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To evaluate the safety and efficacy of transepithelial accelerated corneal crosslinking (CXL) for advanced keratoconus eyes with maximum keratometry (Kmax) values58 diopters (D).Department of Ophthalmology, Eye and ENT Hospital, Fudan University, Shanghai, China.Prospective parallel control study.41 keratoconus eyes from 41 patients (mean age, 21.93 ± 5.48 years) who underwent transepithelial accelerated CXL were included prospectively. The enrolled eyes were divided into 2 groups according to their Kmax values (Group A, Kmax ≥58.0 D; Group B, Kmax58.0 D). The examinations including assessment of uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), corneal topography, and corneal endothelial cell density count were conducted preoperatively, at 1 day, 1 month, 3 months, 6 months, and 1 year postoperatively.All 41 eyes finished 1 year follow-up. No statistical difference was noted between the mean UDVA and CDVA in both groups throughout the follow-up duration. At 1-year postoperative follow-up, the CDVA increased by ≥2 lines in 45% (9/20) and 28.6% (6/21) eyes in Groups A and B, respectively. The mean preoperative Kmax in Groups A and B were 62.51 ± 3.34 D and 49.98 ± 4.32 D, respectively, and that at postoperative 1-year follow-up were 61.94 ± 4.11 D and 50.24 ± 4.72 D, respectively. The Kmax values of 30% (6/20) eyes in Group A and 4.8% (1/21) eyes in Group B decreased by more than 1 D. Deduction of flat K, steep K, mean K, and Kmax showed no significant difference between the 2 groups at 1-year postoperative follow-up. Moreover, 20% (4/20) and 23.8% (5/21) of eyes in Groups A and B, respectively, showed progress at postoperative 1-year follow-up.Transepithelial accelerated CXL can safely treat advanced keratoconus eyes with Kmax values ≥58.0 D with some extent of efficacy and has similar progressive rate as Kmax values58.0 D.

Lead-free bulk ceramics for advanced pulsed power capacitors show relatively low recoverable energy storage density (Wrec) especially at low electric field condition. To address this challenge, we propose an A-site defect engineering to optimize the electric polarization behavior by disrupting the orderly arrangement of A-site ions, in which $${\rm{B}}{{\rm{a}}_{0.105}}{\rm{N}}{{\rm{a}}_{0.325}}{\rm{S}}{{\rm{r}}_{0.245 - 1.5x}}{_{0.5x}}{\rm{B}}{{\rm{i}}_{0.325 + x}}{\rm{Ti}}{{\rm{O}}_3}$$ Ba 0.105 Na 0.325 Sr 0.245 − 1.5 x □ 0.5 x Bi 0.325 + x TiO 3 ($${\rm{BN}}{{\rm{S}}_{0.245 - 1.5x}}{_{0.5x}}{{\rm{B}}_{0.325 + x}}{\rm{T}}$$ BNS 0.245 − 1.5 x □ 0.5 x B 0.325 + x T , x = 0, 0.02, 0.04, 0.06, and 0.08) lead-free ceramics are selected as the representative. The $${\rm{BN}}{{\rm{S}}_{0.245 - 1.5x}}{_{0.5x}}{{\rm{B}}_{0.325 + x}}{\rm{T}}$$ BNS 0.245 − 1.5 x □ 0.5 x B 0.325 + x T ceramics are prepared by using pressureless solid-state sintering and achieve large Wrec (1.8 J/cm3) at a low electric field (@110 kV/cm) when x = 0.06. The value of 1.8 J/cm3 is super high as compared to all other Wrec in lead-free bulk ceramics under a relatively low electric field (< 160 kV/cm). Furthermore, a high dielectric constant of 2930 within 15% fluctuation in a wide temperature range of 40–350 °C is also obtained in $${\rm{BN}}{{\rm{S}}_{0.245 - 1.5x}}{_{0.5x}}{{\rm{B}}_{0.325 + x}}{\rm{T}}$$ BNS 0.245 − 1.5 x □ 0.5 x B 0.325 + x T (x = 0.06) ceramics. The excellent performances can be attributed to the A-site defect engineering, which can reduce remnant polarization (Pr) and improve the thermal evolution of polar nanoregions (PNRs). This work confirms that the $${\rm{BN}}{{\rm{S}}_{0.245 - 1.5x}}{_{0.5x}}{{\rm{B}}_{0.325 + x}}{\rm{T}}$$ BNS 0.245 − 1.5 x □ 0.5 x B 0.325 + x T (x = 0.06) ceramics are desirable for advanced pulsed power capacitors, and will push the development of a series of Bi0.5Na0.5TiO3 (BNT)-based ceramics with high Wrec and high-temperature stability.

Background Hip fracture is common in older adults, and can cause severe post-fracture pain. Fascia iliaca nerve block has consequently been used for preoperative analgesia. Methods We performed a randomized, controlled, double-blind clinical trial and recruited older patients with hip fractures. These patients were randomized into two groups and received ultrasound-guided fascia iliaca compartment block using either the supra-inguinal approach (group F) or the classical approach (group C). Heart rate, blood pressure, and resting and exercising visual analog scales were recorded before the procedure and at 30 min, and 6, 12, and 24 h after completion of the procedure. We recorded the duration of the procedure—as well as complications such as bleeding, hypotension, and intractable vomiting; the sleep duration in a 24 h period was also documented. Results A total of 38 patients completed the trial, and we observed no differences in the baseline characteristics or pre-procedural measurements between the two groups. Compared with the patients in group C, patients in group F exhibited significantly lower exercising VAS scores at 6 and 12 h after the procedure, faster heart rates at 6 and 24 h after the procedure, a longer procedural duration, and a longer sleep duration. There were no differences in the frequencies of complications between the two groups. The percentages of patients who took oral analgesics and the numbers of medications consumed were also not different between the two groups. Conclusions The supra-inguinal FICB provided effective analgesia and improved exercise tolerance compared with the classical approach. Trial registration The trial was registered at the Chinese Clinical Trial Registry (registration number: ChiCTR2100045644, registration date: 2021 April 20).

Individualized chemotherapy, which is at the forefront of acute myeloid leukemia (AML) treatment, has moderately improved outcomes over the past decade. Monitoring the peripheral blood blast burden during induction by flow cytometry has shown significant value in the evaluation of treatment responses. Our previous study reported the day 5 peripheral blast clearance rate (D5-PBCR) as an indicator of early treatment response, and D5-PBCR (+) patients showed poor outcomes. We performed the present phase 2 trial of early intervention in D5-PBCR (+) patients with homoharringtonine (HHT) introduced in the traditional induction regimen with anthracycline and cytarabine. The primary endpoint was complete remission (CR). This study enrolled 151 patients, 65 patients were D5-PBCR (+) and 55 patients completed induction with HHT addition. The overall CR rate after one course of induction was 84.4%, with 87.5% and 80.0% for the D5-PBCR (-) and D5-PBCR (+) groups, respectively. The incidence of grade 3/4 adverse events was comparable between the two groups. At the median follow-up of 53.1 months, median overall survival (OS) was not reached in the entire cohort, and median event-free survival (EFS) was 42.2 months. Neither the OS nor EFS showed significant differences between the D5-PBCR (-) and D5-PBCR (+) groups. Compared to historical data, significant improvements in both OS (p = .020) and EFS (p = .020) were observed in the D5-PBCR (+) group. In conclusion, optimization of induction chemotherapy with idarubicin and cytarabine according to D5-PBCR is feasible in patients with newly diagnosed AML. The addition of HHT demonstrated a good efficacy and safety profile.

