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Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Therapeutic options for PDAC are primarily restricted to surgery in the early stages of the disease or chemotherapy in advanced disease. Only a subset of patients with germline defects in BRCA1/2 genes can potentially benefit from personalized therapy, with the PARP inhibitor olaparib serving as a maintenance treatment for metastatic disease. Although the role of radiotherapy in PDAC remains controversial, the use of radiosensitizers offers hope for improving cancer management. Previously, we have shown that damage-specific DNA binding protein 2 (DDB2) is a potential prognostic and predictive biomarker for chemotherapy response in PDAC. In this study, we investigated the function of DDB2 in radiotherapy response, with and without radiosensitization by olaparib in PDAC cells. Our findings demonstrated DDB2 resistance to radiation effects, thereby improving cell survival and enhancing the repair of ionizing radiation-induced DNA double-strand breaks. We observed that DDB2 expression enhances the cell cycle arrest in the G2 phase by phosphorylating Chk1 and Chk2 cell cycle checkpoints. Additionally, we identified a novel link between DDB2 and PARP1 in the context of radiotherapy, which enhances the expression and activity of PARP1. Our findings highlight the potential of low-DDB2 expression to potentiate the radiosensitization effect of olaparib in PDAC cells. Collectively, this study provides novel insights into the impacts of DDB2 in the radiotherapy response in PDAC, enabling its employment as a potential biomarker to predict resistance to radiation. Furthermore, DDB2 represents a significant step forward in precision radiotherapy by widening the scope of patients who can be benefiting from olaparib as a radiosensitizer. Hence, this research has the potential to enrich the limited use of radiotherapy in the care of patients with PDAC.

Abstract The standard method for identifying active Brown Adipose Tissue (BAT) is [18F]-Fluorodeoxyglucose ([18F]-FDG) PET/CT imaging, which is costly and exposes patients to radiation, making it impractical for population studies. These issues can be addressed with computational methods that predict [18F]-FDG uptake by BAT from CT; earlier population studies pave the way for developing such methods by showing some correlation between the Hounsfield Unit (HU) of BAT in CT and the corresponding [18F]-FDG uptake in PET. In this study, we propose training convolutional neural networks (CNNs) to predict [18F]-FDG uptake by BAT from unenhanced CT scans in the restricted regions that are likely to contain BAT. Using the Attention U-Net architecture, we perform experiments on datasets from four different cohorts, the largest study to date. We segment BAT regions using predicted [18F]-FDG uptake values, achieving 23% to 40% better accuracy than conventional CT thresholding. Additionally, BAT volumes computed from the segmentations distinguish the subjects with and without active BAT with an AUC of 0.8, compared to 0.6 for CT thresholding. These findings suggest CNNs can facilitate large-scale imaging studies more efficiently and cost-effectively using only CT.

Abstract Background Extreme Risk Protection Orders (ERPOs) are civil court orders that prohibit firearm purchase and possession when someone is behaving dangerously and is at risk of harming themselves and/or others. As of June 2024, ERPOs are available in 21 states and the District of Columbia to prevent firearm violence. This paper describes the design and protocol of a six-state study of ERPO use. Methods The six states included are California, Colorado, Connecticut, Florida, Maryland, and Washington. During the 3-year project period (2020–2023), ERPO case files were obtained through public records requests or through agreements with agencies with access to these data in each state. A team of over four dozen research assistants from seven institutions coded 6628 ERPO cases, abstracting 80 variables per case under domains related to respondent characteristics, events and behaviors leading to ERPO petitions, petitioner types, and court outcomes. Research assistants received didactic training through an online learning management system that included virtual training modules, quizzes, practice coding exercises, and two virtual synchronous sessions. A protocol for gaining strong interrater reliability was used. Research assistants also learned strategies for reducing the risk of experiencing secondary trauma through the coding process, identifying its occurrence, and obtaining help. Discussion Addressing firearm violence in the U.S. is a priority. Understanding ERPO use in these six states can inform implementation planning and ERPO uptake, including promising opportunities to enhance safety and prevent firearm-related injuries and deaths. By publishing this protocol, we offer detailed insight into the methods underlying the papers published from these data, and the process of managing data abstraction from ERPO case files across the multi-state and multi-institution teams involved. Such information may also inform future analyses of this data, and future replication efforts. Registration This protocol is registered on Open Science Framework ( https://osf.io/kv4fc/ ).

Abstract Cognitive behavioral therapy improves psychosocial outcomes in rheumatoid arthritis (RA), but access is limited. We conducted a randomized controlled trial to evaluate the efficacy of a cognitive-behavioral digital therapeutic, reclarit, on psychosocial outcomes in adult RA patients with impaired health-related quality of life. Participants were randomized to reclarit plus treatment as usual (TAU) or TAU plus educational and informational material (active control). The primary outcome was SF-36 mental (MCS) and physical (PCS) component summary scores at 3 months, with additional assessments at 6 months. reclarit significantly improved SF-36 MCS scores compared to control (mean difference 3.3 [95% CI 0.7, 5.9]; p = 0.014), with high user satisfaction and sustained improvements at 6 months. Depression, anxiety, fatigue, and social/work functioning also improved significantly, while SF-36 PCS, pain, and disability scores did not differ. In conclusion, reclarit offers immediate, effective, evidence-based and personalized psychological support for RA patients.

Abstract Most plants in natural ecosystems associate with arbuscular mycorrhizal (AM) fungi to survive soil nutrient limitations. To engage in symbiosis, AM fungi secrete effector molecules that, similar to pathogenic effectors, reprogram plant cells. Here we show that the Glomeromycotina-specific SP7 effector family impacts on the alternative splicing program of their hosts. SP7-like effectors localize at nuclear condensates and interact with the plant mRNA processing machinery, most prominently with the splicing factor SR45 and the core splicing proteins U1-70K and U2AF35. Ectopic expression of these effectors in the crop plant potato and in Arabidopsis induced developmental changes that paralleled to the alternative splicing modulation of a specific subset of genes. We propose that SP7-like proteins act as negative regulators of SR45 to modulate the fate of specific mRNAs in arbuscule-containing cells. Unraveling the communication mechanisms between symbiotic fungi and their host plants will help to identify targets to improve plant nutrition.

Abstract Background and aim Traffic-related ultrafine particle pollution near highways is associated with adverse health. Reducing exposure by use of portable air purifiers in homes is one approach to reducing this risk. However, the reaction of residents to having air purifiers in homes is not well studied. Methods Within the framework of our randomized crossover trial of air purifiers in homes near a major highway, we collected data about participants’ use and reactions to air purifiers using questionnaires at their 30-day and 90-day home visits, recorded electricity consumption using HOBO monitors, and conducted structured interviews with participants. Results Nearly all 150 participants reported running the air purifiers virtually 24 h every day in both their living room and their bedroom in the prior month. The units’ HOBO electricity use, from a subset of 45 participants, supported the participants’ responses from the questionnaire. Approximately 80% of participants reported setting their air purifier on the medium setting. Tolerance to air purifier noise increased significantly between the 30-day and 90-day home visits, with approximately two thirds reporting not being bothered at all by the noise. The qualitative interviews in a subset of 26 participants yielded consistent responses to those from the questionnaires. Size of unit, airflow, and energy consumption were additional concerns that emerged during the interviews. Conclusions Results from the questionnaires, HOBO data, and structured interviews all suggest participants had positive reactions towards the presence of in-home APs, and therefore may be receptive to using air purifiers in their homes on a regular basis. Trial registration ClinicalTrials.gov, NCT04279249 . Registered 09 October 2019.

