GWAS-based polygenic risk scoring for predicting cerebral artery dissection in the Chinese population.

OBJECTIVE: Cerebral artery dissection (CeAD) is a rare but serious disease. Genetic risk assessment for CeAD is lacking in Chinese population. We performed genome-wide association study (GWAS) and computed polygenic risk score (PRS) to explore genetic susceptibility factors and prediction model of CeAD based on patients in Huashan Hospital. METHODS: A total of 210 CeAD patients and 280 controls were enrolled from June 2017 to September 2022 in Department of Neurology, Huashan Hospital, Fudan University. We performed GWAS to identify genetic variants associated with CeAD in 140 CeAD patients and 210 control individuals according to a case and control 1:1.5 design rule in the training dataset, while the other 70 patients with CeAD and 70 controls were used as validation. Then Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses were utilized to identify the significant pathways. We constructed a PRS by capturing all independent GWAS SNPs in the analysis and explored the predictivity of PRS, age, and sex for CeAD. RESULTS: Through GWAS analysis of the 140 cases and 210 controls in the training dataset, we identified 13 leading SNPs associated with CeAD at a genome-wide significance level of P < 5 × 10- 8. Among them, 10 SNPs were annotated in or near (in the upstream and downstream regions of ± 500Kb) 10 functional genes. rs34508376 (OR2L13) played a suggestive role in CeAD pathophysiology which was in line with previous observations in aortic aneurysms. The other nine genes were first-time associations in CeAD cases. GO enrichment analyses showed that these 10 genes have known roles in 20 important GO terms clustered into two groups: (1) cellular biological processes (BP); (2) molecular function (MF). We used genome-wide association data to compute PRS including 32 independent SNPs and constructed predictive model for CeAD by using age, sex and PRS as predictors both in training and validation test. The area under curve (AUC) of PRS predictive model for CeAD reached 99% and 95% in the training test and validation test respectively, which were significantly larger than the age and sex models of 83% and 86%. CONCLUSIONS: Our study showed that ten risk loci were associated with CeAD susceptibility, and annotated functional genes had roles in 20 important GO terms clustered into biological process and molecular function. The PRS derived from risk variants was associated with CeAD incidence after adjusting for age and sex both in training test and validation.

Evidence of microbiota-host dysbiosis between periodontitis and cerebral small vessel disease.

OBJECTIVES: To investigate the correlation between periodontitis and cerebral small vessel disease (CSVD) from the clinical and microbiological aspects. SUBJECTS AND METHODS: Periodontitis patients (CP group, n = 31) and CSVD patients (CSVD group, n = 30) were examined for neurological and periodontal condition. Subgingival plaque was collected and performed using 16S rRNA sequencing. Logistic regression and LASSO regression were used to analyze the periodontal parameters and subgingival microbiota related to CSVD, respectively. Inflammatory factors in gingival crevicular fluid (GCF) were also detected and compared between the two groups. RESULTS: Clinical attachment level (CAL), teeth number and plaque index demonstrated a significant difference between CP and CSVD group, meanwhile, CAL was independently associated with CSVD. Besides, the microbial richness and composition were distinct between two groups. Five genera related to periodontal pathogens (Treponema, Prevotella, Streptococcus, Fusobacterium, Porphyromonas) were screened out by LASSO regression, suggesting a potential association with CSVD. Finally, the levels of inflammatory factors in GCF were statistically higher in CSVD group than those in CP group. CONCLUSIONS: Cerebral small vessel disease patients demonstrated worse periodontal condition, meanwhile the interaction between microbiota dysbiosis and host factors (inflammation) leading to a better understanding of the association between periodontitis and CSVD.

Mikulicz's disease combined with IgG4-related hypophysitis: a case report.

