Advancing Digital Health Innovation in Oncology: Priorities for High-Value Digital Transformation in Cancer Care.

Although health care delivery is becoming increasingly digitized, driven by the pursuit of improved access, equity, efficiency, and effectiveness, progress does not appear to be equally distributed across therapeutic areas. Oncology is renowned for leading innovation in research and in care; digital pathology, digital radiology, real-world data, next-generation sequencing, patient-reported outcomes, and precision approaches driven by complex data and biomarkers are hallmarks of the field. However, remote patient monitoring, decentralized approaches to care and research, "hospital at home," and machine learning techniques have yet to be broadly deployed to improve cancer care. In response, the Digital Medicine Society and Moffitt Cancer Center convened a multistakeholder roundtable discussion to bring together leading experts in cancer care and digital innovation. This viewpoint highlights the findings from these discussions, in which experts agreed that digital innovation is lagging in oncology relative to other therapeutic areas. It reports that this lag is most likely attributed to poor articulation of the challenges in cancer care and research best suited to digital solutions, lack of incentives and support, and missing standardized infrastructure to implement digital innovations. It concludes with suggestions for actions needed to bring the promise of digitization to cancer care to improve lives.

Improving eye screening practice among pediatric rheumatology patients receiving hydroxychloroquine.

OBJECTIVE: Hydroxychloroquine (HCQ) is commonly used in the treatment of various autoimmune diseases related to its many benefits and favorable safety profile. Although HCQ retinopathy was considered to be uncommon, a prevalence of 7.5% was described in a recent study making early detection critical. The most updated screening guidelines by the American Academy of Ophthalmology were published in 2016; however, it lacked pediatric-specific recommendations and the overall compliance with screening guidelines was poor in previous studies. We developed a quality improvement (QI) initiative aiming to create institutional screening recommendations. Additionally, to increase eye screening in pediatric rheumatology clinic for patients receiving HCQ from 65% to 85% in 12 months and to sustain that rate for at least 6 months. METHODS: We formed a multidisciplinary team of pediatric rheumatologists and ophthalmologists, clinical pharmacist, clinic nurses, QI specialist, quality data technician and administrative staff. We included patients receiving HCQ and who were evaluated at Nationwide Children's Hospital rheumatology clinic. A key driver diagram was formulated to identify barriers to compliance and determine possible interventions. Main interventions included summarizing screening guidelines in a step by step algorithm, increasing awareness of these guidelines among patients and providers, improving collaboration and communication with ophthalmologists, and initiating pre-visit planning. RESULTS: Baseline performance data included 164 patients. Fifty-four (33%) of those patients were at high risk for HCQ retinopathy. Of them, 50% were on HCQ dose of >5 mg/kg/day and 31.5% had been taking HCQ for ≥5 years. Two center line shifts were noticed over the course of the project. The target of 85% compliance was reached in February 2019 and was sustained until December 2019. CONCLUSIONS: Our study highlights the importance of interdisciplinary communication to increase awareness of screening guidelines among medical providers and patients. Pre-visit planning played a major role in identifying patients and opportunities for optimizing eye screening in patients at risk for HCQ retinopathy. Collaboration between rheumatologists and ophthalmologists is crucial in managing patients on HCQ. The implementation of same-day eye screening allowed this collaboration to be more efficient. Future efforts are being directed at monitoring and improving utilization of the effective interventions.

Pediatric Intracranial Hypertension: a Current Literature Review.

PURPOSE OF REVIEW: The purpose of this review is to provide an update on pediatric intracranial hypertension. RECENT FINDINGS: The annual pediatric incidence is estimated at 0.63 per 100,000 in the USA and 0.71 per 100,000 in Britain. The Idiopathic Intracranial Hypertension Treatment Trial found improvement in visual fields, optical coherence tomography, Frisen grade, and quality of life with acetazolamide compared to placebo in adult patients, and these findings have been translated to the pediatric population. Pediatric intracranial hypertension is a disorder that if left untreated can lead to poor quality of life and morbidity. There are no current treatment studies in pediatrics, but adult data suggests acetazolamide remains an acceptable first-line medication.

Biomimetic Reversible Heat-Stiffening Polymer Nanocomposites.

