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    Catching Tidal Dwarf Galaxies at a Later Evolutionary Stage with ALFALFA

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    We present deep optical imaging and photometry of four objects classified as “Almost-Dark” galaxies in the Arecibo Legacy Fast Arecibo L-band Feed Array (ALFALFA) survey because of their gas-rich nature and extremely faint or missing optical emission in existing catalogs. They have H i masses of 10 ^7 –10 ^9 M _⊙ and distances of ∼9–100 Mpc. Observations with the WIYN 3.5 m telescope and One Degree Imager reveal faint stellar components with central surface brightnesses of ∼24–25 magarcsec2\mathrm{mag}\,{\mathrm{arcsec}}^{-2} in the g band. We also present the results of H i synthesis observations with the Westerbork Synthesis Radio Telescope. These Almost-Dark galaxies have been identified as possible tidal dwarf galaxies (TDGs) based on their proximity to one or more massive galaxies. We demonstrate that AGC 229398 and AGC 333576 likely have the low dark matter content and large effective radii representative of TDGs. They are located much farther from their progenitors than previously studied TDGs, suggesting they are older and more evolved. AGC 219369 is likely dark matter dominated, while AGC 123216 has a dark matter content that is unusually high for a TDG, but low for a normal dwarf galaxy. We consider possible mechanisms for the formation of the TDG candidates such as a traditional major merger scenario and gas ejection from a high-velocity flyby. Blind H i surveys like ALFALFA enable the detection of gas-rich, optically faint TDGs that can be overlooked in other surveys, thereby providing a more complete census of the low-mass galaxy population and an opportunity to study TDGs at a more advanced stage of their life cycle

    Simultaneous and Sequential Use of Molecular Targeted Agents Plus Immune Checkpoint Inhibitors for Advanced Hepatocellular Carcinoma: A Real-World Practice in China

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    Jing Li,1,2,* Liang Huang,1,* Chao Ge,3,* Xingwu Zhu,1 Maixuan Qiu,1 Chaopan Chen,3 Shaohua Wei,2 Yiqun Yan1 1Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, People’s Republic of China; 2Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 3Department of General Surgery, Ningbo Development Zone Hospital, Ningbo, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yiqun Yan, Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, No. 700 North Moyu Road, Shanghai, 201805, People’s Republic of China, Email [email protected] Shaohua Wei, Department of General Surgery, The Second Affiliated Hospital of Soochow University, No. 1055 Shanxiang Road, Suzhou, 215004, People’s Republic of China, Email [email protected]: Molecular targeted agents (MTAs) plus immune checkpoint inhibitors (ICIs) treatment for advanced hepatocellular carcinoma (HCC) has shown an exciting prospect. This study aimed to report the efficacy of the Simultaneous and Sequential use of them in a real-world practice.Patients and Methods: From April 2019 to December 2020, patients with advanced HCC in three Chinese medical centers receiving MTAs and ICIs as their initial systemic therapy were enrolled. Participants were classified into the Simultaneous group (treated with them simultaneously) and the Sequential group (treated with MTAs initially and added ICIs after tumor progression). Toxicity, tumor response, survival outcomes and prognostic factors were investigated.Results: One hundred and ten consecutive patients participated in the study (64 in the Simultaneous group and 46 in the Sequential group). A total of 93 (84.5%) patients experienced treatment-related adverse events (AEs), of which 55 (85.9%) in the Simultaneous group and 38 (82.6%) in the Sequential group (P=0.19). Grade 3/4 AEs were observed in 9 (8.2%) patients. Patients in the Simultaneous group achieved a higher objective response rate than those in the Sequential group (25.0% vs 4.3%, p=0.04). The median overall survival (OS) of the entire cohort was 14.8 [95% confidence interval (CI): 4.6– 25.5] months and the OS rates at 6 and 12 months were 80.6% and 60.9%, respectively. Patients in the Simultaneous group achieved better survival outcomes than those in the Sequential group, but without statistically significant differences. Child-Pugh 6 scores (HR: 2.97, 95% CI: 1.33– 6.61, P=0.008), tumor number ≤ 3 (HR: 0.18, 95% CI: 0.04– 0.78, P=0.022), extrahepatic metastasis (HR: 3.05, 95% CI: 1.35– 6.87, P=0.007) were independent prognostic factors for survival.Conclusion: The combined treatment of MTAs and ICIs shows good tumor response and survival outcomes with acceptable toxicity for advanced HCC in the real-world practice, in particular when they are applied simultaneously.Keywords: hepatocellular carcinoma, systemic therapy, molecular targeted agents, immune checkpoint inhibitor

