEVANCE STATEMENT: The automatic texture feature analysis framework, based on multi-phase abdominal CT, provides robust and reliable predictions for multi-tasks. These valuable insights can serve as a guiding tool for clinical diagnosis and treatment, making medical imaging an essential component in the process. KEY POINTS: • The automatic texture feature analysis framework based on multi-phase abdominal CT can provide more accurate prediction of benign and malignant, histological subtype, pathological stage, nephrectomy risk, pathological grade, and Ki67 index in renal tumor. • The quantitative decomposition of the prediction model was conducted to explore the contribution of the extracted feature. • The study involving 1051 patients from 5 medical centers, along with a heterogeneous external data testing strategy, can be seamlessly transferred to various tasks involving new datasets.

Impact of Dual Bt-Transgenic Maize (2A7) on Soil Microbial Communities and Enzyme Activities: A Comparative Study with Control Variety Z58.

The impacts of transgenic crops on soil microbiology and fertility are critical in determining their biosafety. While transgenic crops can alter soil microbes, their effects are often context-dependent; therefore, the ecological importance of these changes remains a topic of ongoing research. Using high-throughput sequencing, we investigated the effects of Bacillus thuringiensis (Bt) maize expressing the mcry1Ab and mcry2Ab genes (2A7) on soil nutrient dynamics, as well as the diversity and function of soil microbial communities, including bacteria and fungi, within different soil compartments. Our findings revealed a plant-shaped rhizosphere (RS) microbial community as a result of the selective recruitment of microorganisms from the surrounding environment. The transgene insertion had a significant impact on the RS niche, and several species eventually became associated with Z58 and 2A7 plants. For example, Neocosmospora rubicola fungal and Pantoea dispersa bacterial microorganisms were significantly decreased in the dual Bt-transgenic 2A7 rhizosphere but enriched in the Z58 rhizospheres. The activity of soil enzymes such as urease, invertase, and alkaline phosphatase was boosted by Bt-transgenic 2A7. LefSe analysis identified significant bacterial and fungal biomarker species that were responsible for the differential effects of Bt-transgenic 2A7 and control Z58 within rhizosphere soils. Mantel analysis further demonstrated that the root exudates of 2A7 altered nutrient-acquisition enzymes by influencing biomarker taxa. PICRUSt2 functional characterization revealed a significantly higher abundance of the phosphate-starvation-inducible protein in control Z58 than in Bt-transgenic 2A7. Furthermore, taxonomy, alpha (Shannon diversity), and beta diversity analyses all revealed niche-driven microbial profile differentiation. Niche partitioning also had a significant impact on N- and P-related COGs as well. Our findings suggests that Bt-transgenic 2A7 modulates rhizosphere microbial communities by affecting biomarker taxa and soil enzyme activity. These findings will promote sustainable agriculture practices by advancing our knowledge of the ecological effects of Bt crops on soil microbial communities.

In vivo transgenic studies confirm the critical acylation function of LeBAHD56 for shikonin in Lithospermum erythrorhizon.

KEY MESSAGE: LeBAHD56 is preferentially expressed in tissues where shikonin and its derivatives are biosynthesized, and it confers shikonin acylation in vivo. Two WRKY transcriptional factors might regulate LeBAHD56's expression. Shikonin and its derivatives, found in the roots of Lithospermum erythrorhizon, have extensive application in the field of medicine, cosmetics, and other industries. Prior research has demonstrated that LeBAHD1(LeSAT1) is responsible for the biochemical process of shikonin acylation both in vitro and in vivo. However, with the exception of its documented in vitro biochemical function, there is no in vivo genetic evidence supporting the acylation function of the highly homologous gene of LeSAT1, LeBAHD56(LeSAT2), apart from its reported role. Here, we validated the critical acylation function of LeBAHD56 for shikonin using overexpression (OE) and CRISPR/Cas9-based knockout (KO) strategies. The results showed that the OE lines had a significantly higher ratio of acetylshikonin, isobutyrylshikonin or isovalerylshikonin to shikonin than the control. In contrast, the KO lines had a significantly lower ratio of acetylshikonin, isobutyrylshikonin or isovalerylshikonin to shikonin than controls. As for its detailed expression patterns, we found that LeBAHD56 is preferentially expressed in roots and callus cells, which are the biosynthesis sites for shikonin and its derivatives. In addition, we anticipated that a wide range of putative transcription factors might control its transcription and verified the direct binding of two crucial WRKY members to the LeBAHD56 promoter's W-box. Our results not only confirmed the in vivo function of LeBAHD56 in shikonin acylation, but also shed light on its transcriptional regulation.

