A Disentangled Representation Based Brain Image Fusion via Group Lasso Penalty

Complementary and redundant relationships inherently exist between multi-modal medical images captured from the same brain. Fusion processes conducted on intermingled representations can cause information distortion and the loss of discriminative modality information. To fully exploit the interdependency between source images for better feature representation and improve the fusion accuracy, we present the multi-modal brain medical image fusion method in a disentangled pipeline under the deep learning framework. A three-branch auto-encoder with two complementary branches and a redundant branch is designed to extract the exclusive modality features and common structure features from input images. Especially, to promote the disentanglement of complement and redundancy, a complementary group lasso penalty is proposed to constrain the extracted feature maps. Then, based on the disentangled representations, different fusion strategies are adopted for complementary features and redundant features, respectively. The experiments demonstrate the superior performance of the proposed fusion method in terms of structure preservation, visual quality, and running efficiency

Chronic jet lag alters gut microbiome and mycobiome and promotes the progression of MAFLD in HFHFD-fed mice

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide. Circadian disruptors, such as chronic jet lag (CJ), may be new risk factors for MAFLD development. However, the roles of CJ on MAFLD are insufficiently understood, with mechanisms remaining elusive. Studies suggest a link between gut microbiome dysbiosis and MAFLD, but most of the studies are mainly focused on gut bacteria, ignoring other components of gut microbes, such as gut fungi (mycobiome), and few studies have addressed the rhythm of the gut fungi. This study explored the effects of CJ on MAFLD and its related microbiotic and mycobiotic mechanisms in mice fed a high fat and high fructose diet (HFHFD). Forty-eight C57BL6J male mice were divided into four groups: mice on a normal diet exposed to a normal circadian cycle (ND-NC), mice on a normal diet subjected to CJ (ND-CJ), mice on a HFHFD exposed to a normal circadian cycle (HFHFD-NC), and mice on a HFHFD subjected to CJ (HFHFD-CJ). After 16 weeks, the composition and rhythm of microbiota and mycobiome in colon contents were compared among groups. The results showed that CJ exacerbated hepatic steatohepatitis in the HFHFD-fed mice. Compared with HFHFD-NC mice, HFHFD-CJ mice had increases in Aspergillus, Blumeria and lower abundances of Akkermansia, Lactococcus, Prevotella, Clostridium, Bifidobacterium, Wickerhamomyces, and Saccharomycopsis genera. The fungi-bacterial interaction network became more complex after HFHFD and/or CJ interventions. The study revealed that CJ altered the composition and structure of the gut bacteria and fungi, disrupted the rhythmic oscillation of the gut microbiota and mycobiome, affected interactions among the gut microbiome, and promoted the progression of MAFLD in HFHFD mice

Influence of Different Age Cutoff Points on the Prediction of Prognosis of Cancer Patients Receiving ICIs and Potential Mechanistic Exploration

Age is a potential predictive marker for the prognosis of cancer patients treated with immune checkpoint inhibitors (ICIs), but the appropriate age cutoff point is still controversial. We aimed to explore the influence of different age cutoff points on the prediction of prognosis for patients receiving ICIs and explore the mechanism underlying the appropriate age cutoff point from the aspects of gene mutation and expression, immune cell infiltration and so on. We applied cutoff points of 50, 55, 60, 65, 70, and 75 years old to divide 1660 patients from the Memorial Sloan-Kettering Cancer Center (MSKCC) immunotherapy cohort into older and younger groups and performed survival analysis of the six subgroups. The results showed that older patients had better survival than younger patients in accordance with the cutoff point of 50 years old [median overall survival (OS) (95% CI): 13.0 (10.5-15.5) months vs. 20.0 (16.7-23.3) months; p=0.002; unadjusted hazard ratio (HR) (95% CI): 0.77 (0.65-0.91)], whereas no significant difference was observed with other cutoff points. Further analysis of The Cancer Genome Atlas (TCGA) database and the MSKCC immunotherapy cohort data showed that the tumor mutation burden (TMB), neoantigen load (NAL), DNA damage response and repair (DDR) pathway mutation status, mutation frequencies of most genes (except IDH1, BRAF and ATRX), the expression of most immune-related genes and the degree of infiltration of most immune cells (such as CD8+ T cells and M1 macrophages) were higher in the elderly group (aged ≥50 years)

Activation of the DDR Pathway Leads to the Down-Regulation of the TGFβ Pathway and a Better Response to ICIs in Patients With Metastatic Urothelial Carcinoma

