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Evidence for a flavor asymmetry between the ū and d¯ quark distributions in the proton has been found in deep-inelastic scattering and Drell-Yan experiments. The pronounced dependence of this flavor asymmetry on x (fraction of nucleon momentum carried by partons) observed in the Fermilab E866 Drell-Yan experiment suggested a drop of the d¯(x)/ū(x) ratio in the x>0.15 region. We report results from the SeaQuest Fermilab E906 experiment with improved statistical precision for d¯(x)/ū(x) in the large x region up to x=0.45 using the 120 GeV proton beam. Two different methods for extracting the Drell-Yan cross section ratios, σpd/2σpp, from the SeaQuest data give consistent results. The d¯(x)/ū(x) ratios and the d¯(x)-ū(x) differences are deduced from these cross section ratios for 0.13

In Fig. 1c of this Article, the x-axis scale was inadvertently duplicated from Fig. 1b. The original Article has been corrected online.

The fundamental building blocks of the proton-quarks and gluons-have been known for decades. However, we still have an incomplete theoretical and experimental understanding of how these particles and their dynamics give rise to the quantum bound state of the proton and its physical properties, such as its spin1. The two up quarks and the single down quark that comprise the proton in the simplest picture account only for a few per cent of the proton mass, the bulk of which is in the form of quark kinetic and potential energy and gluon energy from the strong force2. An essential feature of this force, as described by quantum chromodynamics, is its ability to create matter-antimatter quark pairs inside the proton that exist only for a very short time. Their fleeting existence makes the antimatter quarks within protons difficult to study, but their existence is discernible in reactions in which a matter-antimatter quark pair annihilates. In this picture of quark-antiquark creation by the strong force, the probability distributions as a function of momentum for the presence of up and down antimatter quarks should be nearly identical, given that their masses are very similar and small compared to the mass of the proton3. Here we provide evidence from muon pair production measurements that these distributions are considerably different, with more abundant down antimatter quarks than up antimatter quarks over a wide range of momenta. These results are expected to revive interest in several proposed mechanisms for the origin of this antimatter asymmetry in the proton that had been disfavoured by previous results4, and point to future measurements that can distinguish between these mechanisms.

The SeaQuest spectrometer at Fermilab was designed to detect oppositely-charged pairs of muons (dimuons) produced by interactions between a 120 GeV proton beam and liquid hydrogen, liquid deuterium and solid nuclear targets. The primary physics program uses the Drell–Yan process to probe antiquark distributions in the target nucleon. The spectrometer consists of a target system, two dipole magnets and four detector stations. The upstream magnet is a closed-aperture solid iron magnet which also serves as the beam dump, while the second magnet is an open aperture magnet. Each of the detector stations consists of scintillator hodoscopes and a high-resolution tracking device. The FPGA-based trigger compares the hodoscope signals to a set of pre-programmed roads to determine if the event contains oppositely-signed, high-mass muon pairs.

This report documents the physics case for building a 2 MW, 8 GeVsuperconducting linac proton driver at Fermilab.

Leptin is a homeostatic regulatory element that signals the presence of adipocyte energy stores, reduces food intake, and increases energy expenditure. Similarly, serotonin (5-HT), a signaling molecule found in both the central and peripheral nervous systems, also controls food intake. Using neuronal tract tracing, pharmacologic and optogenetic approaches, and in vivo microdialysis, combined with behavioral end points, we tested the hypothesis that leptin controls food intake not only by activating hypothalamic leptin receptors (LepRs) but also through activation of LepRs expressed by serotonergic raphe neurons that send projections to the arcuate (ARC). We showed that microinjection of leptin directly into the dorsal raphe nucleus (DRN) reduced food intake in rats. This effect was mediated by LepR-expressing neurons in the DRN, because selective optogenetic activation of these neurons at either their DRN cell bodies or their ARC terminals reduced food intake. Anatomically, we identified a unique population of serotonergic raphe neurons expressing LepRs that send projections to the ARC. Finally, by using in vivo microdialysis, we showed that leptin administration to the DRN increased 5-HT efflux into the ARC, and specific antagonism of the 5-HT2C receptors in the ARC diminished the leptin anorectic effect. Overall, this study identified a novel circuit for leptin-mediated control of food intake through a DRN-ARC pathway, identifying a new level of interaction between leptin and serotonin to control food intake. Characterization of this new pathway creates opportunities for understanding how the brain controls eating behavior and opens alternative routes for the treatment of eating disorders., (© 2024 by the American Diabetes Association.)

