Artificial intelligence and its implications for data privacy.

Contemporary, multidisciplinary research sheds light on data privacy implications of artificial intelligence (AI). This review adopts an AI ecosystem perspective and proposes a process-outcome continuum to classify AI technologies; this perspective helps to understand the nuances of AI relative to psychological aspects of privacy decision-making. Specifically, different types of AI affect traditionally studied privacy decision-making frameworks including the privacy calculus, psychological ownership, and social influence in varied ways. By understanding how the process- or outcome-orientation of an AI technology affects privacy decision-making, we explain how AI creates privacy benefits but also poses challenges. Future research is needed across privacy decision-making, but also more generally at the intersection of privacy and AI, to help foster an ethical, sustainable society.

Lupus IgA1 autoantibodies synergize with IgG to enhance plasmacytoid dendritic cell responses to RNA-containing immune complexes.

Autoantibodies to nuclear antigens are hallmarks of systemic lupus erythematosus (SLE) where they contribute to pathogenesis. However, there remains a gap in our knowledge regarding how different isotypes of autoantibodies contribute to this autoimmune disease, including the production of the critical type I interferon (IFN) cytokines by plasmacytoid dendritic cells (pDCs) in response to immune complexes (ICs). We focused on IgA, which is the second-most prevalent isotype in serum and, along with IgG, is deposited in glomeruli in individuals with lupus nephritis. We show that individuals with SLE have serum IgA autoantibodies against most nuclear antigens, correlating with IgG against the same antigen. We investigated whether IgA autoantibodies against a major SLE autoantigen, Smith ribonucleoprotein (Sm/RNP), played a role in IC activation of pDCs. We found that pDCs expressed the IgA-specific Fc receptor, FcαR, and IgA1 autoantibodies synergized with IgG in RNA-containing ICs to generate robust primary blood pDC IFN-α responses in vitro. pDC responses to these ICs required both FcαR and FcγRIIa, showing synergy between these Fc receptors. Sm/RNP IC binding to and internalization by pDCs were greater when ICs contained both IgA1 and IgG. Circulating pDCs from individuals with SLE had higher binding of IgA1-containing ICs and higher expression of FcαR than pDCs from healthy control individuals. Although pDC FcαR expression correlated with the blood IFN-stimulated gene signature in SLE, Toll-like receptor 7 agonists, but not IFN-α, up-regulated pDC FcαR expression in vitro. Together, we show a mechanism by which IgA1 autoantibodies contribute to SLE pathogenesis.

Cardiotoxicity of CPX-351 in children and adolescents with relapsed AML: a Children's Oncology Group report.

Introduction: Anthracyclines are effective in treating acute myeloid leukemia (AML) but limited by cardiotoxicity. CPX-351, a liposomal daunorubicin and cytarabine, may provide therapeutic benefit with less cardiotoxicity. Acute changes in left ventricular systolic function and cardiac biomarkers were evaluated after a cycle of CPX-351 in children with relapsed AML treated on the phase 1/2 Children's Oncology Group study, AAML1421. Methods: Subjects received 135 units/m2/dose of CPX-351 on days 1, 3, and 5 as cycle 1. Echocardiograms were performed and centrally quantitated at baseline and at the end of cycle 1 (day 29 +/- 1 week). High sensitivity troponin (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at baseline and serially through the end of cycle 1 (days 5, 8, 15, 22 and 29). Differences between baseline and post-CPX-351 echo/biomarker measures were analyzed using Wilcoxon signed rank tests. Linear regression was used to model post-CPX-351 left ventricular ejection fraction (LVEF) with cTnT/NT-proBNP at each time point, controlling for baseline LVEF. Cancer therapy related cardiac dysfunction (CTRCD) was defined as a decline in LVEF of ≥10%-<50%. Results: Twenty-five of 38 heavily anthracycline pre-treated (median 348 mg/m2 daunorubicin equivalents) subjects enrolled on AAML1421 were included in the cardiac analyses. At baseline, centrally quantitated LVEF was <50% in 8 of 25 subjects (32%) with a median LVEF of 53.8% [48.0, 56.9]. Following CPX-351, LVEF declined significantly (ΔLVEF -3.3% [-7.8, 0]) and 6 of 25 subjects (24%) experienced CTRCD. Amongst all subjects, hs-cTnT was modestly increased at end of cycle 1 compared to baseline [baseline hs-cTnT 7.2 (3, 10.6); ΔcTnT 1.80 (0, 6.1), p = 0.03]. NT-proBNP remained stably elevated without significant change. No significant associations were seen between NT-proBNP or cTnT levels and post-CPX-351 LVEF. Discussion: In this single arm study of anthracycline pre-treated children exposed to CPX-351, baseline abnormalities in cardiovascular function were prevalent. Following CPX-351, LVEF decreased, cTnT increased, and NT-proBNP did not change. Longer follow-up is needed to determine whether these changes result in clinically meaningful long-term decrements in cardiac function. An ongoing randomized trial of CPX-351 compared to standard anthracyclines in anthracycline naïve patients will provide further insight into the cardiac effects of CPX-351 (ClinicalTrials.gov; NCT04293562).

