Integrating genomic features for non-invasive early lung cancer detection.

Radiologic screening of high-risk adults reduces lung-cancer-related mortality1,2; however, a small minority of eligible individuals undergo such screening in the United States3,4. The availability of blood-based tests could increase screening uptake. Here we introduce improvements to cancer personalized profiling by deep sequencing (CAPP-Seq)5, a method for the analysis of circulating tumour DNA (ctDNA), to better facilitate screening applications. We show that, although levels are very low in early-stage lung cancers, ctDNA is present prior to treatment in most patients and its presence is strongly prognostic. We also find that the majority of somatic mutations in the cell-free DNA (cfDNA) of patients with lung cancer and of risk-matched controls reflect clonal haematopoiesis and are non-recurrent. Compared with tumour-derived mutations, clonal haematopoiesis mutations occur on longer cfDNA fragments and lack mutational signatures that are associated with tobacco smoking. Integrating these findings with other molecular features, we develop and prospectively validate a machine-learning method termed 'lung cancer likelihood in plasma' (Lung-CLiP), which can robustly discriminate early-stage lung cancer patients from risk-matched controls. This approach achieves performance similar to that of tumour-informed ctDNA detection and enables tuning of assay specificity in order to facilitate distinct clinical applications. Our findings establish the potential of cfDNA for lung cancer screening and highlight the importance of risk-matching cases and controls in cfDNA-based screening studies.

Observation of room-temperature polar skyrmions.

Complex topological configurations are fertile ground for exploring emergent phenomena and exotic phases in condensed-matter physics. For example, the recent discovery of polarization vortices and their associated complex-phase coexistence and response under applied electric fields in superlattices of (PbTiO3)n/(SrTiO3)n suggests the presence of a complex, multi-dimensional system capable of interesting physical responses, such as chirality, negative capacitance and large piezo-electric responses1-3. Here, by varying epitaxial constraints, we discover room-temperature polar-skyrmion bubbles in a lead titanate layer confined by strontium titanate layers, which are imaged by atomic-resolution scanning transmission electron microscopy. Phase-field modelling and second-principles calculations reveal that the polar-skyrmion bubbles have a skyrmion number of +1, and resonant soft-X-ray diffraction experiments show circular dichroism, confirming chirality. Such nanometre-scale polar-skyrmion bubbles are the electric analogues of magnetic skyrmions, and could contribute to the advancement of ferroelectrics towards functionalities incorporating emergent chirality and electrically controllable negative capacitance.

Blocking mitochondrial Zn2+ accumulation after ischemia reduces mitochondrial dysfunction and neuronal injury.

Zn2+ is an important contributor to ischemic brain injury and recent studies support the hypothesis that mitochondria are key sites of its injurious effects. In murine hippocampal slices (both sexes) subjected to oxygen glucose deprivation (OGD), we found that Zn2+ accumulation and its entry into mitochondria precedes and contributes to the induction of acute neuronal death. In addition, if the ischemic episode is short (and sublethal), there is ongoing Zn2+ accumulation in CA1 mitochondria after OGD that may contribute to their delayed dysfunction. Using this slice model of sublethal OGD, we have now examined Zn2+ contributions to the progression of changes evoked by OGD and occurring over 4-5 hours. We detected progressive mitochondrial depolarization occurring from ∼ 2 hours after ischemia, a large increase in spontaneous synaptic activity between 2-3 hours, and mitochondrial swelling and fragmentation at 4 hours. Blockade of the primary route for Zn2+ entry, the mitochondrial Ca2+ uniporter (MCU; with ruthenium red, RR) or Zn2+ chelation shortly after OGD withdrawal substantially attenuated the mitochondrial depolarization and the changes in synaptic activity. RR also largely reversed the mitochondrial swelling. Finally, using an in vivo rat (male) asphyxial cardiac arrest (CA) model of transient global ischemia, we found that ∼8 min asphyxia induces considerable injury of CA1 neurons 4 hours later that is associated with strong Zn2+ accumulation within many damaged mitochondria. These effects were substantially attenuated by infusion of RR upon reperfusion. Our findings highlight mitochondrial Zn2+ accumulation after ischemia as a possible target for neuroprotective therapy.SIGNIFICANCE STATEMENT:Brain ischemia is a leading cause of mortality and long-term disability that still lacks effective treatment. After transient ischemia delayed death of neurons occurs in vulnerable brain regions. There is a critical need to understand mechanisms of this delayed neurodegeneration which can be targeted for neuroprotection. We found progressive and long-lasting mitochondrial Zn2+ accumulation to occur in highly vulnerable CA1 neurons after ischemia. Here we demonstrate that this Zn2+ accumulation contributes strongly to deleterious events occurring after ischemia including mitochondrial dysfunction, swelling and structural changes. We suggest that this mitochondrial Zn2+ entry may constitute a promising target for development of therapeutic interventions to be delivered after termination of an episode of transient global ischemia.

