A Marine Group A isolate relies on other growing bacteria for cell wall formation.

Most of Earth's prokaryotes live under energy limitation, yet the full breadth of strategies that enable survival under such conditions remain poorly understood. Here we report the isolation of a bacterial strain, IA91, belonging to the candidate phylum Marine Group A (SAR406 or 'Candidatus Marinimicrobia') that is unable to synthesize the central cell wall compound peptidoglycan itself. Using cultivation experiments and microscopy, we show that IA91 growth and cell shape depend on other bacteria, deriving peptidoglycan, energy and carbon from exogenous muropeptide cell wall fragments released from growing bacteria. Reliance on exogenous muropeptides is traceable to the phylum's ancestor, with evidence of vertical inheritance across several classes. This dependency may be widespread across bacteria (16 phyla) based on the absence of key peptidoglycan synthesis genes. These results suggest that uptake of exogenous cell wall components could be a relevant and potentially common survival strategy in energy-limited habitats like the deep biosphere.

Oxidative Tandem Cyclization of Aromatic Acids with (Benzo)thiophenes: One-Pot Access to Planar Sulfur-Containing Polycyclic Heteroarenes for Lipid-Droplet-Targeted Probes.

The efficient construction of π-conjugated polycyclic heteroarenes represents a significant task in the field of functional materials. A one-step oxidative tandem cyclization of aromatic acids with (benzo)thiophenes was developed to access planar sulfur-containing polycyclic heteroarenes. This protocol undergoes intermolecular cross-dehydrogenative coupling followed by intramolecular Friedel-Crafts acylation and provides a facile pathway to planar polycyclic compounds from inexpensive reactants. The synthesized heteroarenes serving as lipid-droplet-targeted probes exhibit outstanding performance with favorable biocompatibility and photostability.

Association between intracellular adenosine triphosphate content of CD4+ T lymphocytes and mortality in sepsis patients: A prospective observational study.

OBJECTIVE: This study aimed to link intracellular adenosine triphosphate content in CD4+ T lymphocytes (CD4+ iATP) with sepsis patient mortality, seeking a new predictive biomarker for outcomes and enhanced management. METHODS: 61 sepsis patients admitted to the Intensive Care Unit between October 2021 and November 2022 were enrolled. iATP levels were gauged using whole blood CD4+ T cells stimulated with mitogen PHA-L. Based on CD4+ iATP levels (<132.24 and ≥132.24 ng/mL), patients were categorized into two groups. The primary endpoint was all-cause mortality. To identify factors associated with mortality, both univariate and multivariate Cox proportional hazard analyses were conducted. RESULTS: Of the patients, 40 had high CD4+ iATP levels (≥132.24 ng/mL) and 21 had low levels (<132.24 ng/mL). In a 28-day follow-up, 21 (34.4%) patients perished. Adjusting for confounders like SOFA score, APACHE II score, lactic acid, and albumin, those with low CD4+ iATP had three- to fivefold higher mortality risk compared to high CD4+ iATP patients (61.9% vs. 20.0%; hazard ratio [95% confidence interval], Model 1: 4.515 [1.276-15.974], p = .019, Model 2: 3.512 [1.197-10.306], p = .022). CD4+ iATP correlated positively with white blood cell and neutrophil counts but not with lymphocytes, CD3, and CD4 counts. CONCLUSIONS: Low CD4+ iATP levels were associated with a higher risk of mortality in sepsis patients. Measurement of CD4+ iATP may serve as a useful tool for identifying patients at a higher risk of mortality and could potentially provide a basis for clinical treatment. Further research is warranted to fully elucidate the underlying mechanisms of this association.

Prediction of Large Vessel Occlusion Stroke Using Clinical Registries for Research.

OBJECTIVES: A reliable method of predicting large vessel occlusion (LVO) stroke in data sets without neuroimaging could be retrospectively applied to expand research efforts. METHODS: We conducted a retrospective, cross-sectional cohort analysis of the Get With The Guidelines (GWTG)-Stroke registry. We included adult patients with a final diagnosis of ischemic stroke from 2016 to 2021 who had brain and vascular imaging and excluded those with missing data or posterior circulation stroke. RESULTS: We included 416,022 patients of which 125,381 (30.1%) had LVO. The mean age was 71 years, and 48.2% were female. The area under the receiver operating curve (AUC) for the final model, including age, sex, hypertension, dyslipidemia, atrial fibrillation, diabetes, TOAST stroke mechanism, and NIH Stroke Scale (NIHSS), was 0.79 (95% CI 0.79-0.80). Without TOAST mechanism, the AUC was 0.74. The specificity did not exceed 0.5 using different cut points for the NIHSS. DISCUSSION: We found that 30% of adult acute ischemic stroke patients in GWTG-Stroke have LVO and that the combination of clinical covariates and NIHSS is only moderately predictive of LVO status. These results are consistent with previous studies and suggest it may not be possible to retrospectively predict LVO with high accuracy in data sets without vascular neuroimaging.

