Corrigendum: Cortical gyrification pattern of depression in Parkinson's disease: a neuroimaging marker for disease severity?

[This corrects the article DOI: 10.3389/fnagi.2023.1241516.].

Tumor-derived extracellular vesicle proteins as new biomarkers and targets in precision oncology.

Extracellular vesicles (EVs) are important carriers of signaling molecules, such as nucleic acids, proteins, and lipids, and have become a focus of increasing interest due to their numerous physiological and pathological functions. For a long time, most studies on EV components focused on noncoding RNAs; however, in recent years, extracellular vesicle proteins (EVPs) have been found to play important roles in diagnosis, treatment, and drug resistance and thus have been considered favorable biomarkers and therapeutic targets for various tumors. In this review, we describe the general protocols of research on EVPs and summarize their multifaceted roles in precision medicine applications, including cancer diagnosis, dynamic monitoring of therapeutic efficacy, drug resistance research, tumor microenvironment interaction research, and anticancer drug delivery.

Altered functional-structural coupling may predict Parkinson's patient's depression.

We aimed to elucidate the neurobiological basis of depression in Parkinson's disease and identify potential imaging markers for depression in patients with Parkinson's disease. We recruited 43 normal controls (NC), 46 depressed Parkinson's disease patients (DPD) and 56 non-depressed Parkinson's disease (NDPD). All participants underwent routine T2-weighted, T2Flair, and resting-state scans on the same 3.0 T magnetic resonance imaging (MRI) scanner at our hospital. Pre-processing includes calculating surface-based Regional Homogeneity (2DReHo) and cortical thickness. Then we defined the correlation coefficient between 2DReHo and cortical thickness as the functional-structural coupling index. Between-group comparisons were conducted on the Fisher's Z-transformed correlation coefficients. To identify specific regions of decoupling, the 2DReHo for each participant were divided by cortical thickness at each vertex, followed by threshold-free cluster enhancement (TFCE) multiple comparison correction. Binary logistic regression analysis was performed with DPD as the dependent variable, and significantly altered indicators as the independent variables. Receiver operating characteristic curves were constructed to compare the diagnostic performance of individual predictors and combinations using R and MedCalc software. DPD patients exhibited a significantly lower whole-brain functional-structural coupling index than NDPD patients and NC. Abnormal functional-structural coupling was primarily observed in the left inferior parietal lobule and right primary and early visual cortices in DPD patients. Receiver operating characteristic analysis revealed that the combination of cortical functional-structural coupling, surface-based ReHo, and thickness had the best diagnostic performance, achieving a sensitivity of 65% and specificity of 77.7%. This is the first study to explore the relationship between functional and structural changes in DPD patients and evaluate the diagnostic performance of these altered correlations to predict depression in Parkinson's disease patients. We posit that these changes in functional-structural relationships may serve as imaging biomarkers for depression in Parkinson's disease patients, potentially aiding in the classification and diagnosis of Parkinson's disease. Additionally, our findings provide functional and structural imaging evidence for exploring the neurobiological basis of depression in Parkinson's disease.

Structural and resting-state connection abnormalities of habenula in obsessive-compulsive disorder.

BACKGROUND: Previous studies have suggested that the habenula (Hb) may be involved in the mechanism of obsessive-compulsive disorder (OCD). However, the specific role of Hb in OCD remains unclear. This study aimed to explore the structural and functional abnormalities of Hb in OCD and their relationship with the clinical symptoms. METHODS: Eighty patients with OCD and 85 healthy controls (HCs) were recruited as the primary dataset. The grey matter volume, resting-state functional connectivity (FC), and effective connectivity (EC) of the Hb were calculated and compared between OCD group and HCs. An independent replication dataset was used to verify the stability and robustness of the results. RESULTS: Patients with OCD exhibited smaller Hb volume and increased FC of right Hb-left hippocampus than HCs. Dynamic causal model revealed an increased EC from left hippocampus to right Hb and a less inhibitory causal influence from the right Hb to left hippocampus in the OCD group compared to HCs. Similar results were found in the replication dataset. CONCLUSIONS: This study suggested that abnormal structure of Hb and hippocampus-Hb connectivity may contribute to the pathological basis of OCD.