First Measurement of the Nuclear-Recoil Ionization Yield in Silicon at 100 eV.

We measured the nuclear-recoil ionization yield in silicon with a cryogenic phonon-sensitive gram-scale detector. Neutrons from a monoenergetic beam scatter off of the silicon nuclei at angles corresponding to energy depositions from 4 keV down to 100 eV, the lowest energy probed so far. The results show no sign of an ionization production threshold above 100 eV. These results call for further investigation of the ionization yield theory and a comprehensive determination of the detector response function at energies below the keV scale.

Identification of Fungal Species Associated with Apple Canker in Tarim Basin, China.

Apple canker has decreased yields of the economically important apple (Malus domestica) crop in China in recent years. Pathogen identity is highly challenging and the disease is poorly understood. Specimens of 339 fungi were isolated from apple trees in the primary apple-producing region in the Tarim Basin during the current study. In total, nine species of Cytospora and five species of the family Botryosphaeriaceae were identified by morphological observation and multilocus phylogenetic analyses: internal transcribed spacer (ITS), actin, translation elongation factor (TEF), and ß-tubulin (TUB) gene regions for Cytospora and ITS, TEF, and TUB for Botryosphaeriaceae. Cytospora pyri from the Cytospora genus was the dominant species causing apple canker in the Tarim Basin. C. melnikii, C. tritici, C. euonymina, Diplodia seriata, and Botryosphaeria dothidea have been described as the cause of apple canker in China. Apple (Red Fuji) branches were utilized to assess the pathogenicity of 24 representative fungal isolates from the 14 species, and branches from seven distinct woody plants (Korla pear, walnut, Chinese date, Xinjiang poplar, sand jujube, Populus euphratica, and willow) were utilized to analyze the host range. The main pathogenic fungal species of apple canker around the Tarim Basin were identified and biological characteristics explored. Pathogen diversity and regional source diversity were assessed with host range and pathogenicity. The aim was to provide a theoretical foundation for the prevention and treatment of apple canker.

[LncRNA DRAIC regulates the proliferation, apoptosis, migration and invasion of lung adenocarcinoma cells by targeting let-7i-5p].