Correlation analysis of peripheral platelet markers and disease phenotypes in Alzheimer's disease.

INTRODUCTION: Platelets serve as the primary peripheral reservoir of amyloid beta (Aß). However, there is limited research on platelet markers in routine blood examinations, particularly with regard to the large platelet ratio (P-LCR) in Alzheimer's disease (AD). METHODS: This study included 512 AD patients and 205 healthy controls (HCs). Platelet markers and apolipoprotein E (APOE) 4 status were assessed in all participants. RESULTS: The study revealed that P-LCR was significantly elevated in AD patients compared to HCs. In AD patients carrying APOE4, P-LCR significantly negatively correlated with Montreal Cognitive Assessment scores. There was an observed increasing trend in the rate of change in P-LCR with disease progression. Binary logistic regression analysis indicated that P-LCR may constitute a risk factor for AD, after adjusting for age, sex, APOE4, and body mass index. DISCUSSION: P-LCR is associated with disease severity in AD patients carrying APOE4. P-LCR may be a promising marker to reflect platelet activity in AD patients. HIGHLIGHTS: P-LCR significantly negatively correlated with MoCA scores in AD patients with APOE4. The rate of change in P-LCR showed an increasing trend with disease progression. P-LCR may be a risk factor for AD.

Meta-analysis and systematic review of peripheral platelet-associated biomarkers to explore the pathophysiology of alzheimer's disease.

INTRODUCTION: Platelets are the primary peripheral reserve of amyloid precursor protein (APP), providing more than 90% of blood amyloid-beta (Aß). Some oxidative stress markers and neurotransmitter markers were also differentially expressed in the peripheral platelets of AD. Therefore, the present study explored the differences in platelet-associated biomarkers between AD and healthy controls using meta-analysis and systematic review to reveal the value of platelet in the pathogenesis and development of AD. METHODS: We searched all the related studies that probed into the platelets in AD based on PubMed, Embase, and web of science databases from the establishment to November 04, 2021. RESULTS: Eighty-eight studies were included in the meta-analysis, and the platelets data of 702 AD and 710 controls were analyzed. The results of standardized mean difference (SMD) showed that platelets in AD had lower levels of APP ratio (SMD: -1.89; p < 0.05), ADAM10 (SMD: -1.16; p < 0.05), Na + -K + -ATPase (SMD: -7.23; p < 0.05), but higher levels of HMW/LMW tau (SMD: 0.92; p < 0.05), adenosine A2 receptor (SMD: 4.27; p < 0.05), MAO-B (SMD: 1.73; p < 0.05), NO (SMD: 4.25; p < 0.05) and ONOO- (SMD: 7.33; p < 0.05). In the systematic review, some other platelet markers seem to be meaningful in AD patients. CONCLUSION: The results of the present meta-analysis and systematic review demonstrated that the alterations of APP metabolic enzymes, oxidative stress markers, and neurotransmitter factors in platelets were similar to their changes in the central nervous system of AD, suggesting that platelet could be a good source of peripheral biomarkers and may play an important role in the pathophysiological development of AD.

A novel C19ORF12 mutation in two MPAN sisters treated with deferiprone.

