Electronic effects of conjugated aryl groups on the properties and reactivities of di(arylethynyl)tetracenes.

The photochemical oxidations of acenes can cause challenges with their optoelectronic applications, such as singlet fission and organic transistors. At the same time, these reactions form the basis for many luminescent sensing schemes for 1O2. While diethynyl substitution is arguably the most widely adopted of the various substitution strategies to control oxidation and also improve solubility and processability of long acenes, the extent to which differences between the alkyne groups can influence key properties of long acenes remains largely unknown. This report therefore describes the effects of various arenes and heteroarenes on the electronic structures, optical properites, and reactivity with singlet oxygen for eight 5,12-di(arylethynyl)tetracenes. The fluorescence spectra of these tetracenes span approximately 100 nm, while their observed rate constants for reaction with singlet oxygen correlates strongly with the HOMO level, spanning one order of magnitude. They are also amenable to fluorescent materials that respond ratiometrically to singlet oxygen. Therefore, electronic effects of groups directly conjugated to ethynylacenes offer a useful chemical space for rational acene design.

Analysis of patients with endometrial carcinoma using the ProMise classifier: a pilot study from India.

BACKGROUND: Molecular subtyping of endometrial carcinomas (EC) has been shown to classify tumors into prognostically relevant groups. Characterizing EC with a limited number of markers viz., POLE mutations, p53 mutations, and MMR status, can provide valuable information. DESIGN: Paraffin sections of a cohort of 48 EC from a tertiary care center were characterized for the above-mentioned molecular markers and analyzed in the context of survival. METHODS: Formalin fixed paraffin embedded tissues from 48 EC were characterized for POLE mutations by Sanger sequencing (exons 9-14), for MMR (MLH1, MH2, MSH6) using immunohistochemistry (IHC) and copy number (high/low) using p53 IHC. Mutational status was integrated along with the clinicopathological details and survival analysis performed. RESULTS: Eleven (22.9%) patients were MMR deficient, 3 (6.3%) had POLE mutation, while 2 (4.1%) had both POLE and P53 mutations (regarded as multiple classifiers). Twelve (25%) patients were found to have P53 mutations, while the remaining 20 (41.7%) had no specific molecular profile (NSMP). Median follow-up duration was 43.5 (2-62) months with 8 recurrences and 9 deaths. Tumors with POLE mutation had the most favorable prognosis followed by the NSMP and the MMR mutated group while the P53 and multiple classifier groups had the worst prognosis in terms of OS (Log-rank p: 0.006) and PFS (Log-rank p: 0.001). CONCLUSION: The integration of molecular-clinicopathologic data for endometrial cancer classification, through cost-effective, clinically applicable assays appears to be a highly objective tool that can be adopted even in resource-limited settings. It has the potential to cause a shift in the paradigm of EC pathology and management practice.

Self-efficacy of medical students in a hybrid curriculum course (traditional and problem-based learning) and associated factors.

Self-efficacy consists of the judgment of one's abilities to perform actions required to achieve a given performance, which has been considered predictive of performance. In academics, it means personal convictions in accomplishing a task to a defined degree of quality. Numerous studies have investigated medical students' self-efficacy in traditional and PBL curricula. However, few studies have addressed the hybrid PBL scenario (Hpbl) that simultaneously contemplates PBL, traditional teaching, and practical activities. An even smaller number have evaluated the factors associated with this entity. With these considerations, we aimed to investigate the self-efficacy belief in the hPBL curriculum and the factors associated with this entity. This quantitative observational cross-sectional study was held between August 2022 and November 2022 in Fortaleza, a city in Northeast Brazil with almost 3 million inhabitants. The medical course has 12 semesters. The first two semesters use traditional teaching and cover the basic cycle, followed by the third to eighth semesters which correspond to the pre-clinical and clinical cycle. From the third semester onwards, traditional teaching and PBL are used simultaneously, which we call a hybrid model of PBL. The scale "Scale of Self-efficacy in Higher Education" was applied, a questionnaire validated for the Portuguese language consisting of 34 questions, with answers on a Likert-type scale with ten points, divided into five dimensions. To verify the association between sociodemographic factors and self-efficacy, simple and multiple linear models with robust errors were used. In total, 412 students participated in this study, most of them women (70.1%). The average age of students was 22.9 years. All domains had medians greater than 8, which means strong self-efficacy. The following factors were associated with higher self-efficacy scores in general after the multivariate analysis: female gender (8.6 vs. 8.3, p-value = 0.014), working (8.8 vs. 8.5, p-value = 0.019) and participating in extracurricular activities (8.7 vs. 8.1, p-value = 0.019). We conclude that medical students studying in hybrid learning models showed strong levels of self-efficacy. In addition, participating in extracurricular activities was associated with higher self-efficacy scores and males presented lower levels of self-efficacy.

