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Effects of Coping Resources on Depressive Symptoms in Rural Heart Failure Patient-Caregiver Dyads: An Actor-Partner Interdependence Modeling Analysis
Graven, Lucinda J. , Stearns, Erin, Ledermann, Thomas , Plummer, Shea, Hubble, Marlee, Howren, M. Bryant, Howren, Matthew Bryant , Grant, Joan S. , Abbott, Laurie S.

Journal of Family Nursing | May 11, 2026 | Volume: 32 | Issue: 3 | Pages: 147-158

10.1177/10748407261440167 | PMID 42109052 Get It

Background: Managing heart failure (HF) can be challenging for rural dyads, potentially contributing to depressive symptoms. Coping resources may be important components for dyadic interventions targeting depressive symptoms. Purpose: To explore actor and partner effects of coping resources on depressive symptoms in rural HF dyads. Methods: Using a cross-sectional design, data were collected from 42 rural HF dyads using the Interpersonal Support Evaluation List-12, Social Problem-Solving Inventory Revised-Short, Global Family Function, Family APGAR, and the Center for Epidemiological Studies-Depression scales. Data were analyzed using the Actor-Partner Interdependence Model. Results: Patients were 66.42 and caregivers were 60.83 years old. No partner effects noted. Significant actor effects for patients and caregivers between their own social support and depressive symptoms and their own problem-solving and depressive symptoms were found. There was also a significant actor effect between the caregivers’ family satisfaction and depressive symptoms. Conclusions: Dyadic interventions that enhance coping resources are needed.
Feasibility of Integrating PROMIS Measures into an Interventional Spine Workflow: Lessons from a Basivertebral Nerve Ablation Registry
Cheney, Cole, Springsted, Martha, Pisati, Tejaswini, Dauffenbach, Jason, Springsted, Martha, Dauffenbach, Jason

No container title available | May 11, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.21203/rs.3.rs-9405355/v1 Get It

Abstract Objective To evaluate the feasibility of collecting Patient-Reported Outcomes Measurement Information System (PROMIS) data within an electronic health record (EHR) for patients undergoing basivertebral nerve ablation (BVNA). Design: Retrospective feasibility study. Setting: Academic community-based health system. Subjects: Seventy-one unique patients (73 procedures) treated with BVNA between 2022–2025. Methods PROMIS Pain Interference, Pain Intensity, and Physical Function surveys were administered at baseline and at 3-, 6-, and 12-month follow-up using EHR-embedded automated workflows. In parallel, a structured quality improvement intervention was implemented to improve survey completion via emphasis on baseline survey completion. The intervention included a standardized nursing rooming checkpoint to verify PROMIS completion prior to the procedure, staff education with scripted patient engagement language, real-time EHR visual prompts using dot phrases to identify incomplete surveys, and monthly site-level performance dashboards reviewed with clinical staff and leadership. Completion rates were extracted from institutional dashboards and workflow bottlenecks were identified through process mapping and staff feedback. A two-proportion test compared pre- and post-intervention baseline completion rates. Clinic visit duration was tracked as a balancing measure to evaluate potential workflow burden. Results Seventy-one patients underwent 73 BVNA procedures. Completion rates were 31.82% at baseline, 77.78% at 3 months, 40.00% at 6 months, and 100% at 12 months among patients reaching those timepoints. Longitudinal engagement was 56%, while longitudinal completeness was 33%. Baseline survey completion improved from 31.82% (21/66) before intervention to 100% (6/6) following implementation (z ≈ 3.0, p ≈ 0.003) durable through three months. Clinic workflow efficiency was not adversely affected, with 83% of visits remaining within the standard 30-minute time slot and no statistically significant increase in visit duration (p ≈ 0.36). Conclusions PROMIS data collection during interventional spine care is feasible and can be reliably integrated into routine clinical workflows when supported by targeted quality improvement interventions. Improving baseline survey capture substantially expands the denominator of patients eligible for longitudinal outcome measurement without increasing clinical workload. Hybrid implementation strategies combining automated EHR deployment with structured clinical oversight may enable reliable PROMIS integration in procedural spine practice.
Encounter tool for Shared Decision Making about Adjuvant Treatment of Lung Cancer: Randomized Clinical Trial
Bandi, Satya Sai Sri, Branda¹, Megan E, Chavez¹, Maria Mateo, Bagewadi¹, Shubhangi, Norman², Aurora S., Montori, Victor, Hargraves¹, Iris G., Boehmer¹, Kasey, Stephen¹, Angela, Sagen¹, Christi, Montori¹, Victor M., Brito¹, Juan P, Leventakos, Konstantinos, Branda, Megan E. , Norman, Aurora S, Hargraves, Iris G., Boehmer, Kasey, Stephen, Angela, Sagen, Christi, Montori, Victor , Gionfriddo, Michael R. , HARGRAVES, IRIS G., Boehmer, Kasey R. , Sagen, Christi, Montori, Víctor M.

