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The red-hot U.S. housing market that has enriched property owners in recent years while squeezing renters and first-time home buyers is showing flickers of slowing down. Though rents and home [...]

While polymerization-induced self-assembly (PISA) has become a preferred synthetic route toward amphiphilic block copolymer self-assemblies, predicting their phase behavior from experimental design is extremely challenging, requiring time and work-intensive creation of empirical phase diagrams whenever self-assemblies of novel monomer pairs are sought for specific applications. To alleviate this burden, we develop here the first framework for a data-driven methodology for the probabilistic modeling of PISA morphologies based on a selection and suitable adaption of statistical machine learning methods. As the complexity of PISA precludes generating large volumes of training data with in silicosimulations, we focus on interpretable low variance methods that can be interrogated for conformity with chemical intuition and that promise to work well with only 592 training data points which we curated from the PISA literature. We found that among the evaluated linear models, generalized additive models, and rule and tree ensembles, all but the linear models show a decent interpolation performance with around 0.2 estimated error rate and 1 bit expected cross entropy loss (surprisal) when predicting the mixture of morphologies formed from monomer pairs already encountered in the training data. When considering extrapolation to new monomer combinations, the model performance is weaker but the best model (random forest) still achieves highly nontrivial prediction performance (0.27 error rate, 1.6 bit surprisal), which renders it a good candidate to support the creation of empirical phase diagrams for new monomers and conditions. Indeed, we find in three case studies that, when used to actively learn phase diagrams, the model is able to select a smart set of experiments that lead to satisfactory phase diagrams after observing only relatively few data points (5–16) for the targeted conditions. The data set as well as all model training and evaluation codes are publicly available through the GitHub repository of the last author.

Switching control strategies that unite a potentially high-performance but uncertified controller and a stabilizing albeit conservative controller are shown to be able to balance safety with efficiency, but have been less studied under partial observation of state. To address this gap, we propose a switching control strategy for partially observed linear-Gaussian systems with provable performance guarantees. We show that the proposed switching strategy is both safe and Efficient, in the sense that: (1) the linear-quadratic cost of the system is always bounded even if the original uncertified controller is destabilizing; (2) in the case when the uncertified controller is stabilizing, the performance loss induced by the conservativeness of switching converges super-exponentially to zero. The effectiveness of the switching strategy is also demonstrated via numerical simulation on the Tennessee Eastman Process.

The long-term complications of COVID-19, known as the post-acute sequelae of SARS-CoV-2 infection (PASC), significantly burden healthcare resources. Quantifying the demand for post-acute healthcare is essential for understanding patients’ needs and optimizing the allocation of valuable medical resources for disease management. Driven by this need, we developed a heterogeneous latent transfer learning framework (Latent-TL) to generate critical insights for individual health systems in a distributed research network. Latent-TL enhances learning in a specific health system by borrowing information from all other health systems in the network in a data-driven fashion. By identifying subpopulations with varying healthcare needs, our Latent-TL framework can provide more effective guidance for decision-making. Applying Latent-TL to electronic health record (EHR) data from eight health systems in PEDSnet, a national learning health system in the US, revealed four distinct patient subpopulations with heterogeneous post-acute healthcare demands following COVID-19 infections, varying across subpopulations and hospitals.

Air-self-charging aqueous zinc-ion batteries (AZIBs) are a promising system applied in some special occasions, where no external power source can be provided to recharge the battery. Here, a new π-conjugated aromatic compound 2,7,12-tri(4H-1,2,4-triazol-4-yl)-1H-pyrrolo [3,4-b]pyrrolo[3′,4′:5,6]pyrazino[2,3f]pyrrolo[3′,4′:5,6]pyrazi-no[2,3−h]quinoxaline-1,3,6,8,11,13(2H,7H,12H)-hexaone (THQH) is reported. Because THQH contains multiple redox-active groups (CN and CO) and its insolubility in 2 M ZnSO4, as the cathode material of flexible/coin-type AZIBs, it owns outstanding discharge specific capacity, higher-rate performance and longer cycle life. Various ex-situexperiments and theoretical calculation revealed H+and Zn2+participated in the THQH cathode reaction. Notably, as the discharged flexible Zn//THQH battery is exposed to air, it can be self-recharged viathe redox reaction between oxygen in air and the discharged THQH cathode, along with H+ions removal. The flexible Zn//THQH battery can deliver a discharge capacity of up to 566 mA h g−1at 0.5 A g−1, a higher-rate capability and an excellent self-charging cycle stability (31 cycles) after exposed to air for 28 h, displaying an excellent reusability. This work paves a way for the development of high-performance flexible air self-charging AZIBs.

