A Sulfonated Covalent Organic Framework for Atmospheric Water Harvesting.

We report a sulfonated covalent organic framework (COF) capable of atmospheric water harvesting in arid conditions. The isothermal water uptake profile of the framework was studied, and the network displayed steep water sorption at low relative humidity (RH) in temperatures of up to 45 °C, reaching a water uptake of 0.12 g g-1 at 10 % RH and even 0.08 g g-1 at just 5 % RH, representing some of the most extreme conditions on the planet. We found that the inclusion of sulfonate moieties shifted uptake in the water isotherm profiles to lower RH compared to non-sulfonated equivalents, demonstrating well the benefits of including these hydrophilic sites for water uptake in hot, arid locations. Repeated uptake and desorption cycles were performed on the material without significant detriment to its adsorption performance, demonstrating the potential of the sulfonated COF for real-world implementation.

Nuances in the interpretation and utility of donor-derived cell-free DNA in lung transplantation following allogeneic hematopoietic stem cell transplantation - Case report.

Respiratory complications following allogeneic HSCT can lead to severe morbidity and mortality. Lung transplantation (LT) is a potential treatment for select patients with late-onset non-infectious pulmonary complications post-HSCT. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive biomarker for monitoring the health of allografts following LT. However, its utility in a multi-genome setting of LT after HSCT has not yet been clinically validated. Here we describe a case of a 75-year-old, male patient who underwent single-lung transplantation for BOS related to chronic GVHD and presented with persistently elevated dd-cfDNA levels. In a surveillance biopsy, the patient was diagnosed with mild acute cellular rejection at three months. The patient's lung function remained stable, and the reported dd-cfDNA levels decreased after the rejection episode but remained elevated above levels that would be considered quiescent for LT alone. In this unique setting, as 3 different genomes contributed to the dd-cfDNA% reported value, valuable insight was obtained by performing further analysis to separate the specific SNPs to identify the contribution of recipient, lung-donor, and HSCT-donor cfDNA. This study highlights the potential utility of dd-cfDNA in the multi-genome setting of lung transplant post-HSCT, nuances that need to be considered while interpreting the results, and its value in monitoring lung rejection.

Nivolumab + Tacrolimus + Prednisone ± Ipilimumab for Kidney Transplant Recipients With Advanced Cutaneous Cancers.

PURPOSE: Cancer-related mortality rates among kidney transplant recipients (KTR) are high, but these patients have largely been excluded from trials of immune checkpoint inhibitors because of immunosuppression and risk of treatment-related allograft loss (TRAL). We conducted a prospective clinical trial testing nivolumab (NIVO) + tacrolimus (TACRO) + prednisone (PRED) ± ipilimumab (IPI) in KTR with advanced cutaneous cancers. METHODS: Adult KTR with advanced melanoma or basal, cutaneous squamous, or Merkel cell carcinomas were eligible. Immunosuppression was standardized to TACRO (serum trough 2-5 ng/mL) + PRED 5 mg once daily. Patients then received NIVO 480 mg IV once every 4 weeks. The primary composite end point was partial or complete (tumor) response (CR) or stable disease per RECIST v1.1 without allograft loss at 16W. Patients with progressive disease (PD) could receive IPI 1 mg/kg IV + NIVO 3 mg/kg once every 3 weeks × 4 followed by NIVO. Donor-derived cell-free DNA (dd-cfDNA) levels were measured approximately once every 2 weeks as a potential predictor of allograft rejection. RESULTS: Among eight evaluable patients, none met the trial's primary end point. All eight patients experienced PD on NIVO + TACRO + PRED; TRAL occurred in one patient. Six patients then received IPI + NIVO + TACRO + PRED. Best overall responses: two CR (one with TRAL) and four PD (one with TRAL). In total, 7 of 8 pre-NIVO tumor biopsies contained a paucity of infiltrating immune cells. In total, 2 of 5 on-NIVO biopsies demonstrated moderate immune infiltrates; both patients later experienced a CR to IPI + NIVO. In 2 of 3 patients with TRAL, dd-cfDNA elevations occurred 10 and 15 days before increases in serum creatinine. CONCLUSION: In most KTR with advanced skin cancer, TACRO + PRED provides insufficient allograft protection and compromises immune-mediated tumor regression after administration of NIVO ± IPI. Elevated dd-cfDNA levels can signal treatment-related allograft rejection earlier than rises in serum creatinine.

Development and Validation of a Multiclass Model Defining Molecular Archetypes of Kidney Transplant Rejection: A Large Cohort Study of the Banff Human Organ Transplant Gene Expression Panel.

