Real-World Effectiveness of a Novel AI-Software Dependent Neuromodulation (ASDN) with Remote Monitoring Capability Field Stimulation Device for Chronic Pain: A 24-Month Analysis of Over 2000 Patients

Maja Green,1 Adam Cabble,1 Michael Bailey,2 Maria L Kappell,1 Bart Billet,3 Choll W Kim,4 Jaspal R Singh,5 Manish Suthar,6 Hemant Kalia,7 Shari Kappell,1 Krishnan Chakravarthy1 1Department of Pain Medicine, NXTSTIM Inc., San Diego, CA, USA; 2Department of Neuroscience, Monash University, Clayton, Victoria, Australia; 3Department of Anaesthesiology, AZ Delta Hospital, Roeselare, Belgium; 4Department of Orthopaedic Surgery, Scripps Memorial Hospital, La Jolla, CA, USA; 5Center for Global Health, Weill Cornell Medicine, New York, NY, USA; 6Pain Prevention and Rehabilitation Center, Chesterfield, MO, USA; 7Department of Pain Medicine, Invision Health, Rochester, NY, USACorrespondence: Maja Green, Department of Pain Medicine, NXTSTIM Inc., 5362 Sweetwater Trails, San Diego, CA, 92130, USA, Tel +1 858 910-1778, Email [email protected]: Chronic pain is a leading cause of disability worldwide, and conventional pharmacologic treatments are often limited by side effects, inadequate efficacy, and risk of dependency. Non-invasive neuromodulation therapies such as TENS and EMS offer alternatives but are traditionally constrained by fixed stimulation protocols and low user engagement.Objective: To evaluate the 24-month real-world effectiveness of EcoAI™, an AI-driven wearable system delivering adaptive TENS and EMS for chronic pain management in community settings.Design, Setting, and participants: This retrospective observational cohort study analyzed de-identified data from 2135 adult users across the United States between January 2023 and March 2025. All users completed at least one therapy session and submitted symptom data via a mobile application.Intervention: EcoAI delivers transcutaneous electrical nerve stimulation (TENS) to modulate afferent pain signaling and electrical muscle stimulation (EMS) to improve local circulation and neuromuscular function. An embedded AI engine dynamically adjusts stimulation intensity, waveform, and duration based on user-reported outcomes and physiological markers.Main Outcomes and Measures: Primary outcome: change in self-reported pain score (0– 10 numeric scale). Secondary outcomes: mood, physical function, social engagement, work activity, and overall well-being. Session adherence and device usage patterns were also analyzed.Results: Across 187,930 recorded sessions, median pain scores declined from 6.0 at baseline to 4.0 at 6 months and 3.0 at 24 months. Statistically significant improvements (p < 0.001) were also observed in secondary domains. Optimal outcomes were achieved with 2– 4 sessions per day lasting 20– 59 minutes. Older adults (≥ 60 years) demonstrated greater engagement and pain relief. No serious adverse events were reported.Conclusions and Relevance: In this retrospective, decentralized study, the EcoAI platform demonstrated sustained, multidimensional benefit in adults with chronic pain. These findings support the potential of AI-driven TENS/EMS as a safe, scalable, and personalized adjunct to pharmacologic care.Keywords: chronic pain, transcutaneous electrical nerve stimulation, TENS, electrical muscle stimulation, EMS, field stimulation, remote therapy monitoring, remote patient monitoring, artificial intelligence, digital therapeutics, real-world evidenc

A many-analysts approach to the relation between religiosity and well-being

Supplemental material is available online at: https://www.tandfonline.com/doi/full/10.1080/2153599X.2022.2070255# .The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset ( = 10,535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported = 0.120). For the second research question, this was the case for 65% of the teams (median reported = 0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates.Neil Levy and Robert M. Ross were supported by Australian Research Council (grant number DP180102384); Ryan McKay was supported by Cogito Foundation [grant number R10917]; Sacha Altay was supported by French Agence Nationale de la Recherche (reference 17-EURE-0017 FrontCog and 10-IDEX-0001-02 PSL); Emily Gerdin was supported by National Science Foundation Graduate Research Fellowship (GR100544) [grant number DGE-2139841]; Eric-Jan Wagenmakers was supported by Netherlands Organisation for Scientific Research [grant number 016.Vici.170.083]; Don van Ravenzwaaij was supported by Netherlands Organisation for Scientific Research [grant number 016.Vidi.188.001]; Alexandra Sarafoglou was supported by Netherlands Organisation for Scientific Research [grant number 406-17-568]; Michiel van Elk was supported by John Templeton Foundation [grant number 60663]; James O. Pawelski and Louis Tay were supported by Templeton Religion Trust (TRT 0154). Marcel R. Schreiner, Susanne Frick, Julian Quevedo Pütter and Marcel C. Schmitt were supported by the German Research Foundation [grant number GRK 2277]

NM23 proteins: innocent bystanders or local energy boosters for CFTR?