Myofascial pelvic pain (MFPP) caused by myofascial trigger points (MTrPs) is a major contributor to chronic pelvic pain in women. However, the effect of the patient's self-myofascial release (SMFR) is unclear. This study aimed to investigate the effect of SMFR combined with biofeedback and electrical stimulation (BES) therapy in comparison with BES alone in patients with MFPP.A prospective randomized controlled study was conducted. Sixty-eight patients were randomly allocated into BES-SMFR group (n = 34) and BES group (n = 34). Every patient received 4 weeks of treatment, evaluated at baseline (T0), 4 weeks post-intervention (T4) and 12-week follow-up (T12). The primary outcome was pain intensity. The secondary outcomes were degree of activation of MTrPs, surface electromyography (sEMG) levels and Patient Global Impression of Improvement (PGI-I).Compared with the effect of BES, BES-SMFR treatment significantly decreased pain intensity and the degree of activation of MTrPs in the levator ani (p = 0.02) and obturator internus (p = 0.03), as well as the sEMG levels of the pre-test resting baseline and post-test resting baseline (all p 0.01). The degree of activation of MTrPs in the piriformis and coccygeus (all p 0.05) and the sEMG levels of the quick flicks and endurance contraction were not significantly different. The BES-SMFR treatment improved the PGI-I scale at T4 (p = 0.02) but not at T12 (p = 0.40).This study confirmed that the addition of SMFR to BES treatment resulted in superior outcomes compared with those with BES alone in patients with MFPP.Myofascial pelvic pain (MFPP) is a major contributor of female chronic pelvic pain. Myofascial release has been used commonly for better pain release; however, poor therapeutic effect due to poor patient compliance is common in clinical practice. Therefore, in future research, there is a need to investigate the effect of patient's self-myofascial release (SMFR) technique, which can eliminate the need for frequent office visits and improve patient compliance to some extent, in patients with MFPP.

Background: We described the demographics, cancer subtypes, comorbidities, and outcomes of patients with a history of cancer and coronavirus disease 2019 (COVID-19). Second, we compared patients hospitalized with COVID-19 to patients diagnosed with COVID-19 and patients hospitalized with influenza. Methods: We conducted a cohort study using eight routinely collected health care databases from Spain and the United States, standardized to the Observational Medical Outcome Partnership common data model. Three cohorts of patients with a history of cancer were included: (i) diagnosed with COVID-19, (ii) hospitalized with COVID-19, and (iii) hospitalized with influenza in 2017 to 2018. Patients were followed from index date to 30 days or death. We reported demographics, cancer subtypes, comorbidities, and 30-day outcomes. Results: We included 366,050 and 119,597 patients diagnosed and hospitalized with COVID-19, respectively. Prostate and breast cancers were the most frequent cancers (range: 5%–18% and 1%–14% in the diagnosed cohort, respectively). Hematologic malignancies were also frequent, with non-Hodgkin's lymphoma being among the five most common cancer subtypes in the diagnosed cohort. Overall, patients were aged above 65 years and had multiple comorbidities. Occurrence of death ranged from 2% to 14% and from 6% to 26% in the diagnosed and hospitalized COVID-19 cohorts, respectively. Patients hospitalized with influenza (n = 67,743) had a similar distribution of cancer subtypes, sex, age, and comorbidities but lower occurrence of adverse events. Conclusions: Patients with a history of cancer and COVID-19 had multiple comorbidities and a high occurrence of COVID-19-related events. Hematologic malignancies were frequent. Impact: This study provides epidemiologic characteristics that can inform clinical care and etiologic studies.

BACKGROUND Enteric anastomotic (EA) bleeding is a potentially life-threatening surgical complication associated with enteric anastomosis during simultaneous pancreas and kidney transplantation (SPKT). AIM To investigate whether suture ligation (SL) for submucosal hemostasis during hand-sewn enteric anastomosis could decrease the morbidity of early EA bleeding in SPKT. METHODS We compared the outcomes of 134 patients classified into SL (n = 44) and no SL (NSL) groups (n = 90). This study adheres to the declarations of Istanbul and Helsinki and all donors were neither paid nor coerced. RESULTS During the first postoperative week, the EA bleeding rate in the SL group was lower than that in the NSL group (2.27% vs 15.56%; P = 0.021); no relationship was found between EA bleeding and donor age, mean pancreatic cold ischemia time, platelet count, prothrombin time international normalized rate, activated partial thromboplastin time, and thrombin time. Anastomotic leakage was observed in one case in the SL group at postoperative day (POD) 14 and in one case at POD 16 in the NSL group (P = 0.754). No significant difference was found between the two groups in the patient survival, pancreas graft survival, or kidney graft survival. CONCLUSION SL for submucosal hemostasis during hand-sewn enteric anastomosis in SPKT can decrease the morbidity of early EA bleeding without increasing the anastomotic leakage rate.

AimsTo predict the vault and the EVO-implantable collamer lens (ICL) size by artificial intelligence (AI) and big data analytics.MethodsSix thousand two hundred and ninety-seven eyes implanted with an ICL from 3536 patients were included. The vault values were measured by the anterior segment analyzer (Pentacam HR). Permutation importance and Impurity-based feature importance are used to investigate the importance between the vault and input parameters. Regression models and classification models are applied to predict the vault. The ICL size is set as the target of the prediction, and the vault and the other input features are set as the new inputs for the ICL size prediction. Data were collected from 2015 to 2020. Random Forest, Gradient Boosting and XGBoost were demonstrated satisfying accuracy and mean area under the curve (AUC) scores in vault predicting and ICL sizing.ResultsIn the prediction of the vault, the Random Forest has the best results in the regression model (R2=0.315), then follows the Gradient Boosting (R2=0.291) and XGBoost (R2=0.285). The maximum classification accuracy is 0.828 in Random Forest, and the mean AUC is 0.765. The Random Forest predicts the ICL size with an accuracy of 82.2% and the Gradient Boosting and XGBoost, which are also compatible with 81.5% and 81.8% accuracy, respectively.ConclusionsRandom Forest, Gradient Boosting and XGBoost models are applicable for vault predicting and ICL sizing. AI may assist ophthalmologists in improving ICL surgery safety, designing surgical strategies, and predicting clinical outcomes.

Background Airway mucus acts as an indispensable protective component of innate immune response against invading pathogens. However, airway mucus hypersecretion, largely consisting of mucin 5AC (MUC5AC), is the leading cause of airflow obstruction and airway hyperresponsiveness that contributes to chronic obstructive pulmonary disease (COPD). MicroRNAs (miRNAs) are frequently dysregulated in the pathogenesis of COPD, but the definite role of miRNAs in airway mucus hypersecretion is not well understood. Methods A cell model of mucus hypersecretion was established in 16HBE cells by treatment with TNF-α. Cell viability and apoptosis were assessed using cell counting kit-8 (CCK-8) and flow cytometry, respectively. The aberrant expression of miR-146a-5p and miR-134-5p was assayed in TNF-α-treated 16HBE cells, and the effect of miR-146a-5p and miR-134-5p on regulating MUC5AC expression was evaluated using quantitative real-time PCR (qPCR) and Western blot analysis. Results TNF-α treatment resulted in a significant decrease of cell viability, and increase of cell apoptosis and MUC5AC expression in 16HBE cells. Additionally, the expression of miR-134-5p and miR-146a-5p was markedly decreased in the cell model. Importantly, forced expression of miR-134-5p and miR-146a-5p significantly repressed TNF-α-induced upregulation of MUC5AC. Mechanistically, although miR-134-5p did not affect 16HBE cells viability and apoptosis, miR-134-5p partially blocked TNF-α-induced MUC5AC expression by inhibiting the activation of NF-κB signaling. On the other hand, miR-146a-5p enhanced cell viability and reduced cell apoptosis. miR-146a-5p also repressed TNF-α-induced MUC5AC expression by inhibiting p38 MAPK (mitogen-activated protein kinase) signaling activation. Conclusions The current data demonstrated that both miR-134-5p and miR-146a-5p conferred protection against TNF-α-induced mucus hypersecretion through repressing NF-κB and p38 MAPK signaling, indicating that miR-134-5p and miR-146a-5p may serve as the biomarker for COPD.