Transfer functions forQA/QBinternational regulatory limits for the safe transport of radioactive materials.

This paper presents a proposed revision of the International Atomic Energy Agency transport regulations, related to theA1andA2limit values used to determine the radioactive transport classification. Based on the 'Qsystem', a novel methodology was introduced to deriveQAandQBvalues related to scenarios involving external exposure from a distant source. These values are key parameters that respectively represent the total effective dose and total equivalent dose to the skin, from all primary and secondary particles contributing to radiation exposure. The International Working Group (WGA1/A2) is established and associated with the TRANSSC Technical Expert Group on Radiation Protection. A review of theA1andA2values is performed in response to identified limitations within the existingQsystem. The followed approach is based on Monte Carlo simulations that enabled the development of transfer functions aimed at reducing computational time and increasing the flexibility of dose evaluations for any radionuclide with known particle emission spectra. This method allows updating theQAandQBvalues to account for future data evolutions (decay data, fluence-to-dose conversion coefficients) and standardizing the calculation of regulation limits across all referenced radionuclides and scenarios related to external exposure. The transfer functions are established using three Monte Carlo simulation codes-FLUKA, Geant4, and MCNP-and address the previous limitations of the 'Qsystem', reflecting the latest International Commission for Radiation Protection recommendations and improvements in calculation techniques. The results of the WG show consistent agreement across the codes, with minor discrepancies observed at low primary energies due to statistical uncertainties and different handling of stopping power for electrons/positrons in the codes. This revised approach aligns with current standards and recommendations, ensuring that the radiological consequences of transport accidents are acceptable for the newA1andA2limits from a radiological protection perspective.

Resonant Acoustic Rheometry to Measure Coagulation Kinetics in Hemophilia A and Healthy Plasma: A Novel Viscoelastic Method.

Compared with conventional coagulation tests and factor-specific assays, viscoelastic hemostatic assays (VHAs) can provide a more thorough evaluation of clot formation and lysis but have several limitations including clot deformation. In this proof-of-concept study, we test a noncontact technique, termed resonant acoustic rheometry (RAR), for measuring the kinetics of human plasma coagulation. Specifically, RAR utilizes a dual-mode ultrasound technique to induce and detect surface oscillation of blood samples without direct physical contact and measures the resonant frequency of the surface oscillation over time, which is reflective of the viscoelasticity of the sample. Analysis of RAR results of normal plasma allowed defining a set of parameters for quantifying coagulation. RAR detected a flat-line tracing of resonant frequency in hemophilia A plasma that was corrected with the addition of tissue factor. Our RAR results captured the kinetics of plasma coagulation and the newly defined RAR parameters correlated with increasing tissue factor concentration in both healthy and hemophilia A plasma. These findings demonstrate the feasibility of RAR as a novel approach for VHA, providing the foundation for future studies to compare RAR parameters to conventional coagulation tests, factor-specific assays, and VHA parameters.

Toxicoproteomics of Mono(2-ethylhexyl) phthalate and Perfluorooctanesulfonic Acid in Models of Prostatic Diseases.