Objective: To investigate the effects of lncRNA DRAIC on proliferation, apoptosis, migration and invasion of lung adenocarcinoma cells and its mechanism. Methods: Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expression of DRAIC in lung cancer tissues and corresponding adjacent normal tissues of 40 patients with lung adenocarcinoma who underwent surgery in Tangshan People's Hospital from 2019 to 2020. Lung adenocarcinoma cells A549 and H1299 were cultured in vitro and divided into si-NC group, si-DRAIC group, miR-NC group, let-7i-5p mimics group, si-DRAIC+ inhibitor-NC group, and si-DRAIC+ let-7i-5p inhibitor group. CCK-8 method and clone formation experiment were used to detect cell proliferation. Flow cytometry was used to detect cell apoptosis. Transwell array was used to detect the cell migration and invasion. Western blot was used to detect the protein expressions of Caspase-3, Caspase-9, Bcl-2 and Bax. The double luciferase reporter gene experiment was used to verify the regulatory relationship between DRAIC and let-7i-5p. Independent sample t test was used for comparison between two groups, one-way ANOVA was used for comparison between multiple groups, and Pearson correlation analysis was used for correlation analysis. Results: Compared with adjacent tissues, the expression level of DRAIC in lung adenocarcinoma tissues increased (P<0.05), but the expression level of let-7i-5p decreased (P<0.05). The expression levels of DRAIC and let-7i-5p in lung adenocarcinoma tissues were negatively correlated (r=-0.737, P<0.05). The absorbance value of A549 and H1299 cells in the si-DRAIC group at 48, 72 and 96 hours were lower than those in the si-NC group (P<0.05), the number of clones formed [(91.00±6.08 vs. 136.67±6.51); (50.67±1.53 vs. 76.67±4.51)], the number of migration [(606.67±31.34 vs. 960.00±33.06); (483.33±45.96 vs. 741.67±29.67)], the number of invasion [(185.00±8.19 vs. 447.33±22.05); (365.00±33.87 vs. 688.00±32.97)] were lower than those in the si-NC group (P<0.05). However, the apoptosis rates of cells [(13.43±2.79)% vs. (4.53±0.42)%; (23.77±1.04)% vs. (6.60±1.42)%] were higher than those in the si-NC group (P<0.05). The protein expressions of Caspase-3, Caspase-9 and Bax in si-DRAIC group were higher than those in si-NC group, and the protein expression of Bcl-2 was lower than that in si-NC group (P<0.05). DRAIC is located in the cytoplasm. DRAIC targeted and negatively regulated the expression of let-7i-5p. The absorbance values of A549 and H1299 cells in the let-7i-5p mimics group at 48, 72 and 96 hours were lower than those in the miR-NC group (P<0.05), the number of clones formed [(131.33±14.47 vs. 171.33±6.11); (59.33±4.93 vs. 80.33±7.09)], the number of migration [(137.67±3.06 vs. 579.33±82.03); (425.00±11.14 vs. 669.33±21.13)], the number of invasion [(54.00±4.36 vs. 112.67±11.59); (80.00±4.58 vs. 333.33±16.80)] were lower than those in the miR-NC group (P<0.05). However, the apoptosis rates of cells [(14.57±1.10)% vs. (6.97±1.11)%; (23.97±0.42)% vs. (7.07±1.21)%] were higher than those in the miR-NC group (P<0.05). The protein expressions of Caspase-3, Caspase-9 and Bax in let-7i-5p mimics group were higher than those in miR-NC group, and the protein expression of Bcl-2 was lower than that in miR-NC group (P<0.05). The absorbance values of A549 and H1299 cells in the si-DRAIC+ let-7i-5p inhibitor group at 48, 72 and 96 hours were higher than those in the si-DRAIC+ inhibitor-NC group (P<0.05), the number of clones formed [(82.00±5.29 vs. 59.00±5.57); (77.67±4.93 vs. 41.33±7.57)], the number of migration [(774.33±35.81 vs. 455.67±19.04); (569.67±18.72 vs. 433.67±16.77)], the number of invasion [(670.33±17.21 vs. 451.00±17.52); (263.67±3.06 vs. 182.33±11.93)] were higher than those in the si-DRAIC+ inhibitor-NC group (P<0.05). However, the apoptosis rates of cells [(7.73±0.45)% vs. (19.13±1.50)%; (8.00±0.53)% vs. (28.40±0.53)%] were lower than those in the si-NC group (P<0.05). The protein expressions of Caspase-3, Caspase-9 and Bax in si-DRAIC+ let-7i-5p inhibitor group were higher than those in si-DRAIC+ inhibitor-NC group, and the protein expression of Bcl-2 was lower than that in si-DRAIC+ inhibitor-NC group (P<0.05). Conclusion: DRAIC is highly expressed in lung adenocarcinoma, and DRAIC promotes the proliferation, migration and invasion of lung adenocarcinoma cells and inhibits apoptosis by targeting let-7i-5p.

VCP/p97 inhibitor CB-5083 modulates muscle pathology in a mouse model of VCP inclusion body myopathy.