    Morphological characteristics and atomic evolution behavior of nanojoints in Ag nanowire interconnect network

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    Ag nanowires (AgNWs) have shown great application value in the field of flexible electronics due to their excellent optical and electrical properties, and the quality of its joints of AgNWs in the thin film network directly plays a key role in its performance. In order to further improve the joint quality of AgNWs under thermal excitation, the thermal welding process and atomic evolution behavior of AgNWs were investigated through a combination of in situ experimental and molecular dynamics simulations. The influence of processing time, temperature, and stress distribution due to spatial arrangement on nanojoints was systematically explored. What is more, the failure mechanisms and their atomic interface behavior of the nanojoints were also investigated

    Bioinspired smooth neuromorphic control for robotic arms

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    Beyond providing accurate movements, achieving smooth motion trajectories is a long-standing goal of robotics control theory for arms aiming to replicate natural human movements. Drawing inspiration from biological agents, whose reaching control networks effortlessly give rise to smooth and precise movements, can simplify these control objectives for robot arms. Neuromorphic processors, which mimic the brain’s computational principles, are an ideal platform to approximate the accuracy and smoothness of biological controllers while maximizing their energy efficiency and robustness. However, the incompatibility of conventional control methods with neuromorphic hardware limits the computational efficiency and explainability of their existing adaptations. In contrast, the neuronal subnetworks underlying smooth and accurate reaching movements are effective, minimal, and inherently compatible with neuromorphic hardware. In this work, we emulate these networks with a biologically realistic spiking neural network for motor control on neuromorphic hardware. The proposed controller incorporates experimentally-identified short-term synaptic plasticity and specialized neurons that regulate sensory feedback gain to provide smooth and accurate joint control across a wide motion range. Concurrently, it preserves the minimal complexity of its biological counterpart and is directly deployable on Intel’s neuromorphic processor. Using the joint controller as a building block and inspired by joint coordination in human arms, we scaled up this approach to control real-world robot arms. The trajectories and smooth, bell-shaped velocity profiles of the resulting motions resembled those of humans, verifying the biological relevance of the controller. Notably, the method achieved state-of-the-art control performance while decreasing the motion jerk by 19% to improve motion smoothness. Overall, this work suggests that control solutions inspired by experimentally identified neuronal architectures can provide effective, neuromorphic-controlled robots

    The effect of dexmedetomidine on expression of neuronal nitric oxide synthase in spinal dorsal cord in a rat model with chronic neuropathic pain

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    Background Neuropathic pain typically refers to the pain caused by somatosensory system injury or diseases, which is usually characterized by ambulatory pain, allodynia, and hyperalgesia. Nitric oxide produced by neuronal nitric oxide synthase (nNOS) in the spinal dorsal cord might serve a predominant role in regulating the algesia of neuropathic pain. The high efficacy and safety, as well as the plausible ability in providing comfort, entitle dexmedetomidine (DEX) to an effective anesthetic adjuvant. The aim of this study was to investigate the effect of DEX on the expression of nNOS in spinal dorsal cord in a rat model with chronic neuropathic pain. Methods Male Sprague Dawley (SD) rats were randomly assigned into three groups: sham operation group (sham), (of the sciatic nerve) operation (CCI) group, and dexmedetomidine (DEX) group. Chronic neuropathic pain models in the CCI and DEX groups were established by sciatic nerve ligation. The thermal withdrawal latency (TWL) was measured on day 1 before operation and on day 1, 3, 7 and 14 after operation. Six animals were sacrificed after TWL measurement on day 7, and 14 days after operation, in each group, the L4–6 segment of the spinal cords was extracted for determination of nNOS expression by immunohistochemistry. Results Compared with the sham group, the TWL threshold was significantly decreased and the expression of nNOS was up-regulated after operation in the CCI and DEX groups. Compared with the CCI grou[, the TWL threshold was significantly increased and the expression of nNOS was significantly down-regulated on day 7 and 14 days after operation in the DEX group. Conclusion Down-regulated nNOS in the spinal dorsal cord is involved in the attenuation of neuropathic pain by DEX