Objectives: The assessment of correct positioning of central venous catheters (CVC) is of major concern to avoid complications.Vascular access associations have established the cavo-atrial junction (CAJ) as the most appropriate CVC tip location. Among the different chest X-ray (CXR) landmarks proposed for assessing tip position relative to the CAJ, only the pericardial reflection lies in the same plane as the vascular structures assessed. Although extensively used, CXR has been criticized for its difficulty in estimating catheter tip location.We aimed to evaluate the observer variability to determine tip positioning on CXR. CT imaging was used as a gold standard for tip identification., Material and Methods: 107 CT scans of patients wearing port access catheter devices realized at the XXX University Hospital between January and December 2021 were retrospectively analyzed. Distance from tip to cavo-atrial junction (DCAJ) was measured on topogram projectional imaging (PJ) and axial cross-sectional imaging (CS) by 2 × 2 observers (within and between evaluations). Observational statistics were reported using a paired t-test, repeatability coefficients (RC), and the intraclass correlation coefficient (ICC), and they were displayed comprehensively using Bland-Altman plots., Results: All ICC were >0.9, indicating excellent reliability. The mean difference between observers comparing CS and PJ was 0.13 ± 0.80 cm (P = 0.10) with outer 95% confidence limits of 1.92 cm and -2.17 cm and an RC of 1.79 cm., Conclusion: CXR tip-position reading remains an accurate method for determining CVC localization. However, the assessment variability on CXR is plus or minus 2 cm and should be considered., Advances in Knowledge: Chest X-ray (CXR) for the assessment of tip position is subject to intra-individual and inter-individual variation. On CT, the variability is solely linked to determining the cavoatrial junction (CAJ) and represented about 1 cm. On CXR, there is a twofold challenge: the correct determination of the CAJ and the accurate identification of the catheter tip, leading to a greater variability of 2 cm.In clinical practice, while considering the 3 cm anatomical zone around the CAJ acceptable, operators should be aware of the 2 cm variability resulting from CXR assessment. To account for this variability and avoid the risk of positioning the tip beyond 3 cm from the CAJ (theoretically up to plus or minus 5 cm away from the CAJ), operators should reduce the CXR-based acceptable zone to 1 cm around the CAJ. This change may impact up to thirty percent of procedures., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology.)

Johne's disease in cattle is a significant global animal health challenge. Johne's disease is chronic, affecting the gastrointestinal tract of cattle and other ruminants and is caused by the bacteria Mycobacterium avium ssp. Paratuberculosis. Many countries have introduced schemes and programmes to try and control the spread of Johne's disease, including the UK. Despite efforts to control it, however, Johne's disease remains consistently ranked by UK producers as the top ranked disease negatively affecting productivity, indicating that schemes are not perceived to have solved the problem fully. Building on a global systematic review of the literature on barriers and solutions for Johne's disease control on-farm, we conducted an empirical study with over 400 farmers and 150 veterinary professionals across the UK. The study used workshops and semi-structured interviews to understand better the challenges dairy farmers and veterinarians face in implementing on-farm Johne's disease management schemes with the aim of identifying solutions. The study found that four main challenges are faced in the on-farm control of Johne's - (1) Management of farmer expectations around Johne's disease, with eradication near impossible, (2) Issues regarding space for segregation and the related economics of control (3) A 'free-riding' problem which can be influenced by the voluntary nature of control plans and (4) Challenges in vet-farmer communication, including levels of knowledge. Our findings have relevance for the control of Johne's disease in the UK and other countries, including for regions with voluntary and compulsory control programmes., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The decision to initiate advanced systemics in patients with atopic dermatitis (AD) is complex., Objectives: To explore disease burden and clinical characteristics of patients with moderate-to-severe AD and identify characteristics associated with initiating new systemics., Methods: Data from prospective, longitudinal, non-interventional CorEvitas AD Registry were evaluated. Differences in demographic and clinical characteristics, comorbidities, disease severity (vIGA-AD ™ ; body surface area (BSA); Eczema Area and Severity Index (EASI); SCORing AD [SCORAD]), and patient-reported outcomes (PROs) were assessed between systemic and non-systemic therapy groups., Results: Of 883 patients, 673 were newly prescribed systemics and 210 were not. Non-systemic therapy group had higher than expected rates of severe disease at enrollment based on vIGA-AD = 4 (39%), mean BSA involvement (31%), and mean EASI (19). PROs for non-systemic therapy group indicated elevated burden from AD on quality of life and poor disease control. SCORAD, peak pruritus in the past 24 h, history of biologics, and facial pallor, were significantly associated with initiation of systemics at enrollment., Conclusion: While disease burden likely influences the initiation of systemic therapy, many patients with significant burden are not treated with systemics for unclear reasons. Further research is needed to identify other factors, beyond disease severity, that influence this decision.