BACKGROUND: Pathogenic gain of function variants in Valosin-containing protein (VCP) cause a unique disease characterized by inclusion body myopathy with early-onset Paget disease of bone and frontotemporal dementia (also known as Multisystem proteinopathy (MSP)). Previous studies in drosophila models of VCP disease indicate treatment with VCP inhibitors mitigates disease pathology. Earlier-generation VCP inhibitors display off-target effects and relatively low therapeutic potency. New generation of VCP inhibitors needs to be evaluated in a mouse model of VCP disease. In this study, we tested the safety and efficacy of a novel and potent VCP inhibitor, CB-5083 using VCP patient-derived myoblast cells and an animal model of VCP disease. METHODS: First, we analyzed the effect of CB-5083 in patient-derived myoblasts on the typical disease autophagy and TDP-43 profile by Western blot. Next, we determined the maximum tolerated dosage of CB-5083 in mice and treated the 2-month-old VCPR155H/R155H mice for 5 months with 15 mg/kg CB-5083. We analyzed motor function monthly by Rotarod; and we assessed the end-point blood toxicology, and the muscle and brain pathology, including autophagy and TDP-43 profile, using Western blot and immunohistochemistry. We also treated 12-month-old VCPR155H/+ mice for 6 months and performed similar analysis. Finally, we assessed the potential side effects of CB-5083 on retinal function, using electroretinography in chronically treated VCPR155H/155H mice. RESULTS: In vitro analyses using patient-derived myoblasts confirmed that CB-5083 can modulate expression of the proteins in the autophagy pathways. We found that chronic CB-5083 treatment is well tolerated in the homozygous mice harboring patient-specific VCP variant, R155H, and can ameliorate the muscle pathology characteristic of the disease. VCP-associated pathology biomarkers, such as elevated TDP-43 and p62 levels, were significantly reduced. Finally, to address the potential adverse effect of CB-5083 on visual function observed in a previous oncology clinical trial, we analyzed retinal function in mice treated with moderate doses of CB-5083 for 5 months and documented the absence of permanent ocular toxicity. CONCLUSIONS: Altogether, these findings suggest that long-term use of CB-5083 by moderate doses is safe and can improve VCP disease-associated muscle pathology. Our results provide translationally relevant evidence that VCP inhibitors could be beneficial in the treatment of VCP disease.

Local negative permittivity and topological phase transition in polar skyrmions.

Topological solitons such as magnetic skyrmions have drawn attention as stable quasi-particle-like objects. The recent discovery of polar vortices and skyrmions in ferroelectric oxide superlattices has opened up new vistas to explore topology, emergent phenomena and approaches for manipulating such features with electric fields. Using macroscopic dielectric measurements, coupled with direct scanning convergent beam electron diffraction imaging on the atomic scale, theoretical phase-field simulations and second-principles calculations, we demonstrate that polar skyrmions in (PbTiO3)n/(SrTiO3)n superlattices are distinguished by a sheath of negative permittivity at the periphery of each skyrmion. This enhances the effective dielectric permittivity compared with the individual SrTiO3 and PbTiO3 layers. Moreover, the response of these topologically protected structures to electric field and temperature shows a reversible phase transition from the skyrmion state to a trivial uniform ferroelectric state, accompanied by large tunability of the dielectric permittivity. Pulsed switching measurements show a time-dependent evolution and recovery of the skyrmion state (and macroscopic dielectric response). The interrelationship between topological and dielectric properties presents an opportunity to simultaneously manipulate both by a single, and easily controlled, stimulus, the applied electric field.

Observation of polar vortices in oxide superlattices.