Development and validation of a novel nomogram for predicting overall survival patients with neuroblastoma.

PURPOSE: The aim of this study was to develop a nomogram specially for predicting overall survival (OS) for Chinese patients with neuroblastoma (NB). METHODS: Patients with pathologically confirmed NB who were newly diagnosed and received treatments at our hospital from October 2013 to October 2021 were retrospectively reviewed. The nomogram for OS were built based on Cox regression analysis. The validation of the prognostic model was evaluated by concordance index (C-index), calibration curves, and decision curve analyses (DCAs). RESULTS: A total of 254 patients with NB were included in this study. They were randomly divided into a training cohort (n = 178) and a validation cohort (n = 76) at a ratio of 7:3. Multivariate analyses revealed that prognostic variables significantly related to the OS were age at diagnosis, bone metastasis, hepatic metastasis, INSS stage, MYCN status and DNA ploidy. The nomogram was constructed based on above 6 factors. The C-index values of the nomogram for predicting 3-year and 5-year OS were 0.926 and 0.964, respectively. The calibration curves of the nomogram showed good consistency between nomogram prediction and actual survival. The DCAs showed great clinical usefulness of the nomograms. Furthermore, patients with low-risk identified by our nomogram had much higher OS than those with high-risk (p < 0.001). CONCLUSION: The nomogram we constructed exhibited good predictive performance and could be used to assist clinicians in their decision-making process.

Endophilin A2 controls touch and mechanical allodynia via kinesin-mediated Piezo2 trafficking.

BACKGROUND: Tactile and mechanical pain are crucial to our interaction with the environment, yet the underpinning molecular mechanism is still elusive. Endophilin A2 (EndoA2) is an evolutionarily conserved protein that is documented in the endocytosis pathway. However, the role of EndoA2 in the regulation of mechanical sensitivity and its underlying mechanisms are currently unclear. METHODS: Male and female C57BL/6 mice (8-12 weeks) and male cynomolgus monkeys (7-10 years old) were used in our experiments. Nerve injury-, inflammatory-, and chemotherapy-induced pathological pain models were established for this study. Behavioral tests of touch, mechanical pain, heat pain, and cold pain were performed in mice and nonhuman primates. Western blotting, immunostaining, co-immunoprecipitation, proximity ligation and patch-clamp recordings were performed to gain insight into the mechanisms. RESULTS: The results showed that EndoA2 was primarily distributed in neurofilament-200-positive (NF200+) medium-to-large diameter dorsal root ganglion (DRG) neurons of mice and humans. Loss of EndoA2 in mouse NF200+ DRG neurons selectively impaired the tactile and mechanical allodynia. Furthermore, EndoA2 interacted with the mechanically sensitive ion channel Piezo2 and promoted the membrane trafficking of Piezo2 in DRG neurons. Moreover, as an adaptor protein, EndoA2 also bound to kinesin family member 5B (KIF5B), which was involved in the EndoA2-mediated membrane trafficking process of Piezo2. Loss of EndoA2 in mouse DRG neurons damaged Piezo2-mediated rapidly adapting mechanically activated currents, and re-expression of EndoA2 rescued the MA currents. In addition, interference with EndoA2 also suppressed touch sensitivity and mechanical hypersensitivity in nonhuman primates. CONCLUSIONS: Our data reveal that the KIF5B/EndoA2/Piezo2 complex is essential for Piezo2 trafficking and for sustaining transmission of touch and mechanical hypersensitivity signals. EndoA2 regulates touch and mechanical allodynia via kinesin-mediated Piezo2 trafficking in sensory neurons. Our findings identify a potential new target for the treatment of mechanical pain.

Epicoccum sorghinum Causing Leaf Spot on Polygonatum cyrtonema in China.