Gene expression profiling from formalin-fixed paraffin-embedded (FFPE) renal allograft biopsies is a promising approach for feasibly providing a molecular diagnosis of rejection. However, large-scale studies evaluating the performance of models using NanoString platform data to define molecular archetypes of rejection are lacking. We tested a diverse retrospective cohort of over 1400 FFPE biopsy specimens, rescored according to Banff 2019 criteria and representing 10 of 11 United Network of Organ Sharing regions, using the Banff Human Organ Transplant panel from NanoString and developed a multiclass model from the gene expression data to assign relative probabilities of 4 molecular archetypes: No Rejection, Antibody-Mediated Rejection, T Cell-Mediated Rejection, and Mixed Rejection. Using Least Absolute Shrinkage and Selection Operator regularized regression with 10-fold cross-validation fitted to 1050 biopsies in the discovery cohort and technically validated on an additional 345 biopsies, our model achieved overall accuracy of 85% in the discovery cohort and 80% in the validation cohort, with ≥75% positive predictive value for each class, except for the Mixed Rejection class in the validation cohort (positive predictive value, 53%). This study represents the technical validation of the first model built from a large and diverse sample of diagnostic FFPE biopsy specimens to define and classify molecular archetypes of histologically defined diagnoses as derived from Banff Human Organ Transplant panel gene expression profiling data.

Real-time gigahertz free-space quantum key distribution within an emulated satellite overpass.

Satellite quantum key distribution (SatQKD) intermediated by a trusted satellite in a low-Earth orbit to ground stations along the satellite's path allows remote users to connect securely. To establish a secure connection, a SatQKD session must be conducted to each user over a dynamically changing free-space link, all within just a few hundred seconds. Because of the short time and large losses under which the QKD protocol will be implemented, it has not yet been possible to form a complete key by transmitting all the relevant information required within a single overpass of the satellite. Here, we demonstrate a real-time QKD system that is capable of forming a 4.58-megabit secure key between two nodes within an emulated satellite overpass. We anticipate that our system will set the stage for practical implementations of intercontinental quantum secure communications that can operate over large networks of nodes and enable the secure transmission of data globally.

Measurement of Physicochemical Properties and CO2, N2, Ar, O2, and H2O Unary Adsorption Isotherms of Purolite A110 and Lewatit VP OC 1065 for Application in Direct Air Capture.

Direct air capture (DAC) using solid adsorbents has gained significant attention as a carbon dioxide removal (CDR) technology to help limit global temperature rise to below 2 °C. One large area of focus is the development of new adsorbent materials for DAC. However, the necessary data needed to employ these materials in process models for adsorbent screening are rarely available. Here, we showcase Purolite A110, a commercially available amine-functionalized polymeric resin, as a new candidate adsorbent for DAC and compare its properties to a current benchmark, Lewatit VP OC 1065. For both materials, we report their chemical features and composition, skeletal, particle, and bed density, total pore volume, particle porosity, BET area, thermal stability, and specific heat capacity. We determine their equilibrium sorption properties by measuring the volumetric CO2 isotherms at 288, 298, 308, 333, 343, 353, and 393 K, N2 and H2O isotherms at 288, 298, and 308 K, and Ar and O2 isotherms at 298 K. For CO2, N2, and H2O, we also present the corresponding isotherm model fitting parameters and heats of adsorption. These data can help facilitate process modeling and optimization studies to properly assess these adsorbents at scale.

A Robust and Low-Cost Sulfonated Hypercrosslinked Polymer for Atmospheric Water Harvesting.

The availability of freshwater is rapidly declining due to over-exploitation and climate change, with multiple parts of the globe already facing significant freshwater scarcity. Here, a sulfonated hypercrosslinked polymer able to repeatedly harvest significant amounts of water via direct air capture is reported. Water uptake from relative humidities as low as 10% is demonstrated, mimicking some of the harshest environments on Earth. A water harvesting device is used to show repeated uptake and harvesting without significant detriment to adsorbent performance. Desorption is triggered using simulated sunlight, presenting a low-energy route to water harvesting and adsorbent regeneration. The synthesis of sulfonated hypercrosslinked polymer requires only low-cost and readily available reagents, offering excellent potential for scale-up. Due to an almost limitless supply of water vapor from air in most regions around the globe, this approach can transform our ability to address water security concerns.

Fabrication of graded porous structure of hydroxypropyl cellulose hydrogels via temperature-induced phase separation.