BACKGROUND The purpose of this study is to investigate the correlation between cytokeratin 7 (CK7) and marker of proliferation Ki67 protein expression and clinical characteristics and prognosis of patients with cervical adenocarcinoma after surgery. METHODS A total of 126 patients with cervical adenocarcinoma treated by surgery in our hospital from June 2011 to September 2015 were enrolled in this study. Immunohistochemistry (IHC) was used to detect the expression of CK7 and Ki67 in 126 cases of cervical adenocarcinoma tissues. The chi-square (χ2) test was used to compare the relationship between the positive expression rate of CK7 or Ki67 and clinicopathological features. Kaplan-Meier method was used to analyze the survival of different protein expression groups and Cox proportional hazards regression model was used to analyze the risk factors affecting the prognosis. RESULTS The positive rate of CK7 was correlated with muscle invasion, vascular invasion, differentiation, and lymph node metastasis (all P

The development of next generation Li ion battery has attracted many attentions of researchers due to the rapidly increasing demands to portable energy storage devices. General Li metal/alloy anodes are confronted with challenges of dendritic crystal formation and slow charge/discharge rate. Recently, the prosperity of two-dimensional materials opens a new window for the design of battery anode. In the present study, MoS2/graphene heterostructure is investigate for the anode application of Li ion battery using first-principles calculations. The Li binding energy, open-circuit voltage, and electronic band structures are acquired for various Li concentrations. We found the open-circuit voltage decreases from ~2.28 to ~0.4 V for concentration from 0 to 1. Density of states show the electrical conductivity of the intercalated heterostructures can be significantly enhanced. The charge density differences are used to explain the variations of voltage and density of states. Last, ~0.43 eV diffusion energy barrier of Li implies the possible fast charge/discharge rate. Our study indicate MoS2/graphene heterostructure is promising material as Li ion battery anode.

What is known and objective Optimal airway management is crucial in strabismus surgery due to the inaccessibility of the airway throughout the procedure. Laryngeal mask airway offers advantages over tracheal intubation in ophthalmic surgery as it does not increase the intraocular pressure. The purpose of this study was to determine the median effective dose of propofol required, when combined with 0.2 µg/kg of sufentanil, for smooth insertion of Ambu AuraFlex in the first attempt in children undergoing strabismus surgery, and to compare it with that for Ambu AuraOnce. Methods Forty-three paediatric patients undergoing strabismus surgery under general anaesthesia were recruited. For induction, the initial dosage of propofol was 2 mg/kg in the AuraOnce group or 3 mg/kg in the AuraFlex group. In accordance with Dixon's up-and-down method, the dose of propofol for consecutive patients in each group was adjusted in increments or decrements of 0.25 mg/kg based on the previous patient's "three-point, six-category scale" response to the first attempt of insertion of the randomized device. Insertion of the device was attempted when the bispectral index was ≤60 for 5 s after propofol administration without the use of neuromuscular blocking agents. Results and discussion The median effective dose (95% confidence interval) of propofol was significantly lower in the Ambu AuraOnce group than in the Ambu AuraFlex group (1.92 [1.50-2.32] mg/kg vs. 2.98 [2.49-3.94] mg/kg; p = 0.002). The incidence of dislodgement of the device was significantly higher with the use of the Ambu AuraOnce than with the use of AuraFlex (p = 0.023), whereas insignificant differences were observed between the two groups in the incidence of other perioperative adverse events. What is new and conclusion Ambu AuraFlex requires a significantly higher dose of propofol for insertion and provides more effective and stable airway management in strabismus surgery than AuraOnce.

Ultrasound-guided axillary brachial plexus block is increasingly used in preschool-age patients. However, the minimum effective volume of local anaesthetics has not been determined. With ethical committee approval and written informed consent from the guardians of all paediatric patients, we studied 27 consecutive patients aged 3 to 6 years who were scheduled for hand surgery. After general anaesthesia, eligible patients received a set volume of ultrasound-guided axillary brachial plexus block. We determined the volume of 0.2% ropivacaine for consecutive patients from the preceding patient’s outcome. The initial volume was 0.4 ml/kg. The testing interval was set at 0.05 ml/kg, and the lowest volume was 0.1 ml/kg. The following conditions were defined as a successful block: no heart rate changes, body movement, or ventilatory disorders during the operation; no use of fentanyl in the PACU; and a postoperative sensory block score

Perioperative neurocognitive disorders (PNDs) refer to cognitive decline identified in the preoperative or postoperative period. It has been reported that the incidence of postoperative neurocognitive impairment after noncardiac surgery in patients older than 65 at 1 week was 25.8∼41.4%, and at 3 months 9.9∼12.7%. PNDs will last months or even develop to permanent dementia, leading to prolonged hospital stays, reduced quality of life, and increased mortality within 1 year. Despite the high incidence and poor prognosis of PNDs in the aged population, no effective clinical prediction model has been established to predict postoperative cognitive decline preoperatively. To develop a clinical prediction model for postoperative neurocognitive dysfunction, a prospective observational study (Clinical trial registration number: ChiCTR2000036304) will be performed in the Shanghai General Hospital during January 2021 to October 2022. A sample size of 675 patients aged >65 years old, male or female, and scheduled for elective major noncardiac surgery will be recruited. A battery of neuropsychological tests will be used to test the cognitive function of patients at 1 week, 1 month, and 3 months postoperatively. We will evaluate the associations of PNDs with a bunch of candidate predictors including general characteristics of patients, blood biomarkers, indices associated with anesthesia and surgery, retinal nerve-fiber layer thickness, and frailty index to develop the clinical prediction model by using multiple logistic regression analysis and least absolute shrinkage and the selection operator (LASSO) method. The k-fold cross-validation method will be utilized to validate the clinical prediction model. In conclusion, this study was aimed to develop a clinical prediction model for postoperative cognitive dysfunction of old patients. It is anticipated that the knowledge gained from this study will facilitate clinical decision-making for anesthetists and surgeons managing the aged patients undergoing noncardiac surgery.

BACKGROUND AND AIMS Biliary tract cancer (BTC) is rare and has limited treatment options. We aimed to examine aspirin use on cancer-specific survival in various BTC subtypes, including gallbladder cancer, ampulla of Vater cancer, and cholangiocarcinoma. APPROACH AND RESULTS Nationwide prospective cohort of newly diagnosed BTC between 2007 and 2015 were included and followed until December 31, 2017. Three nationwide databases, namely the Cancer Registration, National Health Insurance, and Death Certification System, were used for computerized data linkage. Aspirin use was defined as one or more prescriptions, and the maximum defined daily dose was used to evaluate the dose-response relationship. Cox's proportional hazards models were applied for estimating HRs and 95% CIs. Analyses accounted for competing risk of cardiovascular deaths, and landmark analyses to avoid immortal time bias were performed. In total, 2,519 of patients with BTC were exposed to aspirin after their diagnosis (15.7%). After a mean follow-up of 1.59 years, the 5-year survival rate was 27.4%. The multivariate-adjusted HR for postdiagnosis aspirin users, as compared with nonusers, was 0.55 (95% CI: 0.51 to 0.58) for BTC-specific death. Adjusted HRs for BTC-specific death were 0.53 (95% CI: 0.48 to 0.59) and 0.42 (95% CI: 0.31 to 0.58) for ≤ 1 and > 1 maximum defined daily dose, respectively, and showed a dose-response trend (P

Addressing microstructure-property relations of polymer nanocomposites is vital for designing advanced dielectrics for electrostatic energy storage. Here, we develop an integrated phase-field model to simulate the dielectric response, charge transport, and breakdown process of polymer nanocomposites. Subsequently, based on 6615 high-throughput calculation results, a machine learning strategy is schemed to evaluate the capability of energy storage. We find that parallel perovskite nanosheets prefer to block and then drive charges to migrate along with the interfaces in x-y plane, which could significantly improve the breakdown strength of polymer nanocomposites. To verify our predictions, we fabricate a polymer nanocomposite P(VDF-HFP)/Ca2Nb3O10, whose highest discharged energy density almost doubles to 35.9 J cm−3 compared with the pristine polymer, mainly benefit from the improved breakdown strength of 853 MV m−1. This work opens a horizon to exploit the great potential of 2D perovskite nanosheets for a wide range of applications of flexible dielectrics with the requirement of high voltage endurance.

