Evidential deep learning for trustworthy prediction of enzyme commission number.

The rapid growth of uncharacterized enzymes and their functional diversity urge accurate and trustworthy computational functional annotation tools. However, current state-of-the-art models lack trustworthiness on the prediction of the multilabel classification problem with thousands of classes. Here, we demonstrate that a novel evidential deep learning model (named ECPICK) makes trustworthy predictions of enzyme commission (EC) numbers with data-driven domain-relevant evidence, which results in significantly enhanced predictive power and the capability to discover potential new motif sites. ECPICK learns complex sequential patterns of amino acids and their hierarchical structures from 20 million enzyme data. ECPICK identifies significant amino acids that contribute to the prediction without multiple sequence alignment. Our intensive assessment showed not only outstanding enhancement of predictive performance on the largest databases of Uniprot, Protein Data Bank (PDB) and Kyoto Encyclopedia of Genes and Genomes (KEGG), but also a capability to discover new motif sites in microorganisms. ECPICK is a reliable EC number prediction tool to identify protein functions of an increasing number of uncharacterized enzymes.

Dilated perivascular spaces and steno-occlusive changes in children and adults with moyamoya disease.

BACKGROUND: Dilated perivascular spaces (DPVS), known as one of imaging markers in cerebral small vessel disease, may be found in patients with moyamoya disease (MMD). However, little is known about DPVS in MMD. The purpose of this study was to investigate the distribution pattern of dPVS in children and adults with MMD and determine whether it is related to steno-occlusive changes of MMD. METHODS: DPVS was scored in basal ganglia (BG) and white matter (WM) on T2-weighted imaging, using a validated 4-point semi-quantitative score. The degree of dPVS was classified as high (score > 2) or low (score ≤ 2) grade. The steno-occlusive changes on MR angiography (MRA) was scored using a validated MRA grading. Asymmetry of DPVS and MRA grading was defined as a difference of 1 grade or higher between hemispheres. RESULTS: Fifty-one patients with MMD (mean age 24.9 ± 21.1 years) were included. Forty-five (88.2%) patients had high WM-DPVS grade (degree 3 or 4). BG-DPVS was found in 72.5% of all patients and all were low grade (degree 1 or 2). The distribution patterns of DPVS degree in BG (P = 1.000) and WM (P = 0.767) were not different between child and adult groups. The asymmetry of WM-DPVS (26%) and MRA grade (42%) were significantly correlated to each other (Kendall's tau-b = 0.604, P < 0.001). CONCLUSIONS: DPVS of high grade in MMD is predominantly found in WM, which was not different between children and adults. The correlation between asymmetry of WM-DPVS degree and MRA grade suggests that weak cerebral artery pulsation due to steno-occlusive changes may affect WM-DPVS in MMD.

Chemical Constituents of Halophyte Suaeda glauca and Their Therapeutic Potential for Hair Loss.

Suaeda glauca, a halophyte in the Amaranthaceae family, exhibits remarkable resilience to high salt and alkali stresses despite the absence of salt glands or vesicles in its leaves. While there is growing pharmacological interest in S. glauca, research on its secondary metabolites remains limited. In this study, chemical constituents of the aerial parts of S. glauca were identified using 1D- and 2D-NMR experiments, and its biological activity concerning hair loss was newly reported. Eight compounds, including alkaloids (1~3), flavonoids (4~6), and phenolics (7 and 8), were isolated. The compounds, except the flavonoids, were isolated for the first time from S. glauca. In the HPLC chromatogram, quercetin-3-O-ß-d-glucoside, kaempferol-3-O-ß-d-glucoside, and kaempferol were identified as major constituents in the extract of S. glauca. Additionally, the therapeutic potential of the extract of S. glauca and the isolated compounds 1~8 on the expressions of VEGF and IGF-1, as well as the regulation of Wnt/ß-catenin signaling, were evaluated in human follicle dermal papilla cells (HFDPCs) and human umbilical vein endothelial cells (HUVECs). Among the eight compounds, compound 4 was the most potent in terms of increasing the expression of VEGF and IGF-1 and the regulation of Wnt/ß-catenin. These findings suggest that S. glauca extract and its compounds are potential new candidates for preventing or treating hair loss.