In view of our aging society, co-management with a geriatrician is becoming increasingly important. While such collaborations have been working successfully in trauma surgery for years, it is still unclear whether they are also helpful for non-trauma patients in orthopedics. The aim of this study was to investigate the effect of such a cooperation in orthopedic non-trauma patients with native and periprosthetic joint infections on the basis of five key areas.A retrospective observational study as a before and after comparison was used to compare routine data from patients with and without orthogeriatric co-management after nontraumatic surgery. Eligible patients for the study were 70 years and older, had a diagnosis of hip, knee, or shoulder infection, and had been hospitalized for at least 14 days. Co-management consisted of close follow-up by a geriatrician, Comprehensive Geriatric Assessment, and "complex early geriatric rehabilitation". The comparison group received therapy as usual, without a geriatrician and without "complex early geriatric rehabilitation". Special attention was paid to delirium, pain, mobility, postoperative complications, and renal function.Analysis was carried out with 59 patients "with" and 63 "without" geriatric co-management. In the co-management group, delirium was detected significantly more often (p < 0.001), significantly lower pain intensities were measured at the time of discharge (p < 0.001), transfer ability had clearly improved more (p = 0.04), and renal function was more frequently noted (p = 0.04). No significant differences were found with respect to principal diagnoses, surgical procedures performed, complication rates, pressure ulcer and delirium incidence, operative revisions, or length of inpatient stay.Orthogeriatric co-management in orthopedic patients with native and periprosthetic joint infections and nontraumatic surgery appears to have positive impacts on recognition and treatment of delirium, pain management, transfer performance, and attention to renal function. Further studies should follow in order to conclusively assess the value of such co-management in orthopedic nontraumatic surgery patients., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Treating seizure-related shoulder injuries is challenging, and an evidence-based consensus to guide clinicians is lacking. The aim of this prospective single-center observational clinical trial was to evaluate the clinical results of a cohort of patients undergoing treatment of seizure-related shoulder injuries, to categorize them according to the lesion's characteristics, with special focus on patients with proximal humerus fracture-dislocations (PHFDs), and to define groups at risk of obtaining unsatisfactory results. We hypothesized that patients with a PHFD, considered the worst-case scenario among these injuries, would report worse clinical results in terms of the quick Disabilities of the Arm, Shoulder, and Hand questionnaire (qDASH) as compared to the other patients., Methods: Patients referred to a tertiary epilepsy center who have seizure-related shoulder injuries and with a minimum follow-up of 1 year were included. A quality-of-life assessment instrument (EQ-5D-5L), a district-specific patient-reported outcome measure (qDASH), and a pain assessment tool (visual analog scale [VAS]) were used for the clinical outcome evaluation. Subjective satisfaction and fear of new shoulder injuries was also documented. Categorization and subgroup analysis according to the presence and features of selected specific lesions were performed., Results: A total of 111 patients were deemed eligible and 83 were available for follow-up (median age 38 years, 30% females), accounting for a total of 107 injured shoulders. After a median follow-up of 3.9 (1.6-8.2) years, overall moderate clinical results were reported. In addition, 34.1% of the patients reported a VAS score ≥35 mm, indicating moderate to severe pain, and 34.1% a qDASH score ≥40 points, indicating severe disability of an upper limb. These percentages rose to, respectively, 45.5% and 48.5% in the subgroup of patients with PHFDs and to 68.8% and 68.8% in patients experiencing posterior PHFD. Overall, 46.9% of the patients considered themselves unsatisfied with the treatment and 62.5% reported a persistent fear of a new shoulder injury., Conclusions: Patients with seizure-related shoulder injuries reported only moderate clinical results at their midterm follow-up. Older age, male sex, and absence or discontinuation of antiepileptic drug (AED) treatment were identified as characterizing features of patients with posterior dislocation episodes. In patients with PHFD, a tendency to worse clinical results was observed, with posterior PHFD patients emerging as a definite subgroup at risk of reporting unsatisfying results after treatment., (Copyright © 2023 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