A novel hydroxypropyl cellulose (gHPC) hydrogel with graded porosity has been fabricated, in which pore size, shape, and mechanical properties vary across the material. The graded porosity was achieved by cross-linking different parts of the hydrogel at temperatures below and above 42 °C, which was found to be the temperature of turbidity onset (lower critical solution temperature, LCST) for the HPC and divinylsulfone cross-linker mixture. Scanning electron microscopy imaging revealed a decreasing pore size along the cross-section of the HPC hydrogel from the top to the bottom layer. HPC hydrogels demonstrate graded mechanical properties whereby the top layer, Zone 1, cross-linked below LCST, can be compressed by about 50% before fracture, whereas the middle and bottom layers (Zone 2 and 3, respectively) cross-linked at 42 °C, can withstand 80% compression before failure. This work demonstrates a straightforward, yet novel, concept of exploiting a graded stimulus to incorporate a graded functionality into porous materials that can withstand mechanical stress and minor elastic deformations.

Hyper crosslinked polymer supported NHC stabilized gold nanoparticles with excellent catalytic performance in flow processes.

Highly active and selective heterogeneous catalysis driven by metallic nanoparticles relies on a high degree of stabilization of such nanomaterials facilitated by strong surface ligands or deposition on solid supports. In order to tackle these challenges, N-heterocyclic carbene stabilized gold nanoparticles (NHC@AuNPs) emerged as promising heterogeneous catalysts. Despite the high degree of stabilization obtained by NHCs as surface ligands, NHC@AuNPs still need to be loaded on support structures to obtain easily recyclable and reliable heterogeneous catalysts. Therefore, the combination of properties obtained by NHCs and support structures as NHC bearing "functional supports" for the stabilization of AuNPs is desirable. Here, we report the synthesis of hyper-crosslinked polymers containing benzimidazolium as NHC precursors to stabilize AuNPs. Following the successful synthesis of hyper-crosslinked polymers (HCP), a two-step procedure was developed to obtain HCP·NHC@AuNPs. Detailed characterization not only revealed the successful NHC formation but also proved that the NHC functions as a stabilizer to the AuNPs in the porous polymer network. Finally, HCP·NHC@AuNPs were evaluated in the catalytic decomposition of 4-nitrophenol. In batch reactions, a conversion of greater than 99% could be achieved in as little as 90 s. To further evaluate the catalytic capability of HCP·NHC@AuNP, the catalytic decomposition of 4-nitrophenol was also performed in a flow setup. Here the catalyst not only showed excellent catalytic conversion but also exceptional recyclability while maintaining the catalytic performance.

Evaluation of CO2 and H2O Adsorption on a Porous Polymer Using DFT and In Situ DRIFT Spectroscopy.

Numerous hyper-cross-linked polymers (HCPs) have been developed as CO2 adsorbents and photocatalysts. Yet, little is known of the CO2 and H2O adsorption mechanisms on amorphous porous polymers. Gaining a better understanding of these mechanisms and determining the adsorption sites are key to the rational design of improved adsorbents and photocatalysts. Herein, we present a unique approach that combines density functional theory (DFT), in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), and multivariate spectral analysis to investigate CO2 and H2O adsorption sites on a triazine-biphenyl HCP. We found that CO2 and H2O adsorb on the same HCP sites albeit with different adsorption strengths. The primary amines of the triazines were identified as favoring strong CO2 binding interactions. Given the potential use of HCPs for CO2 photoreduction, we also investigated CO2 and H2O adsorption under transient light irradiation. Under irradiation, we observed partial CO2 and H2O desorption and a redistribution of interactions between the H2O and CO2 molecules that remain adsorbed at HCP adsorption sites.

US Health Care Expenditures, GDP and Health Policy Reforms: Evidence from End-of-Sample Structural Break Tests.

This research investigates the over-time stability of the aggregate US healthcare expenditure (HCE)-GDP relationship, focusing on periods of healthcare reforms. The most consequential reforms-Medicaid/Medicare and the Affordable Care Act (ACA)-are challenging to study because they occur near the ends of the available data. Using annual national- and state-level data and a battery of structural break tests, we find the HCE-GDP relationship to be overwhelmingly stable. An ancillary analysis around the 2006 Massachusetts healthcare reform, which avoids the confounding effects of the Great Recession and the staggered rollout of the ACA, likewise finds no change.

Validation of a gene expression signature to measure immune quiescence in kidney transplant recipients in the CLIA setting.