The complex interplay of spin, charge, orbital and lattice degrees of freedom provides a plethora of exotic phases and physical phenomena. In recent years, complex spin topologies have emerged as a consequence of the electronic band structure and the interplay between spin and spin-orbit coupling in materials. Here we produce complex topologies of electrical polarization--namely, nanometre-scale vortex-antivortex (that is, clockwise-anticlockwise) arrays that are reminiscent of rotational spin topologies--by making use of the competition between charge, orbital and lattice degrees of freedom in superlattices of alternating lead titanate and strontium titanate layers. Atomic-scale mapping of the polar atomic displacements by scanning transmission electron microscopy reveals the presence of long-range ordered vortex-antivortex arrays that exhibit nearly continuous polarization rotation. Phase-field modelling confirms that the vortex array is the low-energy state for a range of superlattice periods. Within this range, the large gradient energy from the vortex structure is counterbalanced by the corresponding large reduction in overall electrostatic energy (which would otherwise arise from polar discontinuities at the lead titanate/strontium titanate interfaces) and the elastic energy associated with epitaxial constraints and domain formation. These observations have implications for the creation of new states of matter (such as dipolar skyrmions, hedgehog states) and associated phenomena in ferroic materials, such as electrically controllable chirality.

Roles of NLRP3 inflammasome in intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) is one of the leading causes of low back pain and one of the most common health problems in the world. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing-3 (NLRP3) inflammasome, as a pattern recognition receptor, has been shown to be associated with the pathological processes of many diseases in recent years. With the exploration of the mechanism of IVDD, recent studies have shown that activation of the NLRP3 inflammasome is associated with intervertebral disc (IVD) inflammation, pyroptosis, extracellular matrix degradation and apoptosis of IVD cells. In this review, we summarize the structural characteristics of NLRP3 inflammasome and the activation signalling mechanisms. We also describe the role of the NLRP3 inflammasome in the pathological process of IVDD and the application of the targeting the NLRP3 inflammasome in IVDD treatment.

Light Dark Matter Search with a High-Resolution Athermal Phonon Detector Operated above Ground.

We present limits on spin-independent dark matter-nucleon interactions using a 10.6 g Si athermal phonon detector with a baseline energy resolution of σ_{E}=3.86±0.04(stat)_{-0.00}^{+0.19}(syst) eV. This exclusion analysis sets the most stringent dark matter-nucleon scattering cross-section limits achieved by a cryogenic detector for dark matter particle masses from 93 to 140 MeV/c^{2}, with a raw exposure of 9.9 g d acquired at an above-ground facility. This work illustrates the scientific potential of detectors with athermal phonon sensors with eV-scale energy resolution for future dark matter searches.

Constraints on Lightly Ionizing Particles from CDMSlite.

The Cryogenic Dark Matter Search low ionization threshold experiment (CDMSlite) achieved efficient detection of very small recoil energies in its germanium target, resulting in sensitivity to lightly ionizing particles (LIPs) in a previously unexplored region of charge, mass, and velocity parameter space. We report first direct-detection limits calculated using the optimum interval method on the vertical intensity of cosmogenically produced LIPs with an electric charge smaller than e/(3×10^{5}), as well as the strongest limits for charge ≤e/160, with a minimum vertical intensity of 1.36×10^{-7} cm^{-2} s^{-1} sr^{-1} at charge e/160. These results apply over a wide range of LIP masses (5 MeV/c^{2} to 100 TeV/c^{2}) and cover a wide range of ßγ values (0.1-10^{6}), thus excluding nonrelativistic LIPs with ßγ as small as 0.1 for the first time.

Flexible Electrostatic Transducer Array with Displacement Control for Haptic Sensing and Actuation.

We developed flexible electrostatic transducers with both a single element and a 2×2 array format to actuate at a precise displacement across a range of loads with a control circuitry and algorithm. The transducer, composed of a moving buckled film with an integrated electrode and a rigid electrode, can be used to simultaneously generate and sense displacements. A circuit and computer program were designed to demonstrate displacement control and quantify the sensing precision of the transducer. Specifically, we applied a range of voltage and load conditions to the transducer and array and measured the displacement while under loading through capacitive sensing. The change in capacitance was linear with respect to the area of the electrode in contact and matched theoretical predictions when described as a function of the displacement. The transducer was loaded with weights in the range of 5-27 mN and capacitance-driving voltage graphs were obtained. An 8Hz driving frequency was used to move the transducer, while a 10.8kHz signal was used to sense the capacitance. These were used to build a predictive model to correct for sensed load to maintain a average displacement. It was found that a transducer of dimensions 10mm × 40mm was able to maintain displacement under loads of 5-27mN, while a matrix composed of 10mm × 20mm transducers was able to maintain displacement under loads of 2.5-11mN. In general, the detection thresholds of human skin can range between 5-20mN of force and 2-20um of displacement for frequencies between 1Hz and 250Hz, so these values are in line with what is needed to build a functional haptic wearable device. The present work provides a method to quantitatively measure and control a new type of flexible transducer for a variety of haptic applications.