Papilledema and venous stasis in patients with cerebral venous and sinus thrombosis.

BACKGROUND: Cerebral venous and sinus thrombosis (CVST) can cause increased intracranial pressure, often leading to papilledema. In this study, we investigated the association between papilledema and venous stasis on susceptibility weighted imaging (SWI) in CVST. METHODS: Patients with CVST between 2008 and 2020 were reviewed. Patients without fundoscopic examination or SWI were excluded in this study. Venous stasis was evaluated and scored for each cerebral hemisphere: each hemisphere was divided into 5 regions according to the venous drainage territories (superior sagittal sinus, Sylvian veins, transverse sinus and vein of Labbé, deep cerebral veins, and medullary veins) and 1 point was added if venous prominence was confirmed in one territory on SWI. The venous stasis score on SWI between cerebral hemispheres with and without papilledema was compared. RESULTS: Eight of 19 patients with CVST were excluded because of the absence of fundoscopic examination or SWI. Eleven patients (26.5 ± 2.1 years) were included in this study. Papilledema was identified in 6 patients: bilateral papilledema in 4 patients and unilateral papilledema in 2 patients. The venous stasis score on SWI was significantly higher (P = 0.013) in the hemispheres with papilledema (median, 4.0; 95% CI, 3.038-4.562) than in the hemispheres without papilledema (median, 2.5; 95% CI, 0.695-2.805). CONCLUSIONS: This study shows that higher score of venous stasis on SWI is associated with papilledema. Therefore, the venous stasis on SWI may be an imaging surrogate marker of increased intracranial pressure in patients with CVST.

On-Demand Scheduling of Command and Responses for Low-Power Multihop Wireless Networks.

Many IoT applications require a mechanism to disseminate commands and collect responses over a wireless network in order to control and collect data from multiple embedded devices. However, severe collisions may occur if a large number of nodes attempt to respond simultaneously and promptly, not only among the responses, but also with the dissemination of commands. This is because low-power wireless network protocols for dissemination and collection have been designed separately. Tuning the parameters of one side of the protocol has clear trade-off between reliability and latency. To address this challenge, we propose SCoRe, an on-demand scheme for joint scheduling of command and responses on multihop low-power wireless networks to improve both reliability and latency simultaneously at runtime. SCoRe gathers the amount of time required by network nodes for dissemination and collection, and allocates relative timeslots to each node recursively over multihop on-demand when (and only when) disseminating a command. While doing so, information exchange occurs only between local neighbor nodes without a need for global routing table nor time synchronization. We implement SCoRe on a low-power embedded platform, and compare with well-known dissemination and collection schemes through both simulations and testbed experiments on 30 devices. Our evaluation results show that SCoRe can improve both latency and reliability without tuning the parameters for one metric, while the legacy schemes require careful parameter selection to match only one side of SCoRe, never both.

Subvoxel vascular imaging of the midbrain using USPIO-Enhanced MRI.