Aim: Allograft rejection remains a major cause of graft failure in kidney transplantation. Here the authors report the validation of a non-invasive molecular diagnostic assay, AlloMap Kidney, using peripheral blood. Methods: The AlloMap Kidney test is a gene expression profile utilizing the RNA-seq platform to measure immune quiescence in kidney transplant patients. Results/Conclusions: Analytical validation showed robust performance characteristics with an accuracy correlation coefficient of 0.997 and a precision coefficient of variation of 0.049 across testing. Clinical validation from the prospective, multi-center studies of 235 samples (66 rejection and 169 quiescence specimens) demonstrated the sensitivity of 70% and specificity of 66% for allograft rejection, while the negative predictive value was 95% to discriminate rejection from quiescence at 10% prevalence of rejection.

Integrated cell-free DNA and cytokine analysis uncovers distinct tissue injury and immune response patterns in solid organ transplant recipients with COVID-19.

COVID-19 pathogenesis is associated with an exuberant inflammatory response. However, the tissue injury pattern and immune response in solid-organ transplant recipients (SOTRs) taking immunosuppressive therapy have not been well characterized. Here, we perform both cfDNA and cytokine profiling on plasma samples to map tissue damage, including allograft injury and delineate underlying immunopathology. We identified injuries from multiple-tissue types, including hematopoietic cells, vascular endothelium, hepatocyte, adipocyte, pancreas, kidney, heart, and lung in SOTRs with COVID-19 that correlates with disease severity. SOTRs with COVID-19 have higher plasma levels of cytokines such as IFN-λ1, IFN-γ, IL-15, IL-18 IL-1RA, IL-6, MCP-2, and TNF-α as compared to healthy controls, and the levels of GM-CSF, IL-15, IL-6, IL-8, and IL-10 were associated with disease severity in SOTRs. Strikingly, IFN-λ and IP-10 were markedly increased in SOTRs compared to immunocompetent patients with COVID-19. Correlation analyses showed a strong association between monocyte-derived cfDNA and inflammatory cytokines/chemokines in SOTRs with COVID-19. Moreover, compared to other respiratory viral infections, COVID-19 induced pronounced injury in hematopoietic, vascular endothelial and endocrine tissues. Allograft injury, measured as donor-derived cfDNA was elevated in SOTRs with COVID-19, including allografts distant from the primary site of infection. Allograft injury correlated with inflammatory cytokines and cfDNA from immune cells. Furthermore, longitudinal analysis identified a gradual decrease of cfDNA and inflammatory cytokine levels in patients with a favorable outcome. Our findings highlight distinct tissue injury and cytokine features in SOTRs with COVID-19 that correlate with disease severity.

High levels of donor-derived cell-free DNA in a case of graft-versus-host-disease following liver transplantation.

The diagnosis of graft-versus-host-disease (GVHD) after solid organ transplantation is made difficult by its variable clinical presentation and lack of sensitive and specific biomarkers to evaluate the immune state of transplant recipients. Emerging noninvasive diagnostic techniques like the quantification of donor-derived cell-free DNA (dd-cfDNA) for surveillance may improve the current standard-of-care. Herein, we report the use of this methodology in a patient with GVHD and corresponding levels of dd-cfDNA without any evidence of graft injury. Correlation of dd-cfDNA levels with the clinical course and its novel application here could lead to improvements in the rapid diagnosis of GVHD and in monitoring of response to treatment.

Clinical outcomes from the Assessing Donor-derived cell-free DNA Monitoring Insights of kidney Allografts with Longitudinal surveillance (ADMIRAL) study.

The use of routine monitoring of donor-derived cell-free DNA (dd-cfDNA) after kidney transplant may allow clinicians to identify subclinical allograft injury and intervene prior to development of clinically evident graft injury. To evaluate this, data from 1092 kidney transplant recipients monitored for dd-cfDNA over a three-year period was analyzed to assess the association of dd-cfDNA with histologic evidence of allograft rejection. Elevation of dd-cfDNA (0.5% or more) was significantly correlated with clinical and subclinical allograft rejection. dd-cfDNA values of 0.5% or more were associated with a nearly three-fold increase in risk development of de novo donor-specific antibodies (hazard ratio 2.71) and were determined to be elevated a median of 91 days (interquartile range of 30-125 days) ahead of donor specific antibody identification. Persistently elevated dd-cfDNA (more than one result above the 0.5% threshold) predicted over a 25% decline in the estimated glomerular filtration rate over three years (hazard ratio 1.97). Therefore, routine monitoring of dd-cfDNA allowed early identification of clinically important graft injury. Biomarker monitoring complemented histology and traditional laboratory surveillance strategies as a prognostic marker and risk-stratification tool post-transplant. Thus, persistently low dd-cfDNA levels may accurately identify allograft quiescence or absence of injury, paving the way for personalization of immunosuppression trials.