BACKGROUND: Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a rare and devastating disease caused by pathogenic mutations in C19orf12 gene. MPAN is characterized by pathological iron accumulation in the brain and fewer than 100 cases of MPAN have been described. Although the diagnosis of MPAN has achieved a great breakthrough with the application of the whole exome gene sequencing technology, the therapeutic effect of iron chelation therapy in MPAN remains controversial. CASE PRESENTATION: We reported that two sisters from the same family diagnosed with MPAN had dramatically different responses to deferiprone (DFP) treatment. The diagnosis of MPAN were established based on typical clinical manifestations, physical examination, brain magnetic resonance imaging (MRI), cerebrospinal fluid analysis (CSF) and gene sequencing results. The clinical presentations of the two sisters with MPAN due to novel gene locus mutations were similar to those previously reported. There is no other difference in basic information except that the proband had a later onset age and fertility history. Both the proband and his second sister were treated with deferiprone (DFP), but they had dramatically different responses to the treatment. The proband's condition deteriorated sharply after treatment with DFP including psychiatric symptoms and movement disorders. However, the second sister of the proband became relatively stable after receiving the DFP treatment. After four years of follow-up, the patient still denies any new symptoms of neurological deficits. CONCLUSION: The findings of this study enriched the MPAN gene database and indicated that DFP might ameliorate symptom progression in patients without severe autonomic neuropsychiatric impairment at the early stage of the disease.

Design, synthesis and biological evaluation of novel modified dual-target shikonin derivatives for colorectal cancer treatment.

Warburg effect provides energy and material essential for tumor proliferation, the reverse of Warburg effect provides insights into the development of a novel anti-cancer strategy. Pyruvate kinase 2 (PKM2) and pyruvate dehydrogenase kinase 1 (PDK1) are two key enzymes in tumor glucose metabolism pathway that not only contribute to the Warburg effect through accelerating aerobic glycolysis, but also serve as druggable target for colorectal cancer (CRC). Considering that targeting PKM2 or PDK1 alone does not seem to be sufficient to remodel abnormal glucose metabolism and achieve significant antitumor activity, a series of novel benzenesulfonyl shikonin derivatives were designed to regulate PKM2 and PDK1 simultaneously. By means of molecular docking and antiproliferative screen, we found that compound Z10 could act as the combination of PKM2 activator and PDK1 inhibitor, thereby significantly inhibited glycolysis that reshaping tumor metabolism. Moreover, Z10 could inhibit proliferation, migration and induce apoptosis in CRC cell HCT-8. Finally, the in vivo anti-tumor activity of Z10 was evaluated in a colorectal cancer cell xenograft model in nude mice and the results demonstrated that Z10 induced tumor cell apoptosis and inhibited tumor cell proliferation with lower toxicity than shikonin. Our findings indicated that it is feasible to alter tumor energy metabolism through multi-target synergies, and the dual-target benzenesulfonyl shikonin derivative Z10 could be a potential anti-CRC agent.

Anti-N-methyl-D-aspartate receptor encephalitis: a common cause of encephalitis in the intensive care unit.

Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDAR encephalitis) is the most common type of immune-mediated encephalitis. This study aimed to assess the incidence and mortality of anti-NMDAR encephalitis in intensive care unit (ICU) to evaluate the clinical manifestations, laboratory findings, managements and outcomes, and to compare these characteristics with patients with non-anti-NMDAR encephalitis admitted to ICU. Patients admitted to the neurological ICU with suspected encephalitis were included between January 1, 2012 and July 31, 2015. Cerebrospinal fluid (CSF) of enrolled patients was screened for anti-NMDAR antibodies using a cell-based assay. 72 critically ill patients with encephalitis of uncertain etiology were investigated, and 16 patients were positive for anti-NMDAR antibodies in CSF. Compared to patients with non-anti-NMDAR encephalitis, patients with anti-NMDAR encephalitis were younger, more likely to present with the psychiatric symptoms, dyskinesia, and autonomic dysfunction, and had longer ICU stays. The abnormal movements were so difficult to control that complicated the management. The outcome was favorable in ten patients 1 year after the disease onset, and the mortality was as high as 25 % overall. The incidence of anti-NMDAR encephalitis is high among critically ill patients with encephalitis of uncertain etiology. Controlling dyskinesia proved to be a challenge. Persistent dysautonomias were additional difficult to manage confounders. Same points being highlighted in this study may aid clinicians in the management of patients with anti-NMDAR encephalitis in intensive care practice.

Analysis of the Association Between Pathogen Exposure and the Risk of Dementia.