Benign and malignant prostatic diseases are common, costly, and burdensome; moreover, they share fundamental underlying molecular processes. Several ubiquitous contaminants may perturb these processes, possibly via peroxisome proliferator-activated receptor (PPAR) signaling, but the role of environmental exposures─particularly mixtures─in prostatic diseases is undefined. In the present study, nontumorigenic prostate stromal cells and metastatic prostate epithelial cells were exposed to ubiquitous exogenous PPAR ligands under different dosing paradigms, including a mixture, and effects were assessed via mass spectrometry-based global proteomics. In prostate stromal cells, environmentally relevant levels of mono(2-ethylhexyl) phthalate (MEHP), alone and in combination with perfluorooctanesulfonic acid, led to significant changes in proteins involved in key processes underlying prostatic diseases: oxidative stress defense, proteostasis, damage-associated molecular pattern signaling, and innate immune response signaling. A follow-up experiment in metastatic prostate epithelial cells showed that the occupationally relevant levels of MEHP perturbed similar processes, including lipid, cholesterol, steroid, and alcohol metabolism; apoptosis and coagulation regulation; wound response; and aging. This work shows that environmental exposures may contribute to prostatic diseases by perturbing key processes of a proposed adverse outcome pathway, including lipid metabolism, oxidative stress, and inflammation. Future in vivo research will investigate the role of contaminants in prostatic diseases and in preventative agents.

The Choice between Plasma-Based Common Coagulation Tests and Cell-Based Viscoelastic Tests in Monitoring Hemostatic Competence: Not an either-or Proposition.

There has been a significant interest in the last decade in the use of viscoelastic tests (VETs) to determine the hemostatic competence of bleeding patients. Previously, common coagulation tests (CCTs) such as the prothrombin time (PT) and partial thromboplastin time (PTT) were used to assist in the guidance of blood component and hemostatic adjunctive therapy for these patients. However, the experience of decades of VET use in liver failure with transplantation, cardiac surgery, and trauma has now spread to obstetrical hemorrhage and congenital and acquired coagulopathies. Since CCTs measure only 5 to 10% of the lifespan of a clot, these assays have been found to be of limited use for acute surgical and medical conditions, whereby rapid results are required. However, there are medical indications for the PT/PTT that cannot be supplanted by VETs. Therefore, the choice of whether to use a CCT or a VET to guide blood component therapy or hemostatic adjunctive therapy may often require consideration of both methodologies. In this review, we provide examples of the relative indications for CCTs and VETs in monitoring hemostatic competence of bleeding patients.

Skin dose contamination conversion coefficients. Benchmark with three simulation codes.

Handling of radioactive material by operators can lead to contamination at the surface of the skin in case of an accident. The quantification of the dose received by the skin due to a contamination scenario is performed by means of dedicated dose coefficients as it is the case for other radiation protection dose quantities described in the literature. However, most available coefficients do not match realistic scenarios according to state-of-the-art of science and technology. Therefore, this work deals with dedicated dose conversion factors for skin contamination. Since there is an increasing demand on dose coefficients in general, these specific coefficients can be used for various calculations in radiation protection. In this work a method to evaluate such coefficients for the skin contamination dose related to photons, electrons, positrons, alpha and neutron particles is proposed. The coefficients are generated using Monte-Carlo simulations with three well established calculation codes (FLUKA, MCNP, and GEANT4). The results of the various codes are compared against each other for benchmarking purposes. The new dose coefficients allow the computation of the skin received dose, in the case of skin contamination scenario of an individual, taking into account the decay radiation of the radionuclides of interest. To benchmark the quantity derived here, comparisons of radionuclide contamination doses to the skin using the VARSKIN code available in the literature are performed with the results of this work.

Modulation of microglial activation states by spinal cord stimulation in an animal model of neuropathic pain: Comparing high rate, low rate, and differential target multiplexed programming.