[Characteristics and associated factors of early refractive parameters in premature infants].

Objective: To investigate the characteristics and associated factors of early refractive parameters in premature infants. Methods: Case-control study. Premature infants who underwent the first fundus screening in the ophthalmic clinic of Xiamen children's Hospital from May 2018 to February 2019 were collected. The screening time was 4 to 6 weeks after birth or corrected gestational age from 31 to 32 weeks. The premature infants who were diagnosed with mild retinopathy of prematurity (ROP) in one eye or both eyes but did not receive any treatment were divided into ROP group and divided into zone Ⅱ subgroup and zone Ⅲ subgroup according to the region of ROP; the premature infants without ROP were divided into non-ROP group. The gestational age, birth weight, spherical equivalent, anterior chamber depth, vitreous depth, axial length, lens thickness and corneal refractive power were recorded and compared. Independent sample t-test, multiple linear regression analysis and Pearson correlation analysis were used. Results: A total of 180 premature infants, 101 males and 79 females, with gestational age of (30.82±3.10) weeks, corrected gestational age of (37.21±1.44) weeks and birth weight of (1 577.85±572.12) g were included in this study. Ninety premature infants were included in the ROP group (162 eyes, of which 85 right eyes were included in the analysis) and 90 in the non-ROP group (90 right eyes). There was no significant difference in the distribution of gestational age, birth weight and corrected gestational age between the ROP group and non-ROP group (all P>0.05), but there was significant difference in the spherical equivalent between the two groups [(1.90±1.39) D vs. (3.04±1.88) D, t=-4.653, P<0.01], and ROP group was relatively smaller. In the ROP group, the anterior chamber depth was (1.82±0.23) mm, the lens thickness was (4.54±0.18) mm, and the corneal refractive power was (43.99±0.99) D. In the non-ROP group, the anterior chamber depth was (1.91±0.94) mm, the lens thickness was (4.23±0.50) mm, and the corneal refractive power was (43.72±0.92) D. The difference between the two groups was statistically significant (all P<0.01). In ROP group, the anterior chamber depth was shallower, the lens was thicker, and the corneal refractive power was higher. In ROP group, the corneal refractive power of 48 right eyes in zone Ⅱ subgroup and 37 right eyes in Zone Ⅲ subgroup were (43.92±0.78) D and (43.39±1.05) D respectively, and the spherical equivalent were (2.08±0.95) D and (2.52±1.12) D respectively. The corneal refractive power of zone Ⅱ subgroup was higher and the spherical equivalent was smaller, and the differences were statistically significant (all P<0.05). Multiple regression analysis showed that birth weight, gestational age and corneal refractive power were the influencing factors of spherical equivalent (P<0.01). The results of Pearson correlation analysis showed that the gestational age (r=0.182), birth weight (r=0.223) and corneal refractive power (r=-0.125) of premature infants were closely related to the spherical equivalent (all P<0.05). Conclusions: In premature infants, the larger spherical equivalent is related to greater gestational age and heavier birth weight. The refractive parameters of mild ROP are characterized by shallow anterior chamber, thick lens, high corneal refractive power and small spherical equivalent. The spherical equivalent is closely related to the development of ROP. (Chin J Ophthalmol, 2021, 57: 353-357).

Optical creation of a supercrystal with three-dimensional nanoscale periodicity.