Abstract Objective To understand how Long COVID is impacting the health and social conditions of the Black and Latinx communities. Background Emerging research on Long COVID has identified three distinct characteristics, including multi-organ damage, persistent symptoms, and post-hospitalization complications. Given Black and Latinx communities experienced significantly higher COVID rates in the first phase of the pandemic they may be disproportionately impacted by Long COVID. Methods Eleven focus groups were conducted in four languages with diverse Black and Latinx individuals (n = 99) experiencing prolonged symptoms of COVID-19 or caring for family members with prolonged COVID-19 symptoms. Data was analyzed thematically. Results Most participants in non-English language groups reported they were unfamiliar with the diagnosis of long COVID, despite experiencing symptoms. Long COVID impacts spanned financial and housing stability to physical and mental health impacts. Participants reported challenging encounters with health care providers, a lack of support managing symptoms and difficulty performing activities of daily living including work. Conclusions There is a need for multilingual, accessible information about Long COVID symptoms, improved outreach and healthcare delivery, and increased ease of enrollment in long-term disability and economic support programs.

Abstract AI image classification algorithms have shown promising results when applied to skin cancer detection. Most public skin cancer image datasets are comprised of dermoscopic photos and are limited by selection bias, lack of standardization, and lend themselves to development of algorithms that can only be used by skilled clinicians. The SLICE-3D (“Skin Lesion Image Crops Extracted from 3D TBP”) dataset described here addresses those concerns and contains images of over 400,000 distinct skin lesions from seven dermatologic centers from around the world. De-identified images were systematically extracted from sensitive 3D Total Body Photographs and are comparable in optical resolution to smartphone images. Algorithms trained on lower quality images could improve clinical workflows and detect skin cancers earlier if deployed in primary care or non-clinical settings, where photos are captured by non-expert physicians or patients. Such a tool could prompt individuals to visit a specialized dermatologist. This dataset circumvents many inherent limitations of prior datasets and may be used to build upon previous applications of skin imaging for cancer detection.

The implementation of the “power-to-gas” concept, where hydrogen and natural gas are blended and transported in the existing network, requires a quick, on-site method to monitor the content of hydrogen in the mixture. We evaluate a rapid characterisation of this mixture based on the measurement of the speed of sound, using micromachined ultrasonic transducers (MUTs). Two MUT-based prototypes were implemented to analyse a mixture of natural gas and hydrogen under controlled conditions. Changes in the hydrogen content below 2 mol % (in a mixture that was adjusted between 6 mol % and 16 mol %) were discriminated by both devices, including the uncertainty due to the temperature compensation and the time-delay estimation. The obtained values of the speed of sound were consistent with those calculated from independent, non-acoustic measurements performed with a gas chromatograph and a density sensor. An MUT-based flow meter is thus capable of reporting both gas intake and the molar fraction of hydrogen, provided that the source of natural gas is kept constant.

Abstract Despite its high prevalence, the determinants of smelling impairment in COVID-19 remain not fully understood. In this work, we aimed to examine the association between olfactory bulb volume and the clinical trajectory of COVID-19-related smelling impairment in a large-scale magnetic resonance imaging (MRI) analysis. Data of non-vaccinated COVID-19 convalescents recruited within the framework of the prospective Hamburg City Health Study COVID Program between March and December 2020 were analyzed. At baseline, 233 participants underwent MRI and neuropsychological testing as well as a structured questionnaire for olfactory function. Between March and April 2022, olfactory function was assessed at follow-up including quantitative olfactometric testing with Sniffin’ Sticks. This study included 233 individuals recovered from mainly mild to moderate SARS-CoV-2 infections. Longitudinal assessment demonstrated a declining prevalence of self-reported olfactory dysfunction from 67.1% at acute infection, 21.0% at baseline examination and 17.5% at follow-up. Participants with post-acute self-reported olfactory dysfunction had a significantly lower olfactory bulb volume at baseline than normally smelling individuals. Olfactory bulb volume at baseline predicted olfactometric scores at follow-up. Performance in neuropsychological testing was not significantly associated with the olfactory bulb volume. Our work demonstrates an association of long-term self-reported smelling dysfunction and olfactory bulb integrity in a sample of individuals recovered from mainly mild to moderate COVID-19. Collectively, our results highlight olfactory bulb volume as a surrogate marker that may inform diagnosis and guide rehabilitation strategies in COVID-19.

Abstract Background Diabetes mellitus (DM) can impair driving safety due to hypoglycemia, hyperglycemia, diabetic peripheral neuropathy, and diabetic eye diseases. However, few studies have examined the association between DM and driving safety in older adults based on naturalistic driving data. Methods Data for this study came from a multisite naturalistic driving study of drivers aged 65–79 years at baseline. Driving data for the study participants were recorded by in-vehicle recording devices for up to 44 months. We used multivariable negative binomial modeling to estimate adjusted incidence rate ratios (aIRRs) and 95% confidence intervals (CIs) of hard braking events (HBEs, defined as maneuvers with deceleration rates ≥ 0.4 g) associated with DM. Results Of the 2856 study participants eligible for this analysis, 482 (16.9%) reported having DM at baseline, including 354 (12.4%) insulin non-users and 128 (4.5%) insulin users. The incidence rates of HBEs per 1000 miles were 1.13 for drivers without DM, 1.15 for drivers with DM not using insulin, and 1.77 for drivers with DM using insulin. Compared to drivers without DM, the risk of HBEs was 48% higher for drivers with DM using insulin (aIRR 1.48; 95% CI: 1.43, 1.53). Conclusion Older adult drivers with DM using insulin appear to be at increased proneness to vehicular crashes. Driving safety should be taken into consideration in DM care and management.