Antibrush Border Antibody Disease: A Case Series.

Antibrush border antibody (ABBA) disease is a rare cause of kidney disease characterized by progressive renal tubular injury associated with immune complex deposition along the basement membranes of the proximal tubule and circulating autoantibodies to brush border antigens. Several antigens have been identified as targets of autoantibodies in this disease, including low-density lipoprotein receptor related protein 2 (LRP2), cubilin, and amnionless proteins. We present 9 patients from 2 academic medical centers and describe the clinicopathologic characteristics and outcome data. All patients presented with acute kidney injury and proteinuria. Pathology confirmed immune complex deposition along proximal tubular basement membranes in all patients, but the majority (6/8) also showed segmental glomerular subepithelial immune complexes. Two of 3 patients treated with rituximab demonstrated stabilization of kidney function; 1 of these patients had mantle cell lymphoma. One patient with lung cancer showed stabilization of disease after treatment of the malignancy. The remaining patients progressed to end-stage kidney disease with either conservative therapy (3 patients) or immunosuppression with glucocorticoids (2 patients). This series highlights the poor prognosis of ABBA disease, but a potential benefit of anti-B cell therapy or treatment of an underlying malignancy in some cases.

JAK inhibition decreases the autoimmune burden in Down syndrome.

Individuals with Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), display clear signs of immune dysregulation, including high rates of autoimmune disorders and severe complications from infections. Although it is well established that T21 causes increased interferon responses and JAK/STAT signaling, elevated autoantibodies, global immune remodeling, and hypercytokinemia, the interplay between these processes, the clinical manifestations of DS, and potential therapeutic interventions remain ill defined. Here, we report a comprehensive analysis of immune dysregulation at the clinical, cellular, and molecular level in hundreds of individuals with DS. We demonstrate multi-organ autoimmunity of pediatric onset concurrent with unexpected autoantibody-phenotype associations. Importantly, constitutive immune remodeling and hypercytokinemia occur from an early age prior to autoimmune diagnoses or autoantibody production. We then report the interim analysis of a Phase II clinical trial investigating the safety and efficacy of the JAK inhibitor tofacitinib through multiple clinical and molecular endpoints. Analysis of the first 10 participants to complete the 16-week study shows a good safety profile and no serious adverse events. Treatment reduced skin pathology in alopecia areata, psoriasis, and atopic dermatitis, while decreasing interferon scores, cytokine scores, and levels of pathogenic autoantibodies without overt immune suppression. Additional research is needed to define the effects of JAK inhibition on the broader developmental and clinical hallmarks of DS. ClinicalTrials.gov identifier: NCT04246372.

Capturing the Effects of Single Atom Substitutions on the Inhibition Efficiency of Glycogen Synthase Kinase-3ß Inhibitors via Markov State Modeling and Experiments.