Alterations in cortical volume and complexity in Parkinson's disease with depression.

AIMS: The aim of this study is to investigate differences in gray matter volume and cortical complexity between Parkinson's disease with depression (PDD) patients and Parkinson's disease without depression (PDND) patients. METHODS: A total of 41 PDND patients, 36 PDD patients, and 38 healthy controls (HC) were recruited and analyzed by Voxel-based morphometry (VBM) and surface-based morphometry (SBM). Differences in gray matter volume and cortical complexity were compared using the one-way analysis of variance (ANOVA) and correlated with the Hamilton Depression Scale-17 (HAMD-17) scores. RESULTS: PDD patients exhibited significant cortical atrophy in various regions, including bilateral medial parietal-occipital-temporal lobes, right dorsolateral temporal lobes, bilateral parahippocampal gyrus, and bilateral hippocampus, compared to HC and PDND groups. A negative correlation between the GMV of left precuneus and HAMD-17 scores in the PDD group tended to be significant (r = -0.318, p = 0.059). Decreased gyrification index was observed in the bilateral insular and dorsolateral temporal cortex. However, there were no significant differences found in fractal dimension and sulcal depth. CONCLUSION: Our research shows extensive cortical structural changes in the insular cortex, parietal-occipital-temporal lobes, and hippocampal regions in PDD. This provides a morphological perspective for understanding the pathophysiological mechanism underlying depression in Parkinson's disease.

Promising preclinical patient-derived organoid (PDO) and xenograft (PDX) models in upper gastrointestinal cancers: progress and challenges.

Gastrointestinal (GI) cancers (gastric cancer, oesophageal cancer, liver cancer, colorectal cancer, etc.) are the most common cancers with the highest morbidity and mortality in the world. The therapy for most GI cancers is difficult and is associated with a poor prognosis. In China, upper GI cancers, mainly gastric cancer (GC) and oesophageal cancer (EC), are very common due to Chinese people's characteristics, and more than half of patients are diagnosed with distant metastatic or locally advanced disease. Compared to other solid cancers, such as lung cancer and breast cancer, personalized therapies, especially targeted therapy and immunotherapy, in GC and EC are relatively lacking, leading to poor prognosis. For a long time, most studies were carried out by using in vitro cancer cell lines or in vivo cell line-derived xenograft models, which are unable to reproduce the characteristics of tumours derived from patients, leading to the possible misguidance of subsequent clinical validation. The patient-derived models represented by patient-derived organoid (PDO) and xenograft (PDX) models, known for their high preservation of patient tumour features, have emerged as a very popular platform that has been widely used in numerous studies, especially in the research and development of antitumour drugs and personalized medicine. Herein, based on some of the available published literature, we review the research and application status of PDO and PDX models in GC and EC, as well as detail their future challenges and prospects, to promote their use in basic and translational studies or personalized therapy.

Characteristics of neonatal hypoxic-ischemic encephalopathy at high altitude and early results of therapeutic hypothermia.

BACKGROUND: Altitude hypoxia and limited socioeconomic conditions may result in distinctive features of neonatal hypoxic-ischemic encephalopathy (HIE). Therapeutic hypothermia (TH) has not been used at altitude. We examined characteristics of HIE and early outcomes of TH in 3 centers at two high altitudes, 2 at 2,261 m and 1 at 3,650 m. METHODS: The incidence of HIE at NICUs was noted. TH was conducted when personnel and devices were available in 2019~2020. Standard inclusion criteria were used, with the addition of admission age >6 hours and mild HIE. Demographic and clinical data included gestational age, gender, weight, Apgar score, ethnics, age on admission, age at TH and clinical degree of HIE. EEG was monitored for 96 hours during hypothermia and rewarming. MRI was performed before discharge. RESULTS: There was significant difference in ethnics, HIE degree, age at TH across 3 centers. The overall NICU incidence of HIE was 4.0%. Among 566 HIE patients, 114 (20.1%) received TH. 63 (55.3%) patients had moderate/severe HIE. Age at TH >6 hours occurred in 34 (29.8%) patients. EEG discharges showed seizures in 7~11% of patients, whereas spikes/sharp waves in 94~100%, delta brushes in 50~100%. After TH, MRI showed moderate to severe brain injury in 77% of patients, and correlated with center, demographic and clinical variables (Ps≤0.0003). Mortality was 5% during hospitalization and 11% after discharge until 1 year. CONCLUSIONS: At altitude, the incidence of HIE was high and brain injury was severe. TH was limited and often late >6 hours. EEG showed distinct patterns attributable to altitude hypoxia. TH was relatively safe. TRIAL REGISTRATION: The study was registered on February 23, 2019 in Chinese Clinical Trial Register (ChiCTR1900021481).