While numerous studies and patient experiences have demonstrated the efficacy of spinal cord stimulation as a treatment for chronic neuropathic pain, the exact mechanism underlying this therapy is still uncertain. Recent studies highlighting the importance of microglial cells in chronic pain and characterizing microglial activation transcriptomes have created a focus on microglia in pain research. Our group has investigated the modulation of gene expression in neurons and glial cells after spinal cord stimulation (SCS), specifically focusing on transcriptomic changes induced by varying SCS stimulation parameters. Previous work showed that, in rodents subjected to the spared nerve injury (SNI) model of neuropathic pain, a differential target multiplexed programming (DTMP) approach provided significantly better relief of pain-like behavior compared to high rate (HRP) and low rate programming (LRP). While these studies demonstrated the importance of transcriptomic changes in SCS mechanism of action, they did not specifically address the role of SCS in microglial activation. The data presented herein utilizes microglia-specific activation transcriptomes to further understand how an SNI model of chronic pain and subsequent continuous SCS treatment with either DTMP, HRP, or LRP affects microglial activation. Genes for each activation transcriptome were identified within our dataset and gene expression levels were compared with that of healthy animals, naïve to injury and interventional procedures. Pearson correlations indicated that DTMP yields the highest significant correlations to expression levels found in the healthy animals across all microglial activation transcriptomes. In contrast, HRP or LRP yielded weak or very weak correlations for these transcriptomes. This work demonstrates that chronic pain and subsequent SCS treatments can modulate microglial activation transcriptomes, supporting previous research on microglia in chronic pain. Furthermore, this study provides evidence that DTMP is more effective than HRP and LRP at modulating microglial transcriptomes, offering potential insight into the therapeutic efficacy of DTMP.

Training for next-generation gynaecologic surgical & radiation oncologists - opportunities & challenges.

The global increase in cancer burden is a challenge for countries with scarce resources. Amongst all the malignancies, gynaecological cancer still continues to have a high incidence and prevalence leading to significant morbidity and mortality. While a multipronged strategy of decreasing the gynaecological cancer burden is a global priority, one of the key strategies to decrease the morbidity and mortality is to train gynaecological oncology specialists. Most of the developed nations have an established gynaecologic oncology training programme in the form of a well-designed curriculum and skill training. However, in developing countries where the actual disease burden of these cancers is highest, such focused training programmes have only started emerging and evolving over the past two decades. While it is a positive step to initiate such training programmes in a country like India, there are still gaps in the uniformity of curriculum and training. Also, exposure to modern practices in gynaecologic oncology surgery, chemotherapy and technology in radiation oncology, especially brachytherapy, is still insufficient in many centres. This review discusses some of the challenges and opportunities in the still evolving programmes for training gynaecologic oncologists in India.

Qualitative Assessment of Rapid System Transformation to Primary Care Video Visits at an Academic Medical Center.

BACKGROUND: The coronavirus disease 2019 pandemic spurred health systems across the world to quickly shift from in-person visits to safer video visits. OBJECTIVE: To seek stakeholder perspectives on video visits' acceptability and effect 3 weeks after near-total transition to video visits. DESIGN: Semistructured qualitative interviews. SETTING: 6 Stanford general primary care and express care clinics at 6 northern California sites, with 81 providers, 123 staff, and 97 614 patient visits in 2019. PARTICIPANTS: 53 program participants (overlapping roles as medical providers [n = 20], medical assistants [n = 16], nurses [n = 4], technologists [n = 4], and administrators [n = 13]) were interviewed about video visit transition and challenges. INTERVENTION: In 3 weeks, express care and primary care video visits increased from less than 10% to greater than 80% and from less than 10% to greater than 75%, respectively. New video visit providers received video visit training and care quality feedback. New system workflows were created to accommodate the new visit method. MEASUREMENTS: 9 faculty, trained in qualitative research methods, conducted 53 stakeholder interviews in 4 days using purposeful (administrators and technologists) and convenience (medical assistant, nurses, and providers) sampling. A rapid qualitative analytic approach for thematic analysis was used. RESULTS: The analysis revealed 12 themes, including Pandemic as Catalyst; Joy in Medicine; Safety in Medicine; Slipping Through the Cracks; My Role, Redefined; and The New Normal. Themes were analyzed using the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework to identify critical issues for continued program utilization. LIMITATIONS: Evaluation was done immediately after deployment. Although viewpoints may have evolved later, immediate evaluation allowed for prompt program changes and identified broader issues to address for program sustainability. CONCLUSION: After pandemic-related systems transformation at Stanford, critical issues to sustain video visit long-term viability were identified. Specifically, technology ease of use must improve and support multiparty videoconferencing. Providers should be able to care for their patients, regardless of geography. Providers need decision-making support with virtual examination training and home-based patient diagnostics. Finally, ongoing video visit reimbursement should be commensurate with value to the patients' health and well-being. PRIMARY FUNDING SOURCE: Stanford Department of Medicine and Stanford Health Care.

