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Abstract This study aims at identifying risk-related patterns of left ventricular contraction dynamics via novel volume transient characterization. A multicenter cohort of AMI survivors (n = 1021) who underwent Cardiac Magnetic Resonance (CMR) after infarction was considered for the study. The clinical endpoint was the 12-month rate of major adverse cardiac events (MACE, n = 73), consisting of all-cause death, reinfarction, and new congestive heart failure. Cardiac function was characterized from CMR in 3 potential directions: by (1) volume temporal transients (i.e. contraction dynamics); (2) feature tracking strain analysis (i.e. bulk tissue peak contraction); and (3) 3D shape analysis (i.e. 3D contraction morphology). A fully automated pipeline was developed to extract conventional and novel artificial-intelligence-derived metrics of cardiac contraction, and their relationship with MACE was investigated. Any of the 3 proposed directions demonstrated its additional prognostic value on top of established CMR indexes, myocardial injury markers, basic characteristics, and cardiovascular risk factors (P

Abstract Background Hodgkin’s lymphoma (HL) is a hematological malignancy that affects both children and young adults. Traditional treatment is associated with a life-time prevalence of cardiac disease exceeding 50%. In the late 1990s protocols were modified to reduce cancer therapy-related adverse cardiac effects. This study aimed to assess the long-term impact of advances in treatment protocols on the cardiac health of HL survivors (HLS). Methods HLS (n = 246) treated between 1997 and 2007 with anthracycline-based chemotherapy in three centers in Norway were included. Of these, 132 (53%) had also received mediastinal radiotherapy. HLS were compared to controls (n = 58) recruited from the general population and matched for sex, age, smoking status, and heredity for coronary artery disease. All subjects underwent echocardiography, clinical assessment, and blood sampling. Results The HLS were 46 ± 9 years old and had been treated 17 ± 3 years before inclusion in the study. There was no significant difference between HLS and controls in ejection fraction (EF) (58%±5 vs. 59%±4, p = 0.08) or prevalence of heart failure. HLS treated with both anthracyclines and mediastinal radiotherapy (AC + MRT) had slightly worse left ventricular global longitudinal strain than controls (-19.3 ± 2.5% vs. -20.8 ± 2.0%, p

An advertisement must pay attention to the concepts and strategies in advertising because the use of this endorser can be a double-edged knife for the brand. In the vampire effect phenomenon, celebrity endorsers can potentially overshadow the brand so that the audience focuses only on the celebrity, not the brand. Specifically, the phenomenon of a brand that the celebrity endorser overshadows is called high eclipsing an endorsement, and vice versa for the phenomenon of low eclipsing. This research was conducted to develop a framework that discusses the eclipsing phenomenon in celebrity endorsement in the context of stimulus-organism-response (SOR) theory. The participants in this study were undergraduate students in a department at a well-known university in Surabaya. The characteristics of the Participants are domiciled in Surabaya and are between 18-24 years old. Through this study, we can find out how consumers' emotional response is formed when faced with high- and low-eclipsing advertisement stimuli. In addition, this study will also discuss how the differences in purchase intentions are formed from these two different eclipsing endorsement stimuli. The research indicates a significant positive effect between exposure to advertising content featuring both high-eclipsing (HE) and low-eclipsing (LE) celebrity endorsements and emotional response (EM). It implies that leveraging celebrities in advertisements, regardless of their eclipsing status, can evoke a heightened emotional response from the audience. The study suggests a noteworthy association between exposure to advertising content containing celebrity endorsements (CE) and increased purchase intention (PI). Consumers are more likely to desire to purchase a product or service when it is endorsed by a celebrity, indicating the potential effectiveness of this marketing strategy.

Abstract Electromagnetic methods for non-destructive evaluation (NDE) are presented, with which sheet metal components can be identified and their material properties can be characterized. The latter is possible with 3MA, the Micromagnetic Multiparametric Microstructure and stress Analyser. This is a combination of several micromagnetic NDE methods that make it possible to analyse the microstructure in a ferromagnetic material and to determine quantitative values of the mechanical material properties or the stress state. In the case of cold forming, the 3MA application for pre-process testing of sheet metal is discussed. Based on the 3MA information, the formability of the sheets can be predicted. To apply 3MA in-line, the influence of the relative speed and the relative distance between the 3MA probe head and the sheet was investigated. In a second study, a spatially resolved eddy current (EC) method was used to create an image of the intrinsic material microstructure of a component for its identification and traceability. It turned out, that these intrinsic fingerprint images can still be recognized even after subsequent plastic deformation or coating of the surface. This enabled the development of a marker-free traceability method for sheet metal processing. It is based on a low-cost array sensor and a specimen identification using robust and partly redundant features of the fingerprint images processed by machine learning (ML).