In order to overcome the shortcomings of traditional self-charging systems with complex structures, it is necessary to develop new self-charging systems with simple structures. Herein, a flexible chemically self-charging aqueous Zn-ion battery (AZIB) using hexachlorohexaazatrinaphthylene (HCLHATN) cathode with simple structure is constructed. The flexible Zn//HCLHATN battery not only has higher volumetric energy density (10.63 mWh cm−3), but also superior flexibility and good stability. Notably, the redox reaction can happen between O2from air and the discharged HCLHATN cathode, which results in the flexible discharged Zn//HCLHATN battery owning chemically self-charging capability. Thus, such flexible Zn//HCLHATN battery after being exposed to air for 15 h, can not only deliver a high discharge capacity (226 mA h g−1at 0.5 A g−1) and a high rate-capability (169 mA h g−1at 10 A g−1), but also a higher cycle stability (6 cycles) for self-charging and operate smoothly at hybrid modes of galvanostatic or/and chemical charging, showing excellent reusability. Our research renders a new guidance for obtaining high-rate and chemically self-charging flexible AZIBs.

• A 900 nm-thick tungsten film with novel double-layer architecture was prepared by high vacuum magnetron sputtering method. • β-W nucleation is intrinsically favoured on the SiO 2 substrate due to its low surface energy, based on thermodynamic calculation. • The preferred orientation of β-W changes from [200] to [211] with rising layer thickness, which is mainly controlled by elastic strain energy. • The β→α phase transformation is fulfilled by α/β interface propagation rather than local atomic rearrangements. Metastable phase in tungsten film is of great interests in recent years due to its giant spin Hall effects, however, little information has been known on its nucleation, growth and phase transformation. In this paper, a 900 nm-thick tungsten film with double-layer structure (α-W underlayer and β-W above it) was produced on SiO 2 /Si substrate by high vacuum magnetron sputtering at room temperature. The structural properties of β-W were systemically investigated by X-ray diffraction, transmission electron microscopy, thermodynamic calculation, first-principle and phase-field simulations. It is found that the β-W nucleation is energetically favoured on the SiO 2 surface compared to the α-W one. As the film thickening proceeds, β-W[211] turns to be preferred direction of growth owing to the elastic strain energy minimization, which is verified by phase-field simulations. Moreover, the β → α phase transformation takes place near the film-substrate interface while the rest of the film keeps the β-W phase, leading to a double-layer structure. This localized phase transition is induced by lower Gibbs free energy of α-W phase at larger grain sizes, which can be confirmed by thermodynamic calculation. Further in-situ heating TEM analysis of the as-deposited film reveals that the β→α phase transformation is fulfilled by α/β interface propagation rather than local atomic rearrangements. Our findings offer valuable insights into the intrinsic properties of metastable phase in tungsten. [Display omitted] [ABSTRACT FROM AUTHOR]

Eosinophilic inflammation is a feature of allergic asthma. Despite mounting evidence showing that chromatin filaments released from neutrophils mediate various diseases, the understanding of extracellular DNA from eosinophils is limited. Here we show that eosinophil extracellular traps (EETs) in bronchoalveolar lavage fluid are associated with the severity of asthma in patients. Functionally, we find that EETs augment goblet-cell hyperplasia, mucus production, infiltration of inflammatory cells and expressions of type 2 cytokines in experimental non-infection-related asthma using both pharmaceutical and genetic approaches. Multiple clinically relevant allergens trigger EET formation at least partially via thymic stromal lymphopoietin in vivo. Mechanically, EETs activate pulmonary neuroendocrine cells via the CCDC25–ILK–PKCα–CRTC1 pathway, which is potentiated by eosinophil peroxidase. Subsequently, the pulmonary neuroendocrine cells amplify allergic immune responses via neuropeptides and neurotransmitters. Therapeutically, inhibition of CCDC25 alleviates allergic inflammation. Together, our findings demonstrate a previously unknown role of EETs in integrating immunological and neurological cues to drive asthma progression.