As materials for arthroplasty, titanium alloys exhibit the following advantages over conventional steel, cobalt chromium or chromium nickel alloys - good fatigue strength, excellent biocompatibility, low modulus of elasticity, and high corrosion resistance. The previous worse clinical outcome was most likely caused by crevice corrosion and led to reduced use. To warrant safe use, the design should be optimised (sufficient proximal diameter, proximal collar), in order to reduce unwanted deformation in the proximal part of the prosthesis. Additionally, a rough surface (Ra > 2.5 µm) should not be used. Further research in surface treatments (e. g. silicate-silane) could facilitate additional improvement., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: There is a lack of studies investigating the prevalence of syncope-related injuries in a large representative cohort. The aim of this cross-sectional study is to investigate the prevalence of, and variables associated with syncope-related injuries and fractures in a large outpatient population in Germany. Methods: The present study used data from the Disease Analyzer database (IQVIA) and included adults with first-time diagnoses of syncope in 1 of 1284 general practices in Germany between 2005 and 2022 (index date). The prevalence of injuries and separate fractures documented on the index date was examined, and the association of demographic and clinical variables with the risk of syncope-related injuries and fractures was studied using multivariable logistic regression. Results: A total of 143,226 patients (mean age: 57.1 years, 56.9% female) were included in this study. The proportion of injuries was 10.4% and increased from 6.4% in the age group 18-30 to 15.0% in the age group >80 years. Female sex was associated with a slightly higher risk of injury (OR: 1.09; 95% CI: 1.05-1.13) and fractures (OR: 1.17; 95% CI: 1.07-1.28). Osteoporosis was associated with a higher risk of injury (OR: 1.25; 95% CI: 1.16-1.34) and fracture (OR: 1.53; 95% CI: 1.33-1.76), while obesity was only associated with a slightly increased risk of injury. Conclusions: Syncope-related injuries are common among syncope patients. Factors associated with a higher risk of syncope-related injuries, such as female sex, older age, and osteoporosis, can be incorporated into an effective risk stratification and help to improve the outcome of syncope patients.

A painful reduction in shoulder mobility, known as "shoulder stiffness", can occur both as a primary idiopathic condition and as a secondary condition, for example, following surgical procedures. Various factors can contribute to the development of primary shoulder stiffness. In this review we summarize the pathophysiological mechanisms, genetic influences, endocrine disorders, metabolic conditions, as well as other diseases and medical-therapeutic approaches that might have an impact on the development of primary shoulder stiffness., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

We study the interplay between Coulomb blockade and superconductivity in a tunable superconductor-superconductor-normal-metal single-electron transistor. The device is realized by connecting the superconducting island via an oxide barrier to the normal-metal lead and with a break junction to the superconducting lead. The latter enables Cooper pair transport and (multiple) Andreev reflection. We show that these processes are relevant also far above the superconducting gap and that signatures of Coulomb blockade may reoccur at high bias while they are absent for small bias in the strong-coupling regime. Our experimental findings agree with simulations using a rate equation approach in combination with the full counting statistics of multiple Andreev reflection.