Abstract Although highly effective on average, exposure-based treatments do not work equally well for all patients with anxiety disorders. The identification of pre-treatment response-predicting patient characteristics may enable patient stratification. Preliminary research highlights the relevance of inhibitory fronto-limbic networks as such. We aimed to identify pre-treatment neural signatures differing between exposure treatment responders and non-responders in spider phobia and to validate results through rigorous replication. Data of a bi-centric intervention study comprised clinical phenotyping and pre-treatment resting-state functional connectivity (rsFC) data of n = 79 patients with spider phobia (discovery sample) and n = 69 patients (replication sample). RsFC data analyses were accomplished using the Matlab-based CONN-toolbox with harmonized analyses protocols at both sites. Treatment response was defined by a reduction of >30% symptom severity from pre- to post-treatment (Spider Phobia Questionnaire Score, primary outcome). Secondary outcome was defined by a reduction of >50% in a Behavioral Avoidance Test (BAT). Mean within-session fear reduction functioned as a process measure for exposure. Compared to non-responders and pre-treatment, results in the discovery sample seemed to indicate that responders exhibited stronger negative connectivity between frontal and limbic structures and were characterized by heightened connectivity between the amygdala and ventral visual pathway regions. Patients exhibiting high within-session fear reduction showed stronger excitatory connectivity within the prefrontal cortex than patients with low within-session fear reduction. Whereas these results could be replicated by another team using the same data (cross-team replication), cross-site replication of the discovery sample findings in the independent replication sample was unsuccessful. Results seem to support negative fronto-limbic connectivity as promising ingredient to enhance response rates in specific phobia but lack sufficient replication. Further research is needed to obtain a valid basis for clinical decision-making and the development of individually tailored treatment options. Notably, future studies should regularly include replication approaches in their protocols.

This study investigates the potential of low-cost infrared cameras for non-contact monitoring of blood pressure (BP) in individuals with fragile health, particularly the elderly. Previous research has shown success in developing non-contact BP monitoring using RGB cameras. In this study, the Eulerian Video Magnification (EVM) technique is employed to enhance minor variations in skin pixel intensity in specific facial regions captured by an infrared camera from the forehead and palm. The primary focus of this study is to explore the possibility of using infrared cameras for non-contact BP monitoring under low-light or night-time conditions. We have successfully shown that by employing a series of straightforward signal processing techniques and regression analysis, we were able to achieve commendable outcomes in our experimental setup. Specifically, we were able to surpass the stringent accuracy standards set forth by the British Hypertension Society (BHS) and the Association for the Advancement of Medical Instrumentation (AAMI) protocol.

Abstract Objective It is heavily discussed whether larger variety or specialization benefit elite performance at peak age. Therefore, this study aimed to determine technical (number of different swimming strokes) and physiological (number of different race distances) variety required to become an international-class swimmer (> 750 swimming points) based on 1′522′803 race results. Results Correlation analyses showed lower technical variety in higher ranked swimmers (P

Abstract The neutrophil-to-lymphocyte ratio(NLR) is increased in chronic inflammation and myeloproliferative neoplasms (MPN). We hypothesize that NLR is associated with all-cause mortality and mortality by comorbidity burden in the general population and individuals with MPN. We included 835,430 individuals from The Danish General Suburban Population Study, general practitioners, and outpatient clinics. We investigated NLR on mortality stratified by prevalent and incident MPN, essential thrombocythemia (ET), polycythemia vera (PV), myelofibrosis (MF), comorbidity burden (CCI-score), and the Triple-A risk score using hazard ratio (HR) and 95% confidence interval (95%CI). NLR 1–1.9 was the reference level. During a median follow-up of 11.2 years, 197,802 deaths were recorded. All-cause mortality increased for a stepwise increasing NLR with a HR (95%CI) for NLR ≥ 6 of 2.06(2.03–2.09) for the whole population and 2.93(2.44–3.50) in prevalent MPN. ET, PV, and MF had a HR (95%CI) for NLR ≥ 2 of 2.14(1.71–2.69), 2.19(1.89–2.54), and 2.31(1.91–2.80). Results were similar for incident MPN. Mortality was higher for stepwise increasing NLR and CCI-score(p interaction

Abstract Artificial communication with the brain through peripheral nerve stimulation shows promising results in individuals with sensorimotor deficits. However, these efforts lack an intuitive and natural sensory experience. In this study, we design and test a biomimetic neurostimulation framework inspired by nature, capable of “writing” physiologically plausible information back into the peripheral nervous system. Starting from an in-silico model of mechanoreceptors, we develop biomimetic stimulation policies. We then experimentally assess them alongside mechanical touch and common linear neuromodulations. Neural responses resulting from biomimetic neuromodulation are consistently transmitted towards dorsal root ganglion and spinal cord of cats, and their spatio-temporal neural dynamics resemble those naturally induced. We implement these paradigms within the bionic device and test it with patients (ClinicalTrials.gov identifier NCT03350061). He we report that biomimetic neurostimulation improves mobility (primary outcome) and reduces mental effort (secondary outcome) compared to traditional approaches. The outcomes of this neuroscience-driven technology, inspired by the human body, may serve as a model for advancing assistive neurotechnologies.

Abstract Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.

