The challenges of developing neuromorphic vision systems inspired by the human eye come not only from how to recreate the flexibility, sophistication, and adaptability of animal systems, but also how ...to do so with computational efficiency and elegance. Similar to biological systems, these neuromorphic circuits integrate functions of image sensing, memory and processing into the device, and process continuous analog brightness signal in real-time. High-integration, flexibility and ultra-sensitivity are essential for practical artificial vision systems that attempt to emulate biological processing. Here, we present a flexible optoelectronic sensor array of 1024 pixels using a combination of carbon nanotubes and perovskite quantum dots as active materials for an efficient neuromorphic vision system. The device has an extraordinary sensitivity to light with a responsivity of 5.1 × 10
A/W and a specific detectivity of 2 × 10
Jones, and demonstrates neuromorphic reinforcement learning by training the sensor array with a weak light pulse of 1 μW/cm
.
Several studies have compared the molecular responses between e14a2 and e13a2 BCR::ABL1 transcripts in chronic myeloid leukemia (CML) patients treated with front‐line imatinib, but there were very ...limited studies on nilotinib or dasatinib‐treated patients. We retrospectively analyzed the molecular responses in 1124 CML patients with the e14a2 or e13a2 transcript receiving front‐line imatinib, nilotinib or dasatinib treatment. Patients with the e14a2 transcript had higher optimal response rates than those with the e13a2 transcript at 12 months in the imatinib‐treated group, and 6 and 12 months in the nilotinib‐treated group. The optimal response rates were not significantly different between the two transcripts in the dasatinib‐treated group at landmark molecular responses. With a median follow‐up time of 48.4 months, higher cumulative incidences of BCR::ABL1 International Scale ≤1% and major molecular response were observed in patients with the e14a2 rather than the e13a2 transcript receiving front‐line imatinib or nilotinib treatment, but not in dasatinib‐treated patients. The progression‐free survival and overall survival did not differ between the two transcripts in all three treatment groups. In view of the speed and depth of molecular responses, BCR::ABL1 transcript subtypes might provide helpful information in selecting a front‐line tyrosine kinase inhibitor for individual young patients with future potential treatment‐free remission.
Patients with e14a2 transcript had higher optimal response rates than e13a2 transcript at 12 months in the imatinib‐treated group, 6 and 12 months in the nilotinib‐treated group. The optimal response rates between the 2 transcripts were similar in the dasatinib‐treated group at landmark molecular responses. In view of the speed and depth of molecular responses, BCR::ABL1 transcript subtypes might provide helpful information in selecting a front‐line tyrosine kinase inhibitor for individual young patients with future potential treatment‐free remission.
The efficacy and safety of maternal tenofovir disoproxil fumarate (TDF) in reducing mother‐to‐infant hepatitis B virus (HBV) transmissions is not clearly understood. We conducted a prospective, ...multicenter trial and enrolled 118 hepatitis B surface antigen (HBsAg)– and hepatitis B e antigen–positive pregnant women with HBV DNA ≥7.5 log10 IU/mL. The mothers received no medication (control group, n = 56, HBV DNA 8.22 ± 0.39 log10 IU/mL) or TDF 300 mg daily (TDF group, n = 62, HBV DNA 8.18 ± 0.47 log10 IU/mL) from 30‐32 weeks of gestation until 1 month postpartum. Primary outcome was infant HBsAg at 6 months old. At delivery, the TDF group had lower maternal HBV DNA levels (4.29 ± 0.93 versus 8.10 ± 0.56 log10 IU/mL, P < 0.0001). Of the 121/123 newborns, the TDF group had lower rates of HBV DNA positivity at birth (6.15% versus 31.48%, P = 0.0003) and HBsAg positivity at 6 months old (1.54% versus 10.71%, P = 0.0481). Multivariate analysis revealed that the TDF group had lower risk (odds ratio = 0.10, P = 0.0434) and amniocentesis was associated with higher risk (odds ratio 6.82, P = 0.0220) of infant HBsAg positivity. The TDF group had less incidence of maternal alanine aminotransferase (ALT) levels above two times the upper limit of normal for ≥3 months (3.23% versus 14.29%, P = 0.0455), a lesser extent of postpartum elevations of ALT (P = 0.007), and a lower rate of ALT over five times the upper limit of normal (1.64% versus 14.29%, P = 0.0135) at 2 months postpartum. Maternal creatinine and creatinine kinase levels, rates of congenital anomaly, premature birth, and growth parameters in infants were comparable in both groups. At 12 months, one TDF‐group child newly developed HBsAg positivity, presumably due to postnatal infection and inefficient humoral responses to vaccines. Conclusions: Treatment with TDF for highly viremic mothers decreased infant HBV DNA at birth and infant HBsAg positivity at 6 months and ameliorated maternal ALT elevations. (Hepatology 2015;62:375–386
Objective
Distal clavicle fracture classification directly affects the treatment decisions. It is unclear whether the classification systems implemented differ depending on surgeons' backgrounds. ...This study aimed to compare the interobserver agreement of four classification systems used for lateral clavicle fractures by shoulder specialists and general trauma surgeons.