A therapeutic vaccine that prevents recurrent tuberculosis would be a major advance in the development of shorter treatment regimens. We aimed to assess the safety and immunogenicity of the ID93 + GLA-SE vaccine at various doses and injection schedules in patients with previously treated tuberculosis.

Reduced infiltration of anti-tumor lymphocytes remains a major cause of tumor immune evasion and is correlated with poor cancer survival. Here, we found that upregulation of regulator of G protein signaling (RGS)1 in helper TH1 cells and cytotoxic T lymphocytes (CTLs) reduced their trafficking to and survival in tumors and was associated with shorter survival of patients with breast and lung cancer. RGS1 was upregulated by type II interferon (IFN)–signal transducer and activator of transcription (STAT)1 signaling and impaired trafficking of circulating T cells to tumors by inhibiting calcium influx and suppressing activation of the kinases ERK and AKT. RGS1knockdown in adoptively transferred tumor-specific CTLs significantly increased their infiltration and survival in breast and lung tumor grafts and effectively inhibited tumor growth in vivo, which was further improved when combined with programmed death ligand (PD-L)1 checkpoint inhibition. Our findings reveal RGS1 is important for tumor immune evasion and suggest that targeting RGS1 may provide a new strategy for tumor immunotherapy.

Standard flow cytometry-based assays can determine the cytotoxicity of immune effector cells, but it is challenging to monitor the dynamic processes of cytotoxicity. Here, we present a protocol for continuous observation of NK cell-mediated cytotoxicity with microwell arrays using an automated microscope. We describe steps for isolating and labeling primary NK cells, loading cells onto microwell arrays, monitoring target well, and image analysis. This protocol facilitates observation of the dynamics of immune-target cell interactions at the single-cell level.

Aqueous zinc-ion batteries (AZIBs) have attracted much attention for owing to their environmental friendliness, low cost and high safety. Organic compounds have emerged as promising cathode materials for AZIBs due to their abundance of active sites, structural tunability and renewability. Here, a new π-conjugated compound with multiple active sites tris(3-amino-1,2,4-triazolyl) hexaazatriphenylenehexacarboxy triimide (TAT-HATTI) is prepared and evaluated firstly as a cathode material for AZIBs. The TAT-HATTI electrode displays a high discharge specific capacity (531 mAh g−1at 0.05 A g−1), high-rate performance and better cycle stability (capacity retention of 78 % after 1000 cycles at 2 A g−1). The research results reveal that the electrode reaction mechanism involves insertion/extraction of Zn2+and H+ions. Impressively, the assembled flexible aqueous Zn//TAT-HATTI battery exhibits the higher volumetric energy density (4.4 mWh cm−3), high-rate capability, better cycle stability and superior flexibility, owning an application potential in wearable electronics.

AbstractContext:Osteoporosis (OP) is a progressive systemic bone disease. Dual-energy X-ray absorptiometry (DXA) is routinely employed and is considered the gold standard method for the diagnosis of OP.Objective:We aimed to investigate the potential use of combined information from multiple bone turnover markers (BTMs) as a clinical diagnostic tool for OP.Materials and methods:A total of 9053 Chinese postmenopausal women (2464 primary OP patients and 6589 healthy controls) were recruited. Serum levels of six common BTMs, including BAP, BSP, CTX, OPG, OST and sRANKL were assayed. Models based on support vector machine (SVM) were constructed to explore the efficiency of different combinations of multiple BTMs for OP diagnosis.Results:Increasing the number of BTMs used in generating the models increased the predictive power of the SVM models for determining the disease status of study subjects. The highest kappa coefficient for the model with one BTM (BAP) compared to DXA was 0.7783. The full model incorporating all six BTMs resulted in a high kappa coefficient of 0.9786.Conclusion:Our findings showed that although single BTMs were not sufficient for OP diagnosis, appropriate combinations of multiple BTMs incorporated into the SVM models showed almost perfect agreement with the DXA.