No container title available | May 11, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.21203/rs.3.rs-8843093/v1 | PMID 42183367 Get It

Abstract Background Lung cancer is the leading cause of cancer-related death, and the most common cancer diagnosed globally. Approximately 85% of lung cancer cases are non-small cell lung cancer (NSCLC). After initial surgical treatment, adjuvant therapy with conventional or targeted chemotherapy can help optimize survival. These treatments, however, must be tailored to each patients’ problematic situation, including cancer characteristics and goals of care. Shared decision making (SDM) is a method of care by which patients and clinicians work together to form plans of care that advance the patient’s problematic human situation. This method often requires evaluating alternative options, “trying them on” for fit given their practical demands and favorable and unfavorable effects. Tools used within the encounter can facilitate and support SDM conversations, yet none exist for considering care post-surgical treatment of NSCLC. Therefore, we aimed to evaluate the effectiveness of a novel encounter tool for SDM, NSCLC Choice, compared to usual care at improving SDM and reducing decisional conflict for patients with resected early-stage NSCLC considering adjuvant treatment. Methods We will conduct a parallel, patient-level randomized trial comparing NSCLC Choice with usual care. Patients will be eligible if they are adults with stage >1B NSCLC eligible for postsurgical adjuvant chemotherapy. Allocation will be central and post-consent. Patients will be blinded to our trial hypothesis, instead of being invited to evaluate an educational intervention. Our primary outcome is SDM quality, which we will assess using participant reported measures (patient SDM-Q-9) obtained immediately post-encounter and an observer measure estimated from video recording of trial encounters in both arms (OPTION12). With resources to conduct a 100-patient trial, we will have >80% power to detect a 12-point medium difference between arms in patient-reported SDM-Q-9. We will also assess the secondary outcomes of knowledge about the disease and the features of treatment options using an ad hoc questionnaire, decisional conflict using the Decisional Conflict Scale, and patient and clinician satisfaction using the metrics used in prior SDM intervention trials. We will also determine encounter length using video recordings. Discussion In testing NSCLC Choice, we seek to determine the extent to which this intervention can improve care for patients with NSCLC considering adjuvant therapy after surgery. In addition, we expect to determine whether this intervention is satisfactory to participants and feasible in practice. If successful, this study will result in an evidence-based tool for promoting patient-centered conversations around NSCLC and cancer care those fits. Trial Registration: NCT06122064 ClinicalTrials.gov
Functional Outcomes in Bipolar Disorder: Cross-Cohort Analyses from the Global Bipolar Cohort