Background: Previous research has suggested that pathogen infections may serve as potential contributors to dementia. Objective: Consequently, the study aimed to evaluate whether pathogen exposure heightens the risk of dementia. Methods: Between 2006 and 2010, a total of 8,144 individuals from the UK Biobank had data on pathogen antibodies and were included in the baseline assessment. Cox proportional hazard models were employed for the analysis. Results: Out of the 8,144 participants, 107 eventually developed dementia, while 55 participants were diagnosed with Alzheimer's disease (AD). Multivariate Cox regression analysis revealed that the levels of pathogen antibody titers of EBV and C. trachomatis were associated with an increased risk of dementia/AD. The highest quartile of EBV EBNA-1 and EBV VCA p18, and the second quartile of H. pylori VacA significantly increased the risk of dementia compared lower quartile (EBV EBNA-1: HR = 1.938, p = 0.018; EBV VCA p18: HR = 1.824, p = 0.040; H. pylori VacA: HR = 1.890, p = 0.033). Besides, the highest quartile of EBV VCA p18 had a higher risk of AD compared lower quartile (HR = 2.755, p = 0.029). Conclusions: The study demonstrated that exposure to EBV, H. pylori, and C. trachomatis substantially elevated the risk of dementia/AD. Despite the relatively widespread occurrence of EBV infection in the population, elevated pathogen antibody titers were still found to increase the risk of dementia/AD. Besides, since C. trachomatis and C. pneumoniae are quite homologous, this study found that trachomatis (C. trachomatis/C. pneumoniae) may be significantly associated with the risk of AD/dementia.

Associations of cerebrospinal fluid profiles with severity and mortality risk of amyotrophic lateral sclerosis.

Background: The relationship between routine cerebrospinal fluid (CSF) testing and the disease phenotype of amyotrophic lateral sclerosis (ALS) is unclear, and there are some contradictions in current studies. Methods: This study aimed to analyze the relationship between CSF profiles and disease phenotype in ALS patients. We collected 870 ALS patients and 96 control subjects admitted to West China Hospital of Sichuan University. CSF microprotein, albumin, IgG, index of IgG (IgGindex), albumin quotient (QALB), and serum IgG were examined. Results: In ALS patients, CSF IgG, and QALB were significantly increased, while CSF IgGindex was decreased, compared with control subjects. Approximately one-third of ALS patients had higher CSF IgG levels. The multiple linear regression analysis identified that CSF IgGindex was weakly negatively associated with ALS functional rating scale revised (ALSFRS-R) scores (ß = -0.062, p = 0.041). This significance was found in male ALS but not in female ALS. The Cox survival analyses found that upregulated CSF IgG was significantly associated with the increased mortality risk in ALS [HR = 1.219 (1.010-1.470), p = 0.039]. Conclusion: In the current study, the higher CFS IgG was associated with increased mortality risk of ALS. CSF IgGindex may be associated with the severity of ALS. These findings may be sex-specific.

Diagnostic value and correlation analysis of serum cytokine levels in patients with multiple system atrophy.

Background: The association between cytokines in peripheral blood and clinical symptoms of multiple system atrophy (MSA) has been explored in only a few studies with small sample size, and the results were obviously controversial. Otherwise, no studies have explored the diagnostic value of serum cytokines in MSA. Methods: Serum cytokines, including interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α), were measured in 125 MSA patients and 98 healthy controls (HCs). Correlations of these serum cytokines with clinical variables were analyzed in MSA patients. Diagnostic value of cytokines for MSA was plotted by receiver operating curves. Results: No significant differences were found in sex and age between the MSA group and the HCs. TNF-α in MSA patients were significantly higher than those in HCs (area under the curve (AUC) 0.768), while IL-6 and IL-8 were not. Only Hamilton Anxiety Scale (HAMA) has a positive correlation between with TNF-α in MSA patients with age and age at onset as covariates. Serum IL-6 was associated with HAMA, Hamilton Depression Scale (HAMD), the Unified MSA Rating Scale I (UMSARS I) scores, the UMSARS IV and the Instrumental Activity of Daily Living scores. However, IL-8 was not associated with all clinical variables in MSA patients. Regression analysis showed that HAMA and age at onset were significantly associated with TNF-α, and only HAMA was mild related with IL-6 levels in MSA patients. Conclusion: Serum TNF-α and IL-6 levels in MSA patients may be associated with anxiety symptom; however, only TNF-α was shown to be a useful tool in distinguishing between MSA and HCs.

