Search

Abstract Bone conduction implants enable patients to hear via vibrations transmitted to the skull. The main constraint of current bone conduction implants is their maximum output force level. Stimulating closer to the cochlea is hypothesized to increase efficiency and improve force transfer, addressing this limitation. This study evaluated stimulation at four positions in human cadaveric specimens: the cochlear promontory, the posterior wall of the outer ear canal, the lateral semi-circular canal, and the standard Bone-Anchored Hearing Aid (Baha) location. To assess potential hearing sensation, three objective measures were simultaneously recorded. For intracochlear pressure and promontory velocity, stimulating at the lateral semi-circular canal and promontory results in the highest response, with a gain of up to 20 dB. Ear canal pressure shows less conclusive results, with significant differences at only a few frequencies. These findings suggest that stimulation closer to the cochlea offers higher efficiency, which could benefit patients needing higher output force levels than currently available or those eligible for electro-vibrational stimulation, e.g. a cochlear implant combined with a bone conduction device.

Abstract Background As one of the main goals of hip and knee replacements is to improve patients’ health-related quality of life, a meaningful evaluation can be achieved by calculating minimal important changes (MICs) for improvements in patient-reported outcome measures (PROMs). This study aims at providing MICs adjusted for patient characteristics for EQ-5D-3L index score improvements after hip and knee replacements. It adds to existing literature by relying on a large national sample and precise clustering algorithms, and by employing a state-of-the-art methodology for the calculation of improved adjusted MICs. Methodology A retrospective observational study was conducted using the publicly available National Health Service (NHS) PROMs dataset for primary hip and knee replacements. We used information on 252,331 hip replacements and 279,668 knee replacements from all NHS-funded providers in England between 2013 and 2020. Clusters of patients were created based on pre-operative EQ-VAS, depression status, and sex. Unstratified and stratified estimates for meaningful EQ-5D-3L improvements were obtained through anchor-based predictive MICs corrected for the proportion of improved patients and the reliability of transition ratings. Results Stratifying patients showed that MICs varied across subgroups based on pre-operative EQ-VAS, depression status, and sex. MICs were larger for patients with worse pre-operative EQ-VAS scores, while patients with better pre-operative scores required smaller MICs to achieve a meaningful change. We show how after stratification the percentage of patients achieving their stratified MIC was better in line with the actual share of improved patients. Larger MICs were found for patients with depression and for female patients. MICs calculated for knee replacements were consistently lower than those for hip replacements. Conclusions Our findings show the importance of adjusting MICs for patients’ characteristics and should be considered for quality-related choices and policy initiatives.

Abstract Atmospheric rivers (ARs) are narrow corridors of intense water vapor transport, shaping precipitation, floods, and economies. Temporal clustering of ARs tripled losses compared to isolated events, yet the reasons behind this clustering remain unclear. AR orientation further modulates hydrological impacts through terrain interaction. Here we identify unique ARs over the North Pacific and Western U.S. and utilize Cox regression and composite analysis to examine how six major climate modes influence temporal clustering of unique ARs and orientation during extended boreal winter (November to March). Results show that climate modes condition temporal clustering of unique ARs. The Pacific-North American weather pattern strongly modulates the clustering over the Western U.S. from early to late winter. The quasi-biennial oscillation and Pacific decadal oscillation affect late winter clustering, while the Arctic oscillation dominates early winter. Climate modes also strongly influence AR orientation, with ENSO particularly affecting the orientation of temporally clustered ARs.

Abstract Hope is a vital coping mechanism, enabling individuals to effectively confront life’s challenges. This study proposes a technique employing Natural Language Processing (NLP) tools like Linguistic Inquiry and Word Count (LIWC), NRC-emotion-lexicon, and vaderSentiment to analyze social media posts, extracting psycholinguistic, emotional, and sentimental features from a hope speech dataset. The findings of this study reveal distinct cognitive, emotional, and communicative characteristics and psycholinguistic dimensions, emotions, and sentiments associated with different types of hope shared in social media. Furthermore, the study investigates the potential of leveraging this data to classify different types of hope using machine learning algorithms. Notably, models such as LightGBM and CatBoost demonstrate impressive performance, surpassing traditional methods and competing effectively with deep learning techniques. We employed hyperparameter tuning to optimize the models’ parameters and compared their performance using both default and tuned settings. The results highlight the enhanced efficiency achieved through hyperparameter tuning for these models.

Abstract Background Radical prostatectomies can be performed using open retropubic, laparoscopic, or robot-assisted laparoscopic surgery. The literature shows that short-term outcomes (in particular, inpatient complications) differ depending on the type of procedure. To date, these differences have only been examined and confirmed in isolated cases based on national routine data. Methods The data was based on the Swiss Medical Statistics from 2016 to 2018 from a national survey of administrative data from all Swiss hospitals. Cases with the coded main diseases neoplasm of the prostate (ICD C61) and the main treatments of laparoscopic (CHOP 60.5X.20) or retropubic (CHOP 60.5X.30) radical prostatectomies were included, resulting in a total sample size of 8,593 cases. Results A procedure-related complication occurred in 998 cases (11.6%). By surgical procedure, complication rates were 10.1% for robotic-assisted laparoscopic radical prostatectomy 9.0% for conventional laparoscopic radical prostatectomy and 17.1% for open retropubic radical prostatectomy (p

Abstract Potency assessment of monoclonal antibodies or corresponding biosimilars in cell-based assays is an essential prerequisite in biopharmaceutical research and development. However, cellular bioassays are still subject to limitations in sample throughput, speed, and often need costly reagents or labels as they are based on an indirect readout by luminescence or fluorescence. In contrast, whole-cell Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) Mass Spectrometry (MS) has emerged as a direct, fast and label-free technology for functional drug screening being able to unravel the molecular complexity of cellular response to pharmaceutical reagents. However, this approach has not yet been used for cellular testing of biologicals. In this study, we have conceived, developed and benchmarked a label-free MALDI-MS based cell bioassay workflow for the functional assessment of complement-dependent cytotoxicity (CDC) of Rituximab antibody. By computational evaluation of response profiles followed by subsequent m/z feature annotation via fragmentation analysis and trapped ion mobility MS, we identified adenosine triphosphate and glutathione as readily MS-assessable metabolite markers for CDC and demonstrate that robust concentration–response characteristics can be obtained by MALDI-TOF MS. Statistical assay performance indicators suggest that whole-cell MALDI-TOF MS could complement the toolbox for functional cellular testing of biopharmaceuticals.

IntroductionThe 2024 Voice AI Symposium, hosted by the Bridge2AI-Voice Consortium in Tampa, FL, featured two keynote speeches that addressed the intersection of voice AI, healthcare, ethics, and law. Dr. Rupal Patel and Dr. Nicholson Price provided insights into the advancements, applications, and challenges of AI-driven voice tools in healthcare. The symposium aimed to advance cross-disciplinary collaboration and establish frameworks for the ethical use of AI technologies in healthcare.MethodsThe keynote speeches, delivered on May 1st and 2nd, were 30 minutes each, followed by 10-minutes Q&A sessions. The audio was recorded and transcribed using Whisper (v7.13.1). Content summaries were generated with the aid of ChatGPT (v4.0), and the authors reviewed and edited the final transcripts to ensure accuracy and clarity.ResultsDr. Rupal Patel’s keynote, “Reflections and New Frontiers in Voice AI”, explored the potential of voice AI for early detection of health conditions, monitoring disease progression, and promoting non-invasive global health management. She highlighted innovative uses beyond traditional applications, such as examining menopause-related symptoms. Dr. Nicholson Price’s keynote, “Governance for Clinical Voice AI”, addressed the regulatory and ethical challenges posed by AI in healthcare. He stressed the need for context-aware systems and dynamic legal frameworks to address liability and accountability.ConclusionsThe 2024 Voice AI Symposium highlighted the transformative potential of voice AI for early detection, health monitoring, and reducing healthcare disparities. It also underscored the importance of dynamic governance to address the ethical and regulatory challenges of deploying AI in clinical settings.