Small modifications in the chemical structure of ligands are known to dramatically change their ability to inhibit the activity of a protein. Unraveling the mechanisms that govern these dramatic changes requires scrutinizing the dynamics of protein-ligand binding and unbinding at the atomic level. As an exemplary case, we have studied Glycogen Synthase Kinase-3ß (GSK-3ß), a multifunctional kinase that has been implicated in a host of pathological processes. As such, there is a keen interest in identifying ligands that inhibit GSK-3ß activity. One family of compounds that are highly selective and potent inhibitors of GSK-3ß is exemplified by a molecule termed COB-187. COB-187 consists of a five-member heterocyclic ring with a thione at C2, a pyridine substituted methyl at N3, and a hydroxyl and phenyl at C4. We have studied the inhibition of GSK-3ß by COB-187-related ligands that differ in a single heavy atom from each other (either in the location of nitrogen in their pyridine ring, or with the pyridine ring replaced by a phenyl ring), or in the length of the alkyl group joining the pyridine and the N3. The inhibition experiments show a large range of half-maximal inhibitory concentration (IC50) values from 10 nM to 10 µM, implying that these ligands exhibit vastly different propensities to inhibit GSK-3ß. To explain these differences, we perform Markov State Modeling (MSM) using fully atomistic simulations. Our MSM results are in excellent agreement with the experiments in that they accurately capture differences in the binding propensities of the ligands. The simulations show that the binding propensities are related to the ligands' ability to attain a compact conformation where their two aromatic rings are spatially close. We rationalize this result by sampling numerous binding and unbinding events via funnel metadynamics simulations, which show that indeed while approaching the bound state, the ligands prefer to be in their compact conformation. We find that the presence of nitrogen in the aromatic ring increases the probability of attaining the compact conformation. Protein-ligand binding is understood to be dictated by the energetics of interactions and entropic factors, like the release of bound water from the binding pockets. This work shows that changes in the conformational distribution of ligands due to atom-level modifications in the structure play an important role in protein-ligand binding.

Variegated overexpression of chromosome 21 genes reveals molecular and immune subtypes of Down syndrome.

Individuals with Down syndrome, the genetic condition caused by trisomy 21, exhibit strong inter-individual variability in terms of developmental phenotypes and diagnosis of co-occurring conditions. The mechanisms underlying this variable developmental and clinical presentation await elucidation. We report an investigation of human chromosome 21 gene overexpression in hundreds of research participants with Down syndrome, which led to the identification of two major subsets of co-expressed genes. Using clustering analyses, we identified three main molecular subtypes of trisomy 21, based on differential overexpression patterns of chromosome 21 genes. We subsequently performed multiomics comparative analyses among subtypes using whole blood transcriptomes, plasma proteomes and metabolomes, and immune cell profiles. These efforts revealed strong heterogeneity in dysregulation of key pathophysiological processes across the three subtypes, underscored by differential multiomics signatures related to inflammation, immunity, cell growth and proliferation, and metabolism. We also observed distinct patterns of immune cell changes across subtypes. These findings provide insights into the molecular heterogeneity of trisomy 21 and lay the foundation for the development of personalized medicine approaches for the clinical management of Down syndrome.

Interferon-γ induces combined pyroptotic angiopathy and APOL1 expression in human kidney disease.

Elevated interferon (IFN) signaling is associated with kidney diseases including COVID-19, HIV, and apolipoprotein-L1 (APOL1) nephropathy, but whether IFNs directly contribute to nephrotoxicity remains unclear. Using human kidney organoids, primary endothelial cells, and patient samples, we demonstrate that IFN-γ induces pyroptotic angiopathy in combination with APOL1 expression. Single-cell RNA sequencing, immunoblotting, and quantitative fluorescence-based assays reveal that IFN-γ-mediated expression of APOL1 is accompanied by pyroptotic endothelial network degradation in organoids. Pharmacological blockade of IFN-γ signaling inhibits APOL1 expression, prevents upregulation of pyroptosis-associated genes, and rescues vascular networks. Multiomic analyses in patients with COVID-19, proteinuric kidney disease, and collapsing glomerulopathy similarly demonstrate increased IFN signaling and pyroptosis-associated gene expression correlating with accelerated renal disease progression. Our results reveal that IFN-γ signaling simultaneously induces endothelial injury and primes renal cells for pyroptosis, suggesting a combinatorial mechanism for APOL1-mediated collapsing glomerulopathy, which can be targeted therapeutically.

Responsive Versus Continuous Deep Brain Stimulation for Speech in Essential Tremor: A Pilot Study.

BACKGROUND: Responsive deep brain stimulation (rDBS) uses physiological signals to deliver stimulation when needed. rDBS is hypothesized to reduce stimulation-induced speech effects associated with continuous DBS (cDBS) in patients with essential tremor (ET). OBJECTIVE: To determine if rDBS reduces cDBS speech-related side effects while maintaining tremor suppression. METHODS: Eight ET participants with thalamic DBS underwent unilateral rDBS. Both speech evaluations and tremor severity were assessed across three conditions (DBS OFF, cDBS ON, and rDBS ON). Speech was analyzed using intelligibility ratings. Tremor severity was scored using the Fahn-Tolosa-Marin Tremor Rating Scale (TRS). RESULTS: During unilateral cDBS, participants experienced reduced speech intelligibility (P = 0.025) compared to DBS OFF. rDBS was not associated with a deterioration of intelligibility. Both rDBS (P = 0.026) and cDBS (P = 0.038) improved the contralateral TRS score compared to DBS OFF. CONCLUSIONS: rDBS maintained speech intelligibility without loss of tremor suppression. A larger prospective chronic study of rDBS in ET is justified. © 2024 International Parkinson and Movement Disorder Society.

