Tag: pubmed

ACS Chem Biol. 2025 Nov 4. doi: 10.1021/acschembio.5c00715. Online ahead of print.

ABSTRACT

Hexokinase domain containing protein 1 (HKDC1) is a recently discovered fifth human hexokinase isozyme that is significantly upregulated in several disease states, including lung and liver cancers. Cellular studies suggest that HKDC1 is a low activity hexokinase; however, its functional characteristics have remained enigmatic. Here, we describe the kinetic and regulatory features of recombinant human HKDC1, demonstrating it to be a robust hexokinase (k_cat/K_m,glucose = 1.5 × 10⁴ M^-1 s^-1) with a unique glucose K_m value (0.49 ± 0.07 mM) that differs markedly from all other human hexokinase isozymes. The isolated C-terminal domain of HKDC1 displays kinetic characteristics nearly identical to the full-length enzyme, whereas the N-terminal domain is inactive. Unlike all other 100 kDa vertebrate hexokinases characterized to date, HKDC1 is insensitive to product inhibition by physiological concentrations of glucose 6-phosphate, with apparent inhibition constants above 1 mM. The hexokinase activity of HKDC1 is also insensitive to Dinaciclib, a pan cyclin-dependent kinase inhibitor that reportedly disrupts the ability of nuclear localized HKDC1 to phosphorylate retinoblastoma-binding protein 5. Conversely, the hexokinase activity of HKDC1 is potently inhibited by a synthetic glucosamine derivative previously developed for hexokinase 1 and 2, with an IC₅₀ value of 103 ± 6 nM. An HKDC1 variant associated with retinitis pigmentosa, T58M, displays a modest, but statistically significant 2-fold decrease in catalytic efficiency (k_cat/K_m,glucose) compared to the wild-type enzyme. Together, our results provide a detailed functional characterization of recombinant HKDC1 and set the stage for investigating the link between HKDC1 catalysis and human disease.

PMID:41187334 | DOI:10.1021/acschembio.5c00715

Arch Cardiol Mex. 2025 Nov 4. doi: 10.24875/ACM.25000124. Online ahead of print.

ABSTRACT

The objective of this study was to evaluate the efficacy of percutaneous left atrial appendage occlusion (LAAO) compared with anticoagulation in patients with atrial fibrillation (AF) and its impact on the primary prevention of ischemic stroke and all-cause mortality. Patients with non-valvular AF and high thromboembolic risk (CHA₂DS₂-VASc > 2 points) were included. LAAO was compared against the use of direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs). Articles were searched in PubMed, Scopus, and Web of Science up to June 11, 2025. Risk of bias was assessed using the RoB 2 tool and ROBINS-E, while statistical analysis was performed with Review Manager 5.4.1. A total of 10 studies with 5,779 patients were analyzed (2,916 with LAAO and 2,863 with anticoagulation). LAAO reduced, though without statistical significance, the incidence of ischemic stroke (OR: 0.82; 95% CI: 0.66-1.03; p = 0.09). However, it showed a significant reduction in all-cause mortality compared with the overall anticoagulant group (OR: 0.62; 95% CI: 0.46-0.80; p = 0.0004). LAAO emerges as a viable strategy to reduce mortality in patients with AF and high thromboembolic risk, particularly when long-term anticoagulation is not feasible. Its superiority over DOACs and comparable profile to VKAs, along with the absence of periodic INR monitoring and relevant drug interactions, make it an option that may optimize adherence and quality of life.

PMID:41187332 | DOI:10.24875/ACM.25000124

J Med Internet Res. 2025 Nov 4;27:e63816. doi: 10.2196/63816.

ABSTRACT

BACKGROUND: Patient interaction patterns with self-triage modules in mobile health apps during urgent direct-to-consumer telemedicine consultations remain underexplored, despite their critical role in optimizing virtual care pathways.

OBJECTIVE: This study aimed to analyze user navigation behaviors within the screen pathways of a symptom-based self-triage mobile app’s algorithm during remote urgent care assessments.