Calculation and benchmark of fluence-to-local skin equivalent dose coefficients for neutrons with FLUKA, MCNP, and GEANT4 Monte-Carlo codes.

Dose equivalent limits for single organs are recommended by the ICRP (International Commission for the Radiological Protection publication 103). These limits do not lend themselves to be measured. They are assessed by convoluting conversion factors with particle fluences. The Fluence-to-Dose conversion factors are tabulated in the ICRP literature. They allow assessing the organ dose of interest using numerical simulations. In particular, the literature lacks the knowledge of local skin equivalent dose (LSD) coefficients for neutrons. In this article, we compute such values for neutron energies ranging from 1 meV to 15 MeV. We use FLUKA, MCNP and GEANT4 Radiation transport Monte-Carlo simulation codes to perform the calculations. A comparison between these three codes is performed. These calculated values are important for radiation protection studies and radiotherapy applications.

Spatiotemporal Proteomics Reveals the Molecular Consequences of Hormone Treatment in a Mouse Model of Lower Urinary Tract Dysfunction.

Benign prostatic hyperplasia and related lower urinary tract symptoms remain common, costly, and impactful issues for aging males. The etiology and pathogenesis are multifactorial and include steroid hormone changes and inflammation. Noninvasive markers could one day inform personalized medicine, but interindividual variation and lack of healthy age-matched controls hamper research. Experimental models are appealing for insight into disease mechanisms. Here, we present a spatiotemporal proteomics study in a mouse model of hormone-induced urinary dysfunction. Urine samples were collected noninvasively across time: before, during, and after disease onset. A microcomputed tomography analysis implicated the prostate as a spatially relevant contributor to bladder outlet obstruction. Prostates were collected after disease onset and compared with control mice. Notable changes in urine include proteins representing oxidative stress defense and acute phase inflammatory response processes. In the prostate, hormone treatment led to perturbations related to an oxidative stress response and H2O2 metabolism. Several protein changes coincided in both urine and the prostate tissue, including glutathione peroxidase 3, glutathione hydrolase 1 proenzyme, and vitamin D-binding protein. This study supports the concept of noninvasive urinary biomarkers for prostate disease diagnostics. Oxidative stress and acute phase inflammatory processes were identified as key consequences of hormone-induced bladder outlet obstruction. Future research into antioxidants and anti-inflammatories in prostate diseases appears promising.

Resistance to Unwanted Photo-Oxidation of Multi-Acene Molecules.

Although long acenes remain a key class of π-conjugated molecules for numerous applications, photoinduced oxidation upon exposure of the acene to light, often through sensitization of 1O2, is an important reaction requiring mitigation for most applications. In response to this ongoing challenge, this paper presents a series of four new diarylethynyl-substituted long acenes-three tetracenes and one anthradithiophene-in which the arylene pendants are either benzene, naphthalene, or anthracene. UV/vis and fluorescence spectroscopy reveals that the anthracene-substituted derivatives fluoresce poorly (Φ < 0.01). Although all four long acenes react with 1O2 at expected rates when an external photosensitizer is included and show the expected changes in fluorescence to accompany these reactions, the anthracene-substituted derivatives resist direct photoinduced oxidation. Through a combination of mechanistic experiments, we conclude that rapid nonradiative decay of the anthracene-substituted derivatives, perhaps because of inter-arene torsions that emerge in theoretical geometry optimizations, makes these compounds poor photosensitizers for 1O2 or other reactive oxygen species. This discovery opens new design possibilities for extended acene structures with improved photochemical stability.