Incidence of complications among operative pediatric supracondylar humerus fractures using medial and lateral pins: a safe technique for percutaneous medial pin placement.

Cross-pinning of displaced pediatric supracondylar elbow fractures offers a superior stability construct. However, there is a reluctance to use this construct by closed means because of the risk of iatrogenic ulnar nerve injuries associated with percutaneous medial pin placement. This study describes a safe technique for closed reduction percutaneous with medial pin placement. This study reviewed the clinical charts of 232 pediatric patients who underwent closed reduction with cross-pinning of Gartland type II and III supracondylar fractures from 2000 to 2022 at a single institution. All surgeries were performed by the same attending surgeon at the same institution, with the same technique of medial pin placement. The inpatient and outpatient notes were used to record patient demographic information, fracture classification, and postoperative complications. A total of 232 pediatric patients [114 boys, 118 girls; mean age: 5.8 (range: 1-14) years] with Gartland type II (n = 97) and III (n = 135) supracondylar fractures were included in the study. There were a total of seven (3.02%) postoperative complications: four (1.7%) ulnar neuropathies, two (0.86%) pin site infections, and one (0.43%) anterior interosseous nerve palsy. All documented postoperative complications were resolved by the 3-month follow-up visit. There were no complications of deep infection, malunion, or nonunion. With the proper technique, closed reduction with percutaneous medial pin fixation of pediatric supracondylar fractures is safe and produces excellent postoperative outcomes. Level of Evidence: Level IV, case series.

Loss of mitochondrial pyruvate transport initiates cardiac glycogen accumulation and heart failure.

Background: Heart failure involves metabolic alterations including increased glycolysis despite unchanged or decreased glucose oxidation. The mitochondrial pyruvate carrier (MPC) regulates pyruvate entry into the mitochondrial matrix, and cardiac deletion of the MPC in mice causes heart failure. How MPC deletion results in heart failure is unknown. Methods: We performed targeted metabolomics and isotope tracing in wildtype (fl/fl) and cardiac-specific Mpc2-/- (CS-Mpc2-/-) hearts after in vivo injection of U-13C-glucose. Cardiac glycogen was assessed biochemically and by transmission electron microscopy. Cardiac uptake of 2-deoxyglucose was measured and western blotting performed to analyze insulin signaling and enzymatic regulators of glycogen synthesis and degradation. Isotope tracing and glycogen analysis was also performed in hearts from mice fed either low-fat diet or a ketogenic diet previously shown to reverse the CS-Mpc2-/- heart failure. Cardiac glycogen was also assessed in mice infused with angiotensin-II that were fed low-fat or ketogenic diet. Results: Failing CS-Mpc2-/- hearts contained normal levels of ATP and phosphocreatine, yet these hearts displayed increased enrichment from U-13C-glucose and increased glycolytic metabolite pool sizes. 13C enrichment and pool size was also increased for the glycogen intermediate UDP-glucose, as well as increased enrichment of the glycogen pool. Glycogen levels were increased ~6-fold in the failing CS-Mpc2-/- hearts, and glycogen granules were easily detected by electron microscopy. This increased glycogen synthesis occurred despite enhanced inhibitory phosphorylation of glycogen synthase and reduced expression of glycogenin-1. In young, non-failing CS-Mpc2-/- hearts, increased glycolytic 13C enrichment occurred, but glycogen levels remained low and unchanged compared to fl/fl hearts. Feeding a ketogenic diet to CS-Mpc2-/- mice reversed the heart failure and normalized the cardiac glycogen and glycolytic metabolite accumulation. Cardiac glycogen levels were also elevated in mice infused with angiotensin-II, and both the cardiac hypertrophy and glycogen levels were improved by ketogenic diet. Conclusions: Our results indicate that loss of MPC in the heart causes glycogen accumulation and heart failure, while a ketogenic diet can reverse both the glycogen accumulation and heart failure. We conclude that maintaining mitochondrial pyruvate import and metabolism is critical for the heart, unless cardiac pyruvate metabolism is reduced by consumption of a ketogenic diet.