Methods
Radiographs of 20 lateral clavicle fractures representing a full spectrum of adult fracture patterns were analyzed by eight experienced shoulder specialists and eight general trauma surgeons from 10 different hospitals. All cases were graded according to the Orthopedic Trauma Association (OTA), Neer, Jäger/Breitner, and Gongji classification systems. To measure observer agreement, Fleiss' kappa coefficient (κ) was applied and assessed.
Results
When only X‐ray films were presented, both groups achieved fair agreement. However, when the 3D‐CT scan images were provided, improved interobserver agreement was found in the specialist group when the OTA, Jäger/Breitner, and Gongji classification systems were used. In the generalist groups, improved agreement was found when using the Gongji classification system. In terms of interobserver reliability, the OTA, Neer, and Jäger/Breitner classification systems showed better agreement among shoulder specialists, while a slightly lower level of agreement was found using the Gongji classification system. For the OTA classification system, interobserver agreement had a mean kappa value of 0.418, ranging from 0.446 (specialist group) to 0.402 (generalist group). For the Neer classification system, interobserver agreement had a mean kappa value of 0.368, ranging from 0.402 (specialist group) to 0.390 (generalist group). For the Jäger/Breitner classification system, the inter‐observer agreement had a mean kappa value of 0.380, ranging from 0.413 (specialist group) to 0.404 (generalist group). For the Gongji classification system, interobserver agreement had a mean kappa value of 0.455, ranging from 0.480 (specialist group) to 0.485 (generalist group).
Conclusion
Generally speaking, 3D‐CT scans provide a richer experience that can lead to better results in most classification systems of lateral clavicle fractures, highlighting the value of digitization and specialization in diagnosis and treatment. Competitive interobserver agreement was exhibited in the generalist group using the Gongji classification system, suggesting that the Gongji classification is suitable for general trauma surgeons who are not highly experienced in the shoulder field.
A smartphone‐based survey was designed to verify the difference in therapeutic experience between shoulder specialists and general trauma surgeons and to compare the interobserver agreement of four classification systems for lateral clavicle fractures between these two groups of surgeons. The results showed that, when only the X‐ray films were presented, both groups achieved fair agreement. However, when the 3D‐CT scan images were provided, improved interobserver agreement was found in specialists group using the OTA, Jäger/Breitner, and Gongji classification systems and in generalist group using Gongji classification system. The interobserver reliability of the OTA, the Neer, and the Jäger/Breitner classification system showed a better agreement in shoulder specialists, while a competitive agreement between the two groups were found in the Gongji classification system, which may possibly suggest that the Gongji classification is more easy to grasp for general trauma surgeons who are not highly experienced in shoulder field.