METHODS: This observational, retrospective, single-center study analyzed data from users who were aged 18 years and older and who voluntarily sought virtual urgent care through the Einstein Conecta (version 2.0; iOS and Android) at a private Brazilian hospital between May 2022 and December 2023. Patients with incomplete connection records were excluded. User interactions were evaluated based on the number of distinct triage flows accessed per session, the number of screens viewed per flow, the frequency of returns to previous screens, and the time spent within the self-triage module. Descriptive statistical methods were applied for analysis.

RESULTS: Data from 62,006 unique users with a mean age of 36.51 (SD 10.53) years, of whom 54.65% (33,889/62,006) were female, were analyzed. They initiated 194,976 self-triage flows. We found that 36.89% (22,875/62,006) of users completed 1 flow per session; 22.15% (13,734/62,006) users accessed 2 flows; and 27.93% (17,317/62,006) users accessed ≥4 flows (maximum 63 flows). Users receiving an initial emergency department referral recommendation were more likely to initiate subsequent flows than those recommended for virtual assessment. Returning to a previous screen was infrequent (used by 5277/62,006, 8% of users). The average time spent in the first flow was 70.95 (SD 65.26) seconds, with an average of 9.51 (SD 12.84) seconds per screen.

CONCLUSIONS: In this cohort, most users explored alternative pathways beyond the initial self-triage recommendation, particularly when directed to the emergency department, while rarely backtracking within a flow. These findings underscore the need to refine self-triage mechanisms in telemedicine to better align with observed user navigation behaviors and preferences.

PMID:41187328 | DOI:10.2196/63816

JMIR Res Protoc. 2025 Nov 4;14:e78806. doi: 10.2196/78806.

ABSTRACT

BACKGROUND: Neuropathic pain (NP) is characterized as pain arising from lesions of the somatosensory nervous system. However, NP-like features have been found in several chronic secondary musculoskeletal (MSK) pain conditions in the absence of detectable lesion or damage to the somatosensory pathways. Emerging evidence has demonstrated associations between NP-like symptoms and altered neural activity within brain regions implicated in sensory perception and affective-emotional processing of pain with consistent findings of abnormal activity in the right insula (RIns) cortex and dorsal anterior cingulate cortex (dACC). Electroencephalography neurofeedback (EEG-NF) is a brain-computer interface biofeedback technique that allows individuals to self-regulate the real-time cortical brain activities of the regions of interest.

OBJECTIVE: The primary objective of this study is to investigate the feasibility and safety of a novel EEG-NF intervention designed to simultaneously downtrain activity in the RIns and dACC in individuals with a chronic secondary MSK pain condition exhibiting NP-like features. In addition, this study will conduct secondary exploratory analyses to investigate EEG-derived neuronal changes and their associations with clinical and experimental pain outcomes following the EEG-NF training.

METHODS: We will design a single-arm, open-label, pilot-feasibility trial. We will recruit adults aged 35-75 years with a score of ≥19 using the PainDETECT questionnaire and an average pain score of ≥4 on the 11-point Numeric Pain Rating Scale over the last 3 months, with a minimum pain duration of 3 months, to receive active EEG-NF training. Participants will receive auditory feedback as a reward for achieving a predetermined activity threshold of the RIns and dACC. Primary outcomes will evaluate feasibility, acceptability, and safety using both self-reported questionnaires and monitoring data. Collected data will be summarized descriptively, with mean (SD) reported where appropriate. Secondary outcomes will include EEG parameters, self-reported measures, heart rate variability, and quantitative sensory testing. An exploratory within-group pre-post statistical comparison will be conducted for all secondary outcome measures, and correlation analysis will be performed to explore relationships between EEG measures, self-reported outcomes, heart rate variability, and quantitative sensory testing measures.

RESULTS: This study has received approval from the Health and Disability Ethics Committee and is registered with the Australian New Zealand Clinical Trials Registry. Participant recruitment began in April 2025 and is ongoing. As of October 2025, data collection has been completed, with a total of 5 participants enrolled, all of whom have completed the study to date. We expect to complete the study in March 2026. This study will generate data on feasibility, safety, acceptability, and preliminary data to inform a fully powered effectiveness clinical trial.

CONCLUSIONS: The results and data generated will inform the design and sample size calculation for a fully powered randomized controlled trial aimed at evaluating the effectiveness of EEG-NF in targeting NP-like features in individuals with chronic MSK pain.

TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12625000706471; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=389568&isReview=true.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/78806.

PMID:41187327 | DOI:10.2196/78806

J Prosthodont. 2025 Nov 4. doi: 10.1111/jopr.70052. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to develop a novel and efficient digital workflow for designing and manufacturing 3D-printed definitive maxillofacial obturator prostheses based on multi-source data fusion and various digital techniques, as well as to evaluate its feasibility through a randomized self-controlled study.

MATERIALS AND METHODS: Participants with maxillary defects were recruited for the study. A digital impression was obtained by fusing intraoral scanning data and computed tomography (CT) images. The framework and artificial-teeth-obturator were designed separately using multiple dental design software programs, fabricated through additive manufacturing (AM), and finally assembled precisely into one unit with the help of specially designed auxiliary positioning and connecting structures. For comparison, a conventional prosthesis was also made for each participant. The adaptation of both conventional and digital prostheses was evaluated and compared using the silicone rubber lining method through deviation analysis. Additionally, the chairside impression time for both conventional and digital treatments were recorded and compared.

RESULTS: The digital workflow for designing and manufacturing maxillofacial prosthesis was successfully realized. The chairside impression time was shortened (p < 0.001). The adaptation of the digital prosthesis, including framework (349.89 ± 121.56 µm), obturator (420.08 ± 166.01 µm), and the whole prosthesis (408.36 ± 118.05 µm), proved suitable for clinical application. No statistically significant difference was observed between the digital and conventional prostheses.

CONCLUSION: The newly established digital workflow for the fabrication of definitive maxillofacial obturator prostheses reduced chairside impression time and the number of appointments, featuring clinically acceptable adaptation. This approach has potential for future applications in the treatment of patients with maxillofacial defects.

PMID:41187326 | DOI:10.1111/jopr.70052

Clin Chem Lab Med. 2025 Nov 5. doi: 10.1515/cclm-2025-1055. Online ahead of print.

ABSTRACT

OBJECTIVES: To validate urine as a suitable matrix for copeptin measurements, derive a urinary copeptin/creatinine ratio in an apparently healthy sample of the population, and assess pre-analytical conditions such as collection type and storage temperatures that affect stability and recovery.

METHODS: Matrix effect was determined by spiking the manufacturer’s calibrator F simultaneously into pooled serum and aliquots of spot urine sample donated by a single volunteer. Stability was assessed without preservatives as well as 0.0032×g of thymol or 1 mL of 5 M hydrochloric acid. The urinary copeptin-to-creatinine ratio reference limit was derived from random spot urines collected from 120 apparently healthy volunteers who met the selection criteria.

RESULTS: Our in-house derived urinary copeptin-to-creatinine ratio was<2.5 pmol/mmol creatinine, and there was a statistically significant difference in urinary copeptin concentration between males and females, but this was eliminated when corrected for urine creatinine. 24-h and spot urine with and without preservatives were stable for 7 days at 4-8 °C, 23-25 °C, and -20 °C. Limits of blank, limits of detection, and limit of quantitation were 1.1 pmol/L, and 1.81 pmol/L, respectively.

CONCLUSIONS: Urine matrix does not distort the kinetics of the BRAHMS Thermo Fisher Copeptin assay and therefore could be measured with high accuracy. The clinical utility of urinary copeptin is still unknown, however, there is growing interest in this area in patient with autosomal polycystic kidney disease.

PMID:41187321 | DOI:10.1515/cclm-2025-1055

JMIR Ment Health. 2025 Nov 4;12:e73188. doi: 10.2196/73188.

ABSTRACT

BACKGROUND: Although web-based mental health resources have the potential to assist millions, particularly those who face barriers to treatment, most mental health website visitors disengage before accessing resources that can help improve their mental health.

OBJECTIVE: We used a sequential multiple assignment randomized trial to test whether personalized tailoring improved engagement on a self-guided mental health website.