Abstract Air pollution is a serious environmental health concern for humans and other living organisms. This study analyzes the spatial and temporal characteristics of air pollutant concentrations, changes in the degree of pollution, and the wavelet coherence of the air quality index (AQI) with pollutants in various monitoring stations. The analysis is based on long-term time series data (January 2016 to December 2023) of air pollutants (PM2.5, PM10, and O3) from Korla, an oasis city in the northeastern part of the Tarim Basin, China. The concentrations of PM2.5, PM10, and O3 in Korla showed a cyclical trend from 2016 to 2023; PM10 concentrations exhibited all-season exceedance and PM2.5 exhibited exceedance only in spring. PM2.5 and PM10 showed a seasonal distribution of spring > winter > fall > summer; O3 concentrations showed a seasonal distribution of summer > spring > fall > winter. Strong positive wavelet coherence between PM and Air Quality Index (AQI) data series suggests that the AQI data series can effectively characterize fluctuating trends in PM concentrations. Moreover, PM10 levels IV and VI were maintained at approximately 10%, indicating that sand and dust have a substantial influence on air quality and pose potential threats to the health of urban inhabitants. Based on the results of this study, future efforts must strengthen relative countermeasures for sand prevention and control, select urban greening species with anti-pollution capabilities, rationally expand urban green spaces, and restrict regulations for reducing particulate matter emissions within city areas.

Background: Canine transmissible venereal tumour (CTVT) is a widely spread, contagious neoplasm commonly found in dogs. Mostly affects the external genitalia, however, it may also exhibit unusual clinical presentations. Aim: To describe the epidemiology, clinical appearance, cytologic and histopathologic features of dogs with TVT in Morocco. Methods: Within the realm of a nation-wide study on canine and feline tumours in Morocco between September 2020 and March 2023, dogs with histologically diagnosed TVT were identified and data on epidemiologic, clinical as well as cytologic and histologic features compiled and analyzed. Results: A total of 64 cases of canine TVT were diagnosed. 52 dogs were cross-breed (81.2%) while 4 Siberian Huskies (6.2%) and 3 German shepherds (4.7%) were the most affected pure-breed dogs. Median age of dogs at diagnosis was 3 years (range, 1-10years) and male gender was more common (male:female ratio; 1.3:1). Tumour was located exclusively in the genital area in 58 cases (90.6%), whereas 6 dogs (9.4%) had an atypical occurrence of TVT with locations including skin and nasal cavity. Cytology allowed for an early diagnosis in 2 cases. Histology revealed no differences between the genital and extragenital forms. Immunohistochemistry was necessary in 4 cases and revealed positive staining for vimentin and Alpha-1-antitrypsin, negative marking for CD3, CD20 and AE1/AE3, and low cytoplasmic labeling for lysozyme. Conclusion: CTVT is a widely distributed neoplasm in Morocco, mostly showing presence in young, cross-breed, and oftentimes stray dogs. Adequate understanding of this tumour's epidemiological features is necessary for its management and eradication. [Open Vet J 2024; 14(5.000): 1206-1215]

The effective tracking and analysis of moving objects within urban environments presents a complex challenge that necessitates robust geospatial data integration. Open Geospatial Consortium (OGC) APIs offer standardized approaches to managing dynamic geospatial information. This paper presents a case study of real-time moving object tracking including buses and trains in the city of Munakata, Japan, utilizing two prominent OGC APIs: OGC API Moving Features and OGC SensorThings API. The study explores the implementation of both APIs, examining their strengths and limitations in handling real-time location updates and associated sensor data generated by moving buses. The research provides insights into the practical suitability of each API model for dynamic object tracking, offering valuable guidance for practitioners seeking to optimize geospatial data integration within smart cities and intelligent transportation systems.

The time required for genome sequencing and de novo assembly depends on the interaction between laboratory work, sequencing capacity, and the bioinformatics workflow, often constrained by external sequencing services. Bringing together academic biodiversity institutes and a medical diagnostics company with extensive sequencing capabilities, we aimed at generating a high-quality mammalian de novo genome in minimal time. We present the first chromosome-level genome assembly of the Whippet, using PacBio long-read high-fidelity sequencing and reference-guided scaffolding. The final assembly has a contig N50 of 55 Mbp and a scaffold N50 of 65.7 Mbp. The total assembly length is 2.47 Gbp, of which 2.43 Gpb were scaffolded into 39 chromosome-length scaffolds. Annotation using mammalian genomes and transcriptome data yielded 28,383 transcripts, 90.9% complete BUSCO genes, and identified 36.5% repeat content. Sequencing, assembling, and scaffolding the chromosome-level genome of the Whippet took less than a week, adding another high-quality reference genome to the available sequences of domestic dog breeds.

Background: Post-cardiac arrest syndrome (PCAS) after out-of-hospital cardiac arrest (OHCA) poses significant challenges due to its complex pathomechanisms involving inflammation, ischemia, and reperfusion injury. The identification of early available prognostic indicators is essential for optimizing therapeutic decisions and improving patient outcomes. Methods: In this retrospective single-center study, we analyzed real-world data from 463 OHCA patients with either prehospital or in-hospital return of spontaneous circulation (ROSC), treated at the Cardiac Arrest Center of the University Hospital of Marburg (MCAC) from January 2018 to December 2022. We evaluated demographic, prehospital, and clinical variables, including initial rhythms, resuscitation details, and early laboratory results. Statistical analyses included logistic regression to identify predictors of survival and neurological outcomes. Results: Overall, 46.9% (n = 217) of patients survived to discharge, with 70.1% (n = 152) achieving favorable neurological status (CPC 1 or 2). Age, initial shockable rhythm, resuscitation time to return of spontaneous circulation (ROSC), and early laboratory parameters like lactate, C-reactive protein, and glomerular filtration rate were identified as independent and combined Early Predictors of Outcome and Survival (EPOS), with high significant predictive value for survival (AUC 0.86 [95% CI 0.82–0.89]) and favorable neurological outcome (AUC 0.84 [95% CI 0.80–0.88]). Conclusion: Integration of EPOS into clinical procedures may significantly improve clinical decision making and thus patient prognosis in the early time-crucial period after OHCA. However, further validation in other patient cohorts is needed.

The title compound (systematic name: pyridinium 4-methylbenzenesulfonate), C5H6N+·C7H7O3S−, is the pyridinium salt of para-toluenesulfonic acid. In the crystal, classical N—H...O hydrogen bonds as well as C—H...O contacts connect the cationic and anionic entities into sheets lying parallel to the ab plane.

This paper presents the open-source Python software OSADCP developed for the processing of vessel-mounted Acoustic Doppler Current Profiler (VMADCP) data. At this stage, the toolbox is designed for processing VMADCP measurements from open-ocean applications of Teledyne RDI Ocean Surveyor ADCPs and the data acquisition software VMDAS. Based on the VMDAS ENX binary output format, the software contains implementations for cleaning and vector-averaging of single-ping velocity data, verification of the position data, and applying misalignment and amplitude corrections. The procedures of OSADCP are described in detail to encourage the scientific community to use it for their own purposes. The toolbox is an integral part of a workflow implemented on the German marine research vessels in the framework of the Underway Research Data project of the German Marine Research Alliance (DAM). It aims to ensure standardized data acquisition measures, reliable data transfer from the ADCP to shore both near-real-time and in delayed-mode, processing and quality control, and dissemination of the curated data product in the data repository PANGAEA. From PANGAEA, data sets are forwarded to the European marine data hubs Copernicus Marine Service and EMODnet. The workflow that forms the framework for OSADCP is described here as an example of scientific data management that follows the FAIR data guidelines.