Acenes beyond organic electronics: sensing of singlet oxygen and stimuli-responsive materials.

The spectroscopic, electronic, and geometrical properties of acenes have enabled their broad applicability in organic optoelectronics. Beyond these physical characteristics of acenes, acenes also offer characteristic and predictable reaction chemistry, especially their behavior as dienes in cycloaddition reactions. Although these cycloaddition reactions, especially those with singlet oxygen (1O2) as the dienophile, are detrimental for organic electronics, this reactivity has led to several different applications such as sensing of 1O2, the release of cytotoxic reactive oxygen species (ROS), and stimuli-responsive materials for drug delivery. The rational design of acenes in these chemically-responsive applications beyond organic optoelectronics requires an understanding of how chemical structure influences both the physical properties, such as quantum yield of emission, as well as the reactivity of acenes and their cycloadducts. Therefore, the objective of this review is to summarize how cycloaddition reactions of acenes have expanded their applications in different areas of materials chemistry, and in doing so inspire and inform the rational design of acene-based materials with applications beyond organic electronics.

Clinical Effectiveness and Mechanism of Action of Spinal Cord Stimulation for Treating Chronic Low Back and Lower Extremity Pain: a Systematic Review.

PURPOSE OF REVIEW: The purpose of the present systematic review is to provide a current understanding of the mechanism of action and the evidence available to support clinical decision-making. The focus is to summarize randomized controlled trials (RCTs) and nonrandomized or observational studies of spinal cord stimulation in chronic pain to understand clinical effectiveness and the mechanism of action. RECENT FINDINGS: Several recent studies have demonstrated the benefit of spinal cord stimulation in managing chronic pain. Until recently, the mechanism of action was founded on a central paradigm derived from gate control theory, which is the need to stimulate the dorsal column of the spinal cord to generate paresthesia. The recent development of new therapies that do not rely on paresthesia has left the field without a clear mechanism of action that could serve as a strong foundation to further improve clinical outcomes. Consequently, multiple theories have emerged to explain how electrical pulse applied to the spinal cord could alleviate pain, including activation of specific supraspinal pathways, and segmental modulation of the neurological interaction. Recent systematic reviews also have shown the clinical effectiveness of spinal cord stimulation in managing chronic spinal pain, phantom limb pain, complex regional pain syndrome, and other chronic painful conditions. Spinal cord stimulation for the treatment of chronic pain is rapidly evolving with technology at its forefront. This comprehensive focused review evaluated 11 RCTs and 7 nonrandomized/observational studies which provided levels of evidence ranging from I to II.

Quantitative proteomic analysis of a genetically induced prostate inflammation mouse model via custom 4-plex DiLeu isobaric labeling.

Inflammation is involved in many prostate pathologies including infection, benign prostatic hyperplasia, and prostate cancer. Preclinical models are critical to our understanding of disease mechanisms, yet few models are genetically tractable. Here, we present a comparative quantitative proteomic analysis of urine from mice with and without prostate-specific inflammation induced by conditional prostate epithelial IL-1ß expression. Relative quantification and sample multiplexing was achieved using custom 4-plex N,N-dimethyl leucine (DiLeu) isobaric tags and nanoflow ultrahigh-performance liquid chromatography coupled to high-resolution tandem mass spectrometry. Each set of 4-plex DiLeu reagents allows four urine samples to be analyzed simultaneously, providing high-throughput and accurate quantification of urinary proteins. Proteins involved in the acute phase response, including haptoglobin, inter-α-trypsin inhibitor, and α1-antitrypsin 1-1, were differentially represented in the urine of mice with prostate inflammation. Mass spectrometry-based quantitative urinary proteomics represents a promising bioanalytical strategy for biomarker discovery and the elucidation of molecular mechanisms in urological research.

Spectroscopy and Reactivity of Dialkoxy Acenes.