BackgroundWhile the effectiveness of patient-reported outcome measures (PROMs) as an intervention to impact patient pathways has been established for cancer care, it is unknown for other indications. We assessed the cost-effectiveness of a PROM-based monitoring and alert intervention for early detection of critical recovery paths following hip and knee replacement.Methods and findingsThe cost-effectiveness analysis (CEA) is based on a multicentre randomised controlled trial encompassing 3,697 patients with hip replacement and 3,110 patients with knee replacement enrolled from 2019 to 2020 in 9 German hospitals. The analysis was conducted with a subset of 546 hip and 492 knee replacement cases with longitudinal cost data from 24 statutory health insurances. Patients were randomised 1:1 to a PROM-based remote monitoring and alert intervention or to a standard care group. All patients were assessed at 12-months post-surgery via digitally collected PROMs. Patients within the intervention group were additionally assessed at 1-, 3-, and 6-months post-surgery to be contacted in case of critical recovery paths. For the effect evaluation, a PROM-based composite measure (PRO-CM) was developed, combining changes across various PROMs in a single index ranging from 0 to 100. The PRO-CM included 6 PROMs focused on quality of life and various aspects of physical and mental health. The primary outcome was the incremental cost-effectiveness ratio (ICER). The intervention group showed incremental outcomes of 2.54 units PRO-CM (95% confidence interval (CI) [0.93, 4.14]; p = 0.002) for patients with hip and 0.87 (95% CI [-0.94, 2.67]; p = 0.347) for patients with knee replacement. Within the 12-months post-surgery period the intervention group had less costs of 376.43€ (95% CI [-639.74, -113.12]; p = 0.005) in patients with hip, and 375.50€ (95% CI [-767.40, 16.39]; p = 0.060) in patients with knee replacement, revealing a dominant ICER for both procedures. However, it remains unclear which step of the multistage intervention contributes most to the positive effect.ConclusionsThe intervention significantly improved patient outcomes at lower costs in patients with hip replacements when compared with standard care. Further it showed a nonsignificant cost reduction in knee replacement patients. This reinforces the notion that PROMs can be utilised as a cost-effective instrument for remote monitoring in standard care settings.Trial registrationRegistration: German Register for Clinical Studies (DRKS) under DRKS00019916.

IntroductionThe 2024 Voice AI Symposium, presented by the Bridge2AI-Voice Consortium, featured deep-dive educational workshops conducted by experts from diverse fields to explore the latest advancements in voice biomarkers and artificial intelligence (AI) applications in healthcare. Through five workshops, attendees learned about topics including international standardization of vocal biomarker data, real-world deployment of AI solutions, assistive technologies for voice disorders, best practices for voice data collection, and deep learning applications in voice analysis. These workshops aimed to foster collaboration between academia, industry, and healthcare to advance the development and implementation of voice-based AI tools.MethodsEach workshop featured a combination of lectures, case studies, and interactive discussions. Transcripts of audio recordings were generated using Whisper (Version 7.13.1) and summarized by ChatGPT (Version 4.0), then reviewed by the authors. The workshops covered various methodologies, from signal processing and machine learning operations (MLOps) to ethical concerns surrounding AI-powered voice data collection. Practical demonstrations of AI-driven tools for voice disorder management and technical discussions on implementing voice AI models in clinical and non-clinical settings provided attendees with hands-on experience.ResultsKey outcomes included the discussion of international standards to unify stakeholders in vocal biomarker research, practical challenges in deploying AI solutions outside the laboratory, review of Bridge2AI-Voice data collection processes, and the potential of AI to empower individuals with voice disorders. Additionally, presenters shared innovations in ethical AI practices, scalable machine learning frameworks, and advanced data collection techniques using diverse voice datasets. The symposium highlighted the successful integration of AI in detecting and analyzing voice signals for various health applications, with significant advancements in standardization, privacy, and clinical validation processes.DiscussionThe symposium underscored the importance of interdisciplinary collaboration to address the technical, ethical, and clinical challenges in the field of voice biomarkers. While AI models have shown promise in analyzing voice data, challenges such as data variability, security, and scalability remain. Future efforts must focus on refining data collection standards, advancing ethical AI practices, and ensuring diverse dataset inclusion to improve model robustness. By fostering collaboration among researchers, clinicians, and technologists, the symposium laid a foundation for future innovations in AI-driven voice analysis for healthcare diagnostics and treatment.

BackgroundA clinical dashboard is a data-driven clinical decision support tool visualizing multiple key performance indicators in a single report while minimizing time and effort for data gathering. Studies have shown that including patient-reported outcome measures (PROMs) in clinical dashboards supports the clinician’s understanding of how treatments impact patients’ health status, helps identify changes in health-related quality of life at an early stage, and strengthens patient-physician communication. ObjectiveThis study aims to determine design components for clinical dashboards incorporating PROMs to inform software producers and users (ie, physicians). MethodsWe conducted interviews with software producers and users to test preselected design components. Furthermore, the interviews allowed us to derive additional components that are not outlined in existing literature. Finally, we used inductive and deductive coding to derive a guide on which design components need to be considered when building a clinical dashboard incorporating PROMs. ResultsA total of 25 design components were identified, of which 16 were already surfaced during the literature search. Furthermore, 9 additional components were derived inductively during our interviews. The design components are clustered in a generic dashboard, PROM-related, adjacent information, and requirements for adoption components. Both software producers and users agreed on the primary purpose of a clinical dashboard incorporating PROMs to enhance patient communication in outpatient settings. Dashboard benefits include enhanced data visualization and improved workflow efficiency, while interoperability and data collection were named as adoption challenges. Consistency in dashboard design components is preferred across different episodes of care, with adaptations only for disease-specific PROMs. ConclusionsClinical dashboards have the potential to facilitate informed treatment decisions if certain design components are followed. This study establishes a comprehensive framework of design components to guide the development of effective clinical dashboards incorporating PROMs in health care practice.

Abstract Background Body contouring surgery after massive weight loss is associated with different risk factors. Wound healing disorders and seromas commonly occur postoperatively. Bariatric interventions lead to massive weight loss with excess skin and soft tissue. In this study, perioperatively collected laboratory markers of this special patient population were analyzed. Methods Fifty-nine patients were analyzed retrospectively regarding bariatric surgery, weight loss, body contouring surgery, laboratory markers, and complication rates. Results Body contouring surgery (n = 117) was performed in 59 patients. Weight loss was achieved after gastric bypass (40.1%), gastric banding (33.9%), or sleeve gastrectomy (26.0%), with an average of 69.2 kg. The most common body contouring procedure included abdominoplasty (n = 50), followed by thigh lift (n = 29), mammaplasty (n = 19), brachioplasty (n = 14), and upper body lift (n = 5). Analysis of laboratory markers revealed no exceptional and clinically relevant variations. Correlation analysis revealed associations between resection weight, amount of drain fluid, and particular laboratory markers. Conclusion Analysis of perioperative laboratory markers in this special patient population after massive weight loss did not indicate clinically relevant risk factors regardless of the type of bariatric or body contouring surgery. Body contouring surgeries after bariatric interventions prove to be safe and low risk concerning perioperative laboratory markers and postoperative hospitalization.