BACKGROUND: IgG4-related diseases are very uncommon, and its diagnosis and treatment are complicated as it encompasses multiple disciplines. CASE PRESENTATION: A 77-year-old woman was admitted with a jaw mass and nausea and vomiting. Laboratory tests showed elevated serum IgG4, pituitary MRI suggested thickening of the pituitary stalk, and head and neck CT suggested orbital and mandibular masses. Patients with mandibular mass were diagnosed with Mikulicz's disease with IgG4-related hypophysitis. We found no other evidence of causing thickening of the pituitary stalk. She was given oral prednisolone 30 mg daily, and her nausea and vomiting improved significantly, and the mandibular and ocular masses decreased in size. CONCLUSION: Mikulicz's disease combined with IgG4-related hypophysitis is a rare case of IgG4-RD in elderly women. IgG4-RD is one of the causes of head and neck exocrine gland mass and pituitary stalk thickening in the elderly.

Deep medullary veins: a promising neuroimaging marker for mild cognitive impairment in outpatients.

BACKGROUND AND PURPOSE: Mild cognitive impairment is an age-dependent pre-dementia state caused by varied reasons. Early detection of MCI helps handle dementia. Vascular factors are vital for the occurrence of MCI. This study investigates the correlation between deep medullary veins and multi-dimensional cognitive outcomes. MATERIALS AND METHODS: A total of 73 participants with MCI and 32 controls were enrolled. Minimum Mental State Examination and Montreal Cognitive Assessment were used to examine the global cognitive function, and different cognitive domains were measured by specific neuropsychological tests. MRI was used to assess the visibility of the DMV and other neuroimage markers. RESULTS: DMV score was statistically significantly higher in the MCI group compared with the control group (P = 0.009) and independently related to MCI (P = 0.007). Linear regression analysis verified that DMV score was linearly related to global cognition, memory, attention, and executive function after adjusting for cerebrovascular risk factors. CONCLUSION: DMV score was independently related to the onset of MCI, and correlates with overall cognition, memory, attention, and executive function in outpatients.

Antinociceptive effects of bupivacaine injected within the internal abdominis rectus sheath in standing healthy horses.

OBJECTIVE: To evaluate a regional anesthetic technique for blocking the abdominal midline in horses. STUDY DESIGN: Anatomical description and prospective, crossover, placebo-controlled, blinded study. ANIMALS: Adult horses; two cadavers, six healthy animals. METHODS: In stage 1, 0.5% methylene blue with 0.25% bupivacaine (0.5 mL kg-1) was injected using ultrasonography into the internal rectus abdominis sheath (RAS) of two cadavers with a one-point or two-point technique. The dye spread was described after the dissection of the abdomens. In stage 2, each horse was injected with 1 mL kg-1 of 0.9% NaCl (treatment PT) or 0.2% bupivacaine (treatment BT) using a two-point technique. The abdominal midline mechanical nociceptive threshold (MNT) was measured with a 1 mm blunted probe tip and results analyzed with mixed-effect anova. Signs of pelvic limb weakness were recorded. RESULTS: The cadaver dissections showed staining of the ventral branches from the eleventh thoracic (T11) to the second lumbar (L2) nerve with the one-point technique and T9-L2 with the two-point technique. Baseline MNTs were, mean ± standard deviation, 12.6 ± 1.6 N and 12.4 ± 2.4 N in treatments PT and BT, respectively. MNT increased to 18.9 ± 5.8 N (p = 0.010) at 30 minutes, and MNT was between 9.4 ± 2.0 and 15.3 ± 3.4 N from 1 to 8 hours (p > 0.521) in treatment PT. MNTs in treatment BT were 21.1 ± 5.9 to 25.0 ± 0.1 N from 30 minutes to 8 hours (p < 0.001). MNTs after the RAS injections were higher in treatment BT than PT (p = 0.007). No pelvic limb weakness was observed. CONCLUSIONS AND CLINICAL RELEVANCE: Antinociception of at least 8 hours without pelvic limb weakness was observed in the abdominal midline in standing horses after the RAS block. Further investigations are necessary to evaluate suitability for ventral celiotomies.

Clinical and prognostic features of Heidenhain variant of Creutzfeldt-Jakob disease: A retrospective case series study.