Activation-induced cell death (AICD) of T lymphocytes can be exploited by cancers to escape immunological destruction. We demonstrated that tumor-specific cytotoxic T lymphocytes (CTLs) and type 1 helper T (TH1) cells, rather than type 2 helper T cells and regulatory T cells, were sensitive to AICD in breast and lung cancer microenvironments. NKILA, an NF-?B-interacting long noncoding RNA (lncRNA), regulates T cell sensitivity to AICD by inhibiting NF-?B activity. Mechanistically, calcium influx in stimulated T cells via T cell–receptor signaling activates calmodulin, thereby removing deacetylase from the NKILA promoter and enhancing STAT1-mediated transcription. Administering CTLs with NKILA knockdown effectively inhibited growth of breast cancer patient-derived xenografts in mice by increasing CTL infiltration. Clinically, NKILA overexpression in tumor-specific CTLs and TH1 cells correlated with their apoptosis and shorter patient survival. Our findings underscore the importance of lncRNAs in determining tumor-mediated T cell AICD and suggest that engineering lncRNAs in adoptively transferred T cells might provide a novel antitumor immunotherapy.

IMPORTANCE: Cost variation among hospitals has been demonstrated for surgical procedures. Uncovering these differences has helped guide measures taken to reduce health care spending. To date, the fiscal consequence of hospital variation for autologous free flap breast reconstruction is unknown. OBJECTIVE: To investigate factors that influence cost variation for autologous free flap breast reconstruction. DESIGN, SETTING, AND PARTICIPANTS: A secondary cross-sectional analysis was performed using the Healthcare Cost and Utilization Project National Inpatient Sample database from 2008 to 2010. The dates of analysis were September 2016 to February 2017. The setting was a stratified sample of all US community hospitals. Participants were female patients who were diagnosed as having breast cancer or were at high risk for breast cancer and underwent autologous free flap breast reconstruction. MAIN OUTCOMES AND MEASURES: Variables of interest included demographic data, hospital characteristics, length of stay, complications (surgical and systemic), and inpatient cost. The study used univariate and generalized linear mixed models to examine associations between patient and hospital characteristics and cost. RESULTS: A total of 3302 patients were included in the study, with a median age of 50 years (interquartile range, 44-57 years). The mean cost for autologous free flap breast reconstruction was $22 677 (interquartile range, $14 907-$33 391). Flap reconstructions performed at high-volume hospitals were significantly more costly than those performed at low-volume hospitals ($24 360 vs $18 918, P < .001). Logistic regression demonstrated that hospital volume correlated with increased cost (Exp[β], 1.06; 95% CI, 1.02-1.11; P = .003). Fewer surgical complications (16.4% [169 of 1029] vs 23.7% [278 of 1174], P < .001) and systemic complications (24.2% [249 of 1029] vs 31.2% [366 of 1174], P < .001) were experienced in high-volume hospitals compared with low-volume hospitals. Flap procedures performed in the West were the most expensive ($28 289), with a greater odds of increased expenditure (Exp[β], 1.53; 95% CI, 1.46-1.61; P < .001) compared with the Northeast. A significant difference in length of stay was found between the West and Northeast (odds ratio, 1.25; 95% CI, 1.17-1.33). CONCLUSIONS AND RELEVANCE: There is significant cost variation among patients undergoing autologous free flap breast reconstruction. Experience, as measured by a hospital’s volume, provides quality health care with fewer complications but is more costly. Longer length of stay contributed to regional cost variation and may be a target for decreasing expenditure, without compromising care. In the era of bundled health care payment, strategies should be implemented to eliminate cost variation to condense spending while still providing quality care.

Supplemental Digital Content is available in the text.