Yocum, *Anastasia K., Fullerton, *Janice M., Ashton, Melanie M., Overs, Browyn J., Diaz‐Byrd, Claudia , Albarracín-García, Lucía , Alda, Martin, Alexander, Nina , Altimus, Cara M. , Altınbaş, Kürşat, Andreassen, Ole A., Aubin, V. , Baca-García, Enrique, Baune, Bernhard T., Belzeaux, Raoul , Benavente-López, Sergio, Bengesser, Susanne A., Berk, Michael, Biernacka, Joanna, Blumberg, Hilary P., Burdick, Katherine E., Carpiniello, Bernardo, Chang, Chiao-Erh , Chen, Wen Yin, Clark, Scott R., Cleare, Anthony J., Contu, Martina , Dafnas, Konstantinos , Dannlowski, Udo, Dikeos, Dimitris, Dodd, Seetal, Dols, Annemieke, Dubertret, C, Etain, Bruno, Eyler, Lisa T., Fatjó‐Vilas, Mar , Ferentinos, Panagiotis, Ferguson, B. , Fernández, Ana L., Flinkenflügel, Kira, Forester, Brent P. , Fries, Gabriel R., Frye, Mark A., Fuentes-Claramonte, Paola, Gard, Sébastien, Gergel, Tania, Godin, O, Green, MJ, Haffen, E, Hahn, Tim, Havard, Alys, Jamalabadi, Hamidreza, Jansen, Andreas, Jones, I, Jones, Lisa A., Kelsoe, John R., Kircher, Tilo, Klaus, Federica, Kulkarni, Jayashri , Kupka, Ralph W., Leboyer, M, Lenger, Melanie , McElroy, Susan L., Machado-Vieira, Rodrigo, Manchia, Mirko, Martin, Nicolas G., Mata-Iturralde, Laura, Meinert, Susanne, Mitchell, Philip B., Mitra, Romita, Mohebbi, Mohammadreza , Mwangi, Benson, Nenadić, Igor, Nierenberg, Andrew A., Nunes, Abraham, Olié, E, O'Donovan, Clair, Orhan, Melis M., Passerieux, Christine, Perich, Tania, Peters, Amy T. , Petite, Joanne, Pham, Dániel , Pinna, M A, Platzer, Martina, Polosan, Mircea , Pomarol-Clotet, Edith, Porta-Casteràs, Daniel, Potter, Julia R., Quidé, Yann, Regeer, Eline J. , Rheenen, Tamsyn E. Van, Roberts, Gloria, Rodríguez-Cano, Elena, Rossell, Susan L., Sajatovic, Martha, Salvador, Raymond, Samalin, Ludovic, Sánchez-Alonso, Sergio, Sarró, Salvador , Schubert, Klaus O., Schwan, R, Scott, Katie , Shanahan, Megan, Soares, Jair C., Solé, Brisa, Stein, Dan J., Stein, Frederike, Strakowski, Stephen M., Straube, Benjamin, Strawbridge, Rebecca, Sullivan, Patrick F., Teutenberg, Lea, Thiel, Katharina , Thomas-Odenthal, Florian, Toma, Claudio, Usemann, Paula L., Vieta, Eduard, Vilella, Elisabet, Viswanath, Biju, Williams, Lana J., Wu, Mon-Ju, Yatham, Lakshmi N., Young, Allan H., McInnis, Melvin G., Almeida, Jorge, Bora, Emre, Cannon, Dara M., Chang, Yun-Hsuan, Chaumette, Boris, Chen, Jun, Ching, Christopher, Escamilla, Michael , Forstner, Andreas J., Goghari, Vina M. , He, Qin, Huang, Hailiang, Juruena, Mario F.; id_orcid 0000-0001-8558-3396, Kasyanov, Evgeny D., Koenig, B., Kovács, Zoltán , Kulkarni, Alok, Lee, Heon-Jeong, Lee, Jimmy, Liao, Duanping , LICHT, RASMUS W., Melle, Ingrid, Nicolini, Humberto, Okawa-Belizario, Gabriel, Prieto, Miguel L. , Raventós, Henriette , Ardestani, Seyed M. Samimi, Saunders, Erika F., Savitz, Jonathan, Schulze, Thomas G., Serretti, Alessandro, Simhandl, Christian , Straszek, Sune, SOUSA, RAFAEL TEIXEIRA DE , Thompson, Paul M., Tondo, Leonardo, Tourjman, S. Valérie, Zandi, Peter, Quidé, Yann , Overs, Bronwyn J. , Quidé, Yann , Sarró, Salvador , Yocum, Anastasia K. , Fullerton, Janice M. , Ashton, Melanie M. , Alda, Martin , Alonso-Lana, Sílvia , Altınbaş, Kürşat , Andreassen, Ole A , Antoniou, Anastasia , Baca‐García, Enrique , Baune, Bernhard T., López, Sergio Benavente , Berk, Michael , Beunders, Alexandra J.M. , Blumberg, Hilary P. , Brosch, Katharina , Burdick, Katherine E. , Callahan, Tiffany J , Cano, Marta , Cardoner, Narcı́s , Carpiniello, Bernardo , Chen, I‐Ming , Clark, Scott , Cleare, Anthony J. , Dalkner, Nina , Dannlowski, Udo , Dikeos, Dimitris, Dodd, Seetal , Dols, Annemiek , Dubertret, Caroline , Étain, Bruno , Eyler, Lisa T. , Fellendorf, Frederike T. , Flinkenflügel, Kira , Di Florio, Arianna , Fries, Gabriel R. , Frye, Mark A. , Fuentes‐Claramonte, Paola , Gergel, Tania , Godin, Ophélia , Gordon‐Smith, Katherine , Haffen, Emmanuel , Hahn, Tim , Hartmann, Simon , Havard, Alys , Hickie, Ian Bernard , Jamalabadi, Hamidreza , Jansen, Andreas , Kelsoe, John R , Kircher, Tilo , Klaus, Federica , Kuo, Po‐Hsiu , Kupka, Ralph , Lagerberg, Trine Vik , Leboyer, Marion , Lind, Penelope A. , McElroy, Susan L. , Machado‐Vieira, Rodrigo , Manchia, Mirko , Martínez‐Arán, Anabel , Medland, Sarah E. , Meinert, Susanne L. , Miklowitz, David J. , Millett, Caitlin E. , Mitchell, Philip B , Muntané, Gerard , Mwangi, Benson , Nenadić, Igor , Nierenberg, Andrew A. , Nurnberger, John I , Olié, Émilie , Orhan, Melis , Paribello, Pasquale , Passerieux, Christine , Perich, Tania , Pisanu, Claudia , Pomarol‐Clotet, Edith , Casteràs, Daniel Porta , Potter, Julia R, Reininghaus, Eva , Van Rheenen, Tamsyn , Ringin, Elysha , Ritter, Philipp , Roberts, Gloria, Rodríguez‐Cano, Elena , Rossell, Susan Lee , Sajatovic, Martha , Samalin, Ludovic , Scaini, Giselli , Schofield, Peter R. , Schouws, Sigfried N. T. M. , Schubert, Klaus Oliver , Schwan, Raymund , Shanahan, Megan, Siskind, Dan , Soares, Jair C. , Squassina, Alessio , Stein, Dan J. , Stein, Frederike , Strakowski, Stephen M. , Straube, Benjamin , Strawbridge, Rebecca , Stuart, Amanda L. , Teutenberg, Lea , Thomas‐Odenthal, Florian , Toma, Claudio , Torres, Ivan J. , Tsapekos, Dimosthenis , Ueland, Torill , Usemann, Paula L , Vieta, Eduard , Vilella, Elisabet , Viswanath, Biju , Winter, Alexandra , Wootton, Olivia , Wrobel, Anna L , Yatham, Lakshmi N. , Young, Allan H. , McInnis, Melvin G. , Bora, Emre , Cannon, Dara M. , Chaumette, Boris , Forstner, Andreas J. , Grigoroiu‐Serbânescu, Maria , He, Qin , Juruena, Mário F. , Kasyanov, Evgeny Dmitrievich , Koenig, Barbara, Lafer, Beny , Vernal, Ditte Lammers , Lee, Heon‐Jeong , McMahon, Francis J. , McQuillin, Andrew , Melle, Ingrid , Najand, Babak , Nicolini, Humberto , Belizário, Gabriel Okawa , Redlich, Ronny , Ardestani, Seyed Mehdi Samimi , Saunders, Erika F.H. , Savitz, Jonathan B. , Schulze, Thomas , Serretti, Alessandro , Σκώκου, Μαρία , Straszek, Sune Puggaard Vogt , Sousa, Rafael Teixeira de, Thompson, Paul M. , Tondo, Leonardo , Xiong, Ashley