    Binary operations on neuromorphic hardware with application to linear algebraic operations and stochastic equations

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    Non-von Neumann computational hardware, based on neuron-inspired, non-linear elements connected via linear, weighted synapses—so-called neuromorphic systems—is a viable computational substrate. Since neuromorphic systems have been shown to use less power than CPUs for many applications, they are of potential use in autonomous systems such as robots, drones, and satellites, for which power resources are at a premium. The power used by neuromorphic systems is approximately proportional to the number of spiking events produced by neurons on-chip. However, typical information encoding on these chips is in the form of firing rates that unarily encode information. That is, the number of spikes generated by a neuron is meant to be proportional to an encoded value used in a computation or algorithm. Unary encoding is less efficient (produces more spikes) than binary encoding. For this reason, here we present neuromorphic computational mechanisms for implementing binary two’s complement operations. We use the mechanisms to construct a neuromorphic, binary matrix multiplication algorithm that may be used as a primitive for linear differential equation integration, deep networks, and other standard calculations. We also construct a random walk circuit and apply it in Brownian motion simulations. We study how both algorithms scale in circuit size and iteration time

    The association between apparent temperature and psoriasis outpatient visits: a time-series study in Hefei, China

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    Temperature may be an important environmental factor affecting psoriasis. This study aimed to determine the potential association between apparent temperature (AT) and outpatient visits for psoriasis in Hefei, China. Daily psoriasis clinic visits in Hefei were collected from January 1, 2016 to December 31, 2020. A Poisson generalized linear regression model (PGLM) combined with a distributional lagged nonlinear model (DLNM) was used to analyze the impact of AT on psoriasis outpatient visits; the model was adjusted for relative humidity, wind speed, precipitation, PM2.5, NO2, SO2, time trends, Sundays, and holidays. The analyses were stratified by age and sex. A total of 24,351 patients with psoriasis were included in this study. Only a low AT showed a delayed and strong risk effect. Referring to the median AT (16.8 °C), the effect of low AT started at lag 2 days and showed an increasing and then decreasing trend for approximately 5 days; the effect of extreme cold (1st percentile) and cold (5th percentile) peaked at lag 4 days with a relative risk (RR) of 1.117 (95% CI:1.065 to 1.171) and 1.081 (95% CI:1.044 to 1.119), respectively. The effect of mild cold (25th percentile) reached a maximum RR of 1.033 (95% CI:1.017 to 1.048) at lag 6 days. Subgroup analysis showed that low AT risk was more pronounced and longer-lasting in men and individuals aged <45 years. Our study provides evidence that a low AT increases the risk of psoriasis. Men and young people are vulnerable to potential adverse effects. There is a need for enhanced health interventions, medical care, and early warnings for patients