Photochemical oxidation of acenes can benefit or impede their function, depending on the application. Although acenes with alkoxy substituents on reactive sites are important for applications as diverse as drug delivery and organic optoelectronics, the influence of chemical structure on their photochemical oxidation remains unknown. This paper therefore describes the synthesis, spectroscopic properties, and reactivity with singlet oxygen (1 O2 ) of a series of dialkoxyacenes that vary in the number and types of fused rings in the (hetero)acene cores. Reductive alkylation of quinone precursors yielded target dialkoxyacenes with fused backbones ranging from benzodithiophene to tetracenothiophene. Trends of their experimental spectroscopic characteristics were consistent with time-dependent density functional theory (TD-DFT) calculations. NMR studies show that photochemically generated 1 O2 oxidizes all but one of these acenes to the corresponding endoperoxides in organic solvent. The rates of these oxidations correlate with the number and types of fused arenes, with longer dialkoxyacenes generally oxidizing faster than shorter derivatives. Finally, irradiation of these acenes in acidic, oxidizing environments cleaves the ether bonds. This work impacts those working in organic optoelectronics, as well as those interested in harnessing photogenerated reactive oxygen species in functional materials.

Combining Top-Down and Bottom-Up with Photodegradable Layer-by-Layer Films.

Layer-by-layer (LbL) self-assembly of polymer coatings is a bottom-up fabrication technique with broad applicability across a wide range of materials and applications that require control over interfacial properties. While most LbL coatings are chemically uniform in directions both tangent and perpendicular to their substrate, control over the properties of surface coatings as a function of space can enhance their function. To contribute to this rapidly advancing field, our group has focused on the top-down spatiotemporal control possible with photochemically reactive LbL coatings, harnessed through charge-shifting polyelectrolytes enabled by photocleavable ester pendants. The photolysis of the photocleavable esters degrades LbL films containing these polyelectrolytes. The chemical structures of the photocleavable groups dictate the wavelengths responsible for disrupting these coatings, ranging from ultraviolet to near-infrared in our work. In addition, spatially segregating reactive groups into "compartments" within LbL films has enabled us to fabricate reactive free-standing polymer films and multiheight photopatterned coatings. Overall, by combining bottom-up and top-down approaches, photoreactive LbL films enable precise control over the interfacial properties of polymer and composite coatings.

Proof-of-concept study: Homomorphically encrypted data can support real-time learning in personalized cancer medicine.

BACKGROUND: The successful introduction of homomorphic encryption (HE) in clinical research holds promise for improving acceptance of data-sharing protocols, increasing sample sizes, and accelerating learning from real-world data (RWD). A well-scoped use case for HE would pave the way for more widespread adoption in healthcare applications. Determining the efficacy of targeted cancer treatments used off-label for a variety of genetically defined conditions is an excellent candidate for introduction of HE-based learning systems because of a significant unmet need to share and combine confidential data, the use of relatively simple algorithms, and an opportunity to reach large numbers of willing study participants. METHODS: We used published literature to estimate the numbers of patients who might be eligible to receive treatments approved for other indications based on molecular profiles. We then estimated the sample size and number of variables that would be required for a successful system to detect exceptional responses with sufficient power. We generated an appropriately sized, simulated dataset (n = 5000) and used an established HE algorithm to detect exceptional responses and calculate total drug exposure, while the data remained encrypted. RESULTS: Our results demonstrated the feasibility of using an HE-based system to identify exceptional responders and perform calculations on patient data during a hypothetical 3-year study. Although homomorphically encrypted computations are time consuming, the required basic computations (i.e., addition) do not pose a critical bottleneck to the analysis. CONCLUSION: In this proof-of-concept study, based on simulated data, we demonstrate that identifying exceptional responders to targeted cancer treatments represents a valuable and feasible use case. Past solutions to either completely anonymize data or restrict access through stringent data use agreements have limited the utility of abundant and valuable data. Because of its privacy protections, we believe that an HE-based learning system for real-world cancer treatment would entice thousands more patients to voluntarily contribute data through participation in research studies beyond the currently available secondary data populated from hospital electronic health records and administrative claims. Forming collaborations between technical experts, physicians, patient advocates, payers, and researchers, and testing the system on existing RWD are critical next steps to making HE-based learning a reality in healthcare.