Abstract Extreme weather and climate events can have substantial impacts on society and the environment. Compound extremes (two or more extreme events occurring simultaneously or successively) may exert even larger impacts than individual events. Here we examine physical drivers behind variability in hydrometeorological (precipitation and temperature) compound extremes on subseasonal-to-seasonal timescales. Observational evidence presented here through composite analysis indicates that compound extreme frequency is linked to the Madden-Julian oscillation, a unique type of organized tropical convection varying primarily on subseasonal-to-seasonal timescales. The linkage between Madden-Julian oscillation and compound extremes is largely dependent on ENSO phases, which can be seen through different magnitudes or changes in sign of the canonical relationship conditioned on ENSO states. Similarly, the Madden-Julian oscillation can interrupt the canonical ENSO-compound extreme relationship. Our results suggest a potential route to improve subseasonal-to-seasonal prediction of western US compound extremes by considering the combined effect of both Madden-Julian oscillation and ENSO.

Abstract Study goal We compared the survival rates of women with breast cancer (BC) detected within versus outside the mammography screening program (MSP) “donna”. Methods We merged data from the MSP with the data from corresponding cancer registries to categorize BC cases as within MSP (screen-detected and interval carcinomas) and outside the MSP. We analyzed the tumor stage distribution, tumor characteristics and the survival of the women. We further estimated hazard ratios using Cox-regressions to account for different characteristics between groups and corrected the survival rates for lead-time bias. Results We identified 1057 invasive (ICD-10: C50) and in-situ (D05) BC cases within the MSP and 1501 outside the MSP between 2010 and 2019 in the Swiss cantons of St. Gallen and Grisons. BC within the MSP had a higher share of stage I carcinoma (46.5% vs. 33.0%; p

Abstract Corrosion results in large costs and environmental impact but can be controlled by thin oxide films that passivate the metal surfaces and hinder further oxidation or dissolution in an aqueous environment. The structure, chemistry, and thickness of these oxide films play a significant role in determining their anti-corrosion properties and the early-stage oxidation dynamics affect the properties of the developed oxide. Here, we use in situ X-ray Photoelectron Spectroscopy (XPS) to study the early-stage oxidation of a Ni-Cr-Mo alloy at room temperature and up to 400 °C. Cr and Mo begin to oxidize immediately after exposure to O2, and Cr3+, Mo4+, and Mo6+ oxides are formed. In contrast, Ni does not contribute significantly to the oxide film. A self-limiting oxide thickness, which did not depend on temperature below 400 °C, is observed. This is attributed to the consumption of available Cr and Mo near the surface, which results in an enrichment of metallic Ni under the oxide. The self-limited oxide thickness is 6–8 Å, which corresponds to 3–4 atomic layers of cations in the oxide. At 400 °C, sublimation of Mo6+ oxide is observed, resulting in the formation of an almost pure layer of Cr2O3 on the alloy surface. Lastly, a mechanism is presented that explains the formation of the bi-layer oxide structure observed for Ni-Cr-Mo alloys, which involves the enhanced migration of hexavalent Mo ions in the electric field, which drives mass transport during oxidation according to both the Cabrera Mott model and the Point Defect Model.

This article delves into the parallel natures of both the divine law and animal rights within the religious contexts of the Old and New Testaments. Employing a comparative approach, the paper inspects the developing perspectives on the treatment of animals in biblical scriptures, shedding light on the ethical and legal dimensions embedded in religious teachings. The study investigates key subtopics such as sacrificial rituals and moral imperatives, providing a nuanced understanding of the historical development of attitudes towards animals. Additionally, the analysis of this article encompasses ethical considerations, legal implications, and societal attitudes towards animals, drawing connections between ancient laws and contemporary discourse. Moreover, this article will look at the contemporary needs of society and how religious discourse and juristic principles can be applied to ensure the safety and rights of animals.

Robotic devices have recently enhanced cochlear implantation by improving precision resulting in reduced intracochlear damage during electrode insertion. This study aimed to gain first insights into the expected dimensions of the cone-like workspace from the posterior tympanotomy towards the round window membrane.This retrospective chart review analyzed ten postoperative CT scans of adult patients who were implanted with a CI in the past ten years. The dimensions of the cone-like workspace were determined using four landmarks (P1–P4). In the anteroposterior range, P1 and P2 were defined on the edge of the bony layer over the facial nerve and chorda tympani nerve, respectively. In the inferosuperior range, P3 was defined on the bony edge of the incus buttress and P4 was obtained at a distance of 0.45 mm between the facial nerve and the chorda tympani nerve. After selecting the landmarks, the calculations of the dimensions of the surgical access space were done in a standardized coordinate system and presented using descriptive statistics.The cone-like space is limited by two maximal angles, α and β. The average angle α of 19.84 (±3.55) degrees defines the angle towards the round window membrane between P1 and P2. The second average angle β of 53.56 (±10.29) degrees defines the angle towards the round window membrane between P3 and P4. Based on the angles the mean anteroposterior range of 2.25 (±0.42) mm and mean inferosuperior range of 6.73 (±2.42) mm. The distance from the posterior tympanotomy to the round window membrane was estimated at 6.05 (±0.71) mm.These findings present data on the hypothetical maximum workspace in which a future robotically steered insertion tool can be positioned for an optimal automated electrode insertion. A larger sample size is necessary before generalizing these dimensions to a population. Further research including preoperative CT scans is needed for planning robotic-steered cochlear implantation.

Objective To evaluate the Descemet membrane endothelial keratoplasty (DMEK) preparation performance of trainee surgeons in an ex vivo human donor cornea DMEK wet lab simulation setting.Methods Human donor corneoscleral rims unsuitable for transplantation were obtained from Moorfields Lions Eye Bank. At the wet lab, graft stripping was performed by scoring the peripheral endothelium. The trypan blue positive cells (TBPC) and cell density (cells/mm2—reticule count) were counted manually before and after stripping. The procedural time, peripheral and central tears and complete peel-off were also recorded and analysed.Results Eight trainee surgeons attended the wet lab each attempting three DMEKs. Between the first and last attempts a significant decrease was seen in the procedural time (17.6 min vs 10.6 min (p

Abstract Water years (WY) 2017 and 2023 were anomalously wet for California, each alleviating multiyear drought. In both cases, this was unexpected given La Niña conditions, with most seasonal forecasts favoring drier‐than‐normal winters. We analyze over seven decades of precipitation and snow records along with mid‐tropospheric circulation to identify recurring weather patterns driving California precipitation and Sierra Nevada snowpack. Tropical forcing by ENSO causes subtle but important differences in these wet weather patterns, which largely drives the canonical seasonal ENSO‐precipitation relationship. However, the seasonal frequency of these weather patterns is not strongly modulated by ENSO and remains a primary source of uncertainty for seasonal forecasting. Seasonal frequency of ENSO‐independent weather patterns was a major cause of anomalous precipitation in WY2017, record‐setting snow in WY2023, and differences in precipitation outcome during recent El Niño winters 1983, 1998, and 2016. Improved understanding of recurrent atmospheric weather patterns could help to improve seasonal precipitation forecasts.

INTRODUCTION: Quantifying antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and neutralising antibodies may help to understand protection at the individual and population levels. Determination of neutralising antibodies using classical virus neutralisation tests (VNT) is considered the gold standard, but they are costly and time-intensive. Enzyme-linked immunosorbent assay (ELISA)-based surrogate VNTs (sVNT) or anti-SARS-CoV-2 spike protein receptor binding domain immunoglobulins (anti-S-RBD Ig) may be suitable alternatives to VNTs. We aimed to (a) explore the correlations between anti-S-RBD Ig, VNT, and sVNT measurements and (b) describe humoral immunity against SARS-CoV-2 after vaccination, natural infection, and vaccine breakthrough infection in healthy blood donors. METHODS: We measured total anti-SARS-CoV-2 Ig in 5714 serum samples from 2748 healthy individuals visiting the Swiss Red Cross Blood Donation Centre in Basel from 03/2020 to 04/2022. We used the Elecsys® Anti-SARS-CoV-2 immunoassay (Roche) against the N- and S-receptor binding domain (RBD) proteins. In a subset of 548 samples from 123 donors, we conducted sVNTs against the Wuhan wild-type SARS-CoV-2 (SARS-CoV-2 Neutralizing Antibodies Detection Kit; Adipogen™). In 100 samples from 40 donors, we correlated sVNT and VNTs against the wild-type (D614G WU1) virus. Surveys were sent to the blood donors to collect data on their SARS-CoV-2 infection and vaccination status. Using this data, donors were categorised as “vaccination only”, “infection before vaccination”, “post-vaccine breakthrough infection”, and “natural infection only”. RESULTS: Our longitudinal observation study cohort consisted of 50.7% males with a median age of 31 years (range 18–75 y). Anti-SARS-CoV-2 N protein positivity rates per month indicate 57.1% (88/154) of the cohort was infected up to 04/2022. No differences in seropositivity were found between sexes, age groups, blood types (AB0 or RhD), and cytomegalovirus serostatus. We observed a high correlation between anti-S-RBD Ig and inhibition percentage (Spearman’s ρ = 0.92, Kendall’s τ = 0.77, p

The mortality of patients with MI has significantly decreased in recent decades, mainly due to early reperfusion therapy with a probability of surviving of more than 90% if the patient reaches the hospital [...]