BACKGROUND: Heidenhain variant of Creutzfeldt-Jakob disease (CJD) remains a diagnostic challenge in clinical practice. We aimed to describe the clinical and prognostic features of Heidenhain cases, through a case series study. METHODS: We retrospectively reviewed the definite or probable CJD cases admitted to two tertiary referral university hospitals over a decade to identify Heidenhain cases and investigated their survival status by telephone follow-up. Their clinical characteristics, neuroimaging features, electroencephalography (EEG) results, cerebrospinal fluid profiles, and PRNP gene mutations were also analyzed. RESULTS: Of a total of 85 CJD cases, 20 (24%) Heidenhain cases (11 women [55%]; median age, 64 years [range, 44-72 years]) were identified. The median survival time was 22 weeks (range, 5-155 weeks). The median duration of isolated visual symptoms was 3 weeks (range, 1-12 weeks). The most common early visual symptom was blurred vision (16/20, 80%), followed by diplopia (6/20, 30%). The prevalence significantly increased for complex visual hallucination (p = 0.005) and cortical blindness (p = 0.046) as the disease progressed. The positive rate of serial magnetic resonance images (20/20, 100%) was higher than that of serial EEGs (16/20, 80%). Two patients (2/10, 20%) had pathogenic PRNP mutations, E196A and T188K, respectively. Heidenhain cases with PRNP mutations had significantly longer survival time than those without PRNP mutations (p = 0.047). CONCLUSIONS: Besides blurred vision (80%), diplopia (30%) was also a frequent early visual symptom among Heidenhain cases. Heidenhain phenotype can occur in genetic CJD cases. PRNP mutation status might be an important prognostic factor for Heidenhain cases.

A Clustering-Enhanced Memetic Algorithm for the Quadratic Minimum Spanning Tree Problem.

The quadratic minimum spanning tree problem (QMSTP) is a spanning tree optimization problem that considers the interaction cost between pairs of edges arising from a number of practical scenarios. This problem is NP-hard, and therefore there is not a known polynomial time approach to solve it. To find a close-to-optimal solution to the problem in a reasonable time, we present for the first time a clustering-enhanced memetic algorithm (CMA) that combines four components, i.e., (i) population initialization with clustering mechanism, (ii) a tabu-based nearby exploration phase to search nearby local optima in a restricted area, (iii) a three-parent combination operator to generate promising offspring solutions, and (iv) a mutation operator using Lévy distribution to prevent the population from premature. Computational experiments are carried on 36 benchmark instances from 3 standard sets, and the results show that the proposed algorithm is competitive with the state-of-the-art approaches. In particular, it reports improved upper bounds for the 25 most challenging instances with unproven optimal solutions, while matching the best-known results for all but 2 of the remaining instances. Additional analysis highlights the contribution of the clustering mechanism and combination operator to the performance of the algorithm.

Insulin Resistance is Significantly Related with Worse Clinical Outcomes in Non-Diabetic Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis.

OBJECTIVES: to investigate the relationship between insulin resistance (IR) and clinical outcomes in non-diabetic ischemic stroke patients treated with intravenous thrombolysis. METHODS: We recruited non-diabetic ischemic stroke patients treated with intravenous thrombolysis prospectively. IR was defined as homeostasis model assessment-estimated insulin resistance index ≥2.80. Initial stroke severity was assessed using the National Institutes of Health Stroke Scale scores, and infarct volume was measured using DWI. Clinical outcomes were evaluated by neurological improvement and hemorrhagic transformation at 24 hours, and favorable functional prognosis at 90 days. RESULTS: 232 patients were enrolled into this study. IR group was 67 patients, non-IR group was 165 patients. Compared with the non-IR group, the probability of neurological improvement at 24 h ours and favorable functional outcome at 90 days in IR group were all significantly lower (41.79% vs 63.03%, p<0.01; 73.13% vs 89.09%, p<0.01 respectively), whereas the ratio of hemorrhagic transformation was much higher (16.42% vs 4.85%, p<0.01). In multivariable logistic regression, IR was negatively associated with neurological improvement and favorable functional prognosis (OR=0.39, 95%CI, 0.20-0.76, p<0.01; OR= 0.26, 95%CI, 0.07-0.91, p=0.04, respectively), but was positively correlated with hemorrhagic transformation (OR=4.07, 95%CI, 1.13-14.59, p=0.03) after adjusting traditional risk factors. We analyzed 108 infarct volume data further, the median of volume in IR group was 2.27 cm3, higher than that in non-IR group (1.96 cm3), but no statistical difference (p=0.65). CONCLUSIONS: In non-diabetic ischemic stroke patients treated with intravenous thrombolysis, IR was related with worse clinical outcomes, but not with infarct volume.