Inspired by the ability of the sea cucumber to (reversibly) increase the stiffness of its dermis upon exposure to a stimulus, we herein report a stimuli-responsive nanocomposite that can reversibly increase its stiffness upon exposure to warm water. Nanocomposites composed of cellulose nanocrystals (CNCs) that are grafted with a lower critical solution temperature (LCST) polymer embedded within a poly(vinyl acetate) (PVAc) matrix show a dramatic increase in modulus, for example, from 1 to 350 MPa upon exposure to warm water, the hypothesis being that grafting the polymers from the CNCs disrupts the interactions between the nanofibers and minimizes the mechanical reinforcement of the film. However, exposure to water above the LCST leads to the collapse of the polymer chains and subsequent stiffening of the nanocomposite as a result of the enhanced CNC interactions. Backing up this hypothesis are energy conserving dissipative particle dynamics (EDPD) simulations which show that the attractive interactions between CNCs are switched on upon the temperature-induced collapse of the grafted polymer chains, resulting in the formation of a percolating reinforcing network.

Miscanthus Giganteus: A commercially viable sustainable source of cellulose nanocrystals.

With a goal of identifying a new scalable source for cellulose nanocrystals (CNCs), we successfully isolated CNCs from a sustainable, non-invasive grass, Miscanthus x. Giganteus (MxG). Subjecting MxG stalks to base hydrolysis, bleaching and acid hydrolysis allowed access to cellulose nanocrystals (MxG-CNC) in high yields. X-ray diffraction studies showed the crystallinity of the MxG-CNCs increased with subsequent treatment conditions (>90% after HCl hydrolysis). Transmission electron microscopy showed that the MxG-CNC exhibit relatively high aspect ratios (60-70), and small angle neutron scattering showed the crystals were ribbon-like with a width and thickness of 8.5 and 2.8nm respectively. As expected, thermomechanical analysis of nanocomposites fabricated with carboxylic acid functionalized MxG-CNC (MxG-CNC-COOH) and PVAc showed an increase in modulus (above Tg) as filler content was increased. Comparing the properties to PVAc nanocomposites containing CNCs from wood showed at least as good, if not slightly better, reinforcement at the same loading level.

pH-Responsive Cellulose Nanocrystal Gels and Nanocomposites.

We show that functionalization of the surface of cellulose nanocrystals (CNCs) with either carboxylic acid (CNC-CO2H) or amine (CNC-NH2) moieties renders the CNCs pH-responsive. At low pH, where the amine groups are protonated, CNC-NH2 forms aqueous dispersions in water on account of electrostatic repulsions of the ammonium moieties inhibiting aggregation. However, a transition to hydrogels is observed at higher pH where the CNC-NH2 are neutral and the attractive forces based on hydrogen bonding dominate. The opposite behavior is observed for CNC-CO2H, which are dispersible at high pH and form gels in an acidic environment. We further show that these pH-responsive CNCs can be incorporated into a poly(vinyl acetate) matrix to yield mechanically adaptive pH-responsive nanocomposite films.

Expansions of NK-like αßT cells with chronologic aging: novel lymphocyte effectors that compensate for functional deficits of conventional NK cells and T cells.

As the repertoire of αßT cell receptors (TCR) contracts with advancing age, there is an associated age-dependent accumulation of oligoclonal T cells expressing of a variety of receptors (NKR), normally expressed on natural killer (NK) cells. Evidences for differential regulation of expression of particular NKRs between T cells and NK cells suggest that NKR expression on T cells is physiologically programmed rather than a random event of the aging process. Experimental studies show NKRs on aged αßT cells may function either as independent receptors, and/or as costimulatory receptors to the TCR. Considering the reported deficits of conventional αßTCR-driven activation and also functional deficits of classical NK cells, NKR(+) αßT cells likely represent novel immune effectors that are capable of combining innate and adaptive functions. Inasmuch as immunity is a determinant of individual fitness, the type and density of NKRs could be important contributing factors to the wide heterogeneity of health characteristics of older adults, ranging from institutionalized frail elders who are unable to mount immune responses to functionally independent community-dwelling elders who exhibit protective immunity. Understanding the biology of NKR(+) αßT cells could lead to new avenues for age-specific intervention to improve protective immunity.

Association of biomarkers with pre-radiographically defined and radiographically defined knee osteoarthritis in a population-based study.