Distinct changes in global brain synchronization in different motor subtypes of Parkinson's disease.

This study investigated alterations in degree centrality (DC) in different motor subtypes of Parkinson's disease (PD) and analyzed its clinical significance during disease occurrence. A total of 146 subjects were recruited in the study, including 90 patients with PD [51 and 39 with tremor dominant (TD) and akinetic-rigid dominant (ARD) disease, respectively] and 56 healthy controls (HCs). The resting-state functional magnetic resonance imaging data of all the subjects were obtained by 3.0 T magnetic resonance scans. The DC values, an indicator of whole brain synchronization, were calculated and compared among the TD, ARD, and HC groups. Disparities in DC values among the three groups were evaluated by analysis of variance and post hoc two-sample t-tests. Correlation between brain regions with DC differences and clinical variables were performed using partial correlation analysis after controlling for age, gender, and disease duration. Compared to the HCs, both TD and ARD groups demonstrated increased DC values bilaterally in the cerebellum; DC values were decreased in the left putamen and paracentral lobule in the TD group and in the left anterior cingulate gyrus and right supplementary motor area in the ARD group. Compared to the ARD group, the TD group showed decreased DC values in bilateral cerebellar hemispheres and increased DC values in the left anterior cingulate gyrus and right supplementary motor area. The DC of the whole brain showed inconsistencies and shared neural bases among patients with the two subtypes of PD. The differences between brain regions with abnormal DC values may be closely related to different clinical presentations of the two motor subtypes. Our findings provide new insights into the clinical heterogeneity of PD with respect to different motor subtypes.

Cortical gyrification pattern of depression in Parkinson's disease: a neuroimaging marker for disease severity?

Background: Although the study of the neuroanatomical correlates of depression in Parkinson's Disease (PD) is gaining increasing interest, up to now the cortical gyrification pattern of PD-related depression has not been reported. This study was conducted to investigate the local gyrification index (LGI) in PD patients with depression, and its associations with the severity of depression. Methods: LGI values, as measured using FreeSurfer software, were compared between 59 depressed PD (dPD), 27 non-depressed PD (ndPD) patients and 43 healthy controls. The values were also compared between ndPD and mild-depressed PD (mi-dPD), moderate-depressed PD (mo-dPD) and severe-depressed PD (se-dPD) patients as sub-group analyses. Furthermore, we evaluated the correlation between LGI values and depressive symptom scores within dPD group. Results: Compared to ndPD, the dPD patients exhibited decreased LGI in the left parietal, the right superior-frontal, posterior cingulate and paracentral regions, and the LGI values within these areas negatively correlated with the severity of depression. Specially, reduced gyrification was observed in mo-dPD and involving a larger region in se-dPD, but not in mi-dPD group. Conclusion: The present study demonstrated that cortical gyrification is decreased within specific brain regions among PD patients with versus without depression, and those changes were associated with the severity of depression. Our findings suggested that cortical gyrification might be a potential neuroimaging marker for the severity of depression in patients with PD.

Surface-Based Functional Alterations in Early-Onset and Late-Onset Parkinson's Disease: A Multi-Modal MRI Study.