Introduction: In 2020, the SARS-CoV-2 pandemic necessitated an adjustment to the care structure in all medical facilities in Germany. In this study we analysed the effects of the SARS-CoV-2 pandemic using the data from the annual balance sheet of a university department and maximum care provider for orthopaedics and trauma surgery., Methods: Data analysis was performed on the clinic's performance parameters from 2019 and 2020. The analysis included 52943 outpatient and 7980 inpatient cases, together with the Case Mix Index (CMI), and the costs and revenues., Results: As a result of the reduction in scheduled surgeries, the mean number of inpatients in March and April 2020 decreased by 10.4% (p = 0.004). Due to the focus on complex cases, the CMI increased by 29.5% (p = 0.007). The number of outpatient surgical procedures increased by 16.9% (n = 84). Rising costs of consumables due to the purchase of protective equipment were offset by a reduced need for orthopaedic implants., Conclusion: By reducing the number of elective inpatient surgical treatments, the focus was shifted to treating complex cases; this is reflected in the increased CMI. Due to internal compensation mechanisms, the clinic was able to conserve intensive care capacities while still achieving an increase in revenue., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

The global agricultural sector faces a significant number of challenges for a sustainable future, and one of the tools proposed to address these challenges is the use of automation in agriculture. In particular, robotic systems for agricultural tasks are being designed, tested, and increasingly commercialised in many countries. Much touted as an environmentally beneficial technology with the ability to improve data management and reduce the use of chemical inputs while improving yields and addressing labour shortages, agricultural robotics also presents a number of potential ethical challenges - including rural unemployment, the amplification of economic and digital inequalities, and entrenching unsustainable farming practices. As such, development is not uncontroversial, and there have been calls for a responsible approach to their innovation that integrates more substantive inclusion into development processes. This study investigates current approaches to participation and inclusion amongst United Kingdom (UK) agricultural robotics developers. Through semi-structured interviews with key members of the UK agricultural robotics sector, we analyse the stakeholder engagement currently integrated into development processes. We explore who is included, how inclusion is done, and what the inclusion is done for. We reflect on how these findings align with the current literature on stakeholder inclusion in agricultural technology development, and suggest what they could mean for the development of more substantive responsible innovation in agricultural robotics., Competing Interests: Competing interestsThe authors have no competing interests to declare that are relevant to the content of this article., (© The Author(s) 2024.)

Recent developments in 68 Ga-radiopharmaceuticals, including a number of regulatory approvals for clinical use, has created a hitherto unprecedented demand for 68 Ga. Reliable access to enough 68 Ga to meet growing clinical demand using only 68 Ge/ 68 Ga generators has been problematic in recent years. To address this challenge, we have optimized the direct production of 68 Ga on a cyclotron via the 68 Zn(p,n) 68 Ga reaction using a liquid target. This protocol describes the cyclotron-based production of [ 68 Ga]GaCl 3 implemented at the University of Michigan using a liquid target on GE PETtrace instrumentation. The protocol provides 56 ± 4 mCi (n = 3) of [ 68 Ga]GaCl 3 that meets the necessary quality control criteria to use for the preparation of 68 Ga-radiopharmaceuticals for human use., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Improving the quality of malaria clinical case management in health facilities is key to improving health outcomes in patients. The U.S. President's Malaria Initiative Impact Malaria Project has supported implementation of the Outreach Training and Supportive Supervision (OTSS) approach in 11 African countries to improve the quality of malaria care in health facilities through the collection and analysis of observation-based data on health facility readiness and health provider competency in malaria case management. We conducted a secondary analysis of longitudinal data collected during routine supervision in Cameroon (April 2021-March 2022), Mali (October 2020-December 2021), and Niger (November 2020-September 2021) using digitized checklists to assess how service readiness affects health worker competencies in managing patients with fever correctly and providing those with confirmed uncomplicated malaria cases with appropriate treatment and referral. Linear or logistic regression analyses were conducted to assess the effect of facility readiness and its components on observed health worker competencies. All countries demonstrated significant associations between health facility readiness and malaria case management competencies. Data from three rounds of OTSS visits in Cameroon, Mali, and Niger showed a statistically significant positive association between greater facility readiness scores (including the availability of commodities, materials, and trained staff) and health worker competency in case management. These findings provide evidence that health worker performance is likely affected by the tools and training available to them. These results reinforce the need for necessary tools and properly trained staff if high-quality malaria case management services are to be delivered at health facilities.