No container title available | May 11, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.21203/rs.3.rs-9390347/v1 Get It

Abstract Background The Global Bipolar Cohort (GBC) was established to identify existing bipolar disorder (BD) cohorts worldwide and foster collaborations focused on descriptive and analytic outcomes relevant to BD. A distributed analytic framework has been implemented to engage multiple sites without the need for central data pooling. This report describes the GBC endeavor and global functional impairment patterns. Cross-cohort comparisons of functional correlates are limited by heterogeneous measures and data-sharing constraints. Large, culturally diverse comparisons are needed to distinguish broadly reproducible correlates from cohort-specific effects. Participating sites completed a 28-item descriptive survey covering diagnostic methods, cognition, genetics, treatment, functioning, and follow-up strategies. We implemented a harmonized local logistic regression model of dichotomized functional outcome and shared summary statistics only. Results We identified 69 cohorts across five continents. Thirty-seven cohorts contributed functional outcome analyses from 17,130 participants. Outcome measures included clinician-rated disability scales and social indicators such as employment and marital status. The proportion classified with poor functioning ranged from 16% to 77% (mean 50%). In 32 of 37 cohorts, the overall regression model significantly explained variance in functioning. Current depressive symptoms were the most robust and reproducible correlate of poor functional outcome: they were assessed in 29 cohorts, significant in 22 (75.8%), ranked among the top three correlates in 22, and were the top-ranked correlates in 19. Associations between depressive burden and poor functioning were observed across clinician-rated disability scales and work or social indicators, and across geographically diverse cohorts. Comorbid substance use disorder and medication-related variables were associated with poorer functioning in subsets of cohorts, whereas sex, ancestry, bipolar subtype, psychosis history, and premorbid IQ showed weak or inconsistent associations. Cognitive measures, available in a minority of regression models, showed modest and non-uniform effects. Conclusions Across heterogeneous international cohorts, current depressive symptom burden emerged as the most consistent correlate of poor functioning in bipolar disorder. These findings replicate earlier multisite work at a larger scale, show that protocol-based distributed analyses can identify reproducible clinical signals without sharing individual-level data, and support prioritizing detection and treatment of depressive symptoms when aiming to improve real-world functioning. Future work should expand longitudinal harmonization and representation of under-studied populations.
Developmental Dysplasia of the Hip: Management from a Pediatrician Perspective
Alam, Anthony El, Mouawad, Joseph , Takchi, Andrew , Otayek, Joeffroy , Ghanimeh, Joe, Saliba, Elie , Alam, Anthony El , Mouawad, Joseph Antoine , Ghanimeh, Joe Georges , Saliba, Elie

Clinical Medicine Insights: Pediatrics | May 11, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1177/11795565261431184 | PMID 42131112 Get It