Introduction: Firearm injury remains a public health problem, with nearly 50,000 firearm-related deaths in the US in 2021. Extreme risk protection orders (ERPOs) are civil restraining orders that intend to reduce firearm deaths by temporarily removing firearms from individuals who are threatening violence to themselves or others. We described ERPO use by petitioner type and implementation including firearm removal. Methods: All ERPO petitions filed in Colorado (1/1/2020–12/31/2022) were analyzed using an established abstraction tool and team-based approach. Case data abstracted from petitions and court documents were analyzed descriptively. Results: Over three years, there were 353 ERPO petitions filed in Colorado. Only 39 % percent of granted petitions had documentation of firearms being relinquished. The average number firearms relinquished was 1.8 with a range of 1 to 31 firearms. One third (37.7 %) of petitions mentioned a mental health issue, 10 % had a renewal request, and half (54.6 %) of petitions were filed by law enforcement (LE). LE petitions filed were more likely to be granted temporary ERPOs (94.3 % vs 35.0 %, p

Abstract Drowsiness while driving negatively impacts road safety, especially in truck drivers. The present study investigated the feasibility and alerting effects of a daylight-supplementing in-truck lighting system (DS) providing short-wavelength enriched light before, during, and after driving. In a within-participants design, eight truck drivers drove a fully-loaded truck under wintry Scandinavian conditions (low daylight levels) with a DS or placebo system for five days. Subjective and objective measures of alertness were recorded several times daily, and evening melatonin levels were recorded three times per study condition. DS significantly increased daytime light exposure without causing negative side effects while driving. In addition, no negative carry-over effects were observed on evening melatonin and sleepiness levels or on nighttime sleep quality. Moreover, objective alertness (i.e., psychomotor vigilance) before and after driving was significantly improved by bright light exposure. This effect was accompanied by improved subjective alertness in the morning. This field study demonstrated that DS was able to increase daytime light exposure in low-daylight conditions and to improve alertness in truck drivers before and after driving (e.g., during driving rest periods). Further studies are warranted to investigate the effects of daylight-supplementing in-cabin lighting on driving performance and road safety measures.

Abstract Modern, highly evolved nucleoside-processing enzymes are known to exhibit perfect regioselectivity over the glycosylation of purine nucleobases at N9. We herein report an exception to this paradigm. Wild-type nucleoside phosphorylases also furnish N7-xanthosine, a “non-native” ribosylation regioisomer of xanthosine. This unusual nucleoside possesses several atypical physicochemical properties such as redshifted absorption spectra, a high equilibrium constant of phosphorolysis and low acidity. Ultimately, the biosynthesis of this previously unknown natural product illustrates how even highly evolved, essential enzymes from primary metabolism are imperfect catalysts.

The mouthparts and protarsi of adult rove-beetles of the Staphylinine group are examined in detail. We provide descriptions and image plates based on scanning electron micrographs taken from 36 species representing all 10 subfamilies comprising this large staphylinid subunit. We establish groundplan features of the mouthparts for the Staphylinine group and discuss, in detail, aspects and functions of structures that compose the feeding apparatus. A phylogenetic scheme is used to conduct an ancestral character reconstruction of the morphological characters. The potential groundplan features of the characters rendered in our parsimony analysis for the Staphylinine group are: labrum subquadrate or longer than wide; mandible without subapical teeth and retinaculum, with prostheca present, not forming lobe-like projection, and with a mola; maxillary palpomere 4 well-developed, fully sclerotized, similar in width to palpomere 3; ‘glossa’ integrated with prementum plate, sometimes represented by pairs of sensilla basiconica; ‘paraglossa’ with unmodified antero-lateral lobes; labial palpomere 3 from as wide to half as wide as penultimate palpomere. To explain the shape variation of the mandibles, a geometric morphometric analysis was carried out. A character mapping analysis of mandible shapes revealed a trend in the Staphylinine group toward a falcate shape with a narrow base, typically present in some predatory species.

Abstract Building a representative model of a complex dynamical system from empirical evidence remains a highly challenging problem. Classically, these models are described by systems of differential equations that depend on parameters that need to be optimized by comparison with data. In this tutorial, we introduce the most common multi-parameter estimation techniques, highlighting their successes and limitations. We demonstrate how to use the adjoint method, which allows efficient handling of large systems with many unknown parameters, and present prototypical examples across several fields of physics. Our primary objective is to provide a practical introduction to adjoint optimization, catering for a broad audience of scientists and engineers.

Abstract Vaccination with infectious Plasmodium falciparum (Pf) sporozoites (SPZ) administered with antimalarial drugs (PfSPZ-CVac), confers superior sterilizing protection against infection when compared to vaccination with replication-deficient, radiation-attenuated PfSPZ. However, the requirement for drug administration constitutes a major limitation for PfSPZ-CVac. To obviate this limitation, we generated late liver stage-arresting replication competent (LARC) parasites by deletion of the Mei2 and LINUP genes (mei2 – /linup – or LARC2). We show that Plasmodium yoelii (Py) LARC2 sporozoites did not cause breakthrough blood stage infections and engendered durable sterilizing immunity against various infectious sporozoite challenges in diverse strains of mice. We next genetically engineered a PfLARC2 parasite strain that was devoid of extraneous DNA and produced cryopreserved PfSPZ-LARC2. PfSPZ-LARC2 liver stages replicated robustly in liver-humanized mice but displayed severe defects in late liver stage differentiation and did not form liver stage merozoites. This resulted in complete abrogation of parasite transition to viable blood stage infection. Therefore, PfSPZ-LARC2 is the next-generation vaccine strain expected to unite the safety profile of radiation-attenuated PfSPZ with the superior protective efficacy of PfSPZ-CVac.

Abstract Malaria-causing Plasmodium parasites first replicate as liver stages (LS), which then seed symptomatic blood stage (BS) infection. Emerging evidence suggests that these stages impact each other via perturbation of host responses, and this influences the outcome of natural infection. We sought to understand whether the parasite stage interplay would affect live-attenuated whole parasite vaccination, since the efficacy of whole parasite vaccines strongly correlates with their extend of development in the liver. We thus investigated the impact of BS infection on LS development of genetically attenuated and wildtype parasites in female rodent malaria models and observed that for both, LS infection suffered severe suppression during concurrent BS infection. Strikingly and in contrast to previously published studies, we find that the BS-induced iron-regulating hormone hepcidin is not mediating suppression of LS development. Instead, we demonstrate that BS-induced host interferons are the main mediators of LS developmental suppression. The type of interferon involved depended on the BS-causing parasite species. Our study provides important mechanistic insights into the BS-mediated suppression of LS development. This has direct implications for understanding the outcomes of live-attenuated Plasmodium parasite vaccination in malaria-endemic areas and might impact the epidemiology of natural malaria infection.