While morphine has long been widely used in treating acute heart failure (AHF) due to its vasodilatory properties and anticipated anxiolysis, it remains unclear whether the application of morphine to those patients is reasonable. We aim to conduct a systematic review and meta‐analysis to assess the safety of morphine in patients with AHF. We searched PubMed, Cochrane Library, and Embase electronic databases from inception through March 2020. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the outcomes. Seven studies with 172, 226 patients were included. The results showed that morphine usage was not associated with increased in‐hospital mortality (OR: 1.94; 95% CI 0.93 to 4.03; p = 0.08). However, the use of morphine significantly increased the risk of invasive ventilation (OR: 2.72; 95% CI 1.09 to 6.80; p = 0.03). Furthermore, the subgroup analysis indicated that the application of morphine was not associated with increased 7‐day all‐cause mortality in patients with AHF (OR: 1.69; 95% CI 0.80 to 3.22; p = 0.11) but significantly increased the risk of 30‐day all‐cause mortality (OR: 1.59; 95% CI 1.16 to 2.17; p = 0.004). Based on current evidence, our results suggested that although morphine therapy did not significantly increase the risk of short‐term death (in the hospital or within 7 days) in patients with AHF, the risk of long‐term death and invasive ventilation were significantly increased. This result needs to be further confirmed by an ongoing randomized control trial.

The alterations in the gut microbiota have been reported to be correlated with the development of depression. The purpose of this study was to investigate the changes of intestinal microbiota in depressed patients after antidepressant treatment. We recruited 30 MDD patients (MDD group) and 30 healthy controls (control group). The MDD group received individualized treatment with escitalopram at a maximum dose of 20 mg/day. After depressive symptoms improved to a HAMD scale score > 50%, a fecal sample was collected again and used as the follow-up group. The differences of gut microbiota between patients and controls, the characteristics of gut microbiota under treatment and the potential differences in metabolic functions were thus investigated. The Firmicutes/Bacteroidetes ratio was significantly different within three groups, and the ratio of follow-up group was significantly lower than those of the other two groups. Alpha diversity was significantly higher in MDD group than those of the other groups, and the alpha diversity was not significantly different between control and follow-up groups. The beta diversity of some patients resembled participants in the control group. The metabolic function of gut microbiota after treatment was still different from that of the control group. This study suggests that the intestinal flora of depressed patients has a tendency to return to normal under escitalopram treatment.

Large roughness and structure disorder in ferroelectric ultrathin Langmuir-Blodgett (LB) film results in severe space scatter in electrical, ferroelectric and piezoelectric characteristics, thus limiting the nanoscale research and reliability of nano-devices. However, no effective method aiming at large-area uniform organic ferroelectric LB film has ever been reported to date. Herein, we present a facile hot-pressing strategy to prepare relatively large-area poly(vinylidene fluoride) (PVDF) LB film with ultra-smooth surface root mean square (RMS) roughness is 0.3 nm in a 30 μm × 30 μm area comparable to that of metal substrate, which maximized the potential of LB technique to control thickness distribution. More importantly, compared with traditionally annealed LB film, the hot-pressed LB film manifests significantly improved structure uniformity, less fluctuation in ferroelectric characteristics and higher dielectric and piezoelectric responses, owing to the uniform dipole orientation and higher crystalline quality. Besides, different surface charge relaxation behaviors are investigated and the underlying mechanisms are explained in the light of the interplay of surface charge and polarization charge in the case of nanoscale non-uniform switching. We believe that our work not only presents a novel strategy to endow PVDF LB film with unprecedented reliability and improved performance as a competitive candidate for future ferroelectric tunnel junctions (FTJs) and nano electro mechanical systems (NEMS), but also reveals an attracting coupling effect between the surface potential distribution and nanoscale non-uniform switching behavior, which is crucial for the understanding of local transport characterization modulated by band structure, bit signal stability for data-storage application and the related surface charge research, such as charge gradient microscopy (CGM) based on the collection of surface charge on the biased ferroelectric domains.

Two-dimensional (2D) heterostructures show great potential in achieving negative differential resistance (NDR) effects by Esaki diodes and or resonant tunneling diodes. However, most of the reported Esaki diode-based NDR devices realized by bulk 2D films lack sufficient gate tunability, and the tuning of NDR behavior from appearing to vanishing remains elusive. Here, a gate-tunable NDR device is reported based on a vertically stacked black phosphorus (BP) and molybdenum disulfide (MoS2) thin 2D heterojunction. At room temperature, a rectifying ratio of ∼6 orders of magnitude from a reverse rectifying diode to a forward rectifying diode by gate modulation is obtained. Through analyzing the temperature-dependent electrical properties, the tunneling mechanism at a certain gate voltage range is revealed. Moreover, the switchable and continuously gate-tunable NDR behavior is realized with a maximum peak-to-valley ratio of 1.23 at 77 K, as shown in the IDS mappings by sweeping VDS under different VGS. In addition, a compact model for gate-tunable NDR behavior in 2D heterostructures is proposed. To our best knowledge, this is the first demonstration of NDR behavior in BP-MoS2 heterostructures. Consequently, this work sheds light on the gate-tunable NDR devices and reconfigurable logic devices for realizing ternary and reconfigurable logic systems.

Purpose: The current stratification system for acute promyelocytic leukemia (APL) is based on the white blood cell (WBC) and the platelet counts (i.e., Sanz score) over the past two decades. However, the borderlines among different risk groups are sometimes ambiguous, and for some patients, early death and relapse remained challenges. Besides, with the evolving of the treatment strategy from all-trans-retinoic acid (ATRA) and chemotherapy to ATRA–arsenic trioxide-based synergistic targeted therapy, the precise risk stratification with molecular markers is needed. Experimental Design: This study performed a systematic analysis of APL genomics and transcriptomics to identify genetic abnormalities in 348 patients mainly from the APL2012 trial (NCT01987297) to illustrate the potential molecular background of Sanz score and further optimize it. The least absolute shrinkage and selection operator algorithm was used to analyze the gene expression in 323 cases to establish a scoring system (i.e., APL9 score). Results: Through combining NRAS mutations, APL9 score, and WBC, 321 cases can be stratified into two groups with significantly different outcomes. The estimated 5-year overall (P = 0.00031), event-free (P < 0.0001), and disease-free (P = 0.001) survival rates in the revised standard-risk group (95.6%, 93.8%, and 98.1%, respectively) were significantly better than those in the revised high-risk group (82.9%, 77.4%, and 88.4%, respectively), which could be validated using The Cancer Genome Atlas dataset. Conclusions: We have proposed a two-category system for improving prognosis in patients with APL. Molecular markers identified in this study may also provide genomic insights into the disease mechanism for improved therapy.

This paper provides a systematic, comprehensive, up-to-date study of the various artificial intelligence (AI) techniques on the detection and classification of faults on power transmission line. We review the latest start of the art of various intelligent approaches and even discuss the differences and outcomes of implementing intelligent methods in the protection scheme and the integrated protection scheme. Besides, there has been an increase in demand and interest for the application of AI approaches in drone to aid in detection and classification of faults. However, there are not many surveys pertaining to the development of the unmanned aerial vehicle (UAV) for the application of intelligent methods in this field. Thus, we also include in this paper the literature relevant to the implementation of various intelligent approaches in the unmanned aerial vehicle (UAV) for the fault detection and classification on power transmission line. Finally, we discuss the challenges and limitations faced in the implementation and propose ways to bridge the gap in the field for further research. This comprehensive study can act as a platform for new researchers to assess the possible different intelligent methods in detecting and classifying faults on power transmission line with a set of references that were dedicated to the attentive contributions.