Polygonatum cyrtonema Hua (family Asparagaceae) is a traditional Chinese medicinal plant that is widely cultivated in various parts of China, including Hunan Province. In summer 2022, a leaf spot disease was observed in 10% of the P. cyrtonema plants (Huang jing) in 18 hectares of this crop in the Hongjiang District (27°18'4″N, 110°11'1″E) of Hunan Province. The initial symptoms of the disease were brown spots on young leaves, and adjacent tissues gradually changed from green to yellow. The entire leaf then became yellow, withered, and eventually exhibited a thn and black appearance. In total, 12 diseased plants from four sampling sites (three plants per site) were collected for laboratory analysis to address the concerns of P. cyrtonema growers. Symptomatic leaf samples were selected, and the leaf fragments containing infected parts of the plants were disinfected with 75% ethanol for 1 min, then immersed in 2.5% hypochlorite for 45 s. After disinfection, symptomatic leaf samples were rinsed three times with sterile water, placed on potato saccharose agar containing 50 µg/ml kanamycin and incubated at 25°C for 2 days. Subsequently, 12 fungal isolates were isolated from various leaf samples through hyphal tip transferring. Ten of the 12 fungal isolates had similar morphological features, and one of them (isolate hjh) was used as the representative isolate for the study. With a growth rate of 6.3 mm per day, its white colonies transformed into red concentric rings in five days; they gradually became black after 10 days of growth. The chlamydospores were round (4.0-9.9 × 3.1-9.3 µm, n = 30), whereas the conidia were ovate (8.0-12.1 × 3.2-6.5 µm, n = 30). The morphological features of the isolate hjh were similar to the features of Epicoccum spp. (Aveskamp et al. 2010). The internal transcribed spacer (ITS) region (including the partial ITS1 sequence and the 5.8S and ITS2 complete sequences), ß-tubulin (tub) gene, and large subunit (LSU) rRNA gene, were amplified from the isolate hjh using the primer pairs ITS5/ITS4, Bt2a/Bt2b, and LROR/LR5, respectively (Taguiam et al. 2021). BLASTn analysis showed that the ITS (OR253745), tub (OR253764), and LSU (OR253746) sequences generated from the isolate hjh were 98-99% similar to the sequences of E. sorghinum strains CBS 179.80 and CBS 627.68. Subsequently, the ITS, tub, and LSU sequences were combined using Sequence Matrix software; phylogenetic analysis via Bayesian and maximum likelihood methods (Vaidya et al. 2011; Li et al. 2021) classified the isolate hjh into the E. sorghinum clade. To fulfill Koch's postulates, pathogenicity tests were conducted on healthy (lesion-free and disease-free) 2-year-old P. cyrtonema plants. Three healthy plants were inoculated by spraying whole plant until run-off with a spore suspension of the isolate hjh (1 × 106 conidia/ml); Three other healthy plants were sprayed with sterile water as controls. The inoculated plants were incubated in a growth chamber at 25 ± 2°C with 85% humidity for 28 days(Chen et al. 2021). Leaves from the inoculated plants gradually became brown within 15 days. Finally, the plants died 28 days after inoculation. The control plants showed no symptoms throughout the experimental period. Isolates (isolate hjh1, hjh2 and hjh3) that were reisolated from the inoculated plants exhibited morphologically similar characteristics and molecularly identical to the original isolate hjh. To our knowledge, this is the first report of E. sorghinum causing leaf spot disease on P. cyrtonema. The results of this study may facilitate the production of P. cyrtonema in China.

Racial Disparities in Low-Value Care in the Last Year of Life for Medicare Beneficiaries With Neurodegenerative Disease.

Background and Objectives: There are racial disparities in health care services received by patients with neurodegenerative diseases, but little is known about disparities in the last year of life, specifically in high-value and low-value care utilization. This study evaluated racial disparities in the utilization of high-value and low-value care in the last year of life among Medicare beneficiaries with dementia or Parkinson disease. Methods: This was a retrospective, population-based cohort analysis using data from North and South Carolina fee-for-service Medicare claims between 2013 and 2017. We created a decedent cohort of beneficiaries aged 50 years or older at diagnosis with dementia or Parkinson disease. Specific low-value utilization outcomes were selected from the Choosing Wisely initiative, including cancer screening, peripheral artery stenting, and feeding tube placement in the last year of life. Low-value outcomes included hospitalization, emergency department visits, neuroimaging services, and number of days receiving skilled nursing. High-value outcomes included receipt of occupational and physical therapy, hospice care, and medications indicated for dementia and/or Parkinson disease. Results: Among 70,650 decedents, 13,753 were Black, 55,765 were White, 93.1% had dementia, and 7.7% had Parkinson disease. Adjusting for age, sex, Medicaid dual enrollment status, rural vs urban location, state (NC and SC), and comorbidities, Black decedents were more likely to receive low-value care including colorectal cancer screening (adjusted hazard ratio [aHR] 1.46 [1.32-1.61]), peripheral artery stenting (aHR 1.72 [1.43-2.08]), and feeding tube placement (aHR 2.96 [2.70-3.24]) and less likely to receive physical therapy (aHR 0.73 [0.64-0.85)], dementia medications (aHR 0.90 [0.86-0.95]), or Parkinson disease medications (aHR 0.88 [0.75-1.02]) within the last year of life. Black decedents were more likely to be hospitalized (aHR 1.28 [1.25-1.32]), more likely to be admitted to skilled nursing (aHR 1.09 [1.05-1.13]), and less likely to be admitted to hospice (aHR 0.82 [0.79-0.85]) than White decedents. Discussion: We found racial disparities in care utilization among patients with neurodegenerative disease in the last year of life, such that Black decedents were more likely to receive specific low-value care services and less likely to receive high-value supportive care than White decedents, even after adjusting for health status and socioeconomic factors.