Abstract Background Suicide, especially by firearm, remains a leading cause of death in military populations in the USA. Reducing access to firearms, especially during high risk times, may help prevent suicide and other forms of violence. The purpose of this study was to adapt a promising existing lethal means safety intervention (Project Safe Guard, PSG) for cross-cutting violence prevention and peer support in active-duty service communities using community engagement methods. Methods A two-pronged community-engaged research approach was employed, including the Community Translation (CT) process that engaged 15 Service Members from one installation to help adapt PSG successfully. In addition, qualitative data was collected from 40 active-duty service members and military violence prevention specialists through in-depth interviews and focus group discussions. Results Qualitative data and CT feedback led to site-specific PSG adaptations. Participants emphasized the importance of peer-to-peer discussions and highlighted resource allocation, leadership support, and stigma on firearm ownership as potential implementation challenges. Conclusions Findings demonstrate the feasibility of community-engaged research to adapt lethal means safety interventions within military populations. PSG implementation should consider resource allocation, leadership support, and addressing stigma. This study has implications for future policies and standards for performing research on sensitive topics, particularly among military populations.

We show a long-term erosion monitoring of several geomorphologically active gully systems on Little Ice Age lateral moraines in the European Central–Eastern Alps, covering a total time period from 1953 to 2019 and including several survey periods in order to identify corresponding morphodynamic trends. For the implementation, DEM (digital elevation model) of Differences (DoDs) were calculated, based on multitemporal high-resolution digital elevation models from historical aerial images (generated by structure from motion photogrammetry with multi-view stereo) and light detection and ranging from airborne platforms. Two approaches were implemented to achieve the corresponding objectives. First, by calculating linear regression models using the accumulated sediment yield and the corresponding catchment area (on a log–log scale), the range of the variability in the spatial distribution of erosion values within the sites. Second, we use volume calculations to determine the total and the mean sediment yield (as well as erosion rates) of the entire sites. Subsequently, both the sites and the different time periods of both approaches are compared. Based on the slopes of the calculated regression lines, it can be shown that the highest variability in the sediment yield at the sites occurs in the first time period (mainly 1950s to 1970s). This can be attributed to the fact that within some sites the sediment yield per square metre increases clearly more strongly (regression lines with slopes up to 1.5). In contrast, in the later time periods (1970s to mid-2000s and mid-2000s to 2017/2019), there is generally a decrease in 10 out of 12 cases (regression lines with slopes around 1). However, even at sites with an increase in the variability in the sediment yield over time, the earlier high variabilities are no longer reached. This means that the spatial pattern of erosion in the gully heads changes over time as it becomes more uniform. Furthermore, using sediment volume calculations and corresponding erosion rates, we show a generally decreasing trend in geomorphic activity (amount of sediment yield) between the different time periods in 10 out of 12 sites, while 2 sites show an opposite trend, where morphodynamics increase and remain at the same level. Finally, we summarise the results of long-term changes in the morphodynamics of geomorphologically active areas on lateral moraines by presenting the “sediment activity concept”, which, in contrast to theoretical models, is based on actually calculated erosion. The level of geomorphic activity depends strongly on the characteristics of the sites, such as size, slope length, and slope gradient, some of which are associated with deeply incised gullies. It is noticeable that especially areas with influence of dead ice over decades in the lower slope area show high geomorphic activity. Furthermore, we show that system internal factors, as well as the general paraglacial adjustment process, have a greater influence on long-term morphodynamics than changing external weather and climate conditions, which, however, had a slight impact mainly in the last, i.e. most recent, time period (mid-2000s to 2017/2019) and may have led to an increase in erosion at the sites.

The moment distribution method is considered one of the easiest and most reliable analysis methods. However, little attention has been given to modelling the stiffness of each member separately, as currently only one factor is being used to model all structural members without taking into account the loading conditions and curvature of the member. This can significantly influence the results when modelling columns, since unlike beams, which are usually bent in a single curvature configuration, columns can be bent in either a single or double curvature configuration. This paper presents a new set of stiffness factors to model each structural member separately depending on its boundary conditions and curvature. To validate this modification, an example concrete frame was modelled and analysed using the structural analysis software ETABS, and then the results were compared with that obtained from the standard moment distribution method and the modified moment distribution method. The results have revealed a significant enhancement in the accuracy of the obtained results when using the modified moment distribution method compared with the original moment distribution method, especially the values of the columns’ bending moments.

Background/aims To examine demographic and clinical factors associated with ocular pain 1 day after refractive surgery.Methods Prospective study of individuals undergoing refractive surgery. Participants rated their ocular pain on a 0–10 numerical rating scale (NRS) presurgery and 1 day after surgery. Presurgery, participants completed questionnaires on demographics, comorbidities, medications and dry eye and ocular pain symptoms; and an anaesthetised Schirmer test was performed. Acute ocular pain 1 day after surgery was defined as an NRS score of worst pain since surgery ≥3 and this group was compared with individuals with NRS scores

The structural behaviour of textile-reinforced concrete (TRC) components under uniaxial compressive loading has already been studied. However, for practical applications, multi-axial loading conditions are often of great importance. It is well known from steel-reinforced concrete that multiaxial compressive stresses lead to increased compressive strength. The extent to which this assumption can be transferred to TRC components should be investigated. This paper investigates the influence of textile carbon grid reinforcement on the compressive capacity of disc-shaped concrete specimens. The specimens were subjected to a biaxial compressive load in the plane of the reinforcement. Emphasis was placed on the influence parameters of production type of the disc specimens (laminated or poured), impregnation material of the carbon textile (polystyrene or epoxy resin) and number of reinforcement layers. It was found that the general presence of a textile reinforcement as a two-dimensional interference plane had the greatest influence on the compressive capacity of the specimens, while the other parameters investigated played a minor role. Depending on the load ratio in the two compression axes, there were increases or decreases in capacity compared to the uniaxial tests. This has to be taken into account in the design of the corresponding components. Finally, an outlook is given on future investigations planned to support and extend the results presented in this paper.

Key Clinical Message A plunging ranula may present initially as an extensive vallecular cyst and correct diagnosis may be reached with the use of ultrasound, fluid aspiration for amylase detection, and MRI imaging. Abstract The ranula is a pseudocyst of the sublingual salivary gland and can be divided into two known subtypes. The simple ranula and plunging ranula. While the simple type can be found in the floor of the mouth, the plunging ranula usually pervades the mylohoid muscle and presents as a cervical swelling. The presented case should outline the difficulties in diagnostic and treatment of an uncommon expression of a mucocele above the mylohoid muscle without presenting either a cervical or an intraoral swelling, only extending towards the vallecula. We present a previously unreported clinical manifestation of a ranula of an 18‐year old male, which extends posteriorly, remaining confined in the supramylohyoid muscle space. The cystic lesion protrudes in the oropharynx, and clinically appears as an extensive vallecular cyst. On magnetic resonance imaging the initial suspected diagnosis of a vallecular cyst was changed to the final diagnosis of a plunging ranula. The marsupialization of the cyst sac was performed. Outpatient follow‐up revealed a persisting ostium, indicating a continuous extravasation of the sublingual gland. The present case report describes an unusual clinical presentation of a plunging ranula, remaining above the mylohyoid muscle and protruding into the oropharynx, misdirecting to the first suspected diagnosis of a vallecular cyst. The case highlights the useful contribution of the MRI imaging for differential diagnoses and the need for criteria to indicate further investigations.