Stimulation with ultrafast light pulses can realize and manipulate states of matter with emergent structural, electronic and magnetic phenomena. However, these non-equilibrium phases are often transient and the challenge is to stabilize them as persistent states. Here, we show that atomic-scale PbTiO3/SrTiO3 superlattices, counterpoising strain and polarization states in alternate layers, are converted by sub-picosecond optical pulses to a supercrystal phase. This phase persists indefinitely under ambient conditions, has not been created via equilibrium routes, and can be erased by heating. X-ray scattering and microscopy show this unusual phase consists of a coherent three-dimensional structure with polar, strain and charge-ordering periodicities of up to 30 nm. By adjusting only dielectric properties, the phase-field model describes this emergent phase as a photo-induced charge-stabilized supercrystal formed from a two-phase equilibrium state. Our results demonstrate opportunities for light-activated pathways to thermally inaccessible and emergent metastable states.

[Application of portable electroencephalograph in patients with epilepsy and establishment of medical platform].

Objective: To provide a portable electroencephalograph that can facilitate long-term monitoring of epilepsy patients outside the hospital, and establish a medical platform for epilepsy data monitoring and treatment. Methods: From June 2018 to October 2019, twenty-nine patients from Huashan Hospital (superior hospital) and Jing'an District Central Hospital (subordinate hospital) of Fudan University were enrolled in the study. Among them, twenty-eight cases were diagnosed with epilepsy and 1 case was epileptic seizure. Electroencephalogram (EEG) was collected by portable electroencephalograph once a week and followed up for three months. The seizure frequency, seizure form, medication type, EEG lead number and positive rate were recorded. Patients' medical records and EEG data were uploaded to the cloud database to build a medical alliance platform. Doctors of different levels of hospitals couldobtain diagnosis and achieve resource sharing based on the platform. The data was statistically analyzed using SPSS 18.0. Results: The EEG data collected by the portable electroencephalograph hadfewer artifacts, complete sleep cycle, and could record the interictaldischarges. Twenty-nine patientsunderwent a total of 148 EEG monitoring during the three-month follow-up. Eighty-five cases of epileptic discharges were detected, and the EEG positive rate was 57.4%. The positive rate of EEG in patients with generalized seizures (84.9%) was higher than that in patients with focal seizures (42.1%) (P<0.01); the positive rate of EEG in patients with 2-3 antiepileptic drugs and patients with frequent seizures within three months were also higher (P<0.05). Doctors in the superior hospital in the platform make diagnosis and treatment suggestions according to the above data. Elevenseizure-free patients and four patients with fewer seizures and discharges were diverted to the community hospital for follow-up. Fourteen patients with poor seizure control and/or continuous epileptic discharges were diverted to the superior hospitalto adjust the medication. Doctors of subordinate hospital acquired the diagnosis and treatment suggestions through the platform, and then strengthened the daily care and follow-up. Conclusion: Combined with a portable electroencephalograph, the current study establishs a medical platform for patients with epilepsy to achieve long-term monitoring and rational use of medical resources.

[Investigation on the awareness of snoring hazard and prevalence of obstructive sleep apnea among civil servants].

Objective: To investigate the awareness of snoring hazard and prevalence of obstructive sleep apnea (OSA) among civil servants. Methods: A cross-sectional survey was conducted to investigate the awareness of snoring hazards among in-service civil servants who had annual medical examination in a Guangdong provincial institution from September to November 2017. The high-risk group for OSA was screened and diagnosed by sleep monitoring. Results: 1 036 of 1 241 civil servants were enrolled in the study for integral data. 60.1% (623/1 036) of the subjects realized that snoring was harmful to health. The most common source to develop OSA awareness was network (59.6%, 371/623), followed by television (48.0%), relatives and friends (46.6%), newspaper (44.5%) and radio (18.9%). The awareness rate of snoring consequences was as follows: decreased sleep quality (71.9%, 448/623), sudden death (52.2%), daytime sleepiness (44.3%), cardiovascular and cerebrovascular diseases (42.9%), hypertension (24.4%) and sexual dysfunction (16.7%). 22.0% (228 / 1 036) of the cases were classified into high-risk OSA. The prevalence of OSA among high-risk group was 46.05%(105/228)and only 0.9% (2/228) of them had been diagnosed with OSA. Conclusion: Civil servants had awareness of snoring hazard to a certain extent. Among civil servants classified into high-risk OSA, the OSA perveance was high but the rate of diagnosis and treatment was very low.