Long noncoding RNA UCA1 promotes chondrogenic differentiation of human bone marrow mesenchymal stem cells via miRNA-145-5p/SMAD5 and miRNA-124-3p/SMAD4 axis.

Long noncoding RNA (lncRNAs) UCA1 has been known to be critical for the chondrogenic differentiation of marrow mesenchymal stem cells (MSCs). In this study, we explore the effects and mechanisms of UCA1 on the promotion of chondrogenesis of MSCs. During the processes of chondrogenic differentiation of MSCs, UCA1, miRNA-145-5p or miRNA-124-3p was overexpressed into MSCs. UCA1 substantially improved chondrogenesis of MSCs. Furthermore, UCA1 obviously down-regulated the expression of miRNA-145-5p and miRNA-124-3p, which attenuated the chondrogenic differentiation of MSCs. In addition, UCA1 significantly stimulated TGF-ß pathway member SMAD5 and SMAD4, which is targeted by miRNA-145-5p and miRNA-124-3p. Collectively, these outcomes suggest that UCA1 enhances chondrogenic differentiation of MSCs via the miRNA-145-5p/SMAD5 and miRNA-124-3p/SMAD4 axis.

Extracellular matrix protein DMP1 suppresses osteogenic differentiation of Mesenchymal Stem Cells.

Mesenchymal Stem Cells (MSCs) are self-renewing and multipotent stem cells which was investigated for diverse clinical applications. However, complex mechanism of MSCs fate determination is still not fully disclosed. Extracellular matrix (ECM) proteins contribute to maintain MSCs stemness by providing extracellular microenvironment. Increasing evidences show that ECM proteins could also regulate the fate of MSCs directly. Dentin matrix protein 1 (DMP1) is an ECM protein enrich in bone tissue and terminal cells, which well-known in promoting osteoblasts and osteocytes maturation, and facilitate mineralization. Recently, our experiment indicated that DMP1 was also expressed in MSCs of long bone. In present study, it is found that DMP1 expressed in Prx1 positive MSCs. And, DMP1 is down-regulated in early osteoblasts and up-regulated again in mature osteoblasts. DMP1 conditional knockout mice model under Prx1cre was generated to explore whether DMP1 regulates MSCs osteogenic differentiation. Specific ablation of DMP1 in Prx1 positive MSCs increased bone mass in vivo and promoted osteoblasts activity in vitro. This study provides a new understanding of DMP1's function in regulation of osteogenesis: not only an enhancer of bone formation, but also a negative regulator of MSCs differentiation in bone.

Clinical and Economic Outcomes of Telemedicine Programs in the Intensive Care Unit: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the impact of telemedicine programs in intensive care unit (Tele-ICU) on ICU or hospital mortality or ICU or hospital length of stay and to summarize available data on implementation cost of Tele-ICU. METHODS: Controlled trails or observational studies assessing outcomes of interest were identified by searching 7 electronic databases from inception to July 2016 and related journals and conference literatures between 2000 and 2016. Two reviewers independently screened searched records, extracted data, and assessed the quality of included studies. Random-effect models were applied to meta-analyses and sensitivity analysis. RESULTS: Nineteen of 1035 records fulfilled the inclusion criteria. The pooled effects demonstrated that Tele-ICU programs were associated with reductions in ICU mortality (15 studies; risk ratio [RR], 0.83; 95% confidence interval [CI], 0.72 to 0.96; P = .01), hospital mortality (13 studies; RR, 0.74; 95% CIs, 0.58 to 0.96; P = .02), and ICU length of stay (9 studies; mean difference [MD], -0.63; 95% CI, -0.28 to 0.17; P = .007). However, there is no significant association between the reduction in hospital length of stay and Tele-ICU programs. Summary data concerning costs suggested approximately US$50 000 to US$100 000 per Tele-ICU bed was required to implement Tele-ICU programs for the first year. Hospital costs of US$2600 reduction to US$5600 increase per patient were estimated using Tele-ICU programs. CONCLUSIONS: This systematic review and meta-analysis provided limited evidence that Tele-ICU approaches may reduce the ICU and hospital mortality, shorten the ICU length of stay, but have no significant effect in hospital length of stay. Implementation of Tele-ICU programs substantially costs and its long-term cost-effectiveness is still unclear.