There is an urgent need for better detection and understanding of vascular abnormalities at the micro-level, where critical vascular nourishment and cellular metabolic changes occur. This is especially the case for structures such as the midbrain where both the feeding and draining vessels are quite small. Being able to monitor and diagnose vascular changes earlier will aid in better understanding the etiology of the disease and in the development of therapeutics. In this work, thirteen healthy volunteers were scanned with a dual echo susceptibility weighted imaging (SWI) sequence, with a resolution of 0.22 â€‹× â€‹0.44 â€‹× â€‹1 â€‹mm3 at 3T. Ultra-small superparamagnetic iron oxides (USPIO) were used to induce an increase in susceptibility in both arteries and veins. Although the increased vascular susceptibility enhances the visibility of small subvoxel vessels, the accompanying strong signal loss of the large vessels deteriorates the local tissue contrast. To overcome this problem, the SWI data were acquired at different time points during a gradual administration (final concentration â€‹= â€‹4 â€‹mg/kg) of the USPIO agent, Ferumoxytol, and the data was processed to combine the SWI data dynamically, in order to see through these blooming artifacts. The major vessels and their tributaries (such as the collicular artery, peduncular artery, peduncular vein and the lateral mesencephalic vein) were identified on the combined SWI data using arterio-venous maps. Dynamically combined SWI data was then compared with previous histological work to validate that this protocol was able to detect small vessels on the order of 50 â€‹µm-100 â€‹µm. A complex division-based phase unwrapping was also employed to improve the quality of quantitative susceptibility maps by reducing the artifacts due to aliased voxels at the vessel boundaries. The smallest detectable vessel size was then evaluated by revisiting numerical simulations, using estimated true susceptibilities for the basal vein and the posterior cerebral artery in the presence of Ferumoxytol. These simulations suggest that vessels as small as 50 â€‹µm should be visible with the maximum dose of 4 â€‹mg/kg.

Iterative K-Closest Point Algorithms for Colored Point Cloud Registration.

We present two algorithms for aligning two colored point clouds. The two algorithms are designed to minimize a probabilistic cost based on the color-supported soft matching of points in a point cloud to their K-closest points in the other point cloud. The first algorithm, like prior iterative closest point algorithms, refines the pose parameters to minimize the cost. Assuming that the point clouds are obtained from RGB-depth images, our second algorithm regards the measured depth values as variables and minimizes the cost to obtain refined depth values. Experiments with our synthetic dataset show that our pose refinement algorithm gives better results compared to the existing algorithms. Our depth refinement algorithm is shown to achieve more accurate alignments from the outputs of the pose refinement step. Our algorithms are applied to a real-world dataset, providing accurate and visually improved results.

Functional Elements Coatings on Ti-6Al-4V Alloy by Plasma Electrolytic Oxidation for Biomaterials.

In this study, functional elements coatings on Ti-6Al-4V alloy by plasma electrolytic oxidation for biomaterials were studied using various experimental techniques. For this study, Ti-6Al-4V ELI disk (grade 5, Timet Co. Ltd., Japan diameter; 10 mm) were used as the substrate for PEO treatment in the electrolyte containing Ca, P, Si, Zn, and Mn ions. The PEO treatment was performed using a pulsed DC power supply at 280 V for 3 min. The PEO-treated surface was observed with field-emission scanning electron microscope (FE-SEM), and energy dispersive X-ray spectrometry (EDS; Oxford ISIS 310, England), Image Analyzer software, and X-ray diffractometer (TF-XRD, X'pert Philips, Netherlands). The number of pores increases, as the Zn ion content increases. And the number of pores decrease, as the Mn ion content increases. The addition of Zn and Mn ions affects the number and size of pores and the area occupied by the pores. Mn and Zn are distributed around pores and in the pores. Anatase and rutile peaks appear and the HA peak shifted to the left in the case of Mn and Zn ion additions.

Lymphocyte-to-monocyte ratio on day 7 is associated with outcomes in acute ischemic stroke.

The main features of stroke-induced immunosuppression are lymphopenia and deactivation of monocytes in peripheral blood. We hypothesized that lymphocyte-to-monocyte ratio (LMR) in peripheral blood may represent the degree of stroke-induced immunosuppression. To prove this hypothesis, we evaluated whether LMR is associated with risk of post-stroke infection and clinical outcome at 3 months in patients with acute ischemic stroke. We selected patients with stroke in anterior circulation within 24 h from onset. Peripheral blood sampling for differential blood count was performed on days 1 and 7. The LMRs on days 1 and 7 were analyzed to determine associations with excellent outcomes (modified Rankin Scale of score 0-1 at 3 months). One hundred and two patients were included. The initial National Institutes of Health Stroke Scale score (adjusted odd ratio [OR] 0.89; 95% confidence interval [CI], 0.83-0.95; P = 0.001) and LMR on day 7 (adjusted OR 1.49; 95% CI, 1.09-2.02; P = 0.011) were associated with excellent outcomes. LMRs on day 1 were significantly lower in stroke patients with pneumonia (P = 0.007) and pneumonia or urinary tract infection (P = 0.012) than those without infections. LMRs on day 7 were also significantly lower in stroke patients with infection (P = 0.005 in pneumonia, P = 0.003 in urinary tract infection, and P < 0.001 in pneumonia or urinary tract infection) than those without infections. Lower LMRs on day 7 are associated with worse outcomes at 3 months after stroke onset. LMR may be a useful marker for assessing the stroke-induced immunosuppression.