Abstract Medication adherence is vital for patients suffering from Chronic Obstructive Pulmonary Disease (COPD) to mitigate long-term consequences. The impact of poor medication adherence on inferior outcomes like exacerbations leading to hospital admissions is yet to be studied using real-world data. Using Swiss claims data from 2015-2020, we group patients into five categories according to their medication possession ratio. By employing a logistic regression, we quantify each category’s average treatment effect of the medication possession ratio on hospitalized exacerbations. 13,557 COPD patients are included in the analysis. Patients with high medication adherence (daily medication reserve of 80% to 100%) are 51% less likely to incur exacerbation following a hospital stay than patients with the lowest medication adherence (daily medication reserve of 0% to 20%). The study shows that medication adherence varies strongly among Swiss COPD patients. Furthermore, high medication adherence immensely decreases the risk of hospitalized exacerbations.

Abstract Background As patient-reported outcomes (PROs) gain prominence in hip and knee arthroplasty (HA and KA), studies indicate PRO variations between genders. Research on the specific health domains particularly impacted is lacking. Hence, we aim to quantify the gender health gap in PROs for HA/KA patients, differentiating between general health, health-related quality of life (HrQoL), physical functioning, pain, fatigue, and depression. Methods The study included 3,693 HA patients (1,627 men, 2,066 women) and 3,110 KA patients (1,430 men, 1,680 women) receiving surgery between 2020 to 2021 in nine German hospitals, followed up until March 2022. Questionnaires used were: EQ-VAS, EQ-5D-5L, HOOS-PS, KOOS-PS, PROMIS-F-SF, PROMIS-D-SF, and a joint-specific numeric pain scale. PROs at admission, discharge, 12-months post-surgery, and the change from admission to 12-months (PRO-improvement) were compared by gender, tested for differences, and assessed using multivariate linear regressions. To enable comparability, PROs were transformed into z-scores (standard deviations from the mean). Results Observed differences between genders were small in all health domains and differences reduced over time. Men reported significantly better health versus women pre-HA (KA), with a difference of 0.252 (0.224) standard deviations from the mean for pain, 0.353 (0.243) for fatigue (PROMIS-F-SF), 0.327 (0.310) for depression (PROMIS-D-SF), 0.336 (0.273) for functionality (H/KOOS-PS), 0.177 (0.186) for general health (EQ-VAS) and 0.266 (0.196) for HrQoL (EQ-5D-5L). At discharge, the gender health gap reduced and even disappeared for some health dimensions since women improved in health to a greater extent than men. No gender health gap was observed in most PRO-improvements and at month 12. Conclusions Men experiencing slightly better health than women in all health dimensions before surgery while experiencing similar health benefits 12-months post-surgery, might be an indicator of men receiving surgery inappropriately early, women unnecessarily late or both. As studies often investigate the PRO-improvement, they miss pre-surgery gender differences, which could be an important target for improvement initiatives in patient-centric care. Moreover, future research on cutoffs for meaningful between-group PRO differences per measurement time would aid the interpretation of gender health disparities. Trial registration German Register for Clinical Trials, DRKS00019916, 26 November 2019.

Patients seek quality healthcare because they trust their doctors and the healthcare system. However, the use of AI models in medical consultations has undermined this trust. AI systems typically depend on accurate and large volumes of data for training, but in cases of insufficient or incorrect data, this can lead to incomplete or flawed outputs. The inaccuracies in the response generated by AI systems may result in biased outcomes, compromising patient care and further eroding the trust patients place in the healthcare system. In this paper, we describe an innovative approach to distinguishing between responses generated by AI and those written by human doctors during health consultations, using an efficient neural network. As part of our feature extraction approach, we converted text into numerical representations via word-level tokenization, mapping to integer sequences. This allows the neural network to efficiently process text while preserving semantic structure and handling a large vocabulary with fixed sequence lengths. Through rigorous experimentation and evaluation, we showcase the effectiveness and reliability of our proposed neural network architecture, MedXNet, in accurately classifying diverse responses encountered in health consultations. For the classification approach, we combined BiLSTM, Transformer, and CNN layers to capture local and global dependencies in sequence inputs and a dense layer that was fully connected with dropout regularization and softmax activation. We compared MedXNet performance with different RNNs, including LSTM, Bi-LSTM, GRU, and 1D-CNN, across three datasets of increasing complexity. Dataset A represents simple data, dataset B introduces greater complexity, and dataset C poses the highest level of challenge. Our findings revealed that MedXNet outperforms the others with an accuracy of 98.74% on dataset A. Although the accuracy of MedXNet decreased on B, it remains the top performer. With 94.63% accuracy, MedXNet still achieves the highest accuracy in dataset C. Based on these findings, MedXNet demonstrated robustness across a wide range of data complexity levels, making it an ideal classification tool for doctor-written and AI-generated text in health consultations. This can enhance the trust patients have in the responses they receive during online medical consultations.

Abstract Background The Genetic Frontotemporal Initiative Staging Group has proposed clinical criteria for the diagnosis of prodromal frontotemporal dementia (FTD), termed mild cognitive and/or behavioral and/or motor impairment (MCBMI). The objective of the study was to validate the proposed research criteria for MCBMI-FTD in a cohort of genetically confirmed FTD cases against healthy controls. Methods A total of 398 participants were enrolled, 117 of whom were carriers of an FTD pathogenic variant with mild clinical symptoms, while 281 were non-carrier family members (healthy controls (HC)). A subgroup of patients underwent blood neurofilament light (NfL) levels and anterior cingulate atrophy assessment. Results The core clinical criteria correctly classified MCBMI vs HC with an AUC of 0.79 (p < 0.001), while the addition of either blood NfL or anterior cingulate atrophy significantly increased the AUC to 0.84 and 0.82, respectively (p < 0.001). The addition of both markers further increased the AUC to 0.90 (p < 0.001). Conclusions The proposed MCBMI criteria showed very good classification accuracy for identifying the prodromal stage of FTD.

Identifying and categorizing proper nouns in text, known as named entity recognition (NER), is crucial for various natural language processing tasks. However, developing effective NER techniques for low-resource languages like Urdu poses challenges due to limited training data, particularly in the nastaliq script. To address this, our study introduces a novel data augmentation method, “contextual word embeddings augmentation” (CWEA), for Urdu, aiming to enrich existing datasets. The extended dataset, comprising 160,132 tokens and 114,912 labeled entities, significantly enhances the coverage of named entities compared to previous datasets. We evaluated several transformer models on this augmented dataset, including BERT-multilingual, RoBERTa-Urdu-small, BERT-base-cased, and BERT-large-cased. Notably, the BERT-multilingual model outperformed others, achieving the highest macro F1 score of 0.982%. This surpassed the macro f1 scores of the RoBERTa-Urdu-small (0.884%), BERT-large-cased (0.916%), and BERT-base-cased (0.908%) models. Additionally, our neural network model achieved a micro F1 score of 96%, while the RNN model achieved 97% and the BiLSTM model achieved a macro F1 score of 96% on augmented data. Our findings underscore the efficacy of data augmentation techniques in enhancing NER performance for low-resource languages like Urdu.