IntroductionNew diagnostic techniques are a substantial research focus in degenerative cervical myelopathy (DCM). This cross-sectional study determined the significance of cardiac-related spinal cord motion and the extent of spinal stenosis as indicators of mechanical strain on the cord.MethodsEighty-four DCM patients underwent MRI/clinical assessments and were classified as MRI+ [T2-weighted (T2w) hyperintense lesion in MRI] or MRI− (no T2w-hyperintense lesion). Cord motion (displacement assessed by phase-contrast MRI) and spinal stenosis [adapted spinal canal occupation ratio (aSCOR)] were related to neurological (sensory/motor) and neurophysiological readouts [contact heat evoked potentials (CHEPs)] by receiver operating characteristic (ROC) analysis.ResultsMRI+ patients (N = 31; 36.9%) were more impaired compared to MRI− patients (N = 53; 63.1%) based on the modified Japanese Orthopedic Association (mJOA) subscores for upper {MRI+ [median (Interquartile range)]: 4 (4–5); MRI−: 5 (5–5); p

This publication is a fact sheet intended for individuals who are interested in learning basic information about identity theft, victimization, and ways to navigate the process. The publication aims to inform readers and to help victims of identity theft minimize financial and personal setbacks. Written by Axton Betz-Hamilton, Randall A. Cantrell, and Heidi Liss Radunovich, and published by the UF/IFAS Department of Family, Youth and Community Sciences, June 2024.

The software RPExpand, implemented in MATLAB®, provides modal expansions of physical observables in resonant systems, based on contour integrals. Version 2.0 improves the workflow and adds new features. In addition to the poles corresponding to eigenmodes of the systems, zeros of various quantities can be computed. Their derivatives are evaluated if the required information is supplied at the integration points. Furthermore, expansions based on quasinormal modes are supported.

Our research introduces a modular motion planning framework for autonomous vehicles using a sampling-based trajectory planning algorithm. This approach effectively tackles the challenges of solution space construction and optimization in path planning. The algorithm is applicable to both real vehicles and simulations, offering a robust solution for complex autonomous navigation. Our method employs a multi-objective optimization strategy for efficient navigation in static and highly dynamic environments, focusing on optimizing trajectory comfort, safety, and path precision. The algorithm is used to analyze the algorithm performance and success rate in 1750 virtual complex urban and highway scenarios. Our results demonstrate fast calculation times (8ms for 800 trajectories), a high success rate in complex scenarios (88%), and easy adaptability with different modules presented. The most noticeable difference exhibited was the fast trajectory sampling, feasibility check, and cost evaluation step across various trajectory counts. We demonstrate the integration and execution of the framework on real vehicles by evaluating deviations from the controller using a test track. This evaluation highlights the algorithm’s robustness and reliability, ensuring it meets the stringent requirements of real-world autonomous driving scenarios. The code and the additional modules used in this research are publicly available as open-source software and can be accessed at the following link: https://github.com/TUM-AVS/Frenetix-Motion-Planner.

Abstract Background Patient-reported outcomes (PROs) play a crucial role in assessing rheumatic diseases, offering insights into disease evaluation and treatment efficacy. This study focuses on PRO assessment in large vessel vasculitides, including Takayasu Arteritis and Giant Cell Arteritis (GCA). Methods We retrospectively analyzed routine data from patients treated at our rheumatology clinic over a 10-year span. Patient and physician-rated global disease activity scale (G-DAS) scores, measured on a numeric rating scale (0–10 points), were collected at each visit. Clinical variables like age, sex, body mass index (BMI), disease duration, lab values, pain perception, and questionnaire responses were recorded. Linear regression and generalized additive linear regression (GAM analysis) examined associations between PROs and these factors. Results The study included 138 patients, primarily diagnosed with GCA (94.4%). Mean follow-up was 2.5 years (0-7.7). Patient and physician G-DAS exhibited a moderate correlation (Pearson R 0.19, CI 0.14–0.24, p

Abstract Background The perioperative antibiotic prophylaxis with 1st or 2nd generation cephalosporins is evidence-based in orthopedic surgery. There are, however, situations with a high risk of prophylaxis-resistant surgical site infections (SSI). Methods We perform a superiority randomized controlled trial with a 10% margin and a power of 90% in favor of the broad-spectrum prophylaxis. We will randomize orthopedic interventions with a high risk for SSI due to selection of resistant pathogens (open fractures, surgery under therapeutic antibiotics, orthopedic tumor surgery, spine surgery with American Society of Anesthesiologists (ASA) score ≥ 3 points) in a prospective-alternating scheme (1:1, standard prophylaxis with cefuroxime versus a broad-spectrum prophylaxis of a combined single-shot of vancomycin 1 g and gentamicin 5 mg/kg parenterally). The primary outcome is “remission” at 6 weeks for most orthopedic surgeries or at 1 year for surgeries with implant. Secondary outcomes are the risk for prophylaxis-resistant SSI pathogens, revision surgery for any reason, change of antibiotic therapy during the treatment of infection, adverse events, and the postoperative healthcare-associated infections other than SSI within 6 weeks (e.g., urine infections or pneumonia). With event-free surgeries to 95% in the broad-spectrum versus 85% in the standard prophylaxis arm, we need 2 × 207 orthopedic surgeries. Discussion In selected patients with a high risk for infections due to selection of prophylaxis-resistant SSI, a broad-spectrum combination with vancomycin and gentamycin might prevent SSIs (and other postoperative infections) better than the prophylaxis with cefuroxime. Trial registration ClinicalTrial.gov NCT05502380. Registered on 12 August 2022. Protocol version: 2 (3 June 2022)

Abstract The conserved SR-like protein Npl3 promotes splicing of diverse pre-mRNAs. However, the RNA sequence(s) recognized by the RNA Recognition Motifs (RRM1 & RRM2) of Npl3 during the splicing reaction remain elusive. Here, we developed a split-iCRAC approach in yeast to uncover the consensus sequence bound to each RRM. High-resolution NMR structures show that RRM2 recognizes a 5´-GNGG-3´ motif leading to an unusual mille-feuille topology. These structures also reveal how RRM1 preferentially interacts with a CC-dinucleotide upstream of this motif, and how the inter-RRM linker and the region C-terminal to RRM2 contribute to cooperative RNA-binding. Structure-guided functional studies show that Npl3 genetically interacts with U2 snRNP specific factors and we provide evidence that Npl3 melts U2 snRNA stem-loop I, a prerequisite for U2/U6 duplex formation within the catalytic center of the Bact spliceosomal complex. Thus, our findings suggest an unanticipated RNA chaperoning role for Npl3 during spliceosome active site formation.