The growing amount of seismic data necessitates efficient and effective methods to monitor earthquakes. Current methods are computationally expensive, ineffective under noisy environments, or labor intensive. We leverage advances in machine learning to propose an improved solution, ArrayConvNet—a convolutional neural network that uses continuous array data from a seismic network to seamlessly detect and localize events, without the intermediate steps of phase detection, association, travel-time calculation, and inversion. When testing this methodology with events at Hawai‘i, we achieve 99.4% accuracy and predict hypocenter locations within a few kilometers of the U.S. Geological Survey catalog. We demonstrate that training with relocated earthquakes reduces localization errors significantly. We outline several ways to improve the model, including enhanced data augmentation and use of relocated offshore earthquakes recorded by ocean-bottom seismometers. Application to continuous records shows that our algorithm detects 690% as many earthquakes as the published catalog, and 125% as many events than the Hawaiian Volcano Observatory internal catalog. Because of the enhanced detection sensitivity, localization granularity, and minimal computation costs, our solution is valuable, particularly for real-time earthquake monitoring.

As an effective depressant, ultra-fine water mist has broad application prospects in reducing the loss caused by a gas detonation. Ultra-fine water mist can be sprayed into coal mine roadways or natural gas pipelines when detecting the radiation spectrum signal of the explosion, to prevent further expansion of the explosion. A two-dimensional pipeline model was designed to study the effect and mechanism of methane detonation suppression by monodisperse ultra-fine water mist with a diameter of 10 μm. The methane detonation at the stoichiometric concentration (9.5 %) will decay to a deflagration under the suppression of fine water mist of 160 g/m3. When the concentration of fine water mist is less than 160 g/m3, the detonation wave has a slight attenuation in the water mist area, while it returns to a stable detonation state after passing through the mist area. The results also indicate that a water mist above 800 g/m3 can effectively suppress detonation and eventually lead to flame extinguishment. The critical transition concentration of ultra-fine water mist that can decay a methane detonation to a deflagration and the critical extinction concentration of ultra-fine water mist that completely suppresses a detonation within the explosion limit were obtained, providing a visual reference for the suppression of methane explosion accidents in coal mine tunnels or pipelines.

Background: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype. Methods: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer–specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype. Results: There was no evidence of heterogeneous associations between risk factors and mortality by subtype (Padj > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5–25 kg/m2 [HR (95% confidence interval (CI), 1.19 (1.06–1.34)]; current versus never smoking [1.37 (1.27–1.47)], high versus low physical activity [0.43 (0.21–0.86)], age ≥30 years versus 0– Conclusions: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype. Impact: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.

This paper investigates a Stackelberg game between a mutual fund manager and an investor. Throughout the paper, we follow the literature (see, e.g. Li and Sethi. A review of dynamic stackelberg gam...

Motivation Facing the increasing gap between high-throughput sequence data and limited functional insights, computational protein function annotation provides a high-throughput alternative to experimental approaches. However, current methods can have limited applicability while relying on protein data besides sequences, or lack generalizability to novel sequences, species and functions. Results To overcome aforementioned barriers in applicability and generalizability, we propose a novel deep learning model using only sequence information for proteins, named Transformer-based protein function Annotation through joint sequence–Label Embedding (TALE). For generalizability to novel sequences we use self-attention-based transformers to capture global patterns in sequences. For generalizability to unseen or rarely seen functions (tail labels), we embed protein function labels (hierarchical GO terms on directed graphs) together with inputs/features (1D sequences) in a joint latent space. Combining TALE and a sequence similarity-based method, TALE+ outperformed competing methods when only sequence input is available. It even outperformed a state-of-the-art method using network information besides sequence, in two of the three gene ontologies. Furthermore, TALE and TALE+ showed superior generalizability to proteins of low similarity, new species, or rarely annotated functions compared to training data, revealing deep insights into the protein sequence–function relationship. Ablation studies elucidated contributions of algorithmic components toward the accuracy and the generalizability; and a GO term-centric analysis was also provided. Availability and implementation The data, source codes and models are available at https://github.com/Shen-Lab/TALE. Supplementary information Supplementary data are available at Bioinformatics online.

We report high-gain, low-noise-figure, and high linearity analog photonic links at 1064 nm using InP/InGaAs modified uni-traveling-carrier (MUTC) photodiodes. Balanced photodiodes reach output powers of 17.7 dBm, 19.8 dBm, 20.7 dBm, and 22 dBm at 38 GHz, 29 GHz, 27 GHz, and 24.5 GHz, respectively. High common-mode rejection ratio (CMRR) of 25 dB and good linearity with a third-order intercept point (OIP3) of up to 34 dBm were measured at 38 GHz for 10-μm-diameter balanced photodiodes. We demonstrate two analog photonic links with different noise reduction techniques without electronic amplification. In the first link, we use balanced detection with a quadrature-biased Mach–Zehnder modulator (MZM) for noise cancellation. Link gain of 6.8 dB, noise figure (NF) of 25.8 dB and spurious free dynamic range (SFDR3) of 114 dB·Hz2/3 at 38 GHz were achieved. The second link works at low bias modulation for improved signal-to-noise ratio with a single photodetector. Record-high gain (19.3 dB at 26 GHz and 17 dB at 38 GHz) and low noise figure (14.5 dB at 26 GHz and 17 dB at 38 GHz) were demonstrated.

Acute high‐altitude (HA) exposure induces physiological responses of the heart and blood pressure (BP). However, few studies have investigated the responses associated with dipper and non‐dipper BP patterns. In this prospective study, 72 patients underwent echocardiography and 24‐h ambulatory BP testing at sea level and HA. Patients were divided into dipper and non‐dipper groups according to BP at sea level. Acute HA exposure elevated 24‐h systolic and diastolic BP and increased BP variability, particularly in the morning. Moreover, acute exposure increased left ventricular torsion, end‐systolic elastance, effective arterial elastance, and untwisting rate, but reduced peak early diastolic velocity/late diastolic velocity and peak early diastolic velocity/early diastolic velocity, implying enhanced left ventricular systolic function but impaired filling. Dippers showed pronounced increases in night‐time BP, while non‐dippers showed significant elevation in day‐time BP, which blunted differences in nocturnal BP fall, and lowest night‐time and evening BP. Dippers had higher global longitudinal strain, torsion, and untwisting rates after acute HA exposure. Variations in night‐time systolic BP correlated with variations in torsion and global longitudinal strain. Our study firstly demonstrates BP and cardiac function variations during acute HA exposure in different BP patterns and BP increases in dippers at night, while non‐dippers showed day‐time increases. Furthermore, enhanced left ventricular torsion and global longitudinal strain are associated with BP changes. Non‐dippers showed poor cardiac compensatory and maladaptive to acute HA exposure. However, the exact mechanisms involved need further illumination.

Background: Bioinformatics showed that long non-coding RNA (lncRNA) pgm5-as1 was regulated in patients with colorectal cancer (CRC), and miR-484 was also regulated in CRC. We aimed at determining t...