Waterlogging in soil restricts the growth of Gleditsia sinensis seedlings and inhibits the accumulation of lignans and phenolic acids in thorns.

Gleditsia sinensis, commonly known as Chinese Zaojiao, has important economic value and medicinal compounds in its fruits and thorns, making it widely cultivated artificially in China. However, the available literature on the impact of waterlogging on the growth of G. sinensis seedlings and the accumulation of metabolite compounds in its thorns is limited. To address this knowledge gap, G. sinensis seedlings were planted in soil supplemented with pindstrup substrate, which enhances the water-holding capacity of the soil. The analyses of morphological traits and nutrient elements in one-year-old G. sinensis seedlings grown naturally under ambient conditions and metabolite accumulation in its thorns were conducted. The results showed that the waterlogged soil significantly diminished the height, fresh weight, and dry weight of seedling roots and stems (P < 0.05). Furthermore, waterlogging hindered the uptake of iron (Fe) and manganese (Mn), as well as the transport of potassium (K). The identified metabolites within the thorns were categorized into 16 distinct groups. Relative to the control soil, fatty acids and derivatives were the most down-regulated metabolites in the waterlogged soil, accounting for 40.58% of the total metabolites, followed by lignans (38.71%), phenolic acids (34.48%), saccharides and alcohols (34.15%), steroids (16.67%), alkaloids (12.24%), flavonoids (9.28%), and glycerophospholipids (7.41%). Conversely, nucleotides and derivatives experienced the greatest up-regulation in the waterlogged soil, accounting for 50.00% of the total metabolites. In conclusion, waterlogging negatively impacted the growth of G. sinensis seedlings and inhibited the accumulation of metabolites. Hence, when considering the accumulation of secondary metabolites such as lignans and phenolic acids, appropriate management of soil moisture levels should be taken into account.

Landscape of m6A RNA methylation regulators in liver cancer and its therapeutic implications.

Liver cancer remains as the third leading cause of cancer-related death globally as of 2020. Despite the significant progress made in the field of liver cancer treatment, there is still a lack of effective therapies in patients with advanced cancer and the molecular mechanisms underlying liver cancer progression remain largely elusive. N6-methyladenosine (m6A) modification, as the most prevalent and abundant internal RNA modification in eukaryotic RNAs, plays an essential role in regulating RNA metabolism including RNA splicing, stability, translation, degradation. To date, there is mounting evidence showing that m6A dysregulation is closely associated with the onset and development of many tumors including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and hepatoblastoma (HB). In this review, we summarize the last research progress regarding the functions of m6A-related regulators in liver cancer and its underlying mechanisms. Additionally, we also discuss the therapeutic applications of m6A-based inhibitors in liver cancer treatment.

CircHAT1 regulates the proliferation and phenotype switch of vascular smooth muscle cells in lower extremity arteriosclerosis obliterans through targeting SFRS1.