LncRNA HANR Promotes Tumorigenesis and Increase of Chemoresistance in Hepatocellular Carcinoma.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third leading cause of cancer-related death. Critical roles for long non-coding RNAs (lncRNAs) have recently been demonstrated for a variety of cancers, including hepatocellular carcinoma. However, the effect and mechanism of lncRNAs in HCC tumorigenesis and chemoresistance have not been extensively characterized. METHODS: In the current study, we have identified a HCC-expressed lncRNA termed as HANR (HCC associated long non-coding RNA). We identified HANR by microarray analysis and validated its up-regulated expression by quantitative PCR. RNA pull-down and pathway analyses were conducted to evaluate physical and functional interactions with HANR. In vivo experiments were performed to assess tumorigenesis and increase of chemoresistance. In addition, the HANR expression in HCC specimens was detected by FISH. Xenograft and orthotopic mice model was constructed to observe the effect of HANR on tumorigenesis and chemoresistance in vivo. RESULTS: HANR was demonstrated to be up-regulated in HCC patients and HCC cell lines. Increased HANR expression in HCC predicted short survival of patients. Knock-down of HANR markedly retarded cell proliferation, suppressed HCC xenograft/orthotopic tumor growth, induced apoptosis and enhanced chemosensitivity to doxorubicin, while over-expression of HANR showed the opposite effects. It was found that HANR bind to GSKIP for regulating the phosphorylation of GSK3ß in HCC. CONCLUSION: Our results demonstrate that HANR contributes to the development of HCC and is a promising therapeutic target for chemosensitization of HCC cells to doxorubicin, which may represent a promising therapeutic target in the future.

An efficient molten steel slag gas quenching process: Integrating carbon solidification and waste heat recovery.

The iron and steel-making industries have garnered significant attention in research related to low-carbon transitions and the reuse of steel slag. This industry is known for its high carbon emissions and the substantial amount of steel slag it generates. To address these challenges, a waste heat recovery process route has been developed for molten steel slag, which integrates CO2 capture and fixation as well as efficient utilization of steel slag. This process involves the use of lime kiln flue gas from the steel plant as the gas quenching agent, thereby mitigating carbon emissions and facilitating carbonation conversion of steel slag while simultaneously recovering waste heat. The established carbonation model of steel slag reveals that the insufficient diffusion of CO2 gas molecules within the product layer is the underlying mechanism hindering the carbonation performance of steel slag. This finding forms the basis for enhancing the carbonation performance of steel slag. The results of Aspen Plus simulation indicate that 1 t of steel slag (with a carbonation conversion rate of 15.169 %) can fix 55.19 kg of CO2, process 6.08 kmol of flue gas (with a carbon capture rate of 92.733 %), and recover 2.04 GJ of heat, 0.43 GJ of exergy, and 0.68 MWh of operating cost. These findings contribute to the development of sustainable and efficient solutions for steel slag management, with potential applications in the steel production industry and other relevant fields.

Anomaly Detection Method for Lithium-Ion Battery Cells Based on Time Series Decomposition and Improved Manhattan Distance Algorithm.

Abnormalities in individual lithium-ion batteries can cause the entire battery pack to fail, thereby the operation of electric vehicles is affected and safety accidents even occur in severe cases. Therefore, timely and accurate detection of abnormal monomers can prevent safety accidents and reduce property losses. In this paper, a battery cell anomaly detection method is proposed based on time series decomposition and an improved Manhattan distance algorithm for actual operating data of electric vehicles. First, time series decomposition is performed on the voltage data of all battery cells in the battery pack to obtain the voltage trend component of each cell. Then, the improved Manhattan distance algorithm is utilized to calculate and compare the Manhattan distance values between adjacent cell trend components, to determine the abnormal cells inside the battery pack. Furthermore, the Manhattan distance values at the same sampling moment are calculated within the data sequence to detect the specific time when the abnormal cells malfunction. The data analysis and experimental verification results based on actual vehicle operating conditions indicate that this method can accurately identify an abnormal cell within the battery pack and diagnose the specific moment of abnormality in the battery cell at an early stage of failure, with good robustness.