Acute Transient Vestibular Syndrome: Prevalence of Stroke and Efficacy of Bedside Evaluation.

BACKGROUND AND PURPOSE: The aim of this study was to determine the prevalence of stroke and efficacy of bedside evaluation in diagnosing stroke in acute transient vestibular syndrome (ATVS). METHODS: We performed a prospective, single-center, observational study that had consecutively recruited 86 patients presenting with ATVS to the emergency department of Pusan National University Yangsan Hospital from January to December 2014. All patients received a constructed evaluation, including HINTS plus (head impulse, nystagmus patterns, test of skew, and finger rubbing) and brain magnetic resonance imagings. Patients without an obvious cause further received perfusion-weighted imaging. Multivariable logistic regression was used to determine clinical parameters to identify stroke in ATVS. RESULTS: The prevalence of stroke was 27% in ATVS. HINTS plus could not be applied to the majority of patients because of the resolution of the vestibular symptoms, and magnetic resonance imagings were falsely negative in 43% of confirmed strokes. Ten patients (12%) showed unilateral cerebellar hypoperfusion on perfusion-weighted imaging without an infarction on diffusion-weighted imaging, and 8 of them had a focal stenosis or hypoplasia of the corresponding vertebral artery. The higher risk of stroke in ATVS was found in association with craniocervical pain (odds ratio, 9.6; 95% confidence interval, 2.0-45.2) and focal neurological symptoms/signs (odds ratio, 15.2; 95% confidence interval, 2.5-93.8). CONCLUSIONS: Bedside examination and routine magnetic resonance imagings have a limitation in diagnosing strokes presenting with ATVS, and perfusion imaging may help to identify strokes in ATVS of unknown cause. Associated craniocervical pain and focal neurological symptoms/signs are the useful clues for strokes in ATVS.

A Case of Contrast Leakage Mimicking Intraventricular Hemorrhage in a Patient with Intravenous Thrombolysis.

Contrast leakage on non-enhanced brain computed tomography (CT) is a common phenomenon after diagnostic or interventional cerebral angiography in patients with acute ischemic stroke. Contrast leakage is known to be related to the loosening of the blood-brain barrier. Sometimes, the contrast leakage on non-enhanced brain CT has been mistaken for intracranial hemorrhage. Differentiating the contrast leakage from the intracranial hemorrhage on non-enhanced brain CT is a very important issue, because subsequent treatment after intravenous thrombolysis (IVT) or intra-arterial thrombolysis would depend on the result of brain CT after thrombolysis. Recently, we experienced a case of contrast leakage mimicking intraventricular hemorrhage in a patient with IVT. The contrast leakage into the lateral ventricles after IVT is not a common phenomenon. We describe here our case.

Total mismatch of diffusion-weighted imaging and susceptibility-weighted imaging in patients with acute cerebral ischemia.