OBJECTIVE: To evaluate 10 biomarkers in magnetic resonance imaging (MRI)-determined, pre-radiographically defined osteoarthritis (pre-ROA) and radiographically defined OA (ROA) in a population-based cohort of subjects with symptomatic knee pain. METHODS: Two hundred one white subjects with knee pain, ages 40-79 years, were classified into OA subgroups according to MRI-based cartilage (MRC) scores (range 0-4) and Kellgren/Lawrence (K/L) grades of radiographic severity (range 0-4): no OA (MRC score 0, K/L grade<2), pre-ROA (MRC score>or=1, K/L grade<2), or ROA (MRC score>or=1, K/L grade>or=2). Urine and serum samples were assessed for levels of the following biomarkers: urinary biomarkers C-telopeptide of type II collagen (uCTX-II), type II and types I and II collagen cleavage neoepitopes (uC2C and uC1,2C, respectively), and N-telopeptide of type I collagen, and serum biomarkers sC1,2C, sC2C, C-propeptide of type II procollagen (sCPII), chondroitin sulfate 846 epitope, cartilage oligomeric matrix protein, and hyaluronic acid. Multicategory logistic regression was performed to evaluate the association of OA subgroup with individual biomarker levels and biomarker ratios, adjusted for age, sex, and body mass index. RESULTS: The risk of ROA versus no OA increased with increasing levels of uCTX-II (odds ratio [OR] 3.12, 95% confidence interval [95% CI] 1.35-7.21), uC2C (OR 2.13, 95% CI 1.04-4.37), and uC1,2C (OR 2.07, 95% CI 1.06-4.04), and was reduced in association with high levels of sCPII (OR 0.53, 95% CI 0.30-0.94). The risk of pre-ROA versus no OA increased with increasing levels of uC2C (OR 2.06, 95% CI 1.05-4.01) and uC1,2C (OR 2.06, 95% CI 1.12-3.77). The ratios of type II collagen degradation markers to collagen synthesis markers were better than individual biomarkers at differentiating the OA subgroups, e.g., the ratio of [uCTX-II][uC1,2C] to sCPII was associated with a risk of ROA versus no OA of 3.47 (95% CI 1.34-9.03) and a risk of pre-ROA versus no OA of 2.56 (95% CI 1.03-6.40). CONCLUSION: Different cartilage degradation markers are associated with pre-ROA than are associated with ROA, indicating that their use as diagnostic markers depends on the stage of OA. Biomarker ratios contrasting cartilage degradation with cartilage synthesis are better able to differentiate OA stages compared with levels of the individual markers.

A phylogenetic estimation of trophic transition networks for ascomycetous fungi: are lichens cradles of symbiotrophic fungal diversification?

Fungi associated with photosynthetic organisms are major determinants of terrestrial biomass, nutrient cycling, and ecosystem productivity from the poles to the equator. Whereas most fungi are known because of their fruit bodies (e.g., saprotrophs), symptoms (e.g., pathogens), or emergent properties as symbionts (e.g., lichens), the majority of fungal diversity is thought to occur among species that rarely manifest their presence with visual cues on their substrate (e.g., the apparently hyperdiverse fungal endophytes associated with foliage of plants). Fungal endophytes are ubiquitous among all lineages of land plants and live within overtly healthy tissues without causing disease, but the evolutionary origins of these highly diverse symbionts have not been explored. Here, we show that a key to understanding both the evolution of endophytism and the diversification of the most species-rich phylum of Fungi (Ascomycota) lies in endophyte-like fungi that can be isolated from the interior of apparently healthy lichens. These "endolichenic" fungi are distinct from lichen mycobionts or any other previously recognized fungal associates of lichens, represent the same major lineages of Ascomycota as do endophytes, largely parallel the high diversity of endophytes from the arctic to the tropics, and preferentially associate with green algal photobionts in lichen thalli. Using phylogenetic analyses that incorporate these newly recovered fungi and ancestral state reconstructions that take into account phylogenetic uncertainty, we show that endolichenism is an incubator for the evolution of endophytism. In turn, endophytism is evolutionarily transient, with endophytic lineages frequently transitioning to and from pathogenicity. Although symbiotrophic lineages frequently give rise to free-living saprotrophs, reversions to symbiosis are rare. Together, these results provide the basis for estimating trophic transition networks in the Ascomycota and provide a first set of hypotheses regarding the evolution of symbiotrophy and saprotrophy in the most species-rich fungal phylum. [Ancestral state reconstruction; Ascomycota; Bayesian analysis; endolichenic fungi; fungal endophytes; lichens; pathogens; phylogeny; saprotrophy; symbiotrophy; trophic transition network.].