This study evaluates potential associations between the perioperative urinary catheter (UC) carriage and (Gram-negative) surgical site infections (SSIs) after spine surgery. It is a retrospective, single-center, case-control study stratifying group comparisons, case-mix adjustments using multivariate logistic regression analyses. Around half of the patients (2734/5485 surgeries) carried a UC for 1 day (median duration) (interquartile range, 1–1 days). Patients with perioperative UC carriage were compared to those without regarding SSI, in general, and Gram-negative, exclusively. The SSI rate was 1.2% (67/5485), yielding 67 revision surgeries. Gram-negative pathogens caused 16 SSIs. Seven Gram-negative episodes revealed the same pathogen concomitantly in the urine and the spine. In the multivariate analysis, the UC carriage duration was associated with SSI (OR 1.1, 95% confidence interval 1.1–1.1), albeit less than classical risk factors like diabetes (OR 2.2, 95%CI 1.1–4.2), smoking (OR 2.4, 95%CI 1.4–4.3), or higher ASA-Scores (OR 2.3, 95%CI 1.4–3.6). In the second multivariate analysis targeting Gram-negative SSIs, the female sex (OR 3.8, 95%CI 1.4–10.6) and a UC carriage > 1 day (OR 5.5, 95%CI 1.5–20.3) were associated with Gram-negative SSIs. Gram-negative SSIs after spine surgery seem associated with perioperative UC carriage, especially in women. Other SSI risk factors are diabetes, smoking, and higher ASA scores.

Background: Biomechanical analysis of the sagittal alignment of the lumbar spine and pelvis on radiographs is common in clinical practices including chiropractic, physical therapy, scoliosis-related thoraco-lumbo-sacral orthosis (TLSO) management, orthopedics, and neurosurgery. Of specific interest is the assessment of pelvic morphology and the relationship between angle of pelvic incidence, sacral slope, and lumbar lordosis to pain, disability, and clinical treatment of spine conditions. The current state of the literature on the reliability of common methods quantifying these parameters on radiographs is limited. Methods: The objective of this systematic review is to identify and review the available studies on the reliability of different methods of biomechanical analysis of sagittal lumbo-pelvic parameters used in clinical practice. Our review followed the recommendations of the preferred reporting items for systematic reviews and meta-analyses (PRISMA). The design of this systematic review was registered with PROSPERO (CRD42023379873). Results: The search strategy yielded a total of 2387 articles. A total of 1539 articles were screened after deduplication and exclusion by automation tools, leaving 473 full-text articles that were retrieved. After exclusion, 64 articles met the inclusion criteria. The preponderance of the evidence showed good to excellent reliability for biomechanical assessment of sagittal lumbo-pelvic spine alignment. Conclusions: The results of this systematic review of the literature show that sagittal radiographic analysis of spinal biomechanics and alignment of the human lumbo-pelvic spine is a reliable tool for aiding diagnosis and management in clinical settings.

Abstract Background“Lock to Live” (L2L) is a novel web-based decision aid for helping people at risk of suicide reduce access to firearms. Researchers have demonstrated that L2L is feasible to use and acceptable to patients, but little is known about how to implement L2L during web-based mental health care and in-person contact with clinicians. ObjectiveThe goal of this project was to support the implementation and evaluation of L2L during routine primary care and mental health specialty web-based and in-person encounters. MethodsThe L2L implementation and evaluation took place at Kaiser Permanente Washington (KPWA)—a large, regional, nonprofit health care system. Three dimensions from the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) model—ReachAdoptionImplementation ResultsThe initial implementation consisted of updates for clinicians to add a URL and QR code referencing L2L to the safety planning EHR templates. Recommendations about introducing L2L were subsequently derived from the thematic analysis of semistructured interviews with patients (n=36), which included (1) “have an open conversation,” (2) “validate their situation,” (3) “share what to expect,” (4) “make it accessible and memorable,” and (5) “walk through the tool.” Clinicians’ interviews (n=30) showed a strong preference to have L2L included by default in the EHR-based safety planning template (in contrast to adding it manually). During the 2-year observation period, 2739 patients reported prior-month suicide attempt planning or intent and had a documented safety plan during the study period, including 745 (27.2%) who also received L2L. Over four 6-month subperiods of the observation period, L2L adoption rates increased substantially from 2% to 29% among primary care clinicians and from

Abstract Objective Nasal septum perforation (NSP) is a common condition affecting ~1.2% of the general population and is still considered challenging to treat. Therapeutic strategies range from conservative local treatments and septal button closures to over 40 different surgical approaches. This study aimed to present a novel secure approach. Methods We describe our novel and unique NSP closure approach using a “fascia taco,” in which conchal cartilage is enveloped by temporalis fascia like a taco and splints are left in place for 6–8 weeks. A review of patient charts was conducted and questionnaires including the German‐SNOT‐22 and D‐NOSE were sent by mail to all eligible patients who received a fascia taco between 2016 and 2021. Results Thirty‐three patients were identified. The questionnaire response rate was 54.5%. The mean operative time (cut to sew) for all patients who only underwent NSP closure was 90.4 min. The overall success rate in terms of postoperative NSP closure was 81.8%. We found an apparent but nonsignificant association between closure failure and smoking (failure rate 66.6% in smokers vs. 15.4% in nonsmokers; X2 = 3.4188, p = .064). Questionnaire analysis showed a significant postoperative reduction of mean values in D‐NOSE from 60.8 to 33.1 (p = .009) and in German‐SNOT‐22 from 38.6 to 21.2 (p = .005). Conclusion The fascia taco technique is an easy‐to‐apply, safe procedure for NSP closure that is short in duration and associated with a low morbidity, resulting in excellent patient satisfaction. Level of Evidence 4.

IntroductionArtificial Intelligence (AI) has proven effective in classifying skin cancers using dermoscopy images. In experimental settings, algorithms have outperformed expert dermatologists in classifying melanoma and keratinocyte cancers. However, clinical application is limited when algorithms are presented with ‘untrained’ or out-of-distribution lesion categories, often misclassifying benign lesions as malignant, or misclassifying malignant lesions as benign. Another limitation often raised is the lack of clinical context (e.g., medical history) used as input for the AI decision process. The increasing use of Total Body Photography (TBP) in clinical examinations presents new opportunities for AI to perform holistic analysis of the whole patient, rather than a single lesion. Currently there is a lack of existing literature or standards for image annotation of TBP, or on preserving patient privacy during the machine learning process.MethodsThis protocol describes the methods for the acquisition of patient data, including TBP, medical history, and genetic risk factors, to create a comprehensive dataset for machine learning. 500 patients of various risk profiles will be recruited from two clinical sites (Australia and Spain), to undergo temporal total body imaging, complete surveys on sun behaviors and medical history, and provide a DNA sample. This patient-level metadata is applied to image datasets using DICOM labels. Anonymization and masking methods are applied to preserve patient privacy. A two-step annotation process is followed to label skin images for lesion detection and classification using deep learning models. Skin phenotype characteristics are extracted from images, including innate and facultative skin color, nevi distribution, and UV damage. Several algorithms will be developed relating to skin lesion detection, segmentation and classification, 3D mapping, change detection, and risk profiling. Simultaneously, explainable AI (XAI) methods will be incorporated to foster clinician and patient trust. Additionally, a publicly released dataset of anonymized annotated TBP images will be released for an international challenge to advance the development of new algorithms using this type of data.ConclusionThe anticipated results from this protocol are validated AI-based tools to provide holistic risk assessment for individual lesions, and risk stratification of patients to assist clinicians in monitoring for skin cancer.