Qualification of a 21-valent pneumococcal urine antigen detection assay and development of clinical positivity cutoffs.

Aim: Serotype-specific assays detecting pneumococcal polysaccharides in bodily fluids are needed to understand the pneumococcal serotype distribution in non-bacteremic pneumonia. Methods: We developed a urine antigen detection assay and using urine samples from adult outpatients without pneumonia developed positivity cutoffs for both a previously published 15-valent and the new 21-valent assay. Clinical sensitivity was confirmed with samples from patients with invasive pneumococcal disease. Results: Total assay precision ranged from 7.6 to 17.8% coefficient of variation while accuracy ranged between 80 and 150% recovery, except for three serotypes where recoveries ranged from 32 to 60%. Clinical sensitivity was 86.4% and specificity was 96.5% across all 30 serotypes. Conclusion: The assay could potentially assess serotype-distribution in non-infected and infected participants with pneumococcal disease.

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Lifetime Health and Economic Burden of Invasive Pneumococcal Diseases Attributable to V116 Serotypes Among Adults in the United States.

INTRODUCTION: This study aimed to estimate and compare the lifetime clinical and economic burden of invasive pneumococcal diseases (IPD) attributable to the serotypes contained in a new 21-valent pneumococcal conjugate vaccine (V116) vs. the 20-valent pneumococcal conjugate vaccine (PCV20) among adults aged 18 years and above in the USA. METHODS: A state-transition Markov model was used to track IPD cases and deaths as well as the associated direct medical costs (in 2023 US dollars) from a US healthcare payer perspective at 3% annual discount rate. The results were summarized for V116, PCV20, and eight unique serotypes contained in V116. A sensitivity analysis was conducted to determine the most influential inputs on the overall total direct lifetime cost. RESULTS: For the total population of US adults aged 18 years and above in 2021 (approx. 258 million residents), the estimated lifetime numbers of cases of IPD, post-meningitis sequelae (PMS), and IPD-related deaths attributable to the serotypes contained in V116 were approximately 1.4 million, 17,608, and 186,200, respectively, with a total discounted lifetime direct cost of $32.6 billion. A substantial proportion (approx. 31%) of those were attributable to the unique eight serotypes. The corresponding estimates for PCV20 were approximately 35% lower-934,000, 11,500, and 120,000, respectively-with a total discounted direct lifetime cost of $21.9 billion. CONCLUSION: These results show that V116 serotypes (compared to PCV20) are associated with substantially higher clinical and economic burden of IPD. The addition of V116 to vaccination recommendations can help to reduce the residual burden of IPD in US adults.

Victim Sexual Arousal During Nonconsensual Sex: A Scoping Review.

Sexual arousal in male and female victims during nonconsensual sex is an understudied phenomenon with many potential psychological, clinical, and legal implications for survivors. The aim of this scoping review was to assess the literature to determine whether we could estimate the frequency and circumstances of physiological sexual arousal (e.g., erection, lubrication, ejaculation, orgasm) among victims during nonconsensual sex. Six reference database and hand searches led to the screening of 13,894 articles and other reports. Eight articles and one book published between 1977 and 2019 included relevant data from 136 male survivors and 250 female survivors. Results confirmed that physiological sexual arousal (only genital responses were mentioned) can occur in both male and female victims during nonconsensual sex. The frequency of these responses could not be determined because of the widely different methodologies used. In addition, it was not possible to determine the circumstances in which victim sexual arousal was more likely to occur although some were inferred. The results of the scoping review highlight that physiological sexual arousal during nonconsensual sex does occur for victims but has not been studied systematically. There is a clear need to properly assess the type, circumstances, consequences, and frequency of sexual arousal during nonconsensual sex in large and diverse populations of male and female survivors.

Mechanistic insights into SARS-CoV-2 spike protein induction of the chemokine CXCL10.