Abstract Background This prospective study aimed to evaluate the influence of the computer type (tablet or desktop) on accuracy and tracing time of cephalometric analyses. Methods Dental students used a web-based application specifically developed for this purpose to perform cephalometric analyses on tablet and desktop computers. Landmark locations and timestamps were exported to measure the accuracy, successful detection rate and tracing time. Reference landmarks were established by six experienced orthodontists. Statistical analysis included reliability assessment, descriptive statistics, and linear mixed effect models. Results Over a period of 8 semesters a total of 277 cephalometric analyses by 161 students were included. The interrater reliability of the orthodontists establishing the reference coordinates was excellent (ICC > 0.9). For the students, the mean landmark deviation was 2.05 mm and the successful detection rate for the clinically acceptable threshold of 2 mm suggested in the literature was 68.6%, with large variations among landmarks. No effect of the computer type on accuracy and tracing time of the cephalometric analyses could be found. Conclusion The use of tablet computers for cephalometric analyses can be recommended.

Objective/Background: Preference for extended-release, once-nightly sodium oxybate (ON-SXB, FT218) vs twice-nightly immediate-release (IR) oxybate was assessed in participants switching from IR oxybate to ON-SXB in an open-label/switch study, RESTORE (NCT04451668). Patients/Methods: Participants aged ≥16 years with narcolepsy who completed the phase 3 REST-ON trial, were oxybate-naive, or were on a stable IR oxybate dose (≥1 month) were eligible for RESTORE. For participants who switched from twice-nightly dosing to ON-SXB, initial doses were closest or equivalent to their previous nightly IR oxybate dose. These participants completed a questionnaire at baseline about nocturnal adverse events associated with the middle-of-the-night IR oxybate dose in the preceding 3 months, a preference questionnaire after 3 months of stable-dose ON-SXB, and an end-of-study (EOS) questionnaire. Results: There were 130 switch participants; 92/98 (93.9 %) who completed the preference questionnaire preferred ON-SXB. At baseline, 69.2 % reported missing their second IR oxybate dose at least once; in these cases, 80 % felt worse the next day. Approximately 39 % reported taking a second nightly IR oxybate dose >4 h after the first dose, 51 % of whom felt somewhat to extremely groggy/unsteady the next morning; 120 participants (92 %) reported getting out of bed after their second oxybate dose. Of those, 9 (8 %) reported falls and 5 (4 %) reported injuries. Of the switch participants who completed the EOS questionnaire, 91.2 % felt better able to follow the recommended ON-SXB dosing schedule. Conclusions: The second nightly IR oxybate dose presents significant treatment burdens and adherence concerns. Participants overwhelmingly preferred the once-nightly dosing regimen of ON-SXB.

Glaucoma is the leading cause of blindness worldwide. However, its surgical treatment, in particular via trabeculectomy, can be complicated by fibrosis. In current clinical practice, application of the drug, Mitomycin C, prevents or delays fibrosis, but can lead to additional side effects, such as bleb leakage and hypotony. Previous in silico drug screening and in vitro testing has identified the known antibiotic, josamycin, as a possible alternative antifibrotic medication with potentially fewer side effects. However, a suitable ocular delivery mechanism for the hydrophobic drug to the surgical site does not yet exist. Therefore, the focus of this paper is the development of an implantable drug delivery system for sustained delivery of josamycin after glaucoma surgery based on crosslinked γ-cyclodextrin. γ-Cyclodextrin is a commonly used solubilizer which was shown to complex with josamycin, drastically increasing the drug’s solubility in aqueous solutions. A simple γ-cyclodextrin crosslinking method produced biocompatible hydrogels well-suited for implantation. The crosslinked γ − cyclodextrin retained the ability to form complexes with josamycin, resulting in a 4-fold higher drug loading efficiency when compared to linear dextran hydrogels, and prolonged drug release over 4 days.

AbstractPurpose This study investigates how the COVID-19 pandemic (CP) impacted the timeline between initial diagnosis (ID) of prostate carcinoma and subsequent therapy consultation (TC) or radical prostatectomy (RP) due to the implementation of a “minimal contact concept,” which postponed clinical examinations until the day of admission.Methods We analyzed patient data from a tertiary care center from 2018 to September 2021. The focus was on comparing the time intervals from ID to TC and from ID to RP before and during the CP.Results Of 12,255 patients, 6,073 (61.6%) were treated before and 3,791 (38.4%) during the CP. The median time from ID to TC reduced from 37 days (IQR: 21 – 58d) pre-CP to 32 days (IQR: 20 – 50d) during CP (p

IntroductionThe aim of this study was to analyze age-associated myocardial injury and clinical outcome after non-ST-elevation myocardial infarction (NSTEMI).MethodsThis prospective, multicenter study consists of 440 patients with NSTEMI enrolled at 7 centers. All patients were treated with primary percutaneous coronary intervention and underwent cardiac magnetic resonance (CMR) imaging 1–10 days after study inclusion. CMR parameters of myocardial injury and clinical outcome were evaluated by creating 2 subgroups:

Examination of livelihood assets is crucial for displaced people as it informs effective resource allocation and support. This study investigates the livelihood decisions of households displaced by Nepal's Tanahu Hydropower Project using multinomial logistic regression to evaluate how different assets affect their choices. Data were obtained using questionnaires, with a total of 185 questionnaires used for the analysis in this study. Descriptive and inferential statistics were used for data analysis. This study finds that physical assets substantially influence livelihood strategies, promoting diversification and nonfarming activities. Interestingly, social assets have a negative impact, whereas natural, financial, and human assets exert no significant effect. The study highlights the community's focus on economic stability, balancing immediate financial needs with long-term goals such as children's education. However, it reveals ongoing financial struggles, with an average daily income of only 1.962 USD and many households remaining in poverty, particularly those dependent on farming. The study also reflects on the mixed perceptions toward government policies, influenced by factors such as skill gaps and family aspirations. These findings provide essential insights for targeted support and resource allocation to displaced populations.