Background: Implant loosening is the most common reason for revision surgery., Objectives: Contribution of modern cementing technique to the long-term stability of an implant., Methods: Evaluation of the available evidence on modern cementing technique., Results: Modern cementing technique in hip arthroplasty is considered established and leads to better cementing results. In knee arthroplasty, there are also specific recommendations, including intensive cleaning of the bone bed, mixing of bone cement under vacuum and application of bone cement to the implant and the bone., Conclusions: The use of modern cementing technique in hip and knee arthroplasty facilitates cementing, increases safety, and minimizes the risk of mechanical loosening., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Johne's Disease (JD) is an infectious ruminant disease that can cause economic loss for famers through reduced milk yields and infertility and has negative implications for animal welfare. JD is endemic in the dairy populations of many countries and there has been significant effort by governments and industry to try and control it. However, these efforts have had limited success. Many studies look at individual control programmes or the adoption of Johne's control measures; however a wider perspective on what drives farmer participation Johne's control does not currently exist. This study seeks to fill this gap by conducting a systematic review informed by the PRISMA statement. The results suggest that psychological factors such as participation fatigue, cognitive dissidence over animal welfare and not having first-hand experience of the disease act as barriers to Johne's control. To better promote Johne's control, this review emphasises that control programmes need to engage farmers, advisers, and supply chain actors in their design and delivery of control programmes to account for differing attitudes and levels of knowledge., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: A different utilization of health care services due to socioeconomic status on the same health plan contradicts the principle of equal treatment. We investigated the presence and magnitude of socioeconomic differences in utilization of diagnostic imaging and non-pharmaceutical conservative therapies for patients with spinal diseases., Methods: The cohort study based on routine healthcare data from Germany with 11.7 million patient-years between 2012 and 2016 for patients with physician-confirmed spinal diseases (ICD-10: M40-M54), occupation and age 20 to 64 years. A Poisson model estimated the effects of the socioeconomic status (school education, professional education and occupational position) for the risk ratio of receiving diagnostic imaging (radiography, computed tomography, magnetic resonance imaging) and non-pharmaceutical conservative therapies (physical therapy including exercise therapy, manual therapy and massage, spinal manipulative therapy, acupuncture)., Results: Patients received diagnostic imaging in 26%, physical therapy in 32%, spinal manipulative therapy in 25%, and acupuncture in 4% of all patient-years. Similar to previous survey-based studies higher rates of utilization were associated with higher socioeconomic status. These differences were most pronounced for manual therapy, exercise therapy, and magnetic resonance imaging., Conclusions: The observed differences in health care utilization were highly related to socioeconomic status. Socioeconomic differences were higher for more expensive health services. Further research is necessary to identify barriers to equitable access to health services and to take appropriate action to decrease existing social disparities., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The planning and implantation of a customized partial pelvis replacement places high demands on both the surgeon and the entire team (engineer, assistants, surgical team). Thanks to careful preoperative planning and meticulous perioperative execution, customized partial pelvic replacement represents a complex but reliable procedure for defect reconstruction even with highly complex acetabular bone defects or after multiple previous surgeries., (© 2023. The Author(s).)

Introduction: When consulting a specialist in orthopaedics and trauma surgery, personal assessment and manual clinical examination by the doctor on site are essential. Nevertheless, implementation of video consultation hours has been made legally easier in Germany. The present pilot study examines the possibility of video-based assessment of the urgency