Immune checkpoint inhibitors (ICIs) have changed the treatment paradigm of metastatic urothelial carcinoma (mUC), a dominant type of bladder cancer (BC). Previous studies have shown an association between gene mutations in the DNA damage response (DDR) pathway and the immunotherapy response in mUC but have neglected the effect of the activation level of the DDR pathway on the ICI response in mUC. A published immunotherapy cohort with genome, transcriptome and survival data for 348 mUC patients was used. An external cohort (The Cancer Genome Atlas Bladder Cancer) and the GSE78220 cohort were used for validation. The activation level of the DDR pathway was quantified using single-sample gene set enrichment analysis (ssGSEA). Further analysis on the genome, immunogenicity, and the immune microenvironment was conducted using the DDR ssGSEA enrichment score-high (DSSH) group and the DDR ssGSEA enrichment score-low (DSSL) group. In the mUC cohorts, the DSSH group was associated with longer overall survival times (P=0.026; Hazard ratio=0.67; 95%CI: 0.46−0.95). The DSSH group was also associated with higher tumor mutation burden, neoantigen load, immune-activated cell patterns, and immune-related gene expression levels. The GSEA results indicated an immune activation state in DSSH group, which correlated with a down-regulation in the transforming growth factor β receptor signaling pathway. Our study suggests that the activation level of the DDR pathway may be a novel predictive marker for immunotherapy efficacy in patients with mUC

Segawa syndrome caused by TH gene mutation and its mechanism

Dopa-responsive dystonia (DRD), also known as Segawa syndrome, is a rare neurotransmitter disease. The decrease in dopamine caused by tyrosine hydroxylase (TH) gene mutation may lead to dystonia, tremor and severe encephalopathy in children. Although the disease caused by recessive genetic mutation of the tyrosine hydroxylase (TH) gene is rare, we found that the clinical manifestations of seven children with tyrosine hydroxylase gene mutations are similar to dopa-responsive dystonia. To explore the clinical manifestations and possible pathogenesis of the disease, we analyzed the clinical data of seven patients. Next-generation sequencing showed that the TH gene mutation in three children was a reported homozygous mutation (c.698G>A). At the same time, two new mutations of the TH gene were found in other children: c.316_317insCGT, and c.832G>A (p.Ala278Thr). We collected venous blood from four patients with Segawa syndrome and their parents for real-time quantitative polymerase chain reaction analysis of TH gene expression. We predicted the structure and function of proteins on the missense mutation iterative thread assembly refinement (I-TASSER) server and studied the conservation of protein mutation sites. Combined with molecular biology experiments and related literature analysis, the qPCR results of two patients showed that the expression of the TH gene was lower than that in 10 normal controls, and the expression of the TH gene of one mother was lower than the average expression level. We speculated that mutation in the TH gene may clinically manifest by affecting the production of dopamine and catecholamine downstream, which enriches the gene pool of Segawa syndrome. At the same time, the application of levodopa is helpful to the study, diagnosis and treatment of Segawa syndrome

The dynamic conformational landscape of the protein methyltransferase SETD8

Elucidating the conformational heterogeneity of proteins is essential for understanding protein function and developing exogenous ligands. With the rapid development of experimental and computational methods, it is of great interest to integrate these approaches to illuminate the conformational landscapes of target proteins. SETD8 is a protein lysine methyltransferase (PKMT), which functions in vivo via the methylation of histone and nonhistone targets. Utilizing covalent inhibitors and depleting native ligands to trap hidden conformational states, we obtained diverse X-ray structures of SETD8. These structures were used to seed distributed atomistic molecular dynamics simulations that generated a total of six milliseconds of trajectory data. Markov state models, built via an automated machine learning approach and corroborated experimentally, reveal how slow conformational motions and conformational states are relevant to catalysis. These findings provide molecular insight on enzymatic catalysis and allosteric mechanisms of a PKMT via its detailed conformational landscape

No Banquet Can Do without Liquor: Alcohol counterfeiting in the People’s Republic of China

The illegal trade in alcohol has been an empirical manifestation of organised crime with a very long history; yet, the nature of the illegal trade in alcohol has received relatively limited academic attention in recent years despite the fact that it has been linked with significant tax evasion as well as serious health problems and even deaths. The current article focuses on a specific type associated with the illegal trade in alcohol, the counterfeiting of alcohol in China. The article pays particular attention to the counterfeiting of baijiu, Chinese liquor in mainland China. The aim of the article is to offer an account of the social organisation of alcohol counterfeiting business in China by illustrating the counterfeiting process, the actors in the business as well as its possible embeddedness in legal practices and industries/trades. The alcohol counterfeiting business is highly reflective to the market demand and consumer needs. Alcohol counterfeiting in China is characterised primarily by independent actors many of whom are subcontracted to provide commodities and services about the counterfeiting process. The business relies on personal networks – family and extended family members, friends and acquaintances. Relationships between actors in the business are very often based on a customer-supplier relationship or a ‘business-to-business market’. The alcohol counterfeiting business in China highlights the symbiotic relationship between illegal and legal businesses