Abstract Equipping otherwise passive surfaces with electronic functionality enables advanced interactive robotics, consumer products, sensor skins, and structural health monitoring. Concurrently, the rapidly growing number of electronic devices fuels the search for sustainable materials and processes that aid in reducing electronic waste. Wood is CO2‐neutral, omnipresent in the construction industry, in furniture, musical instruments, or packaging, yet so far, its potential for direct integration with electronics remains largely unexplored. Complications arise as traditional methods of equipping wood with electronics often compromise structural integrity and thus limit applications requiring load‐bearing capabilities. Here, seamless fabrication methods that allow the direct enhancement of wooden surfaces with electrically conducting structures, sensors, and microelectronic components based on screen printing of conducting inks or physical vapor deposition of thin metal films in conjunction with laser engraving are presented. Such electronic circuits imperceptibly operate on the surface of structural elements or as parts of decorative wooden furniture. These types of electronic wooden surfaces enable touch‐sensing applications, monitoring temperature, or the curing of varnishes without compromising functionality and mechanical stability. This multidisciplinary approach opens up new avenues for the development of smart wooden structures with embedded electronics, revolutionizing the way it is monitored, controlled, and interacted with wood‐based constructions.

Objectives This scoping review aimed to identify and critically appraise resources for health professionals to identify, diagnose, refer, and support individuals with fetal alcohol spectrum disorder (FASD)—including the extent to which the resources are appropriate for use in communities with First Nations Peoples.Method Seven peer-reviewed databases (April 2022) and 14 grey literature websites (August 2022) were searched. The reference lists of all sources that underwent full-text review were handsearched, and FASD experts were consulted for additional sources. Resources were assessed using the Appraisal of Guidelines for REsearch and Evaluation II instrument and an adapted version of the National Health and Medical Research Council FORM Framework and iCAHE Guideline Quality Checklist.Results A total of 41 resources underwent data extraction and critical appraisal, as screening and/or diagnosis guidelines were excluded because they are covered in other reviews. Most were recently published or updated (n=24), developed in the USA (n=15, 36.6%) or Australia (n=12, 29.3%) and assisted with FASD patient referral or support (n=40). Most management guidelines scored 76%–100% on overall quality assessment (n=5/9) and were recommended for use in the Australian context with modifications (n=7/9). Most of the guides (n=15/22) and factsheets (n=7/10) received a ‘good’ overall score. Few (n=3/41) resources were explicitly designed for or with input from First Nations Australians.Conclusion High-quality resources are available to support health professionals providing referrals and support to individuals with FASD, including language guides. Resources should be codesigned with people living with FASD to capture and integrate their knowledge and preferences.

The digital economy and energy are crucial drivers of economic transformation, and the global development trend is toward the deep integration of the two. Previous studies carried out at the provincial scale, show it is difficult to grasp the change characteristics of prefecture-level cities. From the scale of urban agglomeration, energy management problems in different regions can be more accurately grasped. This study examines the Beijing-Tianjin-Hebei area and its seven surrounding regions, commonly known as the “2 + 26” cities. Panel data from 28 prefecture-level cities between 2011 and 2019 are utilized for analysis. First, the area's energy efficiency was assessed using the DEA-SBM model. Second, the development coordination relationship among the digital system and energy system is evaluated by using the coupling coordination degree model. Finally, the process of coupling coordination of digital-energy systems affecting energy efficiency was examined using a three-step stepwise regression and bootstrap mediation model. The findings demonstrate that: (1) The “2 + 26” cities' energy efficiency is considerably different. The distribution of the high efficiency zone changes from “high in the south and low in the north” to the state of radiating southward with Beijing and Tianjin as the center. (2) “2 + 26” cities are in the dynamic evolution stage of low to medium coupling degree, accounting for 89.3 % of all cities. The coupling coordination degree of digital-energy system has increased throughout the entire city by 49 %. (3) Energy efficiency improved by 64.7 % while the coupling coordination degree of the digital energy system grew by 1 %. The total effect of technical efficiency changes on energy efficiency accounted for 8.2 %. The research results could provide differentiated policy recommendations for regional energy use.