The Xing'an‐Inner Mongolia accretionary belt in the southeastern segment of the Central Asian Orogenic Belt (CAOB) was produced by the long‐lived subduction and eventual closure of the Paleo‐Asian ...Ocean and by the convergence between the North China Craton and the Mongolian microcontinent. Two ophiolite belts have been recognized: the northern Erenhot‐Hegenshan‐Xi‐Ujimqin ophiolite belt and the southern Solonker‐Linxi ophiolite belt. Most basalts in the northern ophiolite belt exhibit characteristics of normal‐type to enriched‐type mid‐ocean ridge basalt affinities with depleted Nd isotopic composition (εNd(t) > +5), comparable to modern Eastern Pacific mid‐ocean ridge basalts. Most basaltic rocks in the southern belt show clear geochemical features of suprasubduction zone‐type oceanic crust, probably formed in an arc/back‐arc environment. The inferred back‐arc extension along the Solonker‐Linxi belt started at circa 280 Ma. Statistics of all the available age data for the ophiolites indicates two cycles of seafloor spreading/subduction, which gave rise to two main epochs of magmatic activity at 500–410 Ma and 360–220 Ma, respectively, with a gap of ~50 million years (Myr). The spatial and temporal distribution of the ophiolites and concurrent igneous rocks favor bilateral subduction toward the two continental margins in the convergence history, with final collision at ~230–220 Ma. In the whole belt, signals of continental collision and Himalayan‐style mountain building are lacking. We thus conclude that the Xing'an‐Inner Mongolia segment of the CAOB experienced two cycles of seafloor subduction, back‐arc extension, and final “Appalachian‐type” soft collision.
Key Points
Ophiolite in the XIMAB of the CAOB formed in both ocean and subduction settings
Ophiolite and associated magmatism reveal two cycles of accretionary events
The XIMAB experienced soft “Appalachian‐type” collision
As a rapidly growing family of 2D transition metal carbides and nitrides, MXenes are recognized as promising materials for the development of future electronics and optoelectronics. So far, the ...reported patterning methods for MXene films lack efficiency, resolution, and compatibility, resulting in limited device integration and performance. Here, a high‐performance MXene image sensor array fabricated by a wafer‐scale combination patterning method of an MXene film is reported. This method combines MXene centrifugation, spin‐coating, photolithography, and dry‐etching and is highly compatible with mainstream semiconductor processing, with a resolution up to 2 µm, which is at least 100 times higher than other large‐area patterning methods reported previously. As a result, a high‐density integrated array of 1024‐pixel Ti3C2Tx/Si photodetectors with a detectivity of 7.73 × 1014 Jones and a light–dark current ratio (Ilight/Idark) of 6.22 × 106, which is the ultrahigh value among all reported MXene‐based photodetectors, is fabricated. This patterning technique paves a way for large‐scale high‐performance MXetronics compatible with mainstream semiconductor processes.
MXenes are promising for future electronics and optoelectronics; however, previously reported patterning methods lack efficiency, resolution, and compatibility with mainstream semiconductor processing. Here, a wafer‐scale combination patterning method with a resolution up to the micrometer scale is developed, resulting in an integrated array of 1024‐pixel Ti3C2Tx/Si photodetectors with a record‐high detectivity of 7.73 × 1014 Jones.
Metastasis in breast cancer usually lead to the majority of deaths on clinical patients. Accordingly, diagnosis of metastasis at the early stage in breast cancer is important to improve the ...prognosis. We observed that Dicer protein levels are significant decrease in highly invasive breast cancer cells and usually correlated with poor clinical outcomes. Following, we aim to clarify the molecular regulatory mechanism of this phenomenon in breast cancer to provide a new therapeutic target. In this study, we obtained that Dicer expression correlated with metastasis and invasion without affect cell stability in breast cancer cells. Importantly, we identified the regulatory mechanism of Dicer protein degradation, the chaperone‐mediated autophagy (CMA)‐mediated degradation that is major mechanism to decrease Dicer protein expression and lead to cancer metastasis. We discovered that heat shock cognate 71‐kDa protein (Hsc70) which as a CMA‐related factor interacts with the CMA‐targeting motif I333A/K334A on Dicer to promote degradation through CMA. Taken together, our findings hint that Dicer highly correlated with cancer metastasis, we reveal the tumor‐promoting effect of CMA‐mediated Dicer degradation in breast cancer.
Background
Dysregulated bile acid (BA) metabolism has been linked to steatosis, inflammation, and fibrosis in nonalcoholic fatty liver disease (NAFLD).
Aim
To determine whether circulating BA levels ...accurately stage liver fibrosis in NAFLD.
Methods
We recruited 550 Chinese adults with biopsy‐proven NAFLD and varying levels of fibrosis. Ultra‐performance liquid chromatography coupled with tandem mass spectrometry was performed to quantify 38 serum BAs.