Erratum: First Dark Matter Constraints from a SuperCDMS Single-Charge Sensitive Detector [Phys. Rev. Lett. 121, 051301 (2018)].

This corrects the article DOI: 10.1103/PhysRevLett.121.051301.

Differential Vulnerability of CA1 versus CA3 Pyramidal Neurons After Ischemia: Possible Relationship to Sources of Zn2+ Accumulation and Its Entry into and Prolonged Effects on Mitochondria.

Excitotoxic mechanisms contribute to the degeneration of hippocampal pyramidal neurons after recurrent seizures and brain ischemia. However, susceptibility differs, with CA1 neurons degenerating preferentially after global ischemia and CA3 neurons after limbic seizures. Whereas most studies address contributions of excitotoxic Ca2+ entry, it is apparent that Zn2+ also contributes, reflecting accumulation in neurons either after synaptic release and entry through postsynaptic channels or upon mobilization from intracellular Zn2+-binding proteins such as metallothionein-III (MT-III). Using mouse hippocampal slices to study acute oxygen glucose deprivation (OGD)-triggered neurodegeneration, we found evidence for early contributions of excitotoxic Ca2+ and Zn2+ accumulation in both CA1 and CA3, as indicated by the ability of Zn2+ chelators or Ca2+ entry blockers to delay pyramidal neuronal death in both regions. However, using knock-out animals (of MT-III and vesicular Zn2+ transporter, ZnT3) and channel blockers revealed substantial differences in relevant Zn2+ sources, with critical contributions of presynaptic release and its permeation through Ca2+- (and Zn2+)-permeable AMPA channels in CA3 and Zn2+ mobilization from MT-III predominating in CA1. To assess the consequences of the intracellular Zn2+ accumulation, we used OGD exposures slightly shorter than those causing acute neuronal death; under these conditions, cytosolic Zn2+ rises persisted for 10-30 min after OGD, followed by recovery over ∼40-60 min. Furthermore, the recovery appeared to be accompanied by mitochondrial Zn2+ accumulation (via the mitochondrial Ca2+ uniporter MCU) in CA1 but not in CA3 neurons and was markedly diminished in MT-III knock-outs, suggesting that it depended upon Zn2+ mobilization from this protein. SIGNIFICANCE STATEMENT: The basis for the differential vulnerabilities of CA1 versus CA3 pyramidal neurons is unclear. The present study of events during and after acute oxygen glucose deprivation highlights a possible important difference, with rapid synaptic entry of Ca2+ and Zn2+ contributing more in CA3, but with delayed and long-lasting accumulation of Zn2+ within mitochondria occurring in CA1 but not CA3 pyramidal neurons. These data may be consistent with observations of prominent mitochondrial dysfunction as a critical early event in the delayed degeneration of CA1 neurons after ischemia and support a hypothesis that mitochondrial Zn2+ accumulation in the early reperfusion period may be a critical and targetable upstream event in the injury cascade.

Phase coexistence and electric-field control of toroidal order in oxide superlattices.

Systems that exhibit phase competition, order parameter coexistence, and emergent order parameter topologies constitute a major part of modern condensed-matter physics. Here, by applying a range of characterization techniques, and simulations, we observe that in PbTiO3/SrTiO3 superlattices all of these effects can be found. By exploring superlattice period-, temperature- and field-dependent evolution of these structures, we observe several new features. First, it is possible to engineer phase coexistence mediated by a first-order phase transition between an emergent, low-temperature vortex phase with electric toroidal order and a high-temperature ferroelectric a1/a2 phase. At room temperature, the coexisting vortex and ferroelectric phases form a mesoscale, fibre-textured hierarchical superstructure. The vortex phase possesses an axial polarization, set by the net polarization of the surrounding ferroelectric domains, such that it possesses a multi-order-parameter state and belongs to a class of gyrotropic electrotoroidal compounds. Finally, application of electric fields to this mixed-phase system permits interconversion between the vortex and the ferroelectric phases concomitant with order-of-magnitude changes in piezoelectric and nonlinear optical responses. Our findings suggest new cross-coupled functionalities.