Objectives: Developmental Dysplasia of the Hip (DDH) is a common congenital anomaly requiring early diagnosis to minimize invasive treatments. This study evaluates Lebanese pediatricians’ knowledge of DDH risk factors, screening methods, and treatment strategies, comparing their practices to American and European guidelines to propose screening recommendations. Methods: A cross-sectional descriptive study was conducted using a confidential questionnaire to assess Lebanese pediatricians’ knowledge and practices regarding DDH. Contact information for pediatricians was obtained from the Lebanese Order of Physicians. Out of 600 emailed and 100 distributed questionnaires, 263 responses were received, and data were analyzed using proportion tests. Results: Of the 263 respondents (19.9% response rate), 84% routinely ordered radiographs at 4 months, while only 0.4% followed recommended guidelines. About 50% performed hip stability tests (Barlow and Ortolani) at 6 months, and 78.32% recommended the Pavlik harness for post-6-month treatment. Additionally, 97% valued periodic reminders about DDH. Significant gaps were identified in training on risk factor identification, physical examination procedures, imaging indications, management of abnormal findings, and treatment choices. Conclusions: The study highlights a critical training gap in DDH screening among Lebanese pediatricians. Implementing routine neonatal screening aligned with international recommendations is essential to reduce delayed diagnosis and its associated economic burden. Improved education and training on DDH screening and treatment are crucial for early detection and better patient outcomes.
Microbial next generation DNA sequencing of aspirated synovial fluid shows concordance with ICM criteria biomarkers for diagnosing periprosthetic joint infection in hip and knee arthroplasty
Tipton, Craig D. , Ancira, Jacob , Shahi, Alisina , Jarvis, Kayla, Omeir, Khalid , Sanford, Nicholas , Tallman, Nick A., Phillips, Caleb D. , McPherson, Edward J. , Tarabichi, Saad , Jarvis, Kayla, White, Jennifer, Parvizi, Javad

Frontiers in Microbiology | May 11, 2026 | Volume: 17 | Issue: No issue available | Pages: No page available

10.3389/fmicb.2026.1816780 | PMID 42199553 Get It

Background The diagnosis of periprosthetic joint infection (PJI) is facilitated by consensus identification of synovial biomarkers, which may be aided by targeted microbial next generation sequencing (NGS) of synovial fluid. The primary objective of the study was to evaluate NGS performance across 3 years to ICM 2018 minor criteria for PJI. Methods Synovial fluid specimens submitted from 2020–2022 by outpatient surgical clinics to MicroGenDX for matched synovial biomarker and NGS analysis were selected for retrospective analysis. Synovial biomarkers tested included C-reactive protein (CRP), white blood cell (WBC) count, and polymorphonuclear (PMN) leukocyte percentage. Synovial fluid analysis compared NGS microbial positivity with positive incidence of PJI determined by scoring of synovial biomarkers using ICM 2018 minor criteria for infection. Results The overall sensitivity, specificity, and accuracy of NGS to ICM diagnosed PJI across 2,011 specimens was 76.4% [95% CI, 0.723–0.801], 92.3% [0.91–0.94], and 88.7% [0.87–0.90], respectively. When comparing the diagnostic performance of NGS and individual biomarkers to infection, NGS was more specific to PJI than synovial CRP (specificity = 0.894, 95% CI: 0.88–0.91), but not PMN or WBC. NGS was positive in 7.7% of ICM negative samples. NGS positive: ICM negative samples were associated with significantly elevated synovial PMN ( p = 0.001) and WBC ( p < 0.0001) compared to NGS negative: ICM negative samples. Across all samples, NGS positivity was associated with significantly elevated results for all tested biomarkers ( p < 0.0001). Eight bacterial species dominated the composition in 68% of samples, whereas 46 different microbes were dominant in the remaining third. Conclusion Microbial targeted NGS positivity was concordant with ICM minor criteria for PJI and should be considered a useful tool for diagnosis. There is a low risk of false positive detections comparable to ICM biomarkers. Elevated biomarkers in NGS positive: ICM negative samples may indicate infection occurring that is poorly captured by the three measured synovial biomarkers. Uncommon species are collectively common to PJI and NGS is uniquely positioned to detect such species as they are frequently missed by conventional microbiological testing, including culture and quantitative PCR. These results suggest formal diagnostic schemes would benefit from the addition of NGS as a diagnostic criterion.
Metabolomic Profile and Antioxidant Capacity of Hungarian Clover ( Trifolium pannonicum Jacq.) and Its Contribution to Agrobiodiversity
Petrović, Mirjana , Zornić, Vladimir , Racić, Nedeljko , Stepić, Marija , Stepić, Katarina , Milenković, Jasmina , Tomić, Dalibor , Vučković, Ivan, Simić, Katarina , Anđelković, Boban , Vučković, Ivan , Vuckovic, Ivan , PETROVIĆ, Mirjana P. , Stepić, Katarina D. , Tomić, Dalibor