Data-based predictions of individual Cognitive Behavioral Therapy (CBT) treatment response are a fundamental step towards precision medicine. Past studies demonstrated only moderate prediction accuracy (i.e. ability to discriminate between responders and non-responders of a given treatment) when using clinical routine data such as demographic and questionnaire data, while neuroimaging data achieved superior prediction accuracy. However, these studies may be considerably biased due to very limited sample sizes and bias-prone methodology. Adequately powered and cross-validated samples are a prerequisite to evaluate predictive performance and to identify the most promising predictors. We therefore analyzed resting state functional magnet resonance imaging (rs-fMRI) data from two large clinical trials to test whether functional neuroimaging data continues to provide good prediction accuracy in much larger samples. Data came from two distinct German multicenter studies on exposure-based CBT for anxiety disorders, the Protect-AD and SpiderVR studies. We separately and independently preprocessed baseline rs-fMRI data from n = 220 patients (Protect-AD) and n = 190 patients (SpiderVR) and extracted a variety of features, including ROI-to-ROI and edge-functional connectivity, sliding-windows, and graph measures. Including these features in sophisticated machine learning pipelines, we found that predictions of individual outcomes never significantly differed from chance level, even when conducting a range of exploratory post-hoc analyses. Moreover, resting state data never provided prediction accuracy beyond the sociodemographic and clinical data. The analyses were independent of each other in terms of selecting methods to process resting state data for prediction input as well as in the used parameters of the machine learning pipelines, corroborating the external validity of the results. These similar findings in two independent studies, analyzed separately, urge caution regarding the interpretation of promising prediction results based on neuroimaging data from small samples and emphasizes that some of the prediction accuracies from previous studies may result from overestimation due to homogeneous data and weak cross-validation schemes. The promise of resting-state neuroimaging data to play an important role in the prediction of CBT treatment outcomes in patients with anxiety disorders remains yet to be delivered.

Abstract Background Several clinical prognostic models for diffuse large B‐cell lymphoma (DLBCL) have been proposed, including the most commonly used International Prognostic Index (IPI), the National Comprehensive Cancer Network IPI (NCCN‐IPI), and models incorporating beta‐2 microglobulin (β2M). However, the role of β2M in DLBCL patients is not fully understood. Methods We identified 6075 patients with newly diagnosed DLBCL treated with immunochemotherapy registered in the Danish Lymphoma Registry. Results A total of 3232 patients had data available to calculate risk scores from each of the nine considered risk models for DLBCL, including a model developed from our population. Three of four models with β2M and NCCN‐IPI performed better than the International Prognostic Indexes (IPI, age‐adjusted IPI, and revised IPI). Five‐year overall survival for high‐ and low‐risk patients were 43.6% and 86.4% for IPI and 34.9% and 96.2% for NCCN‐IPI. In univariate analysis, higher levels of β2M were associated with inferior survival, higher tumor burden (advanced clinical stage and bulky disease), previous malignancy and increased age, and creatinine levels. Furthermore, we developed a model (β2M‐NCCN‐IPI) by adding β2M to NCCN‐IPI (c‐index 0.708) with improved discriminatory ability compared to NCCN‐IPI (c‐index 0.698, p

IntroductionTrail running is an emerging discipline with relatively few studies performed in ecological conditions. The aim of this work was to investigate if and how spatiotemporal parameters (STP) and kinematics differ between initial and final stage of a field trial.MethodsTwenty trail runners (10 F, 10 M) were recruited and ran a solo 9.1 km trial. During the test, participants wore a GPS watch and an IMU-based motion capture system. Running speed, elapsed time, STP and kinematics were compared between initial and final stage, separately for uphill (UH) and downhill (DH) sections.ResultsRunning speed decreased in the final stage (p

Various copper oxide nanotube/indium tin oxide (CuO/ITO) nanocomposite-based chemiresistive gas sensors were fabricated and tested toward hydrogen sulfide (H2S) in the presence and absence of ultra-violet (UV) light excitation at room temperature. Among these different combinations, 60:40 wt.% of CuO:ITO showed the highest sensing performance toward H2S gas (i.e., sensor response (S) = 5.7 toward 40 ppmm (parts per million by mass) H2S gas), which is ̴5.7 times higher than pristine CuO and ITO counterparts. The enhancement in the gas sensing performance by mixing ITO and CuO nanostructures might be due to the formation of p/n heterojunction between ITO nanoparticles and CuO nanotubes. The low limit of detection (LLOD) of 500 ppbm (part per billion by mass) of S = 1.2 was experimentally achieved by photo exciting sensing materials using 400 nm UV light. This might be attributed to the faster adsorption of H2S molecules and higher carrier concentration under light illumination. These sensors also maintained good H2S sensing performance in the presence of water vapors which makes these sensors suitable for practical application. This work paves a way to fabricate low-power H2S gas sensors by eliminating heaters.