METHODS: Data were collected via voluntary response sampling on the Mental Health America website. Inclusion criteria included residing in the United States and viewing a postscreening survey after completing the Patient Health Questionnaire-9 (PHQ-9). Participants were randomized to 1 of 2 postscreening survey conditions: the demographics survey or the Next Steps survey, which included additional tailoring questions assessing perceived need and participants’ intended next steps. Participants who viewed the following screening results page were subsequently randomized to 1 of 5 conditions that displayed nontailored or tailored messages and featured resources, as well as persistent general resources that did not vary by condition. Data were analyzed using logistic regressions predicting disengagement and clicks on featured resources (versus persistent general resources) by condition.

RESULTS: Adding questions to inform tailoring significantly increased the odds of disengaging by 14% (demographics survey: 25%; Next Steps survey: 27.5%; odds ratio [OR] 1.14, 95% CI 1.11-1.16; P<.001). Among participants who viewed a postscreening survey (n=169,647), 87,712 participants were randomized to the demographics survey condition, and 81,935 participants were randomized to the Next Steps survey condition. Among participants who submitted the demographics survey (n=38,490), tailoring resources to demographics reduced the odds of disengaging by 10% (OR 0.90, 95% CI 0.87-0.94; P<.001) and, among those who engaged, increased the odds of clicking a featured resource versus a persistent general resource by 90% (OR 1.90, 95% CI 1.79-2.01; P<.001). Among participants who submitted the Next Steps survey (n=34,204), tailoring messages to perceived need (P=.33), tailoring resources to intended next steps (P=.51), and a combination of both (P=.52) did not significantly reduce the odds of disengaging compared with the nontailored condition. However, tailoring resources to intended next steps and combining a tailored message to perceived need with tailored resources to intended next steps increased the odds of clicking a featured resource by 25% (OR 1.25, 95% CI 1.14-1.37; P<.001) and 34% (OR 1.34, 95% CI 1.23-1.47; P<.001), respectively. Tailoring resources to demographics was significantly more effective in improving engagement than tailoring to perceived need or intended next steps (P≤.004).

CONCLUSIONS: There was a small but statistically significant cost to engagement from adding tailoring questions assessing perceived need and intended next steps. Among the strategies tested in this study, tailoring resources to demographics was the most effective strategy for increasing engagement among visitors who viewed their screening results. This study demonstrates how personalization may increase engagement with mental health websites and provides design implications for future research.

PMID:41187311 | DOI:10.2196/73188

J Clin Oncol. 2025 Nov 4:JCO2500872. doi: 10.1200/JCO-25-00872. Online ahead of print.

ABSTRACT

PURPOSE: This phase III (ClinicalTrials.gov identifier: NCT03665441) study evaluated eryaspase in combination with chemotherapy as second-line treatment in advanced pancreatic ductal adenocarcinoma (PDAC).

PATIENTS AND METHODS: TRYBECA-1 enrolled patients 18 years and older whose disease progressed on or after 1L chemotherapy. Patients were randomly assigned to eryaspase plus chemotherapy (gemcitabine/nab-paclitaxel or fluorouracil [5-FU], leucovorin [LV], and irinotecan/nanoliposomal irinotecan) or chemotherapy. Treatment was administered in a 4-week cycle for each of the following drugs until disease progression or unacceptable toxicity: eryaspase 100 U/kg intravenously on days 1 and 15; gemcitabine 1,000 mg/m² and nab-paclitaxel 125 mg/m² intravenously on days 1, 8 and 15; irinotecan 180 mg/m² (or nanoliposomal irinotecan 70 mg/m²) intravenously on days 1 and 15; 5-FU 2,400 mg/m² as one 46-hour infusion (with a bolus of 400 mg/m²); and LV 400 mg/m² intravenously on days 1 and 15. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety.

RESULTS: A total of 512 patients were randomly assigned (n = 255 for eryaspase and n = 257 for chemotherapy alone). Baseline characteristics were balanced between the two groups. There were 420 deaths, with a median OS of 7.5 months for eryaspase and chemotherapy versus 6.7 months for chemotherapy (hazard ratio [HR], 0.92 [95% CI, 0.76 to 1.11]; P = .374); the median PFS was 3.7 months versus 3.4 months (HR, 0.88 [95% CI, 0.73 to 1.07]; P = .196), and the ORR was 16.1% versus 12.5% (odds ratio, 1.35; [95% CI, 0.81 to 2.24]), respectively. Grade ≥3 adverse events (AEs) included neutropenia (25.4% v 20.3%), asthenia (16.9% v 13.8%), and anemia (17.3% v 12.2%) in the experimental versus control arms, respectively.