Chemistry & Biodiversity | May 11, 2026 | Volume: 23 | Issue: 5 | Pages: No page available

10.1002/cbdv.202503796 | PMID 42108664 Get It

ABSTRACT The search for long‐standing, drought‐tolerant species with consistent annual yields presents both the demands of sustainable agriculture and a significant challenge. Hungarian clover, an underutilized fodder species with a long lifespan, may be a potential solution to these demands. This study represents the first report on the metabolomic profile of this species. We analyzed 52 samples of Hungarian clover and Swedish clover, used as a control species, employing 1 H NMR spectroscopy combined with multivariate data analysis. A total of 24 metabolites were identified, with dominant signals derived from sugars, amino, eucomic acids, and hydroxyeucomic acids. These acids contributed to the higher antioxidant capacity observed in Hungarian clover samples compared to Swedish clover. The application of nuclear magnetic resonance in the pre‐breeding evaluation of fodder species is a well‐justified approach, providing clear insight into the metabolic variations of the examined material and valuable guidance for future breeding activities.
ME1 Programs Latent Effector Capacity and Grounds a Mathematical Model of Reversible T Cell Exhaustion
Liew, Aubrey Y., Li, Ying, Gicobi, Joanina K. , Hirdler, Jacob B. , Dellacecca, Emilia R., Dong, Haidong , Dong, Haidong , Li, Ying, Dellacecca, Emilia R.

No container title available | May 11, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.64898/2026.05.05.722814 Get It

ABSTRACT A central paradox in cancer immunotherapy is that patients harboring apparently exhausted or dysfunctional CD8 + T cells can exhibit rapid and durable responses to immune checkpoint inhibition (ICI). Although such rebound responses do not occur in all ICI-treated patients, resolving this paradox is essential for identifying and therapeutically maximizing reversible T cell exhaustion before clinical benefit is achieved. Here, we identify malic enzyme 1 (ME1) as a key molecular determinant of a latent, epigenetically poised effector CD8 + T cell state that is both necessary and sufficient for responsiveness to ICI. Genetic loss of ME1 abolishes therapeutic efficacy despite intact checkpoint blockade, whereas enforced ME1 expression enables robust antitumor responses even in otherwise ICI-resistant tumor models. Chromatin accessibility profiling, together with bulk and single-cell transcriptomic analyses, demonstrates that ME1 preserves effector readiness by maintaining latent effector capacity as a measurable biological state. These findings also experimentally ground a mechanistically interpretable dynamical model of T cell exhaustion, in which latent effector capacity, E(t), evolves according to a first-order differential equation shaped by activation history and decay. By defining latent effector capacity as a quantifiable, history-dependent state variable, our findings further enable the rational design of AI-driven models to predict patient-specific responsiveness and optimize therapeutic strategies in T cell–based immunotherapy. Together, our results redefine exhaustion as a state of masked potential governed by history-dependent latent effector capacity and provide a unified framework explaining rapid functional rebound, therapeutic heterogeneity, and the boundary between reversible and irreversible T cell exhaustion.
Correlation between in vivo 18 F‐flortaucipir PET and whole‐brain postmortem histological tau signals in Alzheimer's disease
Chao, Yishu , Chen, Y., Chadwick, Trevor A., Harrison, Theresa M., Iaccarino, Leonardo, Heinsen, Helmut, Ushizima, Daniela, Tosun, Duygu, Jagust, William J., Grinberg, Lea T. , Chen, Yuheng, Grinberg, Lea , Chadwick, Trevor, Harrison, Theresa M. , Iaccarino, Leonardo , Heinsen, Helmut, Ushizima, Daniela Mayumi , Jagust, William J.