During a SARS-CoV-2 infection, macrophages recognize viral components resulting in cytokine production. While this response fuels virus elimination, overexpression of cytokines can lead to severe COVID-19. Previous studies suggest that the spike protein (S) of SARS-CoV-2 can elicit cytokine production via the transcription factor NF-κB and the toll-like receptors (TLRs). In this study, we found that: (i) S and the S2 subunit induce CXCL10, a chemokine implicated in severe COVID-19, gene expression by human macrophage cells (THP-1); (ii) a glycogen synthase kinase-3 inhibitor attenuates this induction; (iii) S and S2 do not activate NF-κB but do activate the transcription factor IRF; (iv) S and S2 do not require TLR2 to elicit CXCL10 production or activate IRF; and (v) S and S2 elicit CXCL10 production by peripheral blood mononuclear cells (PBMCs). We also discovered that the cellular response, or lack thereof, to S and S2 is a function of the recombinant S and S2 used. While such a finding raises the possibility of confounding LPS contamination, we offer evidence that potential contaminating LPS does not underly induced increases in CXCL10. Combined, these results provide insights into the complex immune response to SARS-CoV-2 and suggest possible therapeutic targets for severe COVID-19.

Reporting on Health Care and Social Service Provider Approaches to Promoting Alcohol Abstinence During Pregnancy.

Despite the known detrimental health effects of alcohol use during pregnancy, there are still health care (HCP) and social service providers (SSP) who do not promote complete abstinence. The purpose of this study was to explore the current practices of HCPs and SSPs when discussing alcohol use during pregnancy, and to understand their rationale for their specific recommendations. An online survey was completed by 1123 HCPs (n = 588) and SSPs (n = 535) that asked them to identify their approach to discussing alcohol and pregnancy. Participants had the option to further explain their current recommendations regarding alcohol use during pregnancy in an open-ended format. Open-ended responses were analyzed using a content analysis approach (n = 156). The majority of respondents recommend abstinence (83.9% of HCPs, n = 493; 78.4% of SSPs, n = 419), while 9.8% of HCPs (n = 57) and 2.2% of SSPs (n = 12) responded that low levels of consumption may be acceptable. HCPs may recommend low levels of consumption based on other international guidelines, limited evidence to suggest that one unit of alcohol is harmful, and as a harm reduction strategy. SSPs stated that they refer clients to HCPs for recommendations related to alcohol consumption, and that they prefer to provide information based on public health guidelines. This exploratory work may inform the development of resources to support HCPs and SSPs to recommend abstinence from alcohol throughout gestation.

Structure and functionality of surface-active amylose-fatty amine salt inclusion complexes.

Novel value-added starch-based materials can be produced by forming amylose inclusion complexes (AIC) with hydrophobic compounds. There is currently little research on AIC use as polymeric emulsifiers, particularly for AIC with fatty amine salt ligands. This work evaluated AIC emulsifiers by studying the structure and functionality of AIC composed of high amylose corn starch and fatty amine salts (10-18 carbons, including a mixture simulating vegetable oil composition) produced via steam jet cooking. X-ray scattering verified successful AIC formation, with peaks located near 7.0°, 12.8° and 19.9° 2θ. AIC were easily dispersed in water (80-85 °C) and remained in suspension at room temperature for weeks, unlike the uncomplexed ligands or starch. AIC were highly effective emulsifying agents, with emulsifying activity indexes of 213-229 m2g-1 at pH 5, and zeta potentials, a measure of electrostatic repulsion, as high as 43.4 mV. AIC dispersions had surface tension ranging from 24 to 41 mN/m and displayed surface-active properties superior to amylose complexes formed from fatty acid salts and competitive with common starch-based emulsifiers. These findings demonstrate that fatty amine salt AIC are effective emulsifiers that can be made from low-cost sources of fatty amine salts, such as vegetable oil derivatives.

Complementary, alternative, and integrative medicine researchers' practices and perceived barriers related to open science: An international, cross-sectional survey.