Abstract Number ‐ 30: Predictors of Intracranial Hemorrhage and Successful Reperfusion After Mechanical Thrombectomy in Acute Ischemic Stroke

Introduction Mechanical thrombectomy (MT) has become the current standard of care for large vessel occlusion stroke but is associated with an increased risk of intracranial hemorrhage (ICH). Recent study showed that even asymptomatic ICH may decrease the likelihood of an excellent functional outcome at 90 days. This study aims to identify predictors for ICH in patients with acute ischemic stroke undergoing MT. Also, we try to identify the predictors for successful reperfusion TICI 2b/3. Methods We retrospectively reviewed all MT patients who were treated at a single comprehensive stroke center from 12/2016 to 09/2021. Variables included Ethnicity, age, gender, time from last know well to arrival, medical history, antithrombotic use, initial NIHSS, blood glucose, blood pressure, IV tPA, time from door to puncture, time from puncture to first pass, type of LVO, MT devices and TICI score. Primary Outcome was any ICH within 36 hours after MT. Secondary outcome was successful reperfusion, TICI 2b/3. Results Among 273 patients (68.8±14, Male 51.6%), 41.7% was Hispanic. 75 patients (27.5%) experienced any ICH after thrombectomy.Although ICH is common post MT and most of the researchers believe that only symptomatic ICH negatively impacts outcome, it is challenging to get an accurate post MT evaluation. Our patient cohort confirmed that ICH after MT may decrease the likelihood of excellent and favorable outcome upon discharge. Patients with history of drugs or ETOH abuse had higher risk of ICH post MT. TICI 2b/3 was associated with higher chance of favorable mRS (0‐3) upon discharge but paradoxically associated with higher chance of ICH post MT. (OR 3.01).Among all the variables, time from LKW to arrival was significantly shorter in patients achieved TICI 2b/3, 223min VS 414min. Door to puncture time was significantly faster in patients with TICI2b/3, 95min VS 121min. Puncture to first pass time was also significantly faster in patients with TICI2b/3, 19min VS 26min.Multiple logistic regression model showed that lower initial BG and NIHSS, ICA or M1 LVO and shorter door to first pass time were associated with favorable outcomes. Conclusions Compared to other clinical studies (usually only had 5–8% Hispanic patients), our study has significantly better representation of Hispanic population in which 41.7% of our patients are Hispanic. This emphasized the uniqueness and meaning of our study.Our patient cohort confirmed that it is important to avoid any ICH post MT, since it may decrease favorable and excellent outcome upon discharge. Extra attention is needed for patients with history of drugs or ETOH abuse because it is associated with significantly higher risk of ICH post MT in our patient cohort.ICH was commonly seen in TICI 2b/3 patients and may be due to successful reperfusion. Therefore, aggressive BP management (SBP<140) after MT is recommended if TICI 2b/3 achieved to avoid ICH expanding and worsening outcome. Also, angio‐CT scan after TICI 2b/3 may be necessary in the future. Favorable outcomes were reached more often if patients had lower initial BG and NIHSS, ICA or M1 LVO, shorter door to first pass time and can achieve TICI 2b/3 after MT