BACKGROUND AND PURPOSE: Multiple hypointense vessels (MHV) on susceptibility-weighted imaging (SWI) is associated with an increased oxygen demand in acute cerebral ischemia. Occasionally, some patients exhibit extensive MHV on SWI despite of negative diffusion-weighted imaging (DWI), which is a phenomenon called total mismatch DWI-SWI. We analyzed the clinical characteristics and imaging findings in patients with the total DWI-SWI mismatch. MATERIALS AND METHODS: We selected patients with total DWI-SWI mismatch who underwent MRI within 12hours from onset. To evaluate the degree of collateral flow, we graded vessels on post-contrast time-of-flight MR angiography as 3 groups. Perfusion lesion volume was measured using threshold of>6seconds of mean transit time on perfusion-weighted imaging. RESULTS: Total DWI-SWI mismatch was found in 10 (2.7%) out of 370 patients. Four out of 10 patients were excluded due to lack of data on perfusion studies. Hence 6 patients were finally selected in the study. Two patients with internal carotid artery dissection were treated with emergent stenting, one patient with intravenous thrombolysis and mechanical thrombectomy, and two patients with drug-induced hypertension. All of the enrolled patients exhibited extensive MHV on SWI and good collateral flows. The mean perfusion lesion volume was 72.6±15.3ml (range 0-325.0ml). Clinical outcome was favorable in all of the patients (mRS at 3 months, 0). CONCLUSIONS: Our results demonstrate that total mismatch of DWI-SWI is associated with good collateral flow and may be a predictor of good response to treatment in patients with acute cerebral ischemia.

Neuroanatomical correlation of urinary retention in lateral medullary infarction.

We prospectively recruited 10 patients who presented with urinary retention as a neurological deficit that was attributable to lateral medullary infarction. Of these, 9 patients underwent a urodynamic study, which demonstrated detrusor underactivity of the bladder in 7 patients. Urinary retention developed mainly when the lesions involved the lateral tegmentum of the middle or caudal medulla. We concluded that interruption of the descending pathway from the pontine micturition center to the sacral spinal cord in the lateral medulla was responsible for the development of urinary retention.

Anatomical study of the articular branch of the lateral pectoral nerve to the shoulder joint.

PURPOSE: The purpose of this study was to document the distribution of the articular branch of the lateral pectoral nerve (LPN) to the shoulder and to identify a suitable point for its blockade. METHODS: This study involved the dissection of 43 shoulders of 22 unembalmed cadavers (6 male and 16 female) to identify the LPN and its articular branch to the shoulder. To identify the suitable anatomical point for blocking the articular branch of the LPN, several anatomical landmarks around the shoulder were measured. RESULTS: The articular branch of the LPN to the shoulder was present in 29 of 43 cases (67.4 %). The appropriate point to block the articular branch of the LPN was identified at a mean distance of 1.5 cm below the clavicle, on the line connecting the closest points between the clavicle and the coracoid process, and at a mean depth of 1.0 cm from the skin. CONCLUSION: The articular branch of the LPN to the shoulder, as well as the muscular and cutaneous branches of the LPN, covers a portion of the shoulder joint with suprascapular and axillary nerves. Surgeons might consider a peripheral block of the suprascapular, axillary, and LPNs to provide maximum block coverage after shoulder joint surgery.

A Case of Complete Recovery of Fluctuating Monocular Blindness Following Endovascular Treatment in Internal Carotid Artery Dissection.

BACKGROUND: Monocular blindness may appear as the first symptom of internal carotid artery dissection (ICAD). However, there have been no reports that monocular visual loss repeatedly occurs and disappears in response to postural change in ICAD. METHODS: A 33-year-old woman presented with transient monocular blindness (TMB) following acute-onset headache. TMB repeatedly occurred in response to postural change. Two days later, she experienced transient dysarthria and right hemiparesis in upright position. Pupil size and light reflex were normal, but a relative afferent pupillary defect was positive in the left eye. Diffusion-weighted imaging showed no acute lesion, but perfusion-weighted imaging showed perfusion delay in the left ICA territory. Digital subtraction angiography demonstrated a false lumen and an intraluminal filling defect in proximal segment of the left ICA. RESULTS: Carotid stenting was performed urgently. After carotid stenting, left relative afferent pupillary defect disappeared and TMB was not provoked anymore by upright posture. At discharge, left visual acuity was completely normalized. CONCLUSIONS: Because fluctuating visual symptoms in the ICAD may be associated with hemodynamically unstable status, assessment of the perfusion status should be done quickly. Carotid stenting may be helpful to improve the fluctuating visual symptoms and hemodynamically unstable status in selected patient with the ICAD.