BackgroundAlzheimer’s disease (AD) is increasing in prevalence, but effective treatments for its cognitive impairment remain severely limited. This study investigates the impact of ketone body production through dietary manipulation on memory in persons with mild cognitive impairment due to early AD and explores potential mechanisms of action.MethodsWe conducted a 12-week, parallel-group, controlled feasibility trial of a ketogenic diet, the modified Atkins diet (MAD), compared to a control diet in patients with cognitive impairments attributed to AD. We administered neuropsychological assessments, including memory tests, and collected blood samples at baseline and after 12 weeks of intervention. We performed untargeted lipidomic and targeted metabolomic analyses on plasma samples to detect changes over time.ResultsA total of 839 individuals were screened to yield 38 randomized participants, with 20 assigned to receive MAD and 18 assigned to receive a control diet. Due to attrition, only 13 in the MAD arm and nine in the control arm were assessed for the primary endpoint, with two participants meeting ketosis levels used to define MAD adherence criteria. The average change from baseline in the Memory Composite Score was 1.37 (95% CI: −0.87, 4.90) points higher in the MAD group compared to the control group. The effect size of the intervention on baseline MAD change was moderate (Cohen’s D = 0.57, 95% CI: −0.67, 1.33). In the 15 participants (nine MAD, six control) assessed for lipidomic and metabolomic-lipidomics and metabolomics, 13 metabolites and 10 lipids showed significant changes from baseline to 12 weeks, including triacylglycerols (TAGs, 50:5, 52:5, and 52:6), sphingomyelins (SM, 44:3, 46:0, 46:3, and 48:1), acetoacetate, fatty acylcarnitines, glycerol-3-phosphate, and hydroxy fatty acids.ConclusionsAttrition was greatest between baseline and week 6. All participants retained at week 6 completed the study. Despite low rates of adherence by criteria defined a priori, lipidomic and metabolomic analyses indicate significant changes from baseline in circulating lipids and metabolites between MAD and control participants at 12-week postrandomization, and MAD participants showed greater, albeit nonsignificant, improvement in memory.

Aim: Social media (SoMe) are emerging as important tools for research dissemination. Twitter/X promotion has been shown to increase citation rates in well-established journals. We aimed to test the effect of a SoMe promotion strategy on the Mendeley reader counts, the Altmetric Attention Score and the number of citations in an upcoming open-access journal. Methods: The #TweetTheJournal study is a randomized, controlled study. Articles published in seven subsequent issues of the International Journal of Cardiology Heart & Vasculature (April 2021-April 2022) were randomized to a Twitter/X promotion arm (articles were posted four times) and to a control arm (without active posting). Articles with accompanied editorials were excluded. Primary endpoint of the study was Mendeley reader count, secondary endpoints were Altmetric Attention Score and number of citations. Follow-up was one year. Results: SoMe promotion of articles showed no statistically significant difference in Mendeley reader counts or number of citations at one year follow up. SoMe promotion resulted in a statistically significant higher Altmetric Attention Score in the intervention compared to the control group (RR 1.604, 95 % CI 1.024–2.511, p = 0.039). In the overall group, Altmetric Attention Score showed a correlation with Mendeley reader counts (Spearman’s ρ = 0.202, p = 0.010) and Mendeley reader counts correlated significantly with number of citations (Spearman’s ρ = 0.372, p

Objective: Biomechanical Machine Learning (ML) models, particularly deep-learning models, demonstrate the best performance when trained using extensive datasets. However, biomechanical data are frequently limited due to diverse challenges. Effective methods for augmenting data in developing ML models, specifically in the human posture domain, are scarce. Therefore, this study explored the feasibility of leveraging generative artificial intelligence (AI) to produce realistic synthetic posture data by utilizing three-dimensional posture data.Methods: Data were collected from 338 subjects through surface topography. A Variational Autoencoder (VAE) architecture was employed to generate and evaluate synthetic posture data, examining its distinguishability from real data by domain experts, ML classifiers, and Statistical Parametric Mapping (SPM). The benefits of incorporating augmented posture data into the learning process were exemplified by a deep autoencoder (AE) for automated feature representation.Results: Our findings highlight the challenge of differentiating synthetic data from real data for both experts and ML classifiers, underscoring the quality of synthetic data. This observation was also confirmed by SPM. By integrating synthetic data into AE training, the reconstruction error can be reduced compared to using only real data samples. Moreover, this study demonstrates the potential for reduced latent dimensions, while maintaining a reconstruction accuracy comparable to AEs trained exclusively on real data samples.Conclusion: This study emphasizes the prospects of harnessing generative AI to enhance ML tasks in the biomechanics domain.

We derive a bound for entropy production in terms of the mean of normalizable path-antisymmetric observables. The optimal observable for this bound is shown to be the signum of entropy production, which is often easier determined or estimated than entropy production itself. It can be preserved under coarse graining by the use of a simple path grouping algorithm. We demonstrate this relation and its properties using a driven network on a ring, for which the bound saturates for short times for any driving strength. This work can open a way to systematic coarse graining of entropy production.

Abstract Evidence-based indication for tonsil surgery in patients with recurrent acute tonsillitis (RAT) is an ongoing matter of debate. Since introduction of the German tonsillitis guideline in 2015, the indication criteria for tonsil surgery have become much stricter. It is unclear, if this has changed the indication policy. A retrospective population-based study was performed including all 1398 patients with RAT admitted for tonsil surgery in all Thuringian hospitals in 2011, 2015, and 2019. Changes over the years concerning patients’ characteristics, number of tonsillitis episodes in the last 12 months treated with antibiotics (T12), and decision for tonsillectomy or tonsillotomy were analyzed using univariable and multivariable statistics. The surgical rates decreased from 28.56/100,000 population in 2011 to 23.57 in 2015, and to 11.60 in 2019. The relative amount of patients with ≥ 6 T12 increased from 14.1% in 2011 over 13.3% in 2015 to 35.9% in 2019. Most patients received a tonsillectomy (98% of all surgeries). Decision for tonsillotomy was seldom (1.2%). Multinomial logistic regression analysis with the year 2011 as reference showed that compared to the year 2015, the age of the patients undergoing surgery increased in 2015 (Odds ratio [OR] = 1.024; 95% confidence interval [CI] = 1.014–1.034; p