Abstract INTRODUCTION We aimed to expand the range of the frontotemporal dementia (FTD) phenotypes assessed by the Clinical Dementia Rating Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains (CDR plus NACC FTLD). METHODS Neuropsychiatric and motor domains were added to the standard CDR plus NACC FTLD generating a new CDR plus NACC FTLD‐NM scale. This was assessed in 522 mutation carriers and 310 mutation‐negative controls from the Genetic Frontotemporal dementia Initiative (GENFI). RESULTS The new scale led to higher global severity scores than the CDR plus NACC FTLD: 1.4% of participants were now considered prodromal rather than asymptomatic, while 1.3% were now considered symptomatic rather than asymptomatic or prodromal. No participants with a clinical diagnosis of an FTD spectrum disorder were classified as asymptomatic using the new scales. DISCUSSION Adding new domains to the CDR plus NACC FTLD leads to a scale that encompasses the wider phenotypic spectrum of FTD with further work needed to validate its use more widely. Highlights The new Clinical Dementia Rating Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains neuropsychiatric and motor (CDR plus NACC FTLD‐NM) rating scale was significantly positively correlated with the original CDR plus NACC FTLD and negatively correlated with the FTD Rating Scale (FRS). No participants with a clinical diagnosis in the frontotemporal dementia spectrum were classified as asymptomatic with the new CDR plus NACC FTLD‐NM rating scale. Individuals had higher global severity scores with the addition of the neuropsychiatric and motor domains. A receiver operating characteristic analysis of symptomatic diagnosis showed nominally higher areas under the curve for the new scales.

Study region: Raised bog “Königsdorfer-Weidfilz”, Bavaria, Germany. Study focus: This study investigates effects of different rewetting scenarios on water levels in raised bog peat under varying climatic conditions. We apply physically-based models with high temporal and spatial resolutions to compare seasonal and annual water levels. The results were evaluated to determine the significance of these water level changes. Based on these water levels, a qualitative assessment was conducted to determine the percentage of areas that are more or less likely contributing to climate change through greenhouse gas emissions. New hydrological insights: Our study demonstrates the potential for investigating the rewetting of small peatland areas using high-resolution three-dimensional hydrological models. By utilizing a partially rewetted raised bog as a case study, we successfully modeled areas with different drainage states. Our results indicate that the areas rewetted in the respective scenarios behave similarly to the areas that have already been rewetted on site. Our study highlights that additional rewetting measures have a positive impact on reducing climate-active areas with low water levels in raised bogs. When combined with natural vegetation succession and changes in soil properties resulting from the formation of a new functional acrotelm layer after rewetting, these changes further enhance the effectiveness of the rewetting process. Although the influence of relevant dry periods after rewetting remains significant, our results suggest that the resilience of the peatland increases.

In this paper, we further develop a novel, efficient approach to the problem of signal detection against background noise based on a nonlinear residual functional called the neuron-like criterion function (NCF). A detailed comparison of the NCF-based technique and the conventional correlation criterion function (CCF)-based matched-signal detection is performed. For this purpose, we calculated the detection performance curves for both techniques and found the range of the problem parameters in which the NCF-based detector shows a certain advantage. The latter consists of achieving a fixed value of detection probability at a lower threshold value of the input signal-to-noise ratio (SNR) compared to the CCF-based detector. Special attention is given to the practically important scenario of receiving a weak signal against the background of non-stationary noise with a certain trend (positive or negative) of its intensity. For these two specific cases, modified NCFs are given, which are then used for computer simulation. For both broadband and narrow-band signals, the quantitative bounds of the most effective use of the derived NCFs are established and interpreted. The real sea noise data obtained from two underwater acoustic arrays, one stationary on the sea bottom and the other towed near the sea surface, are used for experimental validation. The experimental data processing results confirm the simulation results and make it possible to demonstrate the advantage of the NCF if the noise intensity shows a significant trend over the signal observation interval. The latter case obviously corresponds to the use of the towed array in the coastal area.

Maize (Zea mays L.) is one of the most demanded grain crops in the world. Currently, production has exceeded one billion tons and is increasing by 3–5% annually. Such growth is due to the genetic potential of the crop and the use of heterosis F1 hybrids in production. However, the need to produce first-generation seed annually poses significant challenges and is an economically costly technology. A solution to this problem may be the transfer of the asexual (apomictic) mode of reproduction to maize from its wild relative, eastern gamagrass (Tripsacum dactyloides L.). In this work, we report the production of 56-chromosome apomictic hybrids of maize (Zea mays L.) with eastern gamagrass (T. dactyloides L.) with restored anther fertility. The mode of reproduction of the plant was confirmed by counting chromosomes and sequencing the nuclear gene (Pox3) and chloroplast tRNA-Leu (trnL) gene. These apomictic hybrids had karyotypes of 2n = 56 = [(10Zm(573MB) + 36Td) + 10Zm(611CB)] and 2n = 56 = [(10Zm(611CB) + 36Td) + 10Zm(611CB)]. The resulting hybrids can be widely used as a fodder crop.

The study evaluates the accuracy of predicting intracochlear pressure during bone conduction stimulation using promontory velocity and ear canal pressure, as less invasive alternatives to intracochlear pressure. Stimulating with a percutaneous bone conduction device implanted in six human cadaveric ears, measurements were taken across various intensities, frequencies, and stimulation positions. Results indicate that intracochlear pressure linearly correlates with ear canal pressure (R2 = 0.43, RMSE = 6.85 dB), and promontory velocity (R2 = 0.47, RMSE = 6.60 dB). Normalizing data to mitigate the influence of stimulation position leads to a substantial improvement in these correlations. R2 values increased substantially to 0.93 for both the ear canal pressure and the promontory velocity, with RMSE reduced considerably to 2.02 (for ear canal pressure) and 1.94 dB (for promontory velocity). Conclusively, both ear canal pressure and promontory velocity showed potential in predicting intracochlear pressure and the prediction accuracy notably enhanced when accounting for stimulation position. Ultimately, these findings advocate for the continued use of intracochlear pressure measurements to evaluate future bone conduction devices and illuminate the role of stimulation position in influencing the dynamics of bone conduction pathways.

Summary: Background: In April 2023, the antisense oligonucleotide tofersen was approved by the U.S. Food and Drug Administration (FDA) for treatment of SOD1-amyotrophic lateral sclerosis (ALS), after a decrease of neurofilament light chain (NfL) levels had been demonstrated. Methods: Between 03/2022 and 04/2023, 24 patients with SOD1-ALS from ten German ALS reference centers were followed-up until the cut-off date for ALS functional rating scale revised (ALSFRS-R), progression rate (loss of ALSFRS-R/month), NfL, phosphorylated neurofilament heavy chain (pNfH) in cerebrospinal fluid (CSF), and adverse events. Findings: During the observation period, median ALSFRS-R decreased from 38.0 (IQR 32.0–42.0) to 35.0 (IQR 29.0–42.0), corresponding to a median progression rate of 0.11 (IQR −0.09 to 0.32) points of ALSFRS-R lost per month. Median serum NfL declined from 78.0 pg/ml (IQR 37.0–147.0 pg/ml; n = 23) to 36.0 pg/ml (IQR 22.0–65.0 pg/ml; n = 23; p = 0.02), median pNfH in CSF from 2226 pg/ml (IQR 1061–6138 pg/ml; n = 18) to 1151 pg/ml (IQR 521–2360 pg/ml; n = 18; p = 0.02). In the CSF, we detected a pleocytosis in 73% of patients (11 of 15) and an intrathecal immunoglobulin synthesis (IgG, IgM, or IgA) in 9 out of 10 patients. Two drug-related serious adverse events were reported. Interpretation: Consistent with the VALOR study and its Open Label Extension (OLE), our results confirm a reduction of NfL serum levels, and moreover show a reduction of pNfH in CSF. The therapy was safe, as no persistent symptoms were observed. Pleocytosis and Ig synthesis in CSF with clinical symptoms related to myeloradiculitis in two patients, indicate the potential of an autoimmune reaction. Funding: No funding was received towards this study.