Indoor Location Detection using WLAN

The thesis seeks to improve the accuracy of indoor wireless local area network (WLAN) location detection. The main task of the project is the design and analysis of a solution, which utilizes the packets which are already emitted by WLAN devices. The system consists of a signal receiver and signal processing. The positioning system does not transmit, thus the detection is completely passive. The result of measurements on received frames is used to calculate the WLAN transmitter's position. It does not require any transmissions, thus the detection is completely passive. The result of the measurements can be used to calculate the WLAN transmitter’s position. Location systems are more and more viewed as a necessary element of a WLAN system. Positioning accuracy is the most important issue in location system, especial in the indoor WLAN location detection. Indoor location systems are affected by indoor environment both due to multi-path and man-made effects. To resist these problems, we introduce a way to detect the arrival of the first instance of the signal by detecting the signal header. In our experiment, we timestamp the arrival of an IEEE 802.11b header. In our prototype the logic necessary to do this is implemented in an FPGA, specifically that of the Ettus Research USRP. The additional logic is quite small and might easily be added to the receiver in an access point, thus reducing the deployment cost of a location system in a real network. The proposed solution was experimentally verified. From our experiments, the detection works without requiring any changes to the hardware or software of the mobile device. By exploiting existing IEEE 802.11b transmissions the cost and difficulty of deployment is simplified due to the wide usage of IEEE 802.11b in mobile devices. Additionally, the preamble has good correlation properties making it is easy to detect the arrival of a IEEE 802.11frame. Our implementation is based upon open source hardware and software making it possible to implement this solution. A relatively low cost FPGA can be used as the correlation and timestamp circuit is rather simple (in terms of numbers of gates), making this solution feasible for commercial implementation. The method, implementation, testing, and analysis are presented in detail in the thesis.Avhandlingen syftar till att förbättra noggrannheten i inomhus trådlösa lokala nätverk (WLAN) placering upptäckt. Huvuduppgiften för projektet är design och analys av en lösning som utnyttjar paketen som redan avges av WLAN-enheter. Systemet består av en signal mottagare och signalbehandling. Det kräver inga transmissioner, alltså upptäckt är helt passiv. Resultatet av mätningarna kan användas för att beräkna WLAN-sändarens läge. Målet är att förbättra noggrannheten i inomhus plats uppskattning. Läge system alltmer ses som en nödvändig del av WLAN system. Positioneringsnoggrannheten ses som den viktigaste frågan i läge system, speciellt för inomhusbruk WLAN baserade location. Läge system påverkas mer av inomhusmiljöer än utemiljön, eftersom det finns mer multi-path fading och konstgjorda effekter. Att minska dessa problem, vi införa ett sätt att känna av signalen ankomst genom att förbättra upptäckten av ankomsten av IEEE 802.11-huvudet. Detta kan bidra till att besegra multipath effekt och enkla metoden skulle kunna minska kostnaderna för placering i framtiden kopplingspunkter. Den föreslagna lösningen har verifierats experimentellt. Från vårt experiment fungerar upptäckt utan att kräva några ändringar i hårdvara eller mjukvara för den mobila enheten. Genom att utnyttja befintliga IEEE 802.11b sändningar kostnaden och svårigheten att utbyggnaden är förenklad på grund av den breda användningen av IEEE 802.11b i mobila enheter. Dessutom "preamble" har god korrelation egenskaper som gör det lätt att upptäcka ankomsten av en IEEE 802.11-ramen. Vår genomfört bygger på öppen källkod maskin-och programvara som gör det möjligt att genomföra denna lösning. En relativt låg kostnad FPGA kan användas som korrelation och tidstämpel kretsen är ganska enkel (i termer av antalet logikelement), vilket gör denna lösning vara möjlig för kommersiell tillämpning. Metoden, implementation, testning och analys presenteras i detalj i avhandlingen

Abstract 1122‐000091: Predictors of Symptomatic Hemorrhagic Transformation After Mechanical Thrombectomy in Acute Ischemic Stroke

Introduction: Mechanical thrombectomy (MT) has become the current standard of care for large vessel occlusion stroke but is associated with an increased risk of intracranial hemorrhage (ICH). Although several studies have investigated the risk factors, there is still limited, not well‐established data. This study aims to evaluate the risk factors of HT after MT. Methods: We retrospectively reviewed all MT patients who were treated at a single comprehensive stroke center from 12/2016 to 7/2019. Variables included initial NIHSS, blood glucose, initial systolic blood pressure, age, gender, IV tPA, time from door to recanalization, and TICI score. Outcome measures were HT on post‐procedure or 24‐hour post‐tPA head CT/MRI as well as modified Rankin scale (mRS) upon discharge. Results: Among 74 patients (68.8 ± 14 years, men 47.3%), 9 (12.2%) experienced hemorrhagic transformation after thrombectomy. Average admitting NIHSS was significantly higher in the HT group (22 vs 16.8, p = 0.041). TICI 3 after MT was protective for HT (OR 0.078, 95% CI 0.009‐0.663). IV tPA (OR 3.86, 95% CI 1.448‐10.326) was associated with good neurological outcome at discharge (mRS = 20 may be a reasonable threshold to predict HT after MT. Our findings are consistent with the TICI‐ASPECTS‐glucose (TAG) score to predict sICH; however, we used initial NIHSS as a surrogate for ASPECTS. Further studies may utilize additional quantitative measures such as CTP data to predict HT