Peripheral immunity relate to disease progression and prognosis in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Abnormalities in the peripheral immune system in ALS have been paid attention; however, the results of changes in peripheral immune parameters were inconsistent. METHODS: A total of 1109 ALS patients were enrolled in the study. All patients received clinical evaluation and peripheral immune parameters measurement. The outcomes were analyzed by correlation analysis, multiple linear regression and cox survival analysis. RESULTS: We found that ALS patients had significantly higher percentage of CD4+ T cells (39.3 vs. 37.1%, p < 0.001) and CD4+/CD8+ ratio (1.88 vs. 1.72, p = 0.011), significantly lower IgG (11.73 vs.12.82, p < 0.001) and IgA (2130.70 vs. 2284.8, p = 0.013) compared with the health controls. In the multivariate linear model, we found that each increase of 1.262, 0.278, and 4.44E-4 in ALSFRS-R scores were significantly associated with each increment of lymphocyte count, IgG, and IgA, respectively. However, each decrease of 0.341, 0.068, and 0.682 in ALSFRS-R score was associated with each increment in neutrophils, CD4+ T cells, and CD4+/CD8+ ratio, respectively. Cox survival regression analysis showed that the death risk of ALS patients was related to the levels of C3 (HR 0.592, 95% CI 0.361-0.973). CONCLUSION: We found that there were differences in peripheral immune parameters of ALS patients with the severity of the disease, especially neutrophil, lymphocyte, CD4+ T, and IgG; C3 is an independent predictor of survival in ALS patients. More studies are needed to elucidate the mechanisms associated with altered immune parameters in ALS.

A modified natural small molecule inhibits triple-negative breast cancer growth by interacting with Tubb3.

BACKGROUND: Triple-negative breast cancer (TNBC) is a malignant tumor without specific therapeutic targets and a poor prognosis. Chemotherapy is currently the first-line therapeutic option for TNBC. However, due to the heterogeneity of TNBC, not all of TNBC patients are responsive to chemotherapeutic agents. Therefore, the demand for new targeted agents is critical. ß-tubulin isotype III (Tubb3) is a prognostic factor associated with cancer progression, including breast cancer, and targeting Tubb3 may lead to improve TNBC disease control. Shikonin, the active compound in the roots of Lithospermun erythrorhizon suppresses the growth of various types of tumors, and its efficacy can be improved by altering its chemical structure. PURPOSE: In this work, the anti-TNBC effect of a shikonin derivative (PMMB276) was investigated, and its mechanism was also investigated. STUDY DESIGN/METHODS: This study combines flow cytometry, immunofluorescence staining, immunoblotting, immunoprecipitation, siRNA silencing, and the iTRAQ proteomics assay to analyze the inhibition potential of PMMB276 on TNBC. In vivo study was performed, Balb/c female murine models with or without the small molecule treatments. RESULTS: Herein, we screened 300 in-house synthesized analogs of shikonin against TNBC and identified a novel small molecule, PMMB276; it suppressed cell proliferation, induced apoptosis, and arrested the cell cycle at the G2/M phase, suggesting that it could have a tumor suppressive role in TNBC. Tubb3 was identified as the target of PMMB276 using proteomic and biological activity analyses. Meanwhile, PMMB276 regulated microtubule dynamics in vitro by inducing microtubule depolymerization and it could act as a tubulin stabilizer by a different process than that of paclitaxel. Moreover, suppressing or inhibiting Tubb3 with PMMB276 reduced the growth of breast cancer in an experimental mouse model, indicating that Tubb3 plays a significant role in TNBC progression. CONCLUSION: The findings support the therapeutic potential of PMMB276, a Tubb3 inhibitor, as a treatment for TNBC. Our findings might serve as a foundation for the utilization of shikonin and its derivatives in the development of anti-TNBC.

Classification of asymmetry in mammography via the DenseNet convolutional neural network.