This study used a surface-based method to investigate brain functional alteration patterns in early-onset Parkinson's disease (EOPD) and late-onset Parkinson's disease (LOPD) to provide more reliable imaging indicators for the assessment of the two subtypes. A total of 58 patients with Parkinson's disease were divided into two groups according to age at onset: EOPD (≤50 years; 16 males and 15 females) and LOPD (>50 years; 17 males and 10 females) groups. Two control groups were recruited from the community: young adults (YC; ≤50 years; 8 males and 19 females) and older adults (OC; >50 years; 12 males and 10 females). No significant differences were observed between the EOPD and YC groups or the LOPD and OC groups in terms of age, sex, education, and MMSE scores (p > 0.05). No statistically significant differences were observed between the EOPD and LOPD groups in terms of education, H-Y scale, UPDRS score, or HAMD score (p > 0.05). Data preprocessing and surface-based regional homogeneity (2D-ReHo) calculations were subsequently performed using the MATLAB-based DPABIsurf software. The EOPD group showed decreased 2D-ReHo values in the left premotor area and right dorsal stream visual cortex, along with increased 2D-ReHo values in the left dorsolateral prefrontal cortex. In patients with LOPD, 2D-ReHo values were decreased in bilateral somatosensory and motor areas and the right paracentral lobular and mid-cingulate. The imaging characterization of surface-based regional changes may serve useful as monitoring indicators and will help to better understand the mechanisms underlying divergent clinical presentations.

Neural functional network of early Parkinson's disease based on independent component analysis.

This work explored neural network changes in early Parkinson's disease: Resting-state functional magnetic resonance imaging was used to investigate functional alterations in different stages of Parkinson's disease (PD). Ninety-five PD patients (50 early/mild and 45 early/moderate) and 37 healthy controls (HCs) were included. Independent component analysis revealed significant differences in intra-network connectivity, specifically in the default mode network (DMN) and right frontoparietal network (RFPN), in both PD groups compared to HCs. Inter-network connectivity analysis showed reduced connectivity between the executive control network (ECN) and DMN, as well as ECN-left frontoparietal network (LFPN), in early/mild PD. Early/moderate PD exhibited decreased connectivity in ECN-LFPN, ECN-RFPN, ECN-DMN, and DMN-auditory network, along with increased connectivity in LFPN-cerebellar network. Correlations were found between ECN-DMN and ECN-LFPN connections with UPDRS-III scores in early/mild PD. These findings suggest that PD progression involves dysfunction in multiple intra- and inter-networks, particularly implicating the ECN, and a wider range of abnormal functional networks may mark the progression of the disease.

One-Pot Synthesis of 1,2,3-Triarylindoles through Cascade Reactions Using Calcium Carbide, Iodoarenes, and Aromatic Amines.

An efficient method for the construction of 1,2,3-triarylindoles through one-pot multicomponent reactions using calcium carbide, 3 mol of iodoarenes, and aromatic amines as starting materials was described. A series of target products were obtained by the simultaneous formation of five bonds in one step. The main advantages for this protocol are the use of a convenient alkyne source, wide scope of substrates, and simple workup procedure. The method can be extended to the gram scale.

Reduning alleviates sepsis-induced acute lung injury by reducing apoptosis of pulmonary microvascular endothelial cells.

Introduction: Sepsis-induced acute lung injury (SALI) is a critical illness with high mortality, and pulmonary microvascular endothelial cells (PMECs) barrier dysfunction is a well-documented pathogenesis of SALI. The current study aimed to investigate the underlying mechanism of Reduning (RDN) in the treatment of SALI. Methods: Network pharmacology and molecular dynamics simulation (MDS) were used to confirm the possibility of key active components of RDN combining with AKT1. Hematoxylin-eosin staining (HE) and immunohistochemistry (IHC) were used to investigate the effect of RDN in vivo. Immunofluorescence (IF) and co-immunoprecipitation (CoIP) were used to investigate the relationship between mammalian target of rapamycin (mTOR) and Bax in PMECs. ELISA was used to test the level of TNF-α. Flow cytometry was used to detect apoptosis. JC-1 and electron microscopy were used to evaluate mitochondrial damage. The results showed that RDN likely alleviated SALI via targeting AKT1. Results: In vivo, RDN could evidently decrease the expression levels of apoptosis-related proteins, alleviate mitochondrial damage, reduce lung tissue edema, down-regulate the level of TNF-α in the serum, and improve the mortality of sepsis in mice. In vitro, RDN had a significant effect on reducing the level of apoptosis-related proteins and cell apoptosis rate, while also mitigated mitochondrial damage. Furthermore, RDN could effectively lower the level of Bax in PMECs and increase the level of mTOR both in vivo and in vitro. Notably, mTOR has the ability to directly bind to Bax, and RDN can enhance this binding capability. Discussion: RDN could attenuate SALI through reducing apoptosis of PMECs, which is a promising therapeutic strategy for SALI prevention.