This study aimed to decipher the mechanism of circular ribonucleic acids (circRNAs) in lower extremity arteriosclerosis obliterans (LEASO). First, bioinformatics analysis was performed for screening significantly down-regulated cardiac specific circRNA-circHAT1 in LEASO. The expression of circHAT1 in LEASO clinical samples was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of splicing factor arginine/serine-rich 1 (SFRS1), α-smooth muscle actin (α-SMA), Calponin (CNN1), cyclin D1 (CNND1) and smooth muscle myosin heavy chain 11 (SMHC) in vascular smooth muscle cells (VSMCs) was detected by Western blotting. Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) and Transwell assays were used to evaluate cell proliferation and migration, respectively. RNA immunoprecipitation (RNA-IP) and RNA pulldown verified the interaction between SFRS1 and circHAT1. By reanalyzing the dataset GSE77278, circHAT1 related to VSMC phenotype conversion was screened, and circHAT1 was found to be significantly reduced in peripheral blood mononuclear cells (PBMCs) of LEASO patients compared with healthy controls. Knockdown of circHAT1 significantly promoted the proliferation and migration of VSMC cells and decreased the expression levels of contractile markers. However, overexpression of circHAT1 induced the opposite cell phenotype and promoted the transformation of VSMCs from synthetic to contractile. Besides, overexpression of circHAT1 inhibited platelet-derived growth factor-BB (PDGF-BB)-induced phenotype switch of VSMC cells. Mechanistically, SFRS1 is a direct target of circHAT1 to mediate phenotype switch, proliferation and migration of VSMCs. Overall, circHAT1 regulates SFRS1 to inhibit the cell proliferation, migration and phenotype switch of VSMCs, suggesting that it may be a potential therapeutic target for LEASO.

Trends in Stroke Thrombolysis Care Metrics and Outcomes by Race and Ethnicity, 2003-2021.

Importance: Understanding is needed of racial and ethnic-specific trends in care quality and outcomes associated with the US nationwide quality initiative Target: Stroke (TS) in targeting thrombolysis treatment for acute ischemic stroke. Objective: To examine whether the TS quality initiative was associated with improvement in thrombolysis metrics and outcomes across racial and ethnic groups. Design, Setting, and Participants: This retrospective cohort study included patients who presented within 4.5 hours of ischemic stroke onset at hospitals participating in the Get With The Guidelines-Stroke initiative from January 1, 2003, to December 31, 2021. The data analysis was performed between December 15, 2022, and November 27, 2023. Exposures: TS phases I (2010-2013), II (2014-2018), and III (2019-2021). Main Outcomes and Measures: The primary outcomes were thrombolysis rates and time metrics. Patient function and mortality were secondary outcomes. Results: Analyses included 1 189 234 patients, of whom 1 053 539 arrived to the hospital within 4.5 hours. The cohort included 50.4% female and 49.6% male patients and 2.8% Asian [median (IQR) age, 72 (61-82) years], 15.2% Black [median (IQR) age, 64 (54-75) years], 7.3% Hispanic [median (IQR) age, 68 (56-79) years], and 74.1% White [median (IQR) age, 75 (63-84) years] patients). Unadjusted thrombolysis rates increased in both the pre-TS (2003-2009) and TS periods in all racial and ethnic groups from 10% to 15% in 2003 to 43% to 46% in 2021, but disparities were observed in adjusted analyses and persisted in TS phase III, with Asian, Black, and Hispanic patients having significantly lower odds of receiving thrombolysis than White patients (adjusted odds ratio, 0.85 [95% CI, 0.81-0.90], 0.76 [95% CI, 0.74-0.78], and 0.86 [95% CI, 0.83-0.89], respectively). Door-to-needle (DTN) times improved in all racial and ethnic groups during TS, with DTN times of 60 minutes or less increasing from 26% to 28% in 2009 to 66% to 72% in 2021. However, in adjusted analyses, racial and ethnic disparities emerged. During TS phase III, compared with White patients, Asian, Black, and Hispanic patients had significantly lower odds of receiving thrombolysis with a DTN time of 60 minutes or less compared with White patients (risk-adjusted odds ratios, 0.91 [95% CI, 0.84-0.98], 0.78 [95% CI, 0.75-0.81], and 0.87 [95% CI, 0.83-0.92], respectively). During TS, clinical outcomes improved for all racial and ethnic groups from pre-TS, with TS phase III showing higher odds of ambulation at discharge among Asian, Black, Hispanic, and White patients. Asian, Black, and Hispanic patients were less likely to present within 4.5 hours. Conclusions and Relevance: In this cohort study of patients with ischemic stroke, the TS quality initiative was associated with improvement in thrombolysis frequency, timeliness, and outcomes for all racial and ethnic groups. However, disparities persisted, indicating a need for further interventions.

Time to Anticoagulation Reversal and Outcomes After Intracerebral Hemorrhage.