Susceptibility Vessel Sign for Intra-arterial Thrombus in Acute Posterior Cerebral Artery Infarction.

BACKGROUND: Susceptibility vessel sign (SVS) on susceptibility-weighted imaging (SWI) has a high sensitivity and specificity to detect the intra-arterial thrombus in anterior circulation stroke. However, SVS has not been evaluated in posterior circulation stroke. METHODS: We reviewed the data from patients with acute posterior cerebral artery (PCA) infarction within 24 hours from stroke onset. To elucidate the usefulness of SVS for the detection of intraluminal thrombus in acute PCA infarction, the frequency and location of SVS were compared with those of occlusion on magnetic resonance angiography (MRA) and hyperdense PCA sign on computed tomography (CT). RESULTS: Twenty-five patients with acute PCA infarction were enrolled in the study. The SVS was found in 92% (23 of 25). MRA showed occlusions in 64% (16 of 25). The SVS was identified in 100% (16 of 16) of patients with occlusion on MRA. Patients without occlusion on MRA also showed the SVS in 78% (7 of 9; P = .0233). The positive SVS without occlusion on MRA was mainly identified in patients with occlusion of distal branches of PCA; P3 segment in 4 and P4 segment in 3. However, the hyperdense PCA sign on CT showed in only 8% (2 of 25) of all patients; its sensitivity was significantly lower than those of the SVS on SWI (P < .001). CONCLUSIONS: SWI is more sensitive than MRA for the detection of intraluminal thrombus, especially peripheral one, in patients with acute ischemic stroke of the PCA territory. In addition, irrespective of thrombus location, SWI is significantly superior to CT in detecting thrombus in acute PCA infarction.

Multiple hypointense vessels on susceptibility-weighted imaging in acute ischemic stroke: surrogate marker of oxygen extraction fraction in penumbra?

BACKGROUND: Multiple hypointense vessels (MHV) on susceptibility-weighted imaging (SWI) are frequently observed in patients with acute cerebral ischemia, but their implication has not been clearly established. To elucidate the clinical significance of MHV on SWI, we investigated the association of MHV on SWI with clinical data and other MR markers in patients with acute ischemic stroke. METHODS: We enrolled acute stroke patients with internal carotid or proximal middle cerebral artery occlusion who underwent MRI including SWI within 3 days from stroke onset. Baseline clinical data were reviewed. Stroke severity was measured by the National Institutes of Health Stroke Scale (NIHSS). We graded the degree of MHV on SWI as four groups of none, subtle, relative, or extensive by the modified Alberta Stroke Program Early CT Scan (ASPECTS) system. To evaluate the degree of collateral flow, distal hyperintense vessels (DHV) on FLAIR and vessels on post-contrast time-of-flight MR angiography (TOF MRA) source images were graded respectively as 3 groups: none/subtle/prominent and poor/moderate/good. Diffusion and perfusion lesion volume and diffusion-perfusion mismatch (DPM) ratio were measured in all patients. We analyzed the association of the degree of MHV on SWI with clinical data and MR markers. RESULTS: Eighty patients were included in the study. The mean MR time from stroke onset was 12.4 h (range 0.5-63.0). There is no difference in MR time from stroke onset between groups of MHV on SWI. MHV were observed in 68 (85%) of 80 patients: none in 12, subtle in 11, relative in 13, and extensive in 44. There were no statistically significant associations between MHV on SWI and vascular risk factors. Patients with more extensive MHV on SWI had a smaller diffusion volume (p < 0.001), larger DPM (p < 0.001), and lower initial NIHSS scores (p = 0.022). Prominent DHV was presented in 29 of 44 patients with extensive MHV (p < 0.001). Good collateral flow on TOF MRA source images was presented in 37 of 44 patients with extensive MHV (p < 0.001). CONCLUSIONS: More extensive MHV on SWI in acute ischemic stroke is associated with lower initial NIHSS scores, smaller diffusion lesion volume, better collateral flow, and larger DPM. Our results show the possibility that MHV on SWI may be a useful surrogate marker for predicting increased oxygen extraction fraction and diffusion-perfusion mismatch in acute ischemic hemisphere.