A PREDICTION MODEL FOR SEPSIS IN INFECTED PATIENTS: EARLY ASSESSMENT OF SEPSIS ENGAGEMENT.

ABSTRACT: Purpose: To evaluate significant risk variables for sepsis incidence and develop a predictive model for rapid screening and diagnosis of sepsis in patients from the emergency department (ED). Methods: Sepsis-related risk variables were screened based on the PIRO (Predisposition, Insult, Response, Organ dysfunction) system. Training (n = 1,272) and external validation (n = 568) datasets were collected from Peking Union Medical College Hospital (PUMCH) and Beijing Tsinghua Changgung Hospital (BTCH), respectively. Variables were collected at the time of admission. Sepsis incidences were determined within 72 h after ED admissions. A predictive model, Early Assessment of Sepsis Engagement (EASE), was developed, and an EASE-based nomogram was generated for clinical applications. The predictive ability of EASE was evaluated and compared with the National Early Warning Score (NEWS) scoring system. In addition, internal and external validations were performed. Results: A total of 48 characteristics were identified. The EASE model, which consists of alcohol consumption, lung infection, temperature, respiration rate, heart rate, serum urea nitrogen, and white blood cell count, had an excellent predictive performance. The EASE-based nomogram showed a significantly higher area under curve (AUC) value of 86.5% (95% CI, 84.2%-88.8%) compared with the AUC value of 78.2% for the NEWS scoring system. The AUC of EASE in the external validation dataset was 72.2% (95% CI, 66.6%-77.7%). Both calibration curves of EASE in training and external validation datasets were close to the ideal model and were well-calibrated. Conclusions: The EASE model can predict and screen ED-admitted patients with sepsis. It demonstrated superior diagnostic performance and clinical application promise by external validation and in-parallel comparison with the NEWS scoring system.

Altered intrinsic functional network connectivity is associated with impulsivity and emotion dysregulation in drug-naïve young patients with borderline personality disorder.

BACKGROUND: Despite impulse control and emotion regulation being altered in borderline personality disorder (BPD), the specific mechanism of these clinical features remains unclear. This study investigated the functional connectivity (FC) abnormalities within- and between- default mode network (DMN), salience network (SN), and central executive network (CEN) in BPD, and examined the association between aberrant FC and clinical features. We aimed to explore whether the abnormal large-scale networks underlie the pathophysiology of impulsivity and emotion dysregulation in BPD. METHODS: Forty-one young, drug-naïve patients with BPD (24.98 ± 3.12 years, 20 males) and 42 healthy controls (HCs; 24.74 ± 1.29 years, 17 males) were included in resting-state functional magnetic resonance imaging analyses. Independent component analysis was performed to extract subnetworks of the DMN, CEN, and SN. Additionally, partial correlation was performed to explore the association between brain imaging variables and clinical features in BPD. RESULTS: Compared with HCs, BPD showed significant decreased intra-network FC of right medial prefrontal cortex in the anterior DMN and of right angular gyrus in the right CEN. Intra-network FC of right angular gyrus in the anterior DMN was significantly negatively correlated with attention impulsivity in BPD. The patients also showed decreased inter-network FC between the posterior DMN and left CEN, which was significantly negatively correlated with emotion dysregulation. CONCLUSION: These findings suggest that impaired intra-network FC may underlie the neurophysiological mechanism of impulsivity, and abnormal inter-network FC may elucidate the neurophysiological mechanism of emotion dysregulation in BPD.

CLDN18.2 and 4-1BB bispecific antibody givastomig exerts antitumor activity through CLDN18.2-expressing tumor-directed T-cell activation.