Analysis of the differences in physicochemical properties, volatile compounds, and microbial community structure of pit mud in different time spaces.

Pit mud (PM) is among the key factors determining the quality of Nongxiangxing baijiu, a Chinese liquor. Microorganisms present inside PM are crucial for the unique taste and flavor of this liquor. In this study, headspace solid-phase microextraction was used in combination with gas chromatography and high-throughput sequencing to determine the volatile compounds and microbial community structure of 10- and 40-year PM samples from different spaces. The basic physicochemical properties of the PM were also determined. LEfSe and RDA were used to systematically study the PM in different time spaces. The physicochemical properties and ester content of the 40-year PM were higher than those of the 10-year PM, but the spatial distribution of the two years PM samples exhibited no consistency, except in terms of pH, available phosphorus content, and ester content. In all samples, 29 phyla, 276 families, and 540 genera of bacteria, including four dominant phyla and 20 dominant genera, as well as eight phyla, 24 families, and 34 genera of archaea, including four dominant phyla and seven dominant genera, were identified. The LEfSe analysis yielded 18 differential bacteria and five differential archaea. According to the RDA, the physicochemical properties and ethyl caproate, ethyl octanoate, hexanoic acid, and octanoic acid positively correlated with the differential microorganisms of the 40-year PM, whereas negatively correlated with the differential microorganisms of the 10-year PM. Thus, we inferred that Caproiciproducens, norank_f__Caloramatoraceae, and Methanobrevibacter play a dominant and indispensable role in the PM. This study systematically unveils the differences that affect the quality of PM in different time spaces and offers a theoretical basis for improving the declining PM, promoting PM aging, maintaining cellars, and cultivating an artificial PM at a later stage.

Sleep Pattern, Genetic Susceptibility, and Abdominal Aortic Aneurysm in UK Biobank Participants: Large-Scale Cohort Study.

Background: Abdominal aortic aneurysm (AAA) is an important cause of cardiovascular mortality. Objectives: The authors aimed to explore the associations between sleep patterns and genetic susceptibility to AAA. Methods: We included 344,855 UK Biobank study participants free of AAA at baseline. A sleep pattern was defined by chronotype, sleep duration, insomnia, snoring, and daytime sleepiness, and an overall sleep score was constructed with a range from 0 to 5, where a high score denotes a healthy sleep pattern. Polygenic risk score based on 22 single nucleotide polymorphisms was categorized into tertiles and used to evaluate the genetic risk for AAA. Cox proportional hazards regression models were used to assess the association between sleep, genetic factors, and the incidence of AAA. Results: During a median of 12.59 years of follow-up, 1,622 incident AAA cases were identified. The HR per 1-point increase in the sleep score was 0.91 (95% CI: 0.86-0.96) for AAA. Unhealthy sleep patterns, defined as a sleep score ranging from 0 to 3, were found to be associated with a higher risk of AAA for the intermediate (HR: 1.18, 95% CI: 1.06-1.31) and poor sleep patterns (HR: 1.40, 95% CI: 1.13-1.73), respectively, compared to the healthy pattern. Participants with poor sleep patterns and high genetic risks had a 2.5-fold higher risk of AAA than those with healthy sleep patterns and low genetic risk. Conclusions: In this large prospective study, healthy sleep patterns were associated with a lower risk of AAA among participants with low, intermediate, or high genetic risk.

Ischemic stroke or transient ischemic attack due to cervical and intracranial large-vessel vasculitis secondary to primary Sjögren's syndrome: A case series and literature review.