IMPORTANCE: With the stabilization of breast cancer incidence and substantial improvement in survival, more attention has focused on postmastectomy breast reconstruction (PBR). Despite its demonstrated benefits, wide disparities in the use of PBR remain. Physician-patient communication has an important role in disparities in health care, especially for elective surgical procedures. Recognizing this, the State of New York enacted Public Health Law (NY PBH Law) 2803-o in 2011 mandating that physicians communicate about reconstructive surgery with patients undergoing mastectomy. OBJECTIVE: To evaluate whether mandated physician-patient communication is associated with reduced racial/ethnic disparities in immediate PBR (IPBR). DESIGN, SETTING, AND PARTICIPANTS: This retrospective study used state inpatient data from January 1, 2008, through December 31, 2011, in New York and California to evaluate a final sample of 42 346 women aged 20 to 70 years, including 19 364 from New York (treatment group) and 22 982 from California (comparison group). The primary hypothesis tested the effect of the New York law on racial/ethnic disparities, using California as a comparator. The National Academy of Medicine’s (formerly Institute of Medicine) definition of a disparity was applied, and a difference-in-differences method (before-and-after comparison design) was used to evaluate the association of NY PBH Law 2803-o mandating physician-patient communication with disparities in IPBR. Data were analyzed from July 1, 2016, to February 24, 2017. EXPOSURES: New York PBH Law 2803-o was implemented on January 1, 2011. The preexposure period included January 1, 2008, through December 31, 2010 (3 years); the postexposure period, January 1 through December 31, 2011 (1 year). MAIN OUTCOMES AND MEASURES: The primary outcome was use of IPBR among white, African American, Hispanic, and other minority groups before and after the implementation of NY PBH Law 2803-o. RESULTS: Among the 42 346 women (mean [SD] age, 53 [10] years), 65.3% (27 654) were white, 12.7% (5365) were Hispanic, 9.4% (3976) were African American, and 12.6% (5351) were other minorities. The new legislation was not associated with the overall IPBR rate or disparity in IPBR between whites and African Americans (reduction of 1 percentage point; 95% CI, −0.02 to 0.04), but it was associated with a reduction in disparities in IPBR between Hispanic and white patients by 9 (95% CI, 0.06-0.11) percentage points and between other minorities and white patients by 13 (95% CI, 0.11-0.16) percentage points. CONCLUSIONS AND RELEVANCE: Physician-patient communication may help to address inequity in the use of elective surgical procedures, such as IPBR. However, lack of patient trust and/or effective physician-patient communication may reduce the potential effect of mandatory communication for some subpopulations, including African American individuals.

Supplemental Digital Content is available in the text.

Supplemental Digital Content is available in the text.

The best assay or marker to define mRNA-1273 vaccine–induced antibodies as a correlate of protection (CoP) is unclear. In the COVE trial, participants received two doses of the mRNA-1273 COVID-19 vaccine or placebo. We previously assessed IgG binding antibodies to the spike protein (spike IgG) or receptor binding domain (RBD IgG) and pseudovirus neutralizing antibody 50 or 80% inhibitory dilution titer measured on day 29 or day 57, as correlates of risk (CoRs) and CoPs against symptomatic COVID-19 over 4 months after dose. Here, we assessed a new marker, live virus 50% microneutralization titer (LV-MN50), and compared and combined markers in multivariable analyses. LV-MN50was an inverse CoR, with a hazard ratio of 0.39 (95% confidence interval, 0.19 to 0.83) at day 29 and 0.51 (95% confidence interval, 0.25 to 1.04) at day 57 per 10-fold increase. In multivariable analyses, pseudovirus neutralization titers and anti-spike binding antibodies performed best as CoRs; combining antibody markers did not improve correlates. Pseudovirus neutralization titer was the strongest independent correlate in a multivariable model. Overall, these results supported pseudovirus neutralizing and binding antibody assays as CoRs and CoPs, with the live virus assay as a weaker correlate in this sample set. Day 29 markers performed as well as day 57 markers as CoPs, which could accelerate immunogenicity and immunobridging studies.

Single-cell analysis of tumor-infiltrating lymphocytes obtained before and after preoperative therapy reflects the dynamic interplay of the tumor and immune system during treatment. Here, we present a protocol to implement single-cell analysis of tumor-infiltrating B cells, which were isolated from paired human breast cancers before and after neo-adjuvant chemotherapy. This protocol also facilitates isolation and single-cell analysis of other tumor-infiltrating lymphocytes.