Background It is critical to monitor the optic disc’s vessel density using Optical coherence tomography angiography (OCTA) and evaluate its determinants. In the current study, we investigate the superficial vessel density (VD) of the papillary microvasculature and its determinants in healthy subjects of Southern China. Methods This was a prospective, cross-sectional study. Superficial VD in healthy individuals’ optic disc region was measured by OCTA. The factors associated with ocular and systemic parameters were analyzed using a generalized estimation equation (GEE) model. Results A total of 510 eyes of 260 healthy subjects were analyzed in the study. The total VD in the optic disc area was 17.21 ± 2.15 mm− 1 (95% CI, 17.02–17.40 mm− 1). The VD in the inner ring and the outer ring of the optic disc were significantly higher compared with the central ring, while the VD of the superior quadrant and inferior quadrant was significantly higher compared with the temporal and nasal quadrant. After adjusting for the ocular factors and systemic factors, AL (β = − 0.4917, P = 0.0003), disc area (β = − 0.3748, P = 0.0143), CMT (β = − 0.0183, P = 0.0003) and SSI (β = 1.0588, P Conclusion The mean total VD in the optic disc area was 17.21 ± 2.15 mm− 1 in healthy subjects, and the superior and inferior VD was significantly higher than the temporal and nasal VD. AL, disc area, CMT, and SSI may affect the total VD in the optic disc area and should be considered in clinical practice.

The data for effect of dietary specific carotenoids on depression are limited and controversial. Thus, this study aimed to examine the relationship between dietary carotenoids intakes and the prevalence of depressive symptoms.In the 2015-2016 United States National Health and Nutrition Examination Survey, 4,105 adults with complete data of dietary intake and assessment of depressive symptoms are enrolled. Dietary intake was assessed through two 24-h dietary recall interviews. Depression symptoms were assessed using the nine-item Patient Health Questionnaire. We used logistic regression to assess the relationship between diet carotenoids intake and the prevalence of depressive symptoms, adjusting for the main potential confounders. In addition, daily dietary carotenoids intake was adjusted for daily total energy intake based on the nutrient density model.We found a significant inverse association between dietary beta-cryptoxanthin intake and depressive symptoms, with lowest prevalence in the third tertile (OR: 0.65, 95% CI: 0.47-0.90, p for trend0.001). Dose-response analyses revealed that the prevalence of depressive symptoms decreased with increasing intakes of beta-cryptoxanthin when reached the point above 110 ug/1000 Kcal. No such association was found for alpha-carotene, beta-carotene, lycopene, and lutein/zeaxanthin.Increase the intake of beta-cryptoxathin-rich foods might protect from depressive symptoms. Further prospective studies are requested before dietary recommendation.

Background The most effective treatment for advanced cirrhosis and portal hypertension is liver transplantation (LT). However, splenomegaly and hypersplenism can persist even after LT in patients with massive splenomegaly. Aim To examine the feasibility of performing partial splenectomy during LT in patients with advanced cirrhosis combined with severe splenomegaly and hypersplenism. Methods Between October 2015 and February 2019, 762 orthotopic LTs were performed for patients with end-stage liver diseases in Tianjin First Center Hospital. Eighty-four cases had advanced cirrhosis combined with severe splenomegaly and hypersplenism. Among these patients, 41 received partial splenectomy during LT (PSLT group), and 43 received only LT (LT group). Patient characteristics, intraoperative parameters, and postoperative outcomes were retrospectively analyzed and compared between the two groups. Results The incidence of postoperative hypersplenism (2/41, 4.8%) and recurrent ascites (1/41, 2.4%) in the PSLT group was significantly lower than that in the LT group (22/43, 51.2%; 8/43, 18.6%, respectively). Seventeen patients (17/43, 39.5%) in the LT group required two-stage splenic embolization, and further splenectomy was required in 6 of them. The operation time and intraoperative blood loss in the PSLT group (8.6 ± 1.3 h; 640.8 ± 347.3 mL) were relatively increased compared with the LT group (6.8 ± 0.9 h; 349.4 ± 116.1 mL). The incidence of postoperative bleeding, pulmonary infection, thrombosis and splenic arterial steal syndrome in the PSLT group was not different to that in the LT group, respectively. Conclusion Simultaneous PSLT is an effective treatment and should be performed in patients with advanced cirrhosis combined with severe splenomegaly and hypersplenism to prevent postoperative persistent hypersplenism.

The purpose of this study was to analyze the acute effect of ambient temperature on hospitalization due to acute exacerbation of chronic obstructive pulmonary disease (AECOPD), stroke, and myocardial infarction (MI) in Shenyang, China. We used the distributed delayed nonlinear model to evaluate the impact of ambient temperature on respiratory and cardiovascular diseases. The study population was divided into four groups: < 65 group and ≥ 65 age groups, female and male groups. The < 65 age group of AECOPD patients was more likely to be affected by high ambient temperature, while the ≥ 65 age group of AECOPD patients was more sensitive to low ambient temperature. The hospitalization risk of MI admission increased in the ≥ 65 age group at 1–8 days delay under low ambient temperature conditions. Supplementary Information The online version contains supplementary material available at 10.1007/s11356-020-11934-2.

We propose and demonstrate a novel and simple wavelength switchable multi-wavelength erbium-doped fiber (EDF) laser based on polarization-dependent loss (PDL) modulation with cascaded fiber Bragg gratings (FBGs) as the wavelength comb filter. PDL is generated and controlled by different polarization angles between the polarization state of each lasing line and the optical fiber polarizer in the laser cavity. The PDL modulation balances the difference between the total loss and the wavelength-dependent lasing gain. The relations among gain, loss, and laser output power under different PDL conditions are numerically analyzed on the basis of a simplified Giles model in an EDF laser system. Results show that multi-wavelength lasing lines can be built up by properly tuning the PDLs in different wavelengths. The amount of lasing lines can be switched by changing the PDL intensity in a certain wavelength. In an experiment, the PDL in that certain wavelength is modulated by utilizing four polarization controllable elements, each of which includes an FBG and a corresponding polarization controller (PC). One PC is used to control the polarization state of the reflected lasing line on the center wavelength of the FBG. A four-wavelength individually switchable EDF laser system is demonstrated by utilizing this wavelength switchable method, in which the switching operation for the single-, dual-, triple-, and four-wavelength laser output is verified. The experimental results are consistent with the theoretical results. All wavelength switching operations are conveniently controlled by merely adjusting the PCs. This simple structure and flexible wavelength switchable operations show that this multi-wavelength EDF laser has great potential in practical applications.

Hypersonic vehicles have been paid more and more attention by various countries, and many developed countries have set off a competition of hypersonic technology. Under this background, this paper creatively applies the reconstruction method based on three vanishing points to the reconstruction of complex aircraft for the first time. The shape of aircraft is restored by photos from different angles, which provides a good help for preliminarily understanding and mastering the information of international mainstream advanced aircraft. In this paper, the feasibility of the whole method is verified by the classical X-37B model, and its three-dimensional structure model can be obtained relatively accurately. In terms of aerodynamic performance evaluation, the panel method is adopted to evaluate the aerodynamic performance on the basis of verifying the reliability of the engineering method. And the results show that the lift-to-drag ratio reaches the maximum of 1.22 at the angle of attack of 25°. This is quite similar to the CFD calculation of class X-37B model in other literatures. The accuracy of the model makes up for the error of the engineering estimation method to a certain extent. In view of the inaccuracy of the wing reconstruction, the genetic algorithm is used to optimize its aerodynamic performances. The lift-to-drag ratio of the wing is increased by 26.3% at 25°, which leads to an increase of 4.35% in the optimal angle of attack lift-to-drag ratio of the whole model. At last, the modularization programming approach is adopted in the optimization process, ensuring the generality of this method, and the whole method will have a broad application prospect.