Purpose: To investigate the effectiveness of a deep learning system based on the DenseNet convolutional neural network in diagnosing benign and malignant asymmetric lesions in mammography. Methods: Clinical and image data from 460 women aged 23-82 years (47.57 ± 8.73 years) with asymmetric lesions who underwent mammography at Shenzhen People's Hospital, Shenzhen Luohu District People's Hospital, and Shenzhen Hospital of Peking University from December 2019 to December 2020 were retrospectively analyzed. Two senior radiologists, two junior radiologists, and the DL system read the mammographic images of 460 patients, respectively, and finally recorded the BI-RADS classification of asymmetric lesions. We then used the area under the curve (AUC) of the receiver operating characteristic (ROC) to evaluate the diagnostic efficacy and the difference between AUCs by the Delong method. Results: Specificity (0.909 vs. 0.835, 0.790, χ2=8.21 and 17.22, p＜0.05) and precision (0.872 vs. 0.763, 0.726, χ2=9.23 and 5.22, p＜0.05) of the DL system in the diagnosis of benign and malignant asymmetric lesions were higher than those of junior radiologist A and B, and there was a statistically significant difference between AUCs (0.778 vs. 0.579, 0.564, Z = 4.033 and 4.460, p＜0.05). Furthermore, the AUC (0.778 vs. 0.904, 0.862, Z = 3.191, and 2.167, p＜0.05) of benign and malignant asymmetric lesions diagnosed by the DL system was lower than that of senior radiologist A and senior radiologist B. Conclusions: The DL system based on the DenseNet convolution neural network has high diagnostic efficiency, which can help junior radiologists evaluate benign and malignant asymmetric lesions more accurately. It can also improve diagnostic accuracy and reduce missed diagnoses caused by inexperienced junior radiologists.

Analyses of hospitalization in Alzheimer's disease and Parkinson's disease in a tertiary hospital.

Background: To characterize the pattern of hospitalization in patients with Alzheimer's disease (AD) or Parkinson's disease (PD), and compare the differences to see whether AD patients and PD patients have a different picture of hospitalization. Methods: The clinical features of all consecutive patients from January 2017 to December 2020 were reviewed. We identified AD patients and PD patients from an electronic database in a tertiary medical center. Results: The study group comprised 995 AD patients and 2,298 PD patients who were admitted to the hospital for the first time, and re-hospitalized 231 AD patients and 371 PD patients were also included. AD patients were older than PD patients when they were hospitalized (p < 0.001). AD patients had longer lengths of stay, higher re-hospitalization rates, and higher intrahospital mortality rates than PD patients during hospitalization even after adjusting age and gender. PD patients had higher levels of total cost than AD patients due to the cost of the deep brain stimulation (DBS) insertion. Hospitalizations for AD patients occurred most often in the department of geriatrics, while most PD patients were admitted to the department of neurology. Hospitalization due to the presence of comorbid conditions was much higher in AD patients, but a larger proportion of PD patients were hospitalized due to PD disease itself. Conclusions: The present study found that AD patients and PD patients have a significantly different picture of hospitalization. It is important to implement different management for hospitalized AD and PD, and different emphasis should be given when establishing primary prevention strategies, informing care needs, and guiding healthcare resource planning.

Anti-SRP immune-mediated necrotizing myopathy responsive to ofatumumab: a case report.

Background: Immune-mediated necrotizing myopathies (IMNM) is a rare disease that was first described in 2004. Due to the lack of large case series, there are no formal treatment recommendations for IMNM. Methods: We presented a case of a 47-year-old woman who experienced progressive limb weakness, starting from the lower limbs and gradually affecting the upper limbs. She also reported experiencing dyspnea after engaging in daily activities. When she was admitted to the hospital, her upper limbs were almost unable to move and she could not stand even with support. Her Creatine kinase (CK) level significantly increased (> 3500 u/l). Electromyography showed myogenic damage, anti-Signal recognition particle (anti-SRP) and anti-Ro52 antibodies were highly positive. Pathological biopsy of the right biceps muscle showed necrotizing myopathy in the skeletal muscle. She was ultimately diagnosed with anti-SRP IMNN, and was given monotherapy with methylprednisolone and combination therapy with immunoglobulin, but her symptoms continued to worsen. The patient refused to bear the possible further liver dysfunction and blood system damage caused by Cyclophosphamide and Rituximab, and she chose to try to use Ofatumumab (OFA). Results: After receiving three doses of OFA treatment without any adverse reactions, she reported that her muscle strength had basically recovered and she was able to walk independently. The B cells in the circulatory system have been depleted, and blood markers such as liver function have consistently remained within normal range. During the follow up, her activity tolerance continued to improve. Discussion: We have presented a severe case of SRP-IMNM in which the patient showed poor response to conventional immunotherapy. However, rapid symptom relief was achieved with early sequential use of OFA treatment. This provides a new option for the treatment of SRP-IMNM, and more large-scale studies will be needed in the future to verify our results.