A subpopulation of deeply quiescent, so-called dormant hematopoietic stem cells (dHSCs) resides at the top of the hematopoietic hierarchy and serves as a reserve pool for HSCs. The state of dormancy protects the HSC pool from exhaustion throughout life; however, excessive dormancy may prevent an efficient response to hematological stresses. Despite the significance of dHSCs, the mechanisms maintaining their dormancy remain elusive. Here, we identify CD38 as a novel and broadly applicable surface marker for the enrichment of murine dHSCs. We demonstrate that cyclic adenosine diphosphate ribose (cADPR), the product of CD38 cyclase activity, regulates the expression of the transcription factor c-Fos by increasing the release of Ca2+ from the endoplasmic reticulum (ER). Subsequently, we uncover that c-Fos induces the expression of the cell cycle inhibitor p57Kip2 to drive HSC dormancy. Moreover, we found that CD38 ecto-enzymatic activity at the neighboring CD38-positive cells can promote human HSC quiescence. Together, CD38/cADPR/Ca2+/c-Fos/p57Kip2 axis maintains HSC dormancy. Pharmacological manipulations of this pathway can provide new strategies to improve the success of stem cell transplantation and blood regeneration after injury or disease.

Affective computing (AC), like most other areas of computational research, has benefited tremendously from advances in deep learning (DL). These advances have opened up new horizons in AC research and practice. Yet, as DL dominates the community’s attention, there is a danger of overlooking other emerging trends in artificial intelligence (AI) research. Furthermore, over-reliance on one particular technology may lead to stagnating progress. In an attempt to foster the exploration of complementary directions, we provide a concise, easily digestible overview of emerging trends in AI research that stand to play a vital role in solving some of the remaining challenges in AC research. Our overview is driven by the limitations of the current state of the art as it pertains to AC.

Among the 17 Sustainable Development Goals (SDGs) proposed within the 2030 Agenda and adopted by all the United Nations member states, the 13th SDG is a call for action to combat climate change. Moreover, SDGs 14 and 15 claim the protection and conservation of life below water and life on land, respectively. In this work, we provide a literature-founded overview of application areas, in which computer audition – a powerful but in this context so far hardly considered technology, combining audio signal processing and machine intelligence – is employed to monitor our ecosystem with the potential to identify ecologically critical processes or states. We distinguish between applications related to organisms, such as species richness analysis and plant health monitoring, and applications related to the environment, such as melting ice monitoring or wildfire detection. This work positions computer audition in relation to alternative approaches by discussing methodological strengths and limitations, as well as ethical aspects. We conclude with an urgent call to action to the research community for a greater involvement of audio intelligence methodology in future ecosystem monitoring approaches.

The effect of a transverse magnetic field on two-phase stratified flow in horizontal and inclined channels is studied. The lower heavier phase is assumed to be an electrical conductor (e.g., liquid metal), while the upper lighter phase is fully dielectric (e.g., gas). The flow is defined by prescribed flow rates in each phase, so the unknown frictional pressure gradient and location of the interface separating the phases (holdup) are found as part of the whole solution. It is shown that the solution of such a two-phase Hartmann flow is determined by four dimensionless parameters: the phases’ viscosity and flow-rate ratios, the inclination parameter, and the Hartmann number. The changes in velocity profiles, holdups, and pressure gradients with variations in the magnetic field and the phases’ flow-rate ratio are reported. The potential lubrication effect of the gas layer and pumping power reduction are found to be limited to low magnetic field strength. The effect of the magnetic field strength on the possibility of obtaining countercurrent flow and multiple flow states in concurrent upward and downward flows, and the associated flow characteristics, such as velocity profiles, back-flow phenomena, and pressure gradient, are explored. It is shown that increasing the magnetic field strength reduces the flow-rate range for which multiple solutions are obtained in concurrent flows and the flow-rate range where countercurrent flow is feasible.

Convolutional Neural Networks (CNNs) have garnered significant utilisation within automated image classification systems. CNNs possess the ability to leverage the spatial and temporal correlations inherent in a dataset. This study delves into the use of cutting-edge deep learning for precise image data classification, focusing on overcoming the difficulties brought on by the COVID-19 pandemic. In order to improve the accuracy and robustness of COVID-19 image classification, the study introduces a novel methodology that combines the strength of Deep Convolutional Neural Networks (DCNNs) and Generative Adversarial Networks (GANs). This proposed study helps to mitigate the lack of labelled coronavirus (COVID-19) images, which has been a standard limitation in related research, and improves the model’s ability to distinguish between COVID-19-related patterns and healthy lung images. The study uses a thorough case study and uses a sizable dataset of chest X-ray images covering COVID-19 cases, other respiratory conditions, and healthy lung conditions. The integrated model outperforms conventional DCNN-based techniques in terms of classification accuracy after being trained on this dataset. To address the issues of an unbalanced dataset, GAN will produce synthetic pictures and extract deep features from every image. A thorough understanding of the model’s performance in real-world scenarios is also provided by the study’s meticulous evaluation of the model’s performance using a variety of metrics, including accuracy, precision, recall, and F1-score.

Thermally induced position errors are one of the main error sources on the workpiece caused by the behavior of the machine tool. In today’s industrial environment, the correction of thermal errors is usually based on simple regression approaches, where the characteristic diagrams for correction are generated experimentally. The performance of these approaches is only valid for the corresponding load regimes, which often results in insufficient correction quality in practical applications. Consequently, there is only a limited benefit or even a deterioration in machine behavior if the correction characteristic is based on an inapplicable load case compared to the initial experiment. Simulation-generated characteristic diagrams using finite element models solve this disadvantage, but do not answer the question about the choice of the right characteristic matching the current load situation, and, in addition, calculate very slowly. Structural model-based correction using reduced models, on the other hand, calculates quickly, but requires a high modeling effort for accurate correction. The approach, presented in this contribution, combines simulation-generated characteristic diagrams and a structural model-based decision algorithm for a new hybrid model in order to select the appropriate characteristic diagram for the present load situation in the control system. This paper presents the simulative characteristic diagram generation by a finite element model validated by experiments in a climate chamber and a validated structural model including the concept for the decision algorithm.