Importance: Intracerebral hemorrhage (ICH) is the deadliest stroke subtype, and mortality rates are especially high in anticoagulation-associated ICH. Recently, specific anticoagulation reversal strategies have been developed, but it is not clear whether there is a time-dependent treatment effect for door-to-treatment (DTT) times in clinical practice. Objective: To evaluate whether DTT time is associated with outcome among patients with anticoagulation-associated ICH treated with reversal interventions. Design, Setting, and Participants: This cohort study used data from the American Heart Association Get With The Guidelines-Stroke quality improvement registry. Patients with ICH who presented within 24 hours of symptom onset across 465 US hospitals from 2015 to 2021 were included. Data were analyzed from January to September 2023. Exposures: Anticoagulation-associated ICH. Main Outcomes and Measures: DTT times and outcomes were analyzed using logistic regression modeling, adjusted for demographic, history, baseline, and hospital characteristics, with hospital-specific random intercepts to account for clustering by site. The primary outcome of interest was the composite inpatient mortality and discharge to hospice. Additional prespecified secondary outcomes, including functional outcome (discharge modified Rankin Scale score, ambulatory status, and discharge venue), were also examined. Results: Of 9492 patients with anticoagulation-associated ICH and documented reversal intervention status, 4232 (44.6%) were female, and the median (IQR) age was 77 (68-84) years. A total of 7469 (78.7%) received reversal therapy, including 4616 of 5429 (85.0%) taking warfarin and 2856 of 4069 (70.2%) taking a non-vitamin K antagonist oral anticoagulant. For the 5224 patients taking a reversal intervention with documented workflow times, the median (IQR) onset-to-treatment time was 232 (142-482) minutes and the median (IQR) DTT time was 82 (58-117) minutes, with a DTT time of 60 minutes or less in 1449 (27.7%). A DTT time of 60 minutes or less was associated with decreased mortality and discharge to hospice (adjusted odds ratio, 0.82; 95% CI, 0.69-0.99) but no difference in functional outcome (ie, a modified Rankin Scale score of 0 to 3; adjusted odds ratio, 0.91; 95% CI, 0.67-1.24). Factors associated with a DTT time of 60 minutes or less included White race, higher systolic blood pressure, and lower stroke severity. Conclusions and Relevance: In US hospitals participating in Get With The Guidelines-Stroke, earlier anticoagulation reversal was associated with improved survival for patients with ICH. These findings support intensive efforts to accelerate evaluation and treatment for patients with this devastating form of stroke.

Thrombolysis for ischaemic stroke despite direct oral anticoagulation.

Intravenous thrombolysis is not recommended in anticoagulated patients receiving direct oral anticoagulants (DOACs) and a recent intake within the last 48 hours in US and European guidelines. However, three observational studies now suggest safety of thrombolysis in patients with recent intake of DOACs, and thus support previous experimental data. In this perspective, the current evidence and practical consequences are discussed.

Rationale and design of the GOLDEN BRIDGE II: a cluster-randomised multifaceted intervention trial of an artificial intelligence-based cerebrovascular disease clinical decision support system to improve stroke outcomes and care quality in China.

BACKGROUND: Given the swift advancements in artificial intelligence (AI), the utilisation of AI-based clinical decision support systems (AI-CDSSs) has become increasingly prevalent in the medical domain, particularly in the management of cerebrovascular disease. AIMS: To describe the design, rationale and methods of a cluster-randomised multifaceted intervention trial aimed at investigating the effect of cerebrovascular disease AI-CDSS on the clinical outcomes of patients who had a stroke and on stroke care quality. DESIGN: The GOLDEN BRIDGE II trial is a multicentre, open-label, cluster-randomised multifaceted intervention study. A total of 80 hospitals in China were randomly assigned to the AI-CDSS intervention group or the control group. For eligible participants with acute ischaemic stroke in the AI-CDSS intervention group, cerebrovascular disease AI-CDSS will provide AI-assisted imaging analysis, auxiliary stroke aetiology and pathogenesis analysis, and guideline-based treatment recommendations. In the control group, patients will receive the usual care. The primary outcome is the occurrence of new vascular events (composite of ischaemic stroke, haemorrhagic stroke, myocardial infarction or vascular death) at 3 months after stroke onset. The sample size was estimated to be 21 689 with a 26% relative reduction in the incidence of new composite vascular events at 3 months by using multiple quality-improving interventions provided by AI-CDSS. All analyses will be performed according to the intention-to-treat principle and accounted for clustering using generalised estimating equations. CONCLUSIONS: Once the effectiveness is verified, the cerebrovascular disease AI-CDSS could improve stroke care and outcomes in China. TRIAL REGISTRATION NUMBER: NCT04524624.