Hypercrosslinked Polymers as a Photocatalytic Platform for Visible-Light-Driven CO2 Photoreduction Using H2 O.

The design of robust, high-performance photocatalysts is key for the success of solar fuel production by CO2 conversion. In this study, hypercrosslinked polymer (HCP) photocatalysts have been developed for the selective reduction of CO2 to CO, combining excellent CO2 sorption capacities, good general stabilities, and low production costs. HCPs are active photocatalysts in the visible light range, significantly outperforming the benchmark material, TiO2 P25, using only sacrificial H2 O. It is hypothesized that superior H2 O adsorption capacities facilitate access to photoactive sites, improving photocatalytic conversion rates when compared to sacrificial H2 . These polymers are an intriguing set of organic photocatalysts, displaying no long-range order or extended π-conjugation. The as-synthesized networks are the sole photocatalytic component, requiring no added cocatalyst doping or photosensitizer, representing a highly versatile and exciting platform for solar-energy conversion.

Clinical Validation of an Immune Quiescence Gene Expression Signature in Kidney Transplantation.

Background: Despite advances in immune suppression, kidney allograft rejection and other injuries remain a significant clinical concern, particularly with regards to long-term allograft survival. Evaluation of immune activity can provide information about rejection status and help guide interventions to extend allograft life. Here, we describe the validation of a blood gene expression classifier developed to differentiate immune quiescence from both T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR). Methods: A five-gene classifier (DCAF12, MARCH8, FLT3, IL1R2, and PDCD1) was developed on 56 peripheral blood samples and validated on two sample sets independent of the training cohort. The primary validation set comprised 98 quiescence samples and 18 rejection samples: seven TCMR, ten ABMR, and one mixed rejection. The second validation set included eight quiescence and 11 rejection samples: seven TCMR, two ABMR, and two mixed rejection. AlloSure donor-derived cell-free DNA (dd-cfDNA) was also evaluated. Results: AlloMap Kidney classifier scores in the primary validation set differed significantly between quiescence (median, 9.49; IQR, 7.68-11.53) and rejection (median, 13.09; IQR, 11.25-15.28), with P<0.001. In the second validation set, the cohorts were statistically different (P=0.03) and the medians were similar to the primary validation set. The AUC for discriminating rejection from quiescence was 0.786 for the primary validation and 0.800 for the second validation. AlloMap Kidney results were not significantly correlated with AlloSure, although both were elevated in rejection. The ability to discriminate rejection from quiescence was improved when AlloSure and AlloMap Kidney were used together (AUC, 0.894). Conclusion: Validation of AlloMap Kidney demonstrated the ability to differentiate between rejection and immune quiescence using a range of scores. The diagnostic performance suggests that assessment of the mechanisms of immunologic activity is complementary to allograft injury information derived from AlloSure dd-cfDNA. Together, these biomarkers offer a more comprehensive assessment of allograft health and immune quiescence.

A general ink formulation of 2D crystals for wafer-scale inkjet printing.

Recent advances in inkjet printing of two-dimensional (2D) crystals show great promise for next-generation printed electronics development. Printing nonuniformity, however, results in poor reproducibility in device performance and remains a major impediment to their large-scale manufacturing. At the heart of this challenge lies the coffee-ring effect (CRE), ring-shaped nonuniform deposits formed during postdeposition drying. We present an experimental study of the drying mechanism of a binary solvent ink formulation. We show that Marangoni-enhanced spreading in this formulation inhibits contact line pinning and deforms the droplet shape to naturally suppress the capillary flows that give rise to the CRE. This general formulation supports uniform deposition of 2D crystals and their derivatives, enabling scalable and even wafer-scale device fabrication, moving them closer to industrial-level additive manufacturing.

Valuing the Cancer Mortality Risk Reduction from Lowering the Arsenic Maximum Contaminant Level in New Hampshire Municipal Water Supplies.

This study uses a 2018 stated preference survey to elicit a willingness to pay (WTP) to reduce the cancer morbidity and mortality risk from arsenic exposure through drinking water. Respondents who use a public water supply are willing to pay $35.43 per month for the risk reduction associated with lowering the maximum allowable level of arsenic in drinking water from 10 to a hypothetical level of 3 ppb; households on private wells are willing to pay $29.19. Respondents from households with children were willing to pay significantly more than respondents from households without children. We derive values of a statistical life (VSL) of $4.61 million and $3.48 million per household member, respectively, in households using municipal or well water. Shortly after the initial release of these findings, New Hampshire became the second state to set a maximum allowable level for arsenic below the national limit of 10 ppb.