    Quijote-PNG: The Information Content of the Halo Power Spectrum and Bispectrum

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    We investigate how much can be learnt about four types of primordial non-Gaussianity (PNG) from small-scale measurements of the halo field. Using the quijote-png simulations, we quantify the information content accessible with measurements of the halo power spectrum monopole and quadrupole, the matter power spectrum, the halo–matter cross spectrum, and the halo bispectrum monopole. This analysis is the first to include small, nonlinear scales, up to kmax=0.5hMpc1{k}_{\max }=0.5\,{\rm{h}}\,{\mathrm{Mpc}}^{-1} , and to explore whether these scales can break degeneracies with cosmological and nuisance parameters making use of thousands of N -body simulations. We perform all the halo measurements in redshift space with a single sample comprised of all halos with mass >3.2 × 10 ^13 h ^−1 M _⊙ . For local PNG, measurements of the scale-dependent bias effect from the power spectrum using sample variance cancellation provide significantly tighter constraints than measurements of the halo bispectrum. In this case measurements of the small scales add minimal additional constraining power. In contrast, the information on equilateral and orthogonal PNG is primarily accessible through the bispectrum. For these shapes, small-scale measurements increase the constraining power of the halo bispectrum by up to 4×, though the addition of scales beyond k ≈ 0.3 h Mpc ^−1 improves constraints largely through reducing degeneracies between PNG and the other parameters. These degeneracies are even more powerfully mitigated through combining power spectrum and bispectrum measurements. However, even with combined measurements and small-scale information, equilateral non-Gaussianity remains highly degenerate with σ _8 and our bias model

    Imaging Features of COVID-19-Associated Acute Invasive Fungal Rhinosinusitis

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    Background Acute invasive fungal rhinosinusitis (AIFR) is a rare, rapidly progressive, and life-threatening infection involving the nasal cavity and paranasal sinuses. Purpose of this study is to describe imaging features of coronavirus disease-2019 (COVID-19)-associated AIFR. Methods This was a retrospective observational study. Inclusion criteria: (1) post-COVID-19 patients with fungal rhinosinusitis detected on potassium hydroxide smear or histopathology; (2) onset of symptoms (facial pain, dental pain, facial swelling or discoloration, nasal bleed, periorbital swelling, ptosis, redness of eyes, vision loss) less than 4 weeks; and (3) magnetic resonance imaging/computed tomography (MRI/CT) done within 5 days before surgery. Exclusion criteria: (1) cases of sinusitis without a history of previous COVID-19 infection; and (2) cases in whom fungal hyphae were not demonstrated on pathological examination. Noncontrast CT and dedicated MRI sequences were done initially. Site of involvement, unilateral/bilateral involvement, pattern of mucosal thickening, enhancement pattern, periantral invasion, orbital invasion, intracranial involvement, perineural spread, vascular involvement, and bony involvement were recorded. CT and MRI imaging features were compared. Results Analysis of 90 studies (CT and MRI) in 60 patients was done. Most common site of involvement was ethmoid followed by maxillary sinus. Bilateral disease was more common. Mucosal thickening with T2 hypointense septations was seen in 88.4% MRI studies. Periantral and orbital involvement was seen, respectively, in 84.6% and 55.7% cases of MRI. Intracranial involvement was noted in form of meningitis, cerebritis, abscess, infarct, hemorrhage, cavernous sinus, or perineural invasion. Vascular involvement was noted in form of vascular occlusion (n = 3), vascular narrowing (n = 3), and pseudoaneurysm (n = 2). MRI was more sensitive in detecting periantral invasion, deep infratemporal fossa, cavernous sinus involvement, perineural invasion, optic nerve involvement, and vascular occlusion and narrowing, while CT was superior in identification of bony erosions. Conclusion Early recognition of AIFR in post-COVID-19 patients is important to prevent disease-related morbidity/mortality. Several rarely described findings are noted in our series of AIFR, like optic nerve involvement, pituitary fungal abscess, perineural spread, fungal aneurysms, and arteritis-related posterior circulation infarcts. MRI is superior for early detection of disease and in estimation of extent of disease, compared with CT. Imaging can help in early detection of AIFR, which has a significant impact on patient outcome

    High-resolution esophageal manometry in children

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    Functional disorders of the esophagus are known as esophageal dysmotility disorders. Esophageal manometry can be used to study swallowing disorders, feeding problems, nonobstructive dysphagia, and lower esophageal dysfunction. This paper discusses the recent advances in and reviews the use of high-resolution esophageal manometry in children. The Chicago 4.0 classification should be used judiciously in children. Manometric studies can guide the proper management of dysmotility in children

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