INTRODUCTION AND OBJECTIVE: Open science (OS) aims to make the dissemination of knowledge and the research process transparent and accessible to everyone. With the increasing popularity of complementary, alternative, and integrative medicine (CAIM), our goal was to explore what are CAIM researchers' practices and perceived barriers related to OS. METHODS: We conducted an anonymous online survey of researchers who published in journals listed in Scopus containing the words "complementary", "alternative", or "integrative" medicine in their names. We emailed 6040 researchers our purpose-built electronic survey after extracting their email address from one of their publications in our sample of journals. We questioned their familiarity with different OS concepts, along with their experiences and challenges engaging in these practices over the last 12 months. RESULTS: The survey was completed by 392 researchers (6.5% response rate, 97.1% completion rate). Most respondents were CAIM researchers familiar with the overall concept of OS, indicated by those actively publishing open access (OA) (n = 244, 76.0%), registering a study protocol (n = 148, 48.0%), and using reporting guidelines (n = 181, 59.0%) in the past 12 months. Preprinting, sharing raw data, and sharing study materials were less popular. A lack of funding was reported as the greatest barrier to publishing OA by most respondents (n = 252, 79.0%), and that additional funding is the most significant incentive in applying more OS practices to their research (n = 229,72.2%). With respect to preprinting barriers, 36.3% (n = 110) participants believed there are potential harms in sharing non-peer-reviewed work and 37.0% (n = 112) feared preprinting would reduce the likelihood of their manuscript being accepted by a journal. Respondents were also concerned about intellectual property control regarding sharing data (n = 94, 31.7%) and research study materials (n = 80, 28.7%). CONCLUSIONS: Although many participants were familiar with and practiced aspects of OS, many reported facing barriers relating to lack of funding to enable OS and perceived risks of revealing research ideas and data prior to publication. Future research should monitor the adoption and implementation of OS interventions in CAIM.

Association between oral targeted cancer drug net health benefit, uptake, and spending.

BACKGROUND: Targeted cancer drugs (TCDs) have revolutionized oncology but vary in clinical benefit and patient out-out-pocket (OOP) costs. The ASCO Value Framework uses survival, toxicity, and symptom palliation data to quantify the net health benefit (NHB) of cancer drugs. We evaluated associations between NHB, uptake, and spending on oral TCDs. METHODS: We conducted a retrospective cohort study of patients aged 18-64 years with an incident oral TCD pharmacy claim in 2012-2020 in a nationwide de-identified commercial claims dataset. TCDs were categorized as having high (>60), medium (40-60), and low (<40) NHB scores. We plotted the uptake of TCDs by NHB category and used standard descriptive statistics to evaluate patient OOP and total spending. Generalized linear models evaluated the relationship between spending and TCD NHB, adjusted for cancer indication. RESULTS: We included 8,524 patients with incident claims for eight oral TCDs with nine first-line indications in advanced melanoma, breast, lung, and pancreatic cancer. Medium- and high-NHB TCDs accounted for most TCD prescriptions. Median OOP spending was $18.78 for the first 28-day TCD supply (IQR $0.00-$87.57); 45% of patients paid $0 OOP. Median total spending was $10,118.79 (IQR $6,365.95-$10,600.37) for an incident 28-day TCD supply. Total spending increased $1,083.56 for each 10-point increase in NHB score (95% CI $1,050.27-$1,116.84, p < .01 for H0=$0). CONCLUSION: Low-NHB TCDs were prescribed less frequently than medium- and high-NHB TCDs. Total spending on oral TCDs was high and positively associated with NHB. Commercially insured patients were largely shielded from high OOP spending on oral TCDs.

Effects of acclimation temperature and feed restriction on the metabolic performance of green sturgeon.

Green sturgeon (Acipenser medirostris) are an anadromous threatened species of sturgeon found along the Pacific coast of North America. The southern distinct population segment only spawns in the Sacramento River and is exposed to water temperatures kept artificially cold for the conservation and management of winter-run Chinook salmon (Oncorhynchus tshawytscha). Past research has demonstrated costs of cold-water rearing including reduced growth rates, condition and survivorship of juvenile green sturgeon. Our research investigates how the stressors of water temperature and food limitation influence the metabolic performance of green sturgeon. We reared green sturgeon at two acclimation temperatures (13 and 19°C) and two ration amounts (100% and 40% of optimal feed). We then measured the routine and maximum metabolic rates (RMR and MMR, respectively) of sturgeon acclimated to these rearing conditions across a range of acute temperature exposures (11 to 31°C). Among both temperature acclimation treatments (13 or 19°C), we found that feed restriction reduced RMR across a range of acute temperatures. The influence of feed restriction on RMR and MMR interacted with acclimation temperature. Fish reared at 13°C preserved their MMR and aerobic scope (AS) despite feed restriction, while fish fed reduced rations and acclimated to 19°C showed reduced MMR and AS capacity primarily at temperatures below 16°C. The sympatry of threatened green sturgeon with endangered salmonids produces a conservation conflict, such that cold-water releases for the conservation of at-risk salmonids may constrain the metabolic performance of juvenile green sturgeon. Understanding the impacts of environmental conditions (e.g. temperature, dissolved oxygen) on ecological interactions of green sturgeon will be necessary to determine the influence of salmonid-focused management.