Objectives Microwave ablation (MWA) is used for the treatment of severe secondary hyperparathyroidism (SHPT), but its efficacy and safety still remained unclear. This study aimed to investigate the efficacy and safety of ultrasound (US)-guided MWA in patients with SHPT. Methods The PubMed, Cochrane library, Embase, China national knowledge infrastructure (CNKI) and Wanfang databases were searched to identify published studies that evaluated the efficacy and safety of US-guided MWA in patients with SHPT. The primary outcomes were parathyroid hormone (PTH), serum calcium and phosphorus levels. Results A total of 26 studies with 932 patients were identified. The PTH levels showed significant reduction at 1 month [weighted mean difference (WMD) = 945.33, 95% CI: 797.15∼1093.52] and 6 months (WMD = 1,151.91, 95% CI: 990.93∼1312.89) after MWA of SHPT patients. The serum calcium (WMD = 0.39, 95% CI: 0.30 ∼ 0.48) and phosphorus levels (WMD = 0.64, 95% CI: 0.43 ∼ 0.85) showed significant reduction at 6 months after MWA of SHPT patients. The most common complications observed were hypocalcemia (35.2%) and transient hoarseness (9.2%). No other major complications or death occurred in our study patients. Conclusion These findings suggest MWA as a safe and effective minimally invasive technique for the management of SHPT. PTH, calcium, and phosphorus levels were significantly reduced at 1 and 6 months after MWA.

Steep-slope transistors are required for low-power electronic applications. However, the strategy to lower the subthreshold swing (SS) remains elusive. Here, we present a method based on altering capacitance constitution to lower the SS of 2-D transistors close to thermionic limit (60 mV/dec). By inducing other 2-D materials with opposite carrier type into the channel, the extra junction capacitance is in series with the channel capacitance, leading to lower semiconductor capacitance and lower SS. The electrical performance of conventional 2-D transistor with pure WSe2 channel and WSe2-BP-MoS2 heterojunction channel is studied and compared. The 2-D transistor with pure WSe2 channel shows SS ~ 110 mV/dec. After forming WSe2-BP-MoS2 heterojunction channel, the SS reduces to ~62 mV/dec and maintains over three orders of magnitude. To reveal the mechanism, a compact model based on Landauer formula has been established. The simulation results indicate that lower SS has strong relation with the reduction of semiconductor capacitance. The proposed structure provides a new way to develop steep-slope transistors.

Organic-inorganic hybrid lead halide perovskites are potential candidates for next-generation light-emitting diodes (LEDs) in terms of tunable emission wavelengths, high electroluminescence efficiency, and excellent color purity. However, the device performance is still limited by severe non-radiative recombination losses and operational instability due to a high degree of defect states on the perovskite surface. Here, an effective surface engineering method is developed via the assistance of guanidinium iodide (GAI), which allows the formation of surface-2D heterophased perovskite nanograins and surface defect passivation due to the bonding with undercoordinated halide ions. Efficient and stable red-emission LEDs are realized with the improved optoelectronic properties of GAI-modified perovskite nanograins by suppressing the trap-mediated non-radiative recombination loss. The champion device with a high color purity at 692 nm achieves an external quantum efficiency of 17.1%, which is 2.3 times that of the control device. Furthermore, the operational stability is highly improved, showing a half-lifetime of 563 min at an initial luminance of 1000 cd m-2. The proposed GAI-assisted surface engineering is a promising approach for defect passivation and phase engineering in perovskite films to achieve high-performance perovskite LEDs.

Predicting compound-protein affinity is beneficial for accelerating drug discovery. Doing so without the often-unavailable structure data is gaining interest. However, recent progress in structure-free affinity prediction, made by machine learning, focuses on accuracy but leaves much to be desired for interpretability. Defining intermolecular contacts underlying affinities as a vehicle for interpretability; our large-scale interpretability assessment finds previously used attention mechanisms inadequate. We thus formulate a hierarchical multiobjective learning problem, where predicted contacts form the basis for predicted affinities. We solve the problem by embedding protein sequences (by hierarchical recurrent neural networks) and compound graphs (by graph neural networks) with joint attentions between protein residues and compound atoms. We further introduce three methodological advances to enhance interpretability: (1) structure-aware regularization of attentions using protein sequence-predicted solvent exposure and residue-residue contact maps; (2) supervision of attentions using known intermolecular contacts in training data; and (3) an intrinsically explainable architecture where atomic-level contacts or "relations" lead to molecular-level affinity prediction. The first two and all three advances result in DeepAffinity+ and DeepRelations, respectively. Our methods show generalizability in affinity prediction for molecules that are new and dissimilar to training examples. Moreover, they show superior interpretability compared to state-of-the-art interpretable methods: with similar or better affinity prediction, they boost the AUPRC of contact prediction by around 33-, 35-, 10-, and 9-fold for the default test, new-compound, new-protein, and both-new sets, respectively. We further demonstrate their potential utilities in contact-assisted docking, structure-free binding site prediction, and structure-activity relationship studies without docking. Our study represents the first model development and systematic model assessment dedicated to interpretable machine learning for structure-free compound-protein affinity prediction.

Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide. Age-related nuclear cataract is heritable (h2 = 0.48), but little is known about specific genetic factors underlying this condition. Here we report findings from the largest to date multi-ethnic meta-analysis of genome-wide association studies (discovery cohort N = 14,151 and replication N = 5299) of the International Cataract Genetics Consortium. We confirmed the known genetic association of CRYAA (rs7278468, P = 2.8 × 10−16) with nuclear cataract and identified five new loci associated with this disease: SOX2-OT (rs9842371, P = 1.7 × 10−19), TMPRSS5 (rs4936279, P = 2.5 × 10−10), LINC01412 (rs16823886, P = 1.3 × 10−9), GLTSCR1 (rs1005911, P = 9.8 × 10−9), and COMMD1 (rs62149908, P = 1.2 × 10−8). The results suggest a strong link of age-related nuclear cataract with congenital cataract and eye development genes, and the importance of common genetic variants in maintaining crystalline lens integrity in the aging eye., Here, the authors report a multi-ethnic genome wide association meta-analysis of 12 studies from the International Cataract Genetics Consortium. They find six new loci associated with age-related nuclear cataract, in addition to replicating the association at CRYAA, and suggest a strong genetic link between age-related nuclear and congenital cataracts.

Refraction methods are often applied to model and image near-surface velocity structures. However, near-surface imaging is very challenging, and no single method can resolve all of the land seismic problems across the world. In addition, deep interfaces are difficult to image from land reflection data due to the associated low signal-to-noise ratio. Following previous research, we have developed a refraction wavefield migration method for imaging shallow and deep interfaces via interferometry. Our method includes two steps: converting refractions into virtual reflection gathers and then applying a prestack depth migration method to produce interface images from the virtual reflection gathers. With a regular recording offset of approximately 3 km, this approach produces an image of a shallow interface within the top 1 km. If the recording offset is very long, the refractions may follow a deep path, and the result may reveal a deep interface. We determine several factors that affect the imaging results using synthetics. We also apply the novel method to one data set with regular recording offsets and another with far offsets; both cases produce sharp images, which are further verified by conventional reflection imaging. This method can be applied as a promising imaging tool when handling practical cases involving data with excessively weak or missing reflections but available refractions.

The service industry is a major pillar of China’s urban economy. Rural migrant workers form the backbone workforce in China’s urban service sector. Despite much attention to the work and life of rural migrants in Chinese cities, urban employers’ regulation and rural migrants’ performance of emotional labour in the service sector remain understudied. Drawing on participant observation and in-depth interviews over eight years, we examine how urban employer and rural migrant workers relationally navigate intersecting emotional and migration regimes to contest, (re)produce and (re)configure rural migrants’ power and status in the urban space. We develop the conceptualization of ‘translocal emotional reflexivity’ to elucidate multiplicated emotional regimes and subjectivities between places of origin and arrival, as well as how emotional reflexivity is mobilized to regulate, navigate and negotiate conflictual translocal emotional subjectivities. We discuss the ‘institutionalized individualization’ of emotional labour—a process in which an employer systematically engineers a sense of emotional agency for workers to reimagine, re-appropriate and individualize their emotional performance to serve institutional aims—as a distinctive feature of how the regulation and performance of emotional labour has evolved over the past decade in China.