CONCLUSION: The addition of eryaspase to chemotherapy did not improve OS, PFS, or ORR. AEs were generally consistent with previous reports of chemotherapy. These results do not support additional development of eryaspase in PDAC.

PMID:41187298 | DOI:10.1200/JCO-25-00872

J Am Acad Orthop Surg Glob Res Rev. 2025 Nov 3;9(11). doi: 10.5435/JAAOSGlobal-D-25-00314. eCollection 2025 Nov 1.

ABSTRACT

INTRODUCTION: The J. Robert Gladden Orthopaedic Society (JRGOS) aims to increase diversity in orthopaedic surgery and promote high-quality musculoskeletal care for all. Through targeted research funding, JRGOS supports projects aligned with its mission. Despite awarding over $300,000 in research grants since 2011, the return on investment (ROI) of this program has not been analyzed. This study evaluates the ROI of JRGOS research grants from 2011 to 2023.

METHODS: We conducted a retrospective review of all JRGOS research grants awarded between 2011 and 2023. Data included recipient demographics, grant titles, award year, institution, and amount. PubMed and Google Scholar were used to identify resulting publications as of March 8, 2025. We also recorded recipients’ practice setting and years in practice at the time of award.

RESULTS: From 2011 to 2023, JRGOS awarded 52 grants totaling $308,765. Recipients were 40% female (n = 21) and 60% male (n = 31). Among 26 practicing orthopaedic surgeon recipients, 88% (n = 23) were in academic practice and 12% (n = 3) in private practice, with a median of 3 years (range 0-25) in independent practice. Most grants (73.1%) supported clinical research. The overall ROI, defined as the proportion of grants resulting in at least one publication, was 67.3% (35/52), with practicing orthopaedic surgeons achieving an ROI of 92.3%. In total, 72 publications appeared in 40 journals (mean impact factor 3.6), most commonly in the Journal of Bone and Joint Surgery.

CONCLUSION: JRGOS grants demonstrate high efficiency, with a 67.3% ROI and frequent publication in high-impact journals. Practicing orthopaedic surgeons achieved the highest ROI (92.3%).

PMID:41187297 | DOI:10.5435/JAAOSGlobal-D-25-00314

J Am Acad Orthop Surg Glob Res Rev. 2025 Nov 3;9(11). doi: 10.5435/JAAOSGlobal-D-25-00199. eCollection 2025 Nov 1.

ABSTRACT

INTRODUCTION: Unfortunately, some lumbar fusion patients will experience psychological distress and a deterioration of mental health postoperatively. At the extreme, these changes can lead to self-harm and suicide. This study evaluated the incidence of self-harm within 1 year of elective lumbar fusion procedures to identify risk factors for self-harm events.

METHODS: The PearlDiver Mariner 170 data set from 2010 to 2023 was retrospectively analyzed. Patients undergoing 1-level to 3-level posterior lumbar fusion with minimum 1-year follow-up were included. Patients with a history of self-harm before surgery were excluded. Univariate and multivariate analyses were done to assess risk factors for self-harm. Statistical significance was assessed at P < 0.05.

RESULTS: In total, 138,223 patients were included. The incidence of self-harm within 1 year was 0.40% (549 patients). In the multivariable model, younger age, male sex, and higher Charlson Comorbidity Index scores were risk factors for self-harm. Specific comorbidities associated with increased risk for self-harm included alcohol use disorder, anxiety disorders, depression, tobacco use, and preoperative opioid use (all P < 0.001). The strongest associations between comorbidity and self-harm were seen for depression (odds ratio [OR] = 2.68), anxiety (OR = 2.03), and alcohol use disorder (OR = 1.89).

CONCLUSION: Self-harm is a rare, yet understudied potential complication of lumbar fusion procedures. In this national database study, the incidence of self-harm was 0.4% in the year after elective lumbar fusion. Although some risk factors for self-harm are nonmodifiable, other behavioral and mental health comorbidities may serve to flag patients as targets for early preventive intervention.

PMID:41187295 | DOI:10.5435/JAAOSGlobal-D-25-00199