Cognitive aging has become a public health concern as the mean age of the population is ever-increasing. It is a naturalistic and common process of degenerative and compensatory changes that may result in neurocognitive disorders. While heterogeneous, cognitive aging mostly affects executive functions that may be associated with functional losses during activities of daily living. Cognition-oriented treatments like cognitive training and transcranial direct current stimulation (tDCS) have garnered considerable attention in the past few decades while the exact picture regarding their efficacy in healthy older adults has not been determined yet. The present paper aimed to evaluate the effects of a 3-month intervention of tDCS over the dorsolateral prefrontal cortex (DLPFC) with multimodal cognitive training on the Stroop test and Trail Making Tests A and B performance. One hundred and ninety-three healthy older adults from 2 sites were administered repeated sessions of active/sham tDCS with cognitive training. Baseline, post-intervention, and 1-year performance results between groups were compared using multiple linear regressions. Active tDCS resulted in better Stroop test performance at post-intervention (p = 0.033) but not at 1-year follow-up while no differences between groups were observed in Trail Making Tests A & B performance. The present results may correspond to a modest improvement in conflict monitoring, potentially due to modulation of prefrontal regions, without changing shifting performance. Further investigation is warranted to draw an interference regarding the subdomain-specific impact of repeated tDCS with multimodal cognitive training on executive functions., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

The goal of the current study was to learn about the role of cerebral mitochondrial function on cognition. Based on established cognitive neuroscience, clinical neuropsychology, and cognitive aging literature, we hypothesized mitochondrial function within a focal brain region would map onto cognitive behaviors linked to that brain region. To test this hypothesis, we used phosphorous ( 31 P) magnetic resonance spectroscopy (MRS) to derive indirect markers of mitochondrial function and energy metabolism across two regions of the brain (bifrontal, left temporal). We administered cognitive tasks sensitive to frontal-executive or temporal-hippocampal systems to a sample of 70 cognitively unimpaired older adults with subjective memory complaints and a first-degree family history of Alzheimer's disease and predicted better executive function and recent memory performance would be related to greater frontal and temporal 31 P MRS indirect markers, respectively. Results of separate hierarchical linear regressions indicated better recent memory scores were related to 31 P MRS indirect markers of lower static energy and higher energy reserve within the left temporal voxel; these findings were associated with moderate effect sizes. Contrary to predictions, executive function performance was unrelated to 31 P MRS indirect markers within the bilateral frontal voxel, which may reflect a combination of theoretical and/or methodological issues. Findings represent a snapshot of the relationship between cognition and 31 P MRS indirect markers of mitochondrial function, providing potential avenues for future work investigating mitochondrial underpinnings of cognition. 31 P MRS may provide a sensitive neuroimaging marker for differences in aspects of memory among persons at-risk for mild cognitive impairment or dementia., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Aging is a public health concern with an ever-increasing magnitude worldwide. An array of neuroscience-based approaches like transcranial direct current stimulation (tDCS) and cognitive training have garnered attention in the last decades to ameliorate the effects of cognitive aging in older adults. This study evaluated the effects of 3 months of bilateral tDCS over the frontal cortices with multimodal cognitive training on working memory capacity. Two hundred ninety-two older adults without dementia were allocated to active or sham tDCS paired with cognitive training. These participants received repeated sessions of bilateral tDCS over the bilateral frontal cortices, combined with multimodal cognitive training. Working memory capacity was assessed with the digit span forward, backward, and sequencing tests. No baseline differences between active and sham groups were observed. Multiple linear regressions indicated more improvement of the longest digit span backward from baseline to post-intervention (p = 0.021) and a trend towards greater improvement (p = 0.056) of the longest digit span backward from baseline to 1 year in the active tDCS group. No significant between-group changes were observed for digit span forward or digit span sequencing. The present results provide evidence for the potential for tDCS paired with cognitive training to remediate age-related declines in working memory capacity. These findings are sourced from secondary outcomes in a large randomized clinical trial and thus deserve future targeted investigation in older adult populations., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

Introduction: We examined the relationship between sedentary behavior (SB), moderate-to-vigorous physical activity (MVPA), and white matter hyperintensity (WMH) volumes, a common magnetic resonance imaging (MRI) marker associated with risk of neurodegenerative disease in middle-aged to older adults., Methods: We used data from the UK Biobank ( n  = 14,415; 45 to 81 years) that included accelerometer-derived measures of SB and MVPA, and WMH volumes from MRI., Results: Both MVPA and SB were associated with WMH volumes (β MVPA  = -0.03 [-0.04, -0.01], p  < 0.001; β SB  = 0.02 [0.01, 0.03], p  = 0.007). There was a significant interaction between SB and MVPA on WMH volumes (β SB×MVPA  = -0.015 [-0.028, -0.001], p SB×MVPA  = 0.03) where SB was positively associated with WMHs at low MVPA, and MVPA was negatively associated with WMHs at high SB., Discussion: While this study cannot establish causality, the results highlight the potential importance of considering both MVPA and SB in strategies aimed at reducing the accumulation of WMH volumes in middle-aged to older adults., Highlights: SB is associated with greater WMH volumes and MVPA is associated with lower WMH volumes.Relationships between SB and WMH are strongest at low levels of MVPA.Associations between MVPA and WMH are strongest at high levels of SB.Considering both SB and MVPA may be effective strategies for reducing WMHs., Competing Interests: The authors declare no conflict of interest. Author disclosures are available in the Supporting information., (© 2024 The Author(s). Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Homocysteine (Hcy) is a cardiovascular risk factor implicated in cognitive impairment and cerebrovascular disease but has also been associated with Alzheimer's disease. In 160 healthy older adults (mean age = 69.66 ± 9.95 years), we sought to investigate the association of cortical brain volume with white matter hyperintensity (WMH) burden and a previously identified Hcy-related multivariate network pattern showing reductions in subcortical gray matter (SGM) volumes of hippocampus and nucleus accumbens with relative preservation of basal ganglia. We additionally evaluated the potential role of these brain imaging markers as a series of mediators in a vascular brain pathway leading to age-related cognitive dysfunction in healthy aging. We found reductions in parietal lobar gray matter associated with the Hcy-SGM pattern, which was further associated with WMH burden. Mediation analyses revealed that slowed processing speed related to aging, but not executive functioning or memory, was mediated sequentially through increased WMH lesion volume, greater Hcy-SGM pattern expression, and then smaller parietal lobe volume. Together, these findings suggest that volume reductions in parietal gray matter associated with a pattern of Hcy-related SGM volume differences may be indicative of slowed processing speed in cognitive aging, potentially linking cardiovascular risk to an important aspect of cognitive dysfunction in healthy aging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Song, Bharadwaj, Raichlen, Habeck, Grilli, Huentelman, Hishaw, Trouard and Alexander.)

Companion dogs are a valuable model for aging research, including studies of cognitive decline and dementia. With advanced age, some dogs spontaneously develop cognitive impairments and neuropathology resembling features of Alzheimer's disease. These processes have been studied extensively in laboratory beagles, but the cognitive assays used in that context-which rely on time-consuming operant procedures-are not easily scalable to large samples of community-dwelling companion dogs. We developed a battery of five short-form tasks targeting three aspects of cognition that are impaired in Alzheimer's disease: spatial memory, executive functions, and social cognition. In Experiment 1, we tested a cross-sectional sample of dogs (N = 123) and estimated associations between age and task performance. Older dogs scored lower on measures of spatial learning, memory, and response flexibility, and spent less time near, but more time gazing at, the experimenter. We found no differences in associations between age and performance across dogs of different body masses, a proxy for expected lifespan. In Experiment 2, we demonstrated the feasibility of these measures in clinical settings (N = 35). Dogs meeting clinical criteria for moderate or severe cognitive impairment scored lower, on average, than dogs characterized as mildly impaired and healthy agers, although these distributions overlapped. However, few dogs in our study cohort met the criteria for moderate or severe impairment. The measures presented here show promise for deployment in large-scale longitudinal studies of companion dogs, such as the Dog Aging Project., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

Cognitive training using a visual speed-of-processing task, called the Useful Field of View (UFOV) task, reduced dementia risk and reduced decline in activities of daily living at a 10-year follow-up in older adults. However, there was variability in the achievement of cognitive gains after cognitive training across studies, suggesting moderating factors. Learning trials of visual and verbal learning tasks recruit similar cognitive abilities and have overlapping neural correlates with speed-of-processing/working memory tasks and therefore could serve as potential moderators of cognitive training gains. This study explored the association between the Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R) learning with a commercial UFOV task called Double Decision. Through a secondary analysis of a clinical trial, we assessed the moderation of HVLT-R and BVMT-R learning on Double Decision improvement after a 3-month speed-of-processing/attention and working memory cognitive training intervention in a sample of 75 cognitively healthy older adults. Multiple linear regressions showed that better baseline Double Decision performance was significantly associated with better BVMT-R learning (β =  - .303). This association was not significant for HVLT-R learning (β =  - .142). Moderation analysis showed that those with poorer BVMT-R learning improved the most on the Double Decision task after cognitive training. This suggests that healthy older adults who perform below expectations on cognitive tasks related to the training task may show the greatest training gains. Future cognitive training research studying visual speed-of-processing interventions should account for differing levels of visuospatial learning at baseline, as this could impact the magnitude of training outcomes and efficacy of the intervention., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