Spontaneous isolated posterior inferior cerebellar artery dissection: rare but underdiagnosed cause of ischemic stroke.

BACKGROUND: Spontaneous isolated posterior inferior cerebellar artery dissection (PICAD) is a very rare cause of ischemic stroke. Clinical and radiologic features of ischemic type of isolated spontaneous PICAD are not well established. METHODS: We consecutively enrolled patients who had spontaneous isolated PICAD confirmed by digital subtraction cerebral angiography. Clinical manifestation, magnetic resonance imaging (MRI), and angiography were analyzed. RESULTS: Seven patients were diagnosed as ischemic type of spontaneous isolated PICAD. Patients experienced an occipital headache, followed by vertigo, postural imbalance, or Wallenberg syndrome. Six showed medullar, unilateral, or bilateral cerebellar infarctions on diffusion-weighted imaging (DWI). One presented with transient cerebellar ischemia and negative on DWI. T1-weighted imaging showed high signal intensity in posterior inferior cerebellar artery in only 1 patient. Susceptibility-weighted imaging (SWI) revealed hypointense signal with blooming effect in posterior inferior cerebellar artery in 5 patients. The modified Rankin Scale score at 3 months was 0 or 1 in all patients. CONCLUSIONS: Clinical manifestations in ischemic type of spontaneous isolated PICAD were similar to those of intracranial vertebral artery dissection. Clinical course was relatively stable and benign. SWI was more helpful to suspect abnormality of posterior inferior cerebellar artery than conventional MRI or magnetic resonance angiography in our small series. Cerebral angiography is recommended in patients with clinically suspected spontaneous isolated PICAD for definite diagnosis.

The driving of North American climate extremes by North Pacific stationary-transient wave interference.

Wave interference between transient waves and climatological stationary waves is a useful framework for diagnosing the magnitude of stationary waves. Here, we find that the wave interference over the North Pacific Ocean is an important driver of North American wintertime cold and heavy precipitation extremes in the present climate, but that this relationship is projected to weaken under increasing greenhouse gas emissions. When daily circulation anomalies are in-phase with the climatological mean state, the anomalous transport of heat and moisture causes the enhanced occurrence of cold extremes across the continental U.S. and a significant decrease of heavy precipitation extremes in the western U.S. In a future emissions scenario, the climatological stationary wave over the eastern North Pacific weakens and shifts spatially, which alters and generally weakens the relationship between wave interference and North American climate extremes. Our results underscore that the prediction of changes in regional wave interference is pivotal for understanding the future regional climate variability.

Oxidative photocatalysis on membranes triggers non-canonical pyroptosis.

Intracellular membranes composing organelles of eukaryotes include membrane proteins playing crucial roles in physiological functions. However, a comprehensive understanding of the cellular responses triggered by intracellular membrane-focused oxidative stress remains elusive. Herein, we report an amphiphilic photocatalyst localised in intracellular membranes to damage membrane proteins oxidatively, resulting in non-canonical pyroptosis. Our developed photocatalysis generates hydroxyl radicals and hydrogen peroxides via water oxidation, which is accelerated under hypoxia. Single-molecule magnetic tweezers reveal that photocatalysis-induced oxidation markedly destabilised membrane protein folding. In cell environment, label-free quantification reveals that oxidative damage occurs primarily in membrane proteins related to protein quality control, thereby aggravating mitochondrial and endoplasmic reticulum stress and inducing lytic cell death. Notably, the photocatalysis activates non-canonical inflammasome caspases, resulting in gasdermin D cleavage to its pore-forming fragment and subsequent pyroptosis. These findings suggest that the oxidation of intracellular membrane proteins triggers non-canonical pyroptosis.