Extracellular vesicles of Weizmannia coagulans lilac-01 reduced cell death of primary microglia and increased mitochondrial content in dermal fibroblasts in vitro.

We investigated the properties of extracellular vesicles from the probiotic Weizmannia coagulans lilac-01 (Lilac-01EVs). The phospholipids in the Lilac-01EV membrane were phosphatidylglycerol and mitochondria-specific cardiolipin. We found that applying Lilac-01EVs to primary rat microglia in vitro resulted in a reduction in primary microglial cell death (P < .05). Lilac-01EVs, which contain cardiolipin and phosphatidylglycerol, may have the potential to inhibit cell death in primary microglia. The addition of Lilac-01EVs to senescent human dermal fibroblasts suggested that Lilac-01 EVs increase the mitochondrial content without affecting their membrane potential in these cells.

Discrete Hartley transform-based dual-mode index modulation OFDM for visible light communications.

Using discrete Hartley transform (DHT) instead of discrete Fourier transform (DFT) in the optical index modulation (IM) aided orthogonal frequency division multiplexing (OFDM) systems for visible light communications (VLC) results in improvement in terms of the spectral efficiency, energy efficiency, peak-to-average power ratio, and bit error rate (BER) performance with a lower computational complexity, benefiting from the removal of the Hermitian symmetry. In this paper, by employing dual-mode (DM) index modulation in the DHT-based OFDM systems, more spectral efficient schemes for VLC are proposed. A reduced-complexity maximum likelihood (ML) detector and a simple log-likelihood ratio (LLR) detector for the DM-OFDM-IM systems are presented, achieving a better performance with a lower complexity over the traditional detectors. The spectral efficiency and the average BER are analyzed. The minimum distance between different transmitted subblock vectors is calculated for characterizing the performance. The simulation results demonstrate that the DHT-based DM-OFDM-IM systems achieve significant performance gains over the DHT-based OFDM-IM counterparts and perform better than the DFT-based counterparts in terms of the spectral efficiency and BER performance.

Atrial fibrillation as a novel risk factor for retinal stroke: A protocol for a population-based retrospective cohort study.

Central retinal artery occlusion (CRAO; retinal stroke or eye stroke) is an under-recognized, disabling form of acute ischemic stroke which causes severe visual loss in one eye. The classical risk factor for CRAO is ipsilateral carotid stenosis; however, nearly half of patients with CRAO do not have high-grade carotid stenosis, suggesting that other cardiovascular risk factors may exist for CRAO. Specifically, prior studies have suggested that cardioembolism, driven by underlying atrial fibrillation, may predispose patients to CRAO. We describe the design of an observational, population-based study in this protocol. We evaluate two specific objectives: 1) To determine if atrial fibrillation is an independent risk factor for CRAO after adjusting for medical and cardiovascular risk; 2) To determine if use of oral anticoagulation can modify the risk of CRAO for patients with atrial fibrillation. This protocol lays out our strategy for cohort definition, case and control definition, comorbidity ascertainment, and statistical methods.

Traditional Chinese Medicine Compound (Tongxinluo) and Clinical Outcomes of Patients With Acute Myocardial Infarction: The CTS-AMI Randomized Clinical Trial.