Results
Compared to those without fibrosis, patients with mild fibrosis (stage F1) had significantly higher levels of secondary BAs, and increased diastolic blood pressure (DBP), alanine aminotransferase (ALT), body mass index, and waist circumstance (WC). The combination of serum BAs with WC, DBP, ALT, or Homeostatic Model Assessment for Insulin Resistance performed well in identifying mild fibrosis, in men and women, and in those with/without obesity, with AUROCs 0.80, 0.88, 0.75 and 0.78 in the training set (n = 385), and 0.69, 0.80, 0.61 and 0.69 in the testing set (n = 165), respectively. In comparison, the combination of BAs and clinical/biochemical biomarkers performed less well in identifying significant fibrosis (F2‐4). In women and in non‐obese subjects, AUROCs were 0.75 and 0.71 in the training set, 0.65 and 0.66 in the validation set, respectively. However, these AUROCs were higher than those observed for the fibrosis‐4 index, NAFLD fibrosis score, and Hepamet fibrosis score.
Conclusions
Secondary BA levels were significantly increased in NAFLD, especially in those with mild fibrosis. The combination of serum BAs and clinical/biochemical biomarkers for identifying mild fibrosis merits further assessment.
Secondary bile acids were significantly increased in NAFLD, especially in those with mild fibrosis. The combination of serum bile acids and clinical/biochemical biomarkers for identifying mild fibrosis is worthy of further assessment.
The excessive release of glutamate is a critical element in the neuropathology of epilepsy, and bupivacaine, a local anesthetic agent, has been shown to inhibit the release of glutamate in rat ...cerebrocortical nerve terminals. This study investigated whether bupivacaine produces antiseizure and antiexcitotoxic effects using a kainic acid (KA) rat model, an animal model used for temporal lobe epilepsy, and excitotoxic neurodegeneration experiments. The results showed that administering bupivacaine (0.4 mg/kg or 2 mg/kg) intraperitoneally to rats 30 min before intraperitoneal injection of KA (15 mg/kg) increased seizure latency and reduced the seizure score. In addition, bupivacaine attenuated KA-induced hippocampal neuronal cell death, and this protective effect was accompanied by the inhibition of microglial activation and production of proinflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in the hippocampus. Moreover, bupivacaine shortened the latency of escaping onto the platform in the Morris water maze learning performance test. Collectively, these data suggest that bupivacaine has therapeutic potential for treating epilepsy.
While genetic analyses have revealed ~100 risk loci associated with osteoarthritis (OA), only eight have been linked to hand OA. Besides, these studies were performed in predominantly European and ...Caucasian ancestries. Here, we conducted a genome-wide association study in the Han Chinese population to identify genetic variations associated with the disease. We recruited a total of 1136 individuals (n = 420 hand OA-affected; n = 716 unaffected control subjects) of Han Chinese ancestry. We carried out genotyping using Axiom Asia Precisi on Medicine Research Array, and we employed the RegulomeDB database and RoadMap DNase I Hypersensitivity Sites annotations to further narrow down our potential candidate variants. Genetic variants identified were tested in the Geisinger's hand OA cohort selected from the Geisinger MyCode community health initiative (MyCode
). We also performed a luciferase reporter assay to confirm the potential impact of top candidate single-nucleotide polymorphisms (SNPs) on hand OA. We identified six associated SNPs (
-value = 6.76 × 10
-7.31 × 10
) clustered at 2p13.2 downstream of the
gene. The strongest association signal identified was rs883313 (
-value = 6.76 × 10
, odds ratio (OR) = 1.76), followed by rs12713768 (
-value = 1.36 × 10
, OR = 1.74), near or within the enhancer region closest to the
gene. Our findings showed that the major risk-conferring CC haplotype of SNPs rs12713768 and rs10208040 strong linkage disequilibrium (LD); D' = 1, r
= 0.651 drives 18.9% of enhancer expression activity. Our findings highlight that the SNP rs12713768 is associated with susceptibility to and severity of hand OA in the Han Chinese population and that the suggested retinoic acid signaling pathway may play an important role in its pathogenesis.
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