NM23 proteins NDPK-A and -B bind to the cystic fibrosis (CF) protein CFTR in different ways from kinases such as PKA, CK2 and AMPK or linkers to cell calcium such as calmodulin and annexins. NDPK-A (not -B) interacts with CFTR through reciprocal AMPK binding/control, whereas NDPK-B (not -A) binds directly to CFTR. NDPK-B can activate G proteins without ligand-receptor coupling, so perhaps NDPK-B's binding influences energy supply local to a nucleotide-binding site (NBD1) needed for CFTR to function. Curiously, CFTR (ABC-C7) is a member of the ATP-binding cassette (ABC) protein family that does not obey 'clan rules'; CFTR channels anions and is not a pump, regulates disparate processes, is itself regulated by multiple means and is so pleiotropic that it acts as a hub that orchestrates calcium signaling through its consorts such as calmodulin/annexins. Furthermore, its multiple partners make CFTR dance to different tunes in different cellular and subcellular locations as it recycles from the plasma membrane to endosomes. CFTR function in airway apical membranes is inhibited by smoking which has been dubbed 'acquired CF'. CFTR alone among family members possesses a trap for other proteins that it unfurls as a 'fish-net' and which bears consensus phosphorylation sites for many protein kinases, with PKA being the most canonical. Recently, the site of CFTR's commonest mutation has been proposed as a knock-in mutant that alters allosteric control of kinase CK2 by log orders of activity towards calmodulin and other substrates after CFTR fragmentation. This link from CK2 to calmodulin that binds the R region invokes molecular paths that control lumen formation, which is incomplete in the tracheas of some CF-affected babies. Thus, we are poised to understand the many roles of NDPK-A and -B in CFTR function and, especially lumen formation, which is defective in the gut and lungs of many CF babies

A many-analysts approach to the relation between religiosity and well-being

The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N=10,535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported β=0.120). For the second research question, this was the case for 65% of the teams (median reported β=0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates

Purification of rat liver particulate neutral ribonuclease and comparison of properties with pancreas and serum ribonucleases.

Rat liver particulate neutral ribonuclease (EC 3.1.4.22) was extensively purified (up to 40000-fold). It is shown to be an endonuclease, specific for pyrimidine bases, hydrolysing 5'-phosphate ester bonds. The enzyme specificity, Km, pH optimum, stability in acid medium and thermal stability at high temperature are the same as those of rat pancreatic and serum ribonucleases. Like pancreatic and serum neutral ribonucleases, the hepatic enzyme is sensitive to the liver natural inhibitor. This inhibitor was purified 8000-fold; its association with ribonuclease follows zero-order kinetics. These identical properties for ribonuclease of rat liver, pancreas and serum support the hypothesis [Bartholeyns, Peeters-Joris & Baudhuin (1975) Eur. J. Biochem. 60, 385-393] of an extrahepatic origin for the liver enzyme, the plasma ribonuclease of pancreatic origin being taken up by endocytosis in the liver. Neutral ribonuclease activity was detected in all rat organs investigated; its distribution among tissues is different from the distribution of the natural ribonuclear inhibitor

Differential computation analysis : hiding your white-box designs is not enough

Although all current scientific white-box approaches of standardized cryptographic primitives are broken, there is still a large number of companies which sell "secure" white-box products. In this paper a new approach to assess the security of white-box implementations is presented which requires neither knowledge about the look-up tables used nor any reverse engineering effort. This differential computation analysis (DCA) attack is the software counterpart of the differential power analysis attack as applied by the cryptographic hardware community. We developed plugins to widely available dynamic binary instrumentation frameworks to produce software execution traces which contain information about the memory addresses being accessed. We show how DCA can extract the secret key from all publicly (non-commercial) available white-box programs implementing standardized cryptography by analyzing these traces to identify secret-key dependent correlations