Importance: Tongxinluo, a traditional Chinese medicine compound, has shown promise in in vitro, animal, and small human studies for myocardial infarction, but has not been rigorously evaluated in large randomized clinical trials. Objective: To investigate whether Tongxinluo could improve clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Design, Setting, and Participants: Randomized, double-blind, placebo-controlled clinical trial was conducted among patients with STEMI within 24 hours of symptom onset from 124 hospitals in China. Patients were enrolled from May 2019 to December 2020; the last date of follow-up was December 15, 2021. Interventions: Patients were randomized 1:1 to receive either Tongxinluo or placebo orally for 12 months (a loading dose of 2.08 g after randomization, followed by the maintenance dose of 1.04 g, 3 times a day), in addition to STEMI guideline-directed treatments. Main Outcomes and Measures: The primary end point was 30-day major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiac death, myocardial reinfarction, emergent coronary revascularization, and stroke. Follow-up for MACCEs occurred every 3 months to 1 year. Results: Among 3797 patients who were randomized, 3777 (Tongxinluo: 1889 and placebo: 1888; mean age, 61 years; 76.9% male) were included in the primary analysis. Thirty-day MACCEs occurred in 64 patients (3.4%) in the Tongxinluo group vs 99 patients (5.2%) in the control group (relative risk [RR], 0.64 [95% CI, 0.47 to 0.88]; risk difference [RD], -1.8% [95% CI, -3.2% to -0.6%]). Individual components of 30-day MACCEs, including cardiac death (56 [3.0%] vs 80 [4.2%]; RR, 0.70 [95% CI, 0.50 to 0.99]; RD, -1.2% [95% CI, -2.5% to -0.1%]), were also significantly lower in the Tongxinluo group than the placebo group. By 1 year, the Tongxinluo group continued to have lower rates of MACCEs (100 [5.3%] vs 157 [8.3%]; HR, 0.64 [95% CI, 0.49 to 0.82]; RD, -3.0% [95% CI, -4.6% to -1.4%]) and cardiac death (85 [4.5%] vs 116 [6.1%]; HR, 0.73 [95% CI, 0.55 to 0.97]; RD, -1.6% [95% CI, -3.1% to -0.2%]). There were no significant differences in other secondary end points including 30-day stroke; major bleeding at 30 days and 1 year; 1-year all-cause mortality; and in-stent thrombosis (<24 hours; 1-30 days; 1-12 months). More adverse drug reactions occurred in the Tongxinluo group than the placebo group (40 [2.1%] vs 21 [1.1%]; P = .02), mainly driven by gastrointestinal symptoms. Conclusions and Relevance: In patients with STEMI, the Chinese patent medicine Tongxinluo, as an adjunctive therapy in addition to STEMI guideline-directed treatments, significantly improved both 30-day and 1-year clinical outcomes. Further research is needed to determine the mechanism of action of Tongxinluo in STEMI. Trial Registration: ClinicalTrials.gov Identifier: NCT03792035.

Performance of Thrombectomy-Capable, Comprehensive, and Primary Stroke Centers in Reperfusion Therapies for Acute Ischemic Stroke: Report From the Get With The Guidelines-Stroke Registry.

BACKGROUND: The thrombectomy-capable stroke center (TSC) is a recently introduced intermediate tier of accreditation for hospitals at which patients with acute ischemic stroke receive care. The comparative quality and clinical outcomes of reperfusion therapies at TSCs, primary stroke centers (PSCs), and comprehensive stroke centers (CSCs) have not been well delineated. METHODS: We conducted a retrospective, observational, cohort study from 2018 to 2020 that included patients with acute ischemic stroke who received endovascular thrombectomy (EVT) and intravenous thrombolysis reperfusion therapies at CSCs, TSCs, or PSCs. Participants were recruited from Get With The Guidelines-Stroke registry. Study end points included timeliness of intravenous thrombolysis and EVT, successful reperfusion, discharge destination, discharge mortality, and functional independence at discharge. RESULTS: Among 84 903 patients, 48 682 received EVT, of whom 73% were treated at CSCs, 22% at PSCs, and 4% at TSCs. The median annual EVT volume was 76 for CSCs, 55 for TSCs, and 32 for PSCs. Patient differences by center status included higher National Institutes of Health Stroke Scale score, longer onset-to-arrival time, and higher transfer-in rates for CSCs, TSCs, and PSCs, respectively. In adjusted analyses, the likelihood of achieving the goal door-to-needle time was higher in CSCs compared with PSCs (odds ratio [OR], 1.39 [95% CI, 1.17-1.66]) and in TSCs compared with PSCs (OR, 1.45 [95% CI, 1.08-1.96]). Likewise, the odds of achieving the goal door-to-puncture time were higher in CSCs compared with PSCs (OR, 1.58 [95% CI, 1.13-2.21]). CSCs and TSCs also demonstrated better clinical efficacy outcomes compared with PSCs. The odds of discharge to home or rehabilitation were higher in CSCs compared with PSCs (OR, 1.18 [95% CI, 1.06-1.31]), whereas the odds of in-hospital mortality or discharge to hospice were lower in both CSCs compared with PSCs (OR, 0.87 [95% CI, 0.81-0.94]) and TSCs compared with PSCs (OR, 0.86 [95% CI, 0.75-0.98]). There were no significant differences in any of the quality-of-care metrics and clinical outcomes between TSCs and CSCs. CONCLUSIONS: In this study representing national US practice, CSCs and TSCs exceeded PSCs in key quality-of-care reperfusion metrics and outcomes, whereas TSCs and CSCs demonstrated a similar performance. With more than one-fifth of all EVT procedures during the study period conducted at PSCs, it may be desirable to explore national initiatives aimed at facilitating the elevation of eligible PSCs to a higher certification status.