Triple-transgenic soybean in conjunction with glyphosate drive patterns in the rhizosphere microbial community assembly.

Plant roots continuously influence the rhizosphere, which also serves as a recruitment site for microorganisms with desirable functions. The development of genetically engineered (GE) crop varieties has offered unparalleled yield advantages. However, in-depth research on the effects of GE crops on the rhizosphere microbiome is currently insufficient. We used a triple-transgenic soybean cultivar (JD606) that is resistant to insects, glyphosate, and drought, along with its control, ZP661, and JD606 treated with glyphosate (JD606G). Using 16S and ITS rDNA sequencing, their effects on the taxonomy and function of the bacterial and fungal communities in the rhizosphere, surrounding, and bulk soil compartment niches were determined. Alpha diversity demonstrated a strong influence of JD606 and JD606G on bacterial Shannon diversity. Both treatments significantly altered the soil's pH and nitrogen content. Beta diversity identified the soil compartment niche as a key factor with a significant probability of influencing the bacterial and fungal communities associated with soybeans. Further analysis showed that the rhizosphere effect had a considerable impact on bacterial communities in JD606 and JD606G soils but not on fungal communities. Microbacterium, Bradyrhizobium, and Chryseobacterium were found as key rhizobacterial nodes. In addition, the LEfSe analysis identified biomarker taxa with plant-beneficial attributes, demonstrating rhizosphere-driven microbial recruitment. FUNGuild, Bugbase, and FAPROTAX functional predictions showed that ZP661 soils had more plant pathogen-associated microbes, while JD606 and JD606G soils had more stress-tolerance, nitrogen, and carbon cycle-related microbes. Bacterial rhizosphere networks had more intricate topologies than fungal networks. Furthermore, correlation analysis revealed that the bacteria and fungi with higher abundances exhibited varying degrees of positive and negative correlations. Our findings shed new light on the niche partitioning of bacterial and fungal communities in soil. It also indicates that following triple-transgenic soybean cultivation and glyphosate application, plant roots recruit microbes with beneficial taxonomic and functional traits in the rhizosphere.

Freezing of gait in Parkinson's disease with glucocerebrosidase mutations: prevalence, clinical correlates and effect on quality of life.

Objectives: Mutations in glucocerebrosidase (GBA1) can change the clinical phenotype of Parkinson's disease (PD). This study aimed to explore the clinical characteristics of freezing of gait (FOG) in PD patients with GBA1 mutations. Methods: A whole-exome sequencing analysis was used to identify the GBA1 mutations (pathogenic or likely pathogenic) and exclude other PD-related gene mutations. A forward binary logistic regression model was conducted to identify the associated factors of FOG. The stepwise multiple linear regression analysis models were used to explore the effect of FOG on quality of life. Results: The prevalence of FOG in patients with GBA1 mutations (30/95, 31.6%) was significantly higher than those in patients without GBA1 mutations (152/760, 20%) (p = 0.009). A higher (i.e., worse) Unified PD Rating Scale part III score (OR = 1.126, 95%CI = 1.061-1.194, p < 0.001) and a lower (i.e., worse) Montreal Cognitive Assessment score (OR = 0.830, 95%CI = 0.713-0.967, p = 0.017) were significantly associated with FOG in PD patients with GBA1 mutations. The presence of FOG was significantly associated with the decreased (i.e., worse) score of PD Questionnaire 39 after adjustment for sex, age, disease duration, motor score, and non-motor score (B = 14.981, p = 0.001). Conclusion: FOG is a relatively common disabling symptom in PD patients with GBA1 mutations, which is affected by motor disability and cognitive decline. Quality of life is reduced in patients with FOG and GBA1 mutations.