Introduction: Primary Sjögren's syndrome (PSS) is a systemic autoimmune disease that mainly affects exocrine glands. Little is known about PSS associated cervical and intracranial cerebral large-vessel vasculitis outside of individual case reports. Methods: We present 5 cases of ischemic stroke or transient ischemic stroke (TIA) caused by PSS associated cervical and intracranial large-vessel vasculitis. Literature review was performed to summarize and identify the demographic, clinical features, treatment, and prognosis of this condition. Results: The review resulted in 8 included articles with 8 patients, plus our 5 new patients, leading to a total of 13 subjects included in the analysis. The median age was 43 (range, 17-69) years old, among which 69.2 % (9/13) were female, and 92.3 % (12/13) came from Asia. Among them, 84.6 % (11/13) presented with cerebral infarction and 70.0 % (7/10) with watershed infarction. Middle cerebral artery (MCA) (6/13, 46.2 %) and internal carotid artery (ICA) (6/13, 46.2 %) were the most frequently involved arteries. Remarkable vessel wall concentric thickening and enhancement was observed in 57.1 % (4/7) patients and intravascular thrombi was identified in 28.6 % (2/7) patients. Glucocorticoid combined with non-glucocorticoid immunosuppressants (8/12, 66.7 %) were the most often chosen medication therapy and 4 patients received surgical intervention. Conclusion: Asian females are the most vulnerable population to ischemic stroke or TIA due to PSS associated cervical and intracranial large-vessel vasculitis. Cerebral infarctions were characterized by recurrence and watershed pattern. Magnetic resonance vessel wall imaging (MR-VWI) helps to identify the inflammatory pathology of large vessel lesion in PSS.

Computer vision models enable mixed linear modeling to predict arbuscular mycorrhizal fungal colonization using fungal morphology.

The presence of Arbuscular Mycorrhizal Fungi (AMF) in vascular land plant roots is one of the most ancient of symbioses supporting nitrogen and phosphorus exchange for photosynthetically derived carbon. Here we provide a multi-scale modeling approach to predict AMF colonization of a worldwide crop from a Recombinant Inbred Line (RIL) population derived from Sorghum bicolor and S. propinquum. The high-throughput phenotyping methods of fungal structures here rely on a Mask Region-based Convolutional Neural Network (Mask R-CNN) in computer vision for pixel-wise fungal structure segmentations and mixed linear models to explore the relations of AMF colonization, root niche, and fungal structure allocation. Models proposed capture over 95% of the variation in AMF colonization as a function of root niche and relative abundance of fungal structures in each plant. Arbuscule allocation is a significant predictor of AMF colonization among sibling plants. Arbuscules and extraradical hyphae implicated in nutrient exchange predict highest AMF colonization in the top root section. Our work demonstrates that deep learning can be used by the community for the high-throughput phenotyping of AMF in plant roots. Mixed linear modeling provides a framework for testing hypotheses about AMF colonization phenotypes as a function of root niche and fungal structure allocations.

Wide-ranging genetic variation in sensitivity to rapamycin in Drosophila melanogaster.

The progress made in aging research using laboratory organisms is undeniable. Yet, with few exceptions, these studies are conducted in a limited number of isogenic strains. The path from laboratory discoveries to treatment in human populations is complicated by the reality of genetic variation in nature. To model the effect of genetic variation on the action of the drug rapamycin, here we use the growth of Drosophila melanogaster larvae. We screened 140 lines from the Drosophila Genetic References Panel for the extent of developmental delay and found wide-ranging variation in their response, from lines whose development time is nearly doubled by rapamycin, to those that appear to be completely resistant. Sensitivity did not associate with any single genetic marker, nor with any gene. However, variation at the level of genetic pathways was associated with rapamycin sensitivity and might provide insight into sensitivity. In contrast to the genetic analysis, metabolomic analysis showed a strong response of the metabolome to rapamycin, but only among the sensitive larvae. In particular, we found that rapamycin altered levels of amino acids in sensitive larvae, and in a direction strikingly similar to the metabolome response to nutrient deprivation. This work demonstrates the need to evaluate interventions across genetic backgrounds and highlights the potential of omic approaches to reveal biomarkers of drug efficacy and to shed light on mechanisms underlying sensitivity to interventions aimed at increasing lifespan.