BACKGROUND: Claudin18.2 (CLDN18.2) is a tight junction protein that has been identified as a clinically proven target in gastric cancer. Stimulation of 4-1BB with agonistic antibodies is also a promising strategy for immunotherapy and 4-1BB+ T cells were reported to be present within the tumor microenvironment of patients with gastric cancer. However, hepatotoxicity-mediated by 4-1BB activation was observed in clinical trials of agonistic anti-4-1BB monoclonal antibodies. METHODS: To specifically activate the 4-1BB+ T cells in tumor and avoid the on-target liver toxicity, we developed a novel CLDN18.2×4-1BB bispecific antibody (termed 'givastomig' or 'ABL111'; also known as TJ-CD4B or TJ033721) that was designed to activate 4-1BB signaling in a CLDN18.2 engagement-dependent manner. RESULTS: 4-1BB+ T cells were observed to be coexisted with CLDN18.2+ tumor cells in proximity by multiplex immunohistochemical staining of tumor tissues from patients with gastric cancer (n=60). Givastomig/ABL111 could bind to cell lines expressing various levels of CLDN18.2 with a high affinity and induce 4-1BB activation in vitro only in the context of CLDN18.2 binding. The magnitude of T-cell activation by givastomig/ABL111 treatment was closely correlated with the CLDN18.2 expression level of tumor cells from gastric cancer patient-derived xenograft model. Mechanistically, givastomig/ABL111 treatment could upregulate the expression of a panel of pro-inflammatory and interferon-γ-responsive genes in human peripheral blood mononuclear cells when co-cultured with CLDN18.2+ tumor cells. Furthermore, in humanized 4-1BB transgenic mice inoculated with human CLDN18.2-expressing tumor cells, givastomig/ABL111 induced a localized immune activation in tumor as evident by the increased ratio of CD8+/regulatory T cell, leading to the superior antitumor activity and long-lasting memory response against tumor rechallenge. Givastomig/ABL111 was well tolerated, with no systemic immune response and hepatotoxicity in monkeys. CONCLUSIONS: Givastomig/ABL111 is a novel CLDN18.2×4-1BB bispecific antibody which has the potential to treat patients with gastric cancer with a wide range of CLDN18.2 expression level through the restricted activation of 4-1BB+ T cells in tumor microenvironment to avoid the risk of liver toxicity and systemic immune response.

Polyacrylonitrile/UV329/titanium oxide composite nanofibrous membranes with enhanced UV protection and filtration performance.

Ultraviolet (UV) radiation is extremely dangerous to humans and can contribute to immunosuppression, erythema, early ageing and skin cancer. UV protection finishing may greatly influence the handling and permeability of fabrics, while UV-proof fibres can guarantee close contact between UV-resistant agents and fabric without affecting the handling of the fabric. In this study, polyacrylonitrile (PAN)/UV absorber 329 (UV329)/titanium dioxide (TiO2) composite nanofibrous membranes with complex, highly efficient UV resistance were fabricated via electrospinning. UV329 was included in the composite to further strengthen the UV resistance properties via absorption function, while TiO2 inorganic nanoparticles were added to provide UV shielding function. The presence of UV329 and TiO2 in the membranes was confirmed using Fourier-transform infrared spectroscopy, which also showed the absence of chemical bonds between PAN and the anti-UV agents. The PAN/UV329/TiO2 membranes exhibited a UV protection factor of 1352 and a UVA transmittance of 0.6%, which indicate their extraordinary UV resistance properties. Additionally, filtration performance was investigated in order to expand the application field of the UV-resistant PAN/UV329/TiO2 membranes, and the composite nanofibrous membranes showed a UV filtration efficiency of 99.57% and a pressure drop of 145 Pa. The proposed multi-functional nanofibrous membranes have broad application prospects in outdoor protective clothing and window air filters.

Application Prospect of the SOFA Score and Related Modification Research Progress in Sepsis.