Background: Trabecular metal augments (TMAs) have been extensively used in revision total hip arthroplasty (THA) to address acetabular bone defects. However, limited data exists regarding TMA utilization during primary THA. This study aims to assess the clinical and radiographic outcomes of TMAs used during primary THA. Methods: A single-institution retrospective case series of primary THA patients treated with TMA between 2010 and 2019 was performed. Patient demographics, complications, and revisions were recorded. Cup position, center of rotation, leg length, and radiolucent lines were assessed radiographically. The Kaplan-Meier method was used to compute implant survivorship. Results: Twenty-six patients (30 hips) were included with average age of 52.6 ± 15.3 years (range: 22-78) and mean follow-up of 4.1 ± 2.1 years (range: 2.0-8.9). Most TMAs were indicated for developmental dysplasia of the hip (n = 18; 60.0%). On average, hip center of rotation was lowered 1.5 ± 1.3 cm and lateralized 1.2 ± 1.5 cm, while leg length and global offset were increased by 2.4 ± 1.2 cm and 0.4 ± 1.0 cm, respectively. At final follow-up, 3 hips (10.0%) required revision: one (3.3%) for aseptic loosening and 2 (6.7%) for instability. No patients had progressive radiolucent lines at final follow-up. Five-year survival with aseptic loosening and all-cause revision as endpoints was 100% (95% confidence interval: 90.0%-100.0%) and 92.1% (95% confidence interval: 81.3%-100.0%), respectively. One patient required revision for aseptic loosening after the 5-year mark. Conclusions: Trabecular metal augmentation during primary THA demonstrates satisfactory early to mid-term outcomes. TMA is a viable option for complex primary THA when bone loss is encountered or secondary support is required. Level of Evidence: Level IV.

Since the the dawn of the 21st century, water security has occupied a pivotal position in fostering sustainable development. However, frequency of extreme weather events due to climate change and higher intensity of anthropogenic events, water security problems in Northwest China are becoming increasingly prominent. This paper elucidates water security levels and predicts future trends of Northwest China. Firstly, the Driving Force-Pressure-State-Impact-Response (DPSIR) conceptual framework served as the foundation for the establishment of the water security evaluation index system. Then used the entropy weight method to calculate the weight of indicators and the five-element connection degree method was used to assess the water security levels. The period for the data used in the study was from 2010 to 2019. Finally, a grey prediction model was employed to forecast the water security levels from 2023 to 2030. The findings showed that: (1) From 2010 to 2019, the water security situation gradually developed to a very high level in Northwest China: Shaanxi Province mostly attained a high level, and the water security grades of Ningxia Hui Autonomous Region and Xinjiang Uygur Autonomous Region were mostly at a very low level. (2) Generally, from 2023 to 2030, the water security level will continue to improve. The water security grades of Shaanxi, Gansu, and Qinghai will mostly be at the medium level, while that of Ningxia Hui Autonomous Region and Xinjiang Uygur Autonomous Region will be at the low level. (3) The five dimensions of water security in Northwest China demonstrated a fluctuating yet consistently upward trend. (4) Based on the results, suggestions were put forward regarding water security and sustainable development in Northwest China.

Neovascular age-related macular degeneration (nAMD) is a frequent cause of vision loss among the elderly in the Western world. Current disease management with repeated injections of anti-VEGF agents accumulates the risk for adverse events and constitutes a burden for society and the individual patient. Sustained suppression of VEGF using gene therapy is an attractive alternative, which we explored using adeno-associated virus (AAV)-based delivery of novel RNA interference (RNAi) effectors in a porcine model of choroidal neovascularization (CNV). The potency of VEGFA-targeting, Ago2-dependent short hairpin RNAs placed in pri-microRNA scaffolds (miR-agshRNA) was established in vitro and in vivo in mice. Subsequently, AAV serotype 8 (AAV2.8) vectors encoding VEGFA-targeting or irrelevant miR-agshRNAs under the control of a tissue-specific promotor were delivered to the porcine retina via subretinal injection before CNV induction by laser. Notably, VEGFA-targeting miR-agshRNAs resulted in a significant and sizable reduction of CNV compared with the non-targeting control. We also demonstrated that single-stranded and self-complementary AAV2.8 vectors efficiently transduce porcine retinal pigment epithelium cells but differ in their transduction characteristics and retinal safety. Collectively, our data demonstrated a robust anti-angiogenic effect of VEGFA-targeting miR-aghsRNAs in a large translational animal model, thereby suggesting AAV-based delivery of anti-VEGFA RNAi therapeutics as a valuable tool for the management of nAMD.

Tungsten trioxide (WO3) is one of most widely investigated metal oxide semiconductors as gas sensing material because of tunable sensing performance toward different analytes through composition modulation (e.g., dopants) and various morphology and crystallinity. In this work, we synthesized WO3 nanofibers with different diameter and crystallinity through electrospinning of ammonium metatungstate hydrate (AMH)/polyvinyl pyrrolidone (PVP) nanofibers via design of experiments (DOE) followed by thermal heat treatment with the smaller average diameter being 23.0 nm. Through varying the calcination process, WO3 nanofibers with different crystallinity were also synthesized, with the smaller average grain size being 23.0 nm. These nanofibers were then exposed to many analytes (i.e., H2S, acetone, toluene, ethanol, ethyl benzene, NO2, NO, and methane) under different operating temperatures (i.e., 250 to 450 °C) to investigate their effect toward sensing response. These systematic studies indicated that nanocrystalline WO3 nanofibers with the smaller diameter (i.e., 20 nm) and/or smaller average grain sizes (i.e.,18.7 nm) exhibited best sensing performance independent of target analytes. The barrier energy was also correlated with the gas sensing performance experimentally.