Alzheimer's & Dementia | May 11, 2026 | Volume: 22 | Issue: 5 | Pages: No page available

10.1002/alz.71453 | PMID 42108381 Get It

Abstract INTRODUCTION Clinicopathological studies offer crucial interpretations of 18 F‐flortaucipir (FTP) tau positron emission tomography (PET) signal but are limited by methods. We leveraged whole‐brain, quantitative immunohistochemical (IHC) Alzheimer's Disease (AD) tau density maps to comprehensively evaluate the FTP tracer. METHODS We generated IHC maps for three AD‐tau antibodies—AT8, AT100, and MC1—using two human brains histologically staged at Braak IV and VI. FTP‐PET scans were acquired 6 and 10 weeks prior to death. Using region‐wise and voxelwise methods, we correlated FTP‐PET with IHC signals. RESULTS Only AT8 (p‐tau Ser202/Thr205; neuronal and neuritic tau pathology) showed a notable correlation with FTP standardized uptake value ratios (SUVRs) in the Braak VI case (Spearman's rank correlation coefficient [r s ] = 0.461, p < 0.001). FTP SUVRs failed to capture medial temporal lobe (MTL) tau burden, whereas neocortical regions showed lower IHC burden but more variability in FTP uptake. DISCUSSION Although FTP signals correlate well with AT8‐positive tau in the more advanced case, they underestimate the severity of MTL burden, potentially confounding assessments of tau‐targeted therapies.
Reliability of remote self‐administered Web‐based digital cognitive measures and comparison to in‐person neuropsychological tests: Stricker Learning Span, Symbols Test, and the Mayo Test Drive Screening Battery Composite
Hughes, Morgan A., Frank, Ryan D. , Taylor, Rita L. , Fan, Winnie Z. , Christianson, Teresa J., Kremers, Walter K. , Stricker, John L. , Lucas, John A. , Aduen, Paula, Graff‐Radford, Neill R., Graff-Radford, Jonathan, Petersen, Ronald C., Aduen, Paula A., Kremers, Walter K , Hughes, Morgan A., Machulda, Mary M. , Hassenstab, Jason , Mielke, Michelle M. , Day, Gregory S. , Graff‐Radford, Neill R. , Jack, Clifford R. , Graff‐Radford, Jonathan , Petersen, Ronald C. , Stricker, Nikki H.

Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring | May 11, 2026 | Volume: 18 | Issue: 2 | Pages: No page available

10.1002/dad2.70338 | PMID 42125541 Get It

Abstract INTRODUCTION We describe the reliability of remote self‐administered digital cognitive measures completed via the Mayo Test Drive (MTD) web‐based platform. METHODS A total of 1846 participants (mean age = 70, SD = 12, range 31–101; 48% male; 96% White; 99% non‐Hispanic; 97% cognitively unimpaired) with two to four complete MTD sessions at ∼7.5‐month intervals were included. Test‐retest reliability was assessed using single‐rating, absolute‐agreement, and two‐way mixed intraclass correlation coefficients (ICCs) with 95% confidence intervals. ICCs for in‐person‐administered traditional neuropsychological measures were compared to MTD for a subset of 244 participants. Analyses also compared reliability across demographic, residential, and session context subgroups. RESULTS Reliability was good for the MTD Composite (total ICC = 0.79 [0.77, 0.80]), and moderate‐to‐good for the primary outcome variables for each MTD subtest (total ICCs 0.70–0.83 for Stricker Learning Span and Symbols). The reliability of the remote self‐administered MTD was similar to in‐person‐administered cognitive measures. DISCUSSION MTD showed moderate‐to‐good reliability, supporting its use in longitudinal monitoring.