Purpose. To compare the corneal biomechanical properties between post-LASIK ectasia and primary keratoconus. Methods. A total of 42 eyes of 42 patients with matching age and central corneal thickness (CCT) were divided into two groups according to diagnosis of post-LASIK ectasia (PLE group; n = 21; age range: 22–47 years) and primary keratoconus (KC group; n = 21; age range: 21–47 years). The corneal biomechanical properties were assessed using Scheimpflug-based technology (Corvis ST; Oculus Optikgeräte, Wetzlar, Germany). The paired t-test and linear regression analysis were performed. Results. The PLE group had significantly higher mean stiffness parameter at the first applanation (SP-A1; 76.65 ± 21.66 vs 52.72 ± 13.65, p ≤ 0.001 ) and mean stress-strain index (SSI) (SSI: 0.78 ± 0.16 versus 0.64 ± 0.12, p = 0.001 ) than the KC group. SP-A1 was positively correlated with CCT in the PLE group (Pearson’s r = 0.816, p ≤ 0.001 ), but not in the KC group (Pearson’s r = −0.014, p = 0.952 ). No statistical correlation was observed between SSI and CCT in either group (Pearson’s r = 0.292, p = 0.199 , and Pearson’s r = 0.004, p = 0.985 , respectively). Conclusions. In our case series, KC manifested more severe than PLE in biomechanical properties. Since SSI measurements were independent of corneal thickness, it can be used for corneal biomechanical assessment.

Objective To improve the accuracy of clinical diagnosis by analyzing different contrast-enhanced ultrasound (CEUS) imagines of specific subtypes of uterine leiomyomas. Methods A total of 147 female patients received preoperative CEUS examination. The scanning plane of the biggest tumors for CEUS was found by common B-mode ultrasonographic scanning on pelvic cavity, then 1.5 mL SonoVue were injected into the median cubital vein. According to the CEUS images, the lesion enhanced time, enhanced level and enhanced morphology were recorded. The time-intensity curve was acquired and analyzed, meanwhile, the relevant parameters were calculated, including rise time (RT), peak intensity (PI), time to peak (TTP) and mean transit time (MTT). Results In cellular uterine leiomyoma group, the percentage of high enhancement, early enhancement was higher, equal enhancement and synchronic enhancement were lower than those in the common uterine leiomyomas group. In hysteromyoma with hyaline degeneration group, the percentage of high enhancement, early enhancement was lower, while low enhancement and delayed enhancement were higher than those in the common uterine leiomyomas group. The ratio of PI in cellular uterine leiomyoma group was the highest, but the ratios of RT, TTP and MTT were the lowest of the three benign groups. The ratio of PI in hysteromyoma with hyaline degeneration group was the lowest, while the ratios of RT and TTP was the highest among the three benign groups. Conclusion Different pathological types of uterine leiomyomas have their own signal performance on CEUS. CEUS can be used to infer their pathological types and help differential diagnosis.

Background Hereditary multiple exostoses (HME), a rare genetic pediatric disorder, has a peculiar pathogenic mechanism. The results of previous studies have shown that HME is associated with mutations of the EXT1 and EXT2 genes at a molecular genetics level. In our study, two families who received therapy in the Department of Orthopedics of Shanghai Children's Hospital between June, 2017 and November, 2018 were recruited, and a mutational analysis of the EXT1 genes was conducted to further elucidating the relationship between HME and EXT1. Methods Venous blood samples were collected from individuals with HME and their families. Exon sequencing and RT-PCR were performed to comprehensively analyze 11 exons of the EXT1 gene. Results The deletion of exon 7 and the 2397 G>T mutation in exon 7 caused deletion mutation and nonsense mutation only in the HME patients. The mutations in exon 7 were tested and verified by Sanger sequencing. RT-PCR showed that the mRNA expression of EXT1 was significantly decreased in the mutation samples compared with the normal samples, which exerted a great influence on the function of EXT1. Conclusions This study identified new mutation sites for the pathogenesis of HME and further clarified the relationship between HME and EXT1.

Objective To observe the clinical therapeutic effect of adjuvant treatment with heat-sensitive moxibustion for coronavirus disease 2019 (COVID-19) of the ordinary type. Methods A total of 42 patients with COVID-19 of the ordinary type were adopted. Shenque (神阙 CV8) and Tiānshū (天枢 ST25) were selected. Heat-sensitive moxibustion was operated according to the required standard, 40 min to 60 min each time, once daily. Before and after moxibustion, the improvements in clinical symptoms were evaluated, such as chest oppression, poor appetite, lassitude and negative emotions. Results (1) The number of cases and the incidence was 21 cases (50.0%), 24 cases (57.1%) and 26 cases (61.9%) for chest oppression, poor appetite and lassitude before heat-sensitive moxibustion. The number of cases was reduced to be 10 cases (23.8%), 7 cases (16.7%) and 4 cases (9.5%) after the 1st treatment of heat-sensitive moxibustion for chest oppression, poor appetite, and lassitude. It was reduced to be 11 cases (26.2%), 8 cases (19.0%) and 4 cases (9.5%) after the 2nd treatment of moxibustion and it was reduced to be 18 cases (42.9%), 10 cases (23.8%) and 6 cases (14.3%) after the 3rd treatment of moxibustion. The incidences of the symptoms were all reduced obviously as compared with those before treatment. (2) Before treatment with heat-sensitive moxibustion, there were 24 cases of negative emotions (57.1%). It was reduced to be 16 cases (38.1%), 11 cases (26.2%) and 3 cases (7.1%) after the 1st, 2nd and 3rd treatment of heat-sensitive moxibustion successively. The incidences were all reduced obviously as compared with those before treatment. (3) After the 1st treatment, the active acceptance rate of heat-sensitive moxibustion was 100% (42/42) in the patients, higher than 11.9% (5/42) before treatment. Conclusion Adjuvant treatment with heat-sensitive moxibustion effectively relieves the symptoms of COVID-19 such as chest oppression, poor appetite and lassitude, and alleviates the negative emotions, such as tension and anxiety. This therapy improves the therapeutic effect of COVID-19 and deserves to be promoted in clinical practice.

Although massive data is quickly accumulating on protein sequence and structure, there is a small and limited number of protein architectural types (or structural folds). This study is addressing the following question: how well could one reveal underlying sequence-structure relationships and design protein sequences for an arbitrary, potentially novel, structural fold? In response to the question, we have developed novel deep generative models, namely, semisupervised gcWGAN (guided, conditional, Wasserstein Generative Adversarial Networks). To overcome training difficulties and improve design qualities, we build our models on conditional Wasserstein GAN (WGAN) that uses Wasserstein distance in the loss function. Our major contributions include (1) constructing a low-dimensional and generalizable representation of the fold space for the conditional input, (2) developing an ultrafast sequence-to-fold predictor (or oracle) and incorporating its feedback into WGAN as a loss to guide model training, and (3) exploiting sequence data with and without paired structures to enable a semisupervised training strategy. Assessed by the oracle over 100 novel folds not in the training set, gcWGAN generates more successful designs and covers 3.5 times more target folds compared to a competing data-driven method (cVAE). Assessed by sequence- and structure-based predictors, gcWGAN designs are physically and biologically sound. Assessed by a structure predictor over representative novel folds, including one not even part of basis folds, gcWGAN designs have comparable or better fold accuracy yet much more sequence diversity and novelty than cVAE. The ultrafast data-driven model is further shown to boost the success of a principle-driven de novo method (RosettaDesign), through generating design seeds and tailoring design space. In conclusion, gcWGAN explores uncharted sequence space to design proteins by learning generalizable principles from current sequence-structure data. Data, source codes, and trained models are available at https://github.com/Shen-Lab/gcWGAN.