ObjectiveThis study aimed to investigate the impact of early vestibular rehabilitation training combined with corticosteroids initiated within 2 weeks, compared with corticosteroid treatment, after the peripheral acute vestibular syndrome (pAVS) onset.Data sourcesPubMed, CINAHL, EMBASE, and SCOPUS. From inception to January 24, 2024. The International Prospective Register of Systematic Reviews approved this study (CRD42023422308).ResultsFive studies involving 235 patients were included in this systematic review and meta-analysis. The subjective outcome measure Dizziness Handicap Inventory (DHI) was pooled for a meta-analysis and was statistically significantly in favor of early vestibular rehabilitation training (early VRT) plus corticosteroids compared with corticosteroids alone: at one-month follow-up (p = 0.00) and 12 months follow-up (p = 0.01). DHI was a critical outcome for measuring the differences in effect of early VRT. The objective outcome measures of caloric lateralization, cervical vestibular-evoked myogenic potentials, and posturography were gathered for a narrative synthesis.ConclusionThis meta-analysis showed that early VRT in combination with corticosteroids was more effective for treating pAVS than corticosteroid treatment alone. No adverse effects were reported for early VRT.

An appropriately designed pharmacokinetic (PK) assay that is sensitive for anti-drug antibody (ADA) impact on relevant exposure is an alternative strategy to understand the neutralizing potential of ADAs. However, guidance on how to develop such PK assays and how to confirm the functional ADA impact on exposure is missing. Here, the PK assay of a T-cell-engaging bispecific antibody, cibisatamab, was developed based on its mechanism of action (MoA). Using critical monoclonal anti-idiotypic (anti-ID) antibody positive controls as ADA surrogates, the impact on exposure was evaluated pre-clinically. In a phase I clinical trial (NCT02324257), initial data suggest that the combination of ADA and PK assays for correlation of the ADA response with cibisatamab exposure. To understand the neutralizing potential of patient-derived ADAs on drug activity, advanced ADA characterization has been performed. Structural binding analysis of ADAs to antibody domains of the drug and its impact on targeting were assessed. For this purpose, relevant patient ADA binding features were identified and compared with the specific monoclonal anti-ID antibody-positive controls. Comparable results of target binding inhibition and similar impacts on exposure suggest that the observed reduction of Cmax and Ctrough levels in patients is caused by the neutralizing potential of ADAs and allows a correlation between ADA response and loss of exposure. Therefore, the described study provides important functional aspects for the development of an appropriately designed PK assay for bispecific antibodies as an alternative option towards understanding the neutralizing ADA impact on exposure.

IntroductionMuscle invasive bladder cancer (MIBC) remains a prevalent cancer with limited therapeutic options, obviating the need for innovative therapies. The epidermal growth factor receptor (EGFR) is a linchpin in tumor progression and presents a potential therapeutic target in MIBC. Additionally, the EGFR ligands AREG and EREG have shown associations with response to anti-EGFR therapy and improved progression-free survival in colorectal carcinoma.Materials and methodsWe investigated the prognostic significance of EGFR, AREG, and EREG in MIBC. Gene expression and copy number analyses were performed via qRT-PCR on tissue samples from 100 patients with MIBC who underwent radical cystectomy at the University Hospital Mannheim (MA; median age 72, interquartile range [IQR] 64–78 years, 25% female). Results were validated in 361 patients from the 2017 TCGA MIBC cohort (median age 69, IQR 60–77 years, 27% female), in the Chungbuk and MDACC cohort. Gene expressions were correlated with clinicopathologic parameters using the Mann-Whitney test, Kruskal-Wallis- test and Spearman correlation. For overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) gene expression was analyzed with Kaplan-Meier and Cox-proportional hazard models.ResultsSignificant gene expression differences in EGFR, AREG, and EREG could be detected in all cohorts. In the TCGA cohort, EGFR expression was significantly elevated in patients with EGFR amplification and KRAS wildtype. High AREG expression independently predicted longer OS (HR = 0.35, CI 0.19 - 0.63, p = 0.0004) and CSS (HR = 0.42, CI 0.18 – 0.95, p = 0.0378) in the MA cohort. In the TCGA cohort, high EGFR, AREG, and EREG expression correlated with shorter OS (AREG: HR = 1.57, CI 1.12 – 2.20, p = 0.0090) and DFS (EGFR: HR = 1.91, CI 1.31 – 2.8, p = 0.0008). EGFR amplification was also associated with reduced DFS.DiscussionHigh EGFR and EREG indicate worse survival in patients with MIBC. The prognostic role of AREG should further be investigated in large, prospective series. Divergent survival outcomes between the four cohorts should be interpreted cautiously, considering differences in analysis methods and demographics. Further in vitro investigations are necessary to elucidate the functional mechanisms underlying the associations observed in this study.