In 2016, the SOFA score was proposed as the main evaluation system for diagnosis in the definition of sepsis 3.0, and the SOFA score has become a new research focus in sepsis. Some people are skeptical about diagnosing sepsis using the SOFA score. Experts and scholars from different regions have proposed different, modified versions of SOFA score to make up for the related problems with the use of the SOFA score in the diagnosis of sepsis. While synthesizing the different improved versions of SOFA proposed by experts and scholars in various regions, this paper also summarizes the relevant definitions of sepsis put forward in recent years to build a clear, improved application framework of SOFA score. In addition, the comparison between machine learning and SOFA scores related to sepsis is described and discussed in the article. Taken together, by summarizing the application of the improved SOFA score proposed in recent years in the related definition of sepsis, we believe that the SOFA score is still an effective means of diagnosing sepsis, but in the process of the continuous refinement and development of sepsis in the future, the SOFA score needs to be further refined and improved to provide more accurate coping strategies for different patient populations or application directions regarding sepsis. Against the big data background, machine learning has immeasurable value and significance, but its future applications should add more humanistic references and assistance.

Abnormal intra- and inter-network functional connectivity of brain networks in early-onset Parkinson's disease and late-onset Parkinson's disease.

Objective: The purpose of this study is to look into the altered functional connectivity of brain networks in Early-Onset Parkinson's Disease (EOPD) and Late-Onset Parkinson's Disease (LOPD), as well as their relationship to clinical symptoms. Methods: A total of 50 patients with Parkinson' disease (28 EOPD and 22 LOPD) and 49 healthy controls (25 Young Controls and 24 Old Controls) were admitted to our study. Employing independent component analysis, we constructed the brain networks of EOPD and Young Controls, LOPD and Old Controls, respectively, and obtained the functional connectivity alterations in brain networks. Results: Cerebellar network (CN), Sensorimotor Network (SMN), Executive Control Network (ECN), and Default Mode Network (DMN) were selected as networks of interest. Compared with their corresponding health controls, EOPD showed increased functional connectivity within the SMN and ECN and no abnormalities of inter-network functional connectivity were found, LOPD demonstrated increased functional connectivity within the ECN while decreased functional connectivity within the CN. Furthermore, in LOPD, functional connectivity between the SMN and DMN was increased. The functional connectivity of the post-central gyrus within the SMN in EOPD was inversely correlated with the Unified Parkinson's Disease Rating Scale Part III scores. Age, age of onset, and MMSE scores are significantly different between EOPD and LOPD (p < 0.05). Conclusion: There is abnormal functional connectivity of networks in EOPD and LOPD, which could be the manifestation of the associated pathological damage or compensation.

Diagnostic and predictive values of pyroptosis-related genes in sepsis.

Background: Sepsis is an organ dysfunction syndrome caused by the body's dysregulated response to infection. Yet, due to the heterogeneity of this disease process, the diagnosis and definition of sepsis is a critical issue in clinical work. Existing methods for early diagnosis of sepsis have low specificity. Aims: This study evaluated the diagnostic and predictive values of pyroptosis-related genes in normal and sepsis patients and their role in the immune microenvironment using multiple bioinformatics analyses and machine-learning methods. Methods: Pediatric sepsis microarray datasets were screened from the GEO database and the differentially expressed genes (DEGs) associated with pyroptosis were analyzed. DEGs were then subjected to multiple bioinformatics analyses. The differential immune landscape between sepsis and healthy controls was explored by screening diagnostic genes using various machine-learning models. Also, the diagnostic value of these diagnosis-related genes in sepsis (miRNAs that have regulatory relationships with genes and related drugs that have regulatory relationships) were analyzed in the internal test set and external test. Results: Eight genes (CLEC5A, MALT1, NAIP, NLRC4, SERPINB1, SIRT1, STAT3, and TLR2) related to sepsis diagnosis were screened by multiple machine learning algorithms. The CIBERSORT algorithm confirmed that these genes were significantly correlated with the infiltration abundance of some immune cells and immune checkpoint sites (all P<0.05). SIRT1, STAT3, and TLR2 were identified by the DGIdb database as potentially regulated by multiple drugs. Finally, 7 genes were verified to have significantly different expressions between the sepsis group and the control group (P<0.05). Conclusion: The pyroptosis-related genes identified and verified in this study may provide a useful reference for the prediction and assessment of sepsis.