Objective: White matter hyperintensity (WMH) volume is a neuroimaging marker of lesion load related to small vessel disease that has been associated with cognitive aging and Alzheimer's disease (AD) risk., Method: The present study sought to examine whether regional WMH volume mediates the relationship between APOE ε4 status, a strong genetic risk factor for AD, and cognition and if this association is moderated by age group differences within a sample of 187 healthy older adults (APOE ε4 status [carrier/non-carrier] = 56/131)., Results: After we controlled for sex, education, and vascular risk factors, ANCOVA analyses revealed significant age group by APOE ε4 status interactions for right parietal and left temporal WMH volumes. Within the young-old group (50-69 years), ε4 carriers had greater right parietal and left temporal WMH volumes than non-carriers. However, in the old-old group (70-89 years), right parietal and left temporal WMH volumes were comparable across APOE ε4 groups. Further, within ε4 non-carriers, old-old adults had greater right parietal and left temporal WMH volumes than young-old adults, but there were no significant differences across age groups in ε4 carriers. Follow-up moderated mediation analyses revealed that, in the young-old, but not the old-old group, there were significant indirect effects of ε4 status on memory and executive functions through left temporal WMH volume., Conclusions: These findings suggest that, among healthy young-old adults, increased left temporal WMH volume, in the context of the ε4 allele, may represent an early marker of cognitive aging with the potential to lead to greater risk for AD.

Aging is a major risk for cognitive decline and transition to dementia. One well-known age-related change involves decreased brain efficiency and energy production, mediated in part by changes in mitochondrial function. Damaged or dysfunctional mitochondria have been implicated in the pathogenesis of age-related neurodegenerative conditions like Alzheimer's disease (AD). The aim of the current study was to investigate mitochondrial function over frontal and temporal regions in a sample of 70 cognitively normal older adults with subjective memory complaints and a first-degree family history of AD. We hypothesized cerebral mitochondrial function and energy metabolism would be greater in temporal as compared to frontal regions based on the high energy consumption in the temporal lobes (i.e., hippocampus). To test this hypothesis, we used phosphorous ( 31 P) magnetic resonance spectroscopy (MRS) which is a non-invasive and powerful method for investigating in vivo mitochondrial function via high energy phosphates and phospholipid metabolism ratios. We used a single voxel method (left temporal and bilateral prefrontal) to achieve optimal sensitivity. Results of separate repeated measures analyses of variance showed 31 P MRS ratios of static energy, energy reserve, energy consumption, energy demand, and phospholipid membrane metabolism were greater in the left temporal than bilateral prefrontal voxels. Our findings that all 31 P MRS ratios were greater in temporal than bifrontal regions support our hypothesis. Future studies are needed to determine whether findings are related to cognition in older adults., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

Declines in several cognitive domains, most notably processing speed, occur in non-pathological aging. Given the exponential growth of the older adult population, declines in cognition serve as a significant public health issue that must be addressed. Promising studies have shown that cognitive training in older adults, particularly using the useful field of view (UFOV) paradigm, can improve cognition with moderate to large effect sizes. Additionally, meta-analyses have found that transcranial direct current stimulation (tDCS), a non-invasive form of brain stimulation, can improve cognition in attention/processing speed and working memory. However, only a handful of studies have looked at concomitant tDCS and cognitive training, usually with short interventions and small sample sizes. The current study assessed the effect of a tDCS (active versus sham) and a 3-month cognitive training intervention on task-based functional connectivity during completion of the UFOV task in a large older adult sample (N = 153). We found significant increased functional connectivity between the left and right pars triangularis (the ROIs closest to the electrodes) following active, but not sham tDCS. Additionally, we see trending behavioral improvements associated with these functional connectivity changes in the active tDCS group, but not sham. Collectively, these findings suggest that tDCS and cognitive training can be an effective modulator of task-based functional connectivity above and beyond a cognitive training intervention alone., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

Higher levels of physical activity are known to benefit aspects of brain health across the lifespan. However, the role of sedentary behavior (SB) is less well understood. In this review we summarize and discuss evidence on the role of SB on brain health (including cognitive performance, structural or functional brain measures, and dementia risk) for different age groups, critically compare assessment approaches to capture SB, and offer insights into emerging opportunities to assess SB via digital technologies. Across the lifespan, specific characteristics of SB (particularly whether they are cognitively active or cognitively passive) potentially act as moderators influencing the associations between SB and specific brain health outcomes. We outline challenges and opportunities for future research aiming to provide more robust empirical evidence on these observations., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Hippocampal volume is particularly sensitive to the accumulation of total brain white matter hyperintensity volume (WMH) in aging, but how the regional distribution of WMH volume differentially impacts the hippocampus has been less studied. In a cohort of 194 healthy older adults ages 50-89, we used a multivariate statistical method, the Scaled Subprofile Model (SSM), to (1) identify patterns of regional WMH differences related to left and right hippocampal volumes, (2) examine associations between the multimodal neuroimaging covariance patterns and demographic characteristics, and (3) investigate the relation of the patterns to subjective and objective memory in healthy aging. We established network covariance patterns of regional WMH volume differences associated with greater left and right hippocampal volumes, which were characterized by reductions in left temporal and right parietal WMH volumes and relative increases in bilateral occipital WMH volumes. Additionally, we observed lower expression of these hippocampal-related regional WMH patterns were significantly associated with increasing age and greater subjective memory complaints, but not objective memory performance in this healthy older adult cohort. Our findings indicate that, in cognitively healthy older adults, left and right hippocampal volume reductions were associated with differences in the regional distribution of WMH volumes, which were exacerbated by advancing age and related to greater subjective memory complaints. Multivariate network analyses, like SSM, may help elucidate important early effects of regional WMH volume on brain and cognitive aging in healthy older adults., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Van Etten, Bharadwaj, Grilli, Raichlen, Hishaw, Huentelman, Trouard and Alexander.)

Background: Pharmacological interventions for depression and anxiety in older adults often have significant side effects, presenting the need for more tolerable alternatives. Transcranial direct current stimulation (tDCS) is a promising non-pharmacological intervention for depression in clinical populations. However, its effects on depression and anxiety symptoms, particularly in older adults from the general public, are understudied., Objective: We conducted a secondary analysis of the Augmenting Cognitive Training in Older Adults (ACT) trial to assess tDCS efficacy in reducing psychological symptoms in older adults. We hypothesized that active stimulation would yield greater reductions in depression and state anxiety compared to sham post-intervention and at the one-year follow-up. We also explored tDCS effects in subgroups characterized by baseline symptom severity., Methods: A sample of 378 older adults recruited from the community completed a 12-week tDCS intervention with cognitive or education training. Electrodes were placed at F3/F4, and participants received active or sham tDCS during training sessions. We assessed the association between tDCS group and changes in depression, state anxiety, and trait anxiety from baseline to post-intervention and one-year controlling for covariates., Results: The active tDCS group demonstrated greater reductions in depression and state anxiety compared to sham post-intervention, particularly in individuals with mild depression and moderate/severe state anxiety at baseline. Furthermore, the active tDCS group with moderate/severe state anxiety maintained greater symptom reductions at one-year., Conclusions: tDCS effectively reduced depression and state anxiety symptoms in a large sample of older adults. These findings highlight the importance of considering symptom severity when identifying those who may benefit most from this intervention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)