The challenges faced by universities and private industry in estimating their emissions for decarbonisation are similar, but the task of linking emissions to university operations, namely procurement, is complex and time-consuming due to the wide range and types of purchases. Here, participatory action research is used to address these challenges, with a group of Danish universities to investigate the functions and improve the completeness of university GHG inventories. The research enabled knowledge sharing and collaboration, leading to a better understanding of the complexities and possibilities of GHG inventories. The main conclusions drawn from discussions are that the GHG inventory should serve multiple functions; an inward-facing decision support material, and an externally-facing communication tool. EXIOBASE, an environmentally extended input-output model, was identified as a useful tool for future inventories, particularly in procurement, due to its comprehensive spend-based assessment of purchases also relevant to universities. With more universities adopting spend-based practices, the presented conclusions shed light on potential risks of this method that have not yet been discussed in this context. A consensus on methodological trade-offs, relevant activities, and data considerations for a GHG inventory are reached and reflected on. As suppliers can increasingly deliver product specific climate related information, a data ontology is needed to appropriately incorporate supplier-specific data into consistent inventories without conflicting with methodological principles and upholding proprietary requirements of suppliers. Addressing challenges identified through this collaborative investigation will expand on the dialogue in the literature and help shape how universities conduct and use GHG inventories. Keywords: Sustainable university; Action Research; Consequential Attributional; GHG Protocol.

Objectives: Although diversity has been demonstrated to benefit research groups, women remain underrepresented in most scientific disciplines, including Laboratory Medicine and Clinical Chemistry. In order to promote diversity and equality in scientific communities, understanding the gender distribution of authorship is crucial. Methods: This study included a total of 30,268 Web of Science-listed Clinical Chemistry and Laboratory Medicine publications from the United States of America, Canada, and the member countries of the European Federation of Clinical Chemistry and Laboratory Medicine from 2005 to 2022. In addition to the publication productivity of female and male authors over time, gender-specific publication characteristics and country-specific gender distributions of authorships were examined. Results: Overall, publications with female first authors increased by 49 % between 2005 and 2022, averaging 42 % female first authors. Eastern Europe (60 %) and Southern Europe (51 %) had particularly high proportions of female first authors. While female last authorship was the most predictive of female first authorship, with an odds ratio of 2.01 (95 % CI: 1.91–2.12, p

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83–0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.

IntroductionThe Philadelphia chromosome-negative myeloproliferative neoplasms are a group of slowly progressing haematological malignancies primarily characterised by an overproduction of myeloid blood cells. Patients are treated with various drugs, including the JAK1/2 inhibitor ruxolitinib. Mathematical modelling can help propose and test hypotheses of how the treatment works.Materials and methodsWe present an extension of the Cancitis model, which describes the development of myeloproliferative neoplasms and their interactions with inflammation, that explicitly models progenitor cells and can account for treatment with ruxolitinib through effects on the malignant stem cell response to cytokine signalling and the death rate of malignant progenitor cells. The model has been fitted to individual patients’ data for the JAK2 V617F variant allele frequency from the COMFORT-II and RESPONSE studies for patients who had substantial reductions (20 percentage points or 90% of the baseline value) in their JAK2 V617F variant allele frequency (n = 24 in total).ResultsThe model fits very well to the patient data with an average root mean square error of 0.0249 (2.49%) when allowing ruxolitinib treatment to affect both malignant stem and progenitor cells. This average root mean square error is much lower than if allowing ruxolitinib treatment to affect only malignant stem or only malignant progenitor cells (average root mean square errors of 0.138 (13.8%) and 0.0874 (8.74%), respectively).DiscussionSystematic simulation studies and fitting of the model to the patient data suggest that an initial reduction of the malignant cell burden followed by a monotonic increase can be recapitulated by the model assuming that ruxolitinib affects only the death rate of malignant progenitor cells. For patients exhibiting a long-term reduction of the malignant cells, the model predicts that ruxolitinib also affects stem cell parameters, such as the malignant stem cells’ response to cytokine signalling.

Elite winter sports have become increasingly professionalized and commercialized, often accompanied by congested competition schedules. This has brought the topic of load management, i.e., planning, monitoring, and adaptation, enormous attention in the scientific community. In this review, we summarize the general knowledge from various sports about training load and its effects on injuries and illnesses. After outlining the fundamentals of load monitoring, we present common monitoring tools, i.e., neuromuscular performance tests, heart rate measures, blood-based biomarkers, and questionnaires and discuss their potentials and pitfalls in application. Studies have identified training load-related variables, but also other factors such as travelling, previous injuries, or age contributing to the occurrence of illness and injury. Based on our findings, the use of monitoring tools must be context-specific and long-term, considering statistical aspects as well. Promising study designs and future perspectives are finally highlighted, with the general conclusion that there is still a clear need for research on this topic in general and in the field of winter sports in particular.

Abstract Loess-paleosol sequences have been used in Asia to study climate and environmental changes during the Quaternary. The scarcity of age control datasets and proxy indices analysis data for Asian loess has limited our understanding of loess depositional processes and the reconstruction of paleoclimatic changes from loess-paleosol records. In this study, we present a dataset that includes 1785 quartz optically stimulated luminescence ages and 1038 K-feldspar post-infrared infrared stimulated luminescence ages from 128 loess-paleosol sequences located in different regions of Asia. We generate 38 high-resolution age-depth models of loess records based on the provided datasets. We provide data on 12,365 grain size records, 14,964 magnetic susceptibility records, 2204 CaCO3 content records, and 3326 color reflection records. This dataset contains the most detailed and accurate chronologies and proxy index data for loess records in Asia yet published. It provides fundamental data for understanding the spatial-temporal variations in loess depositional processes and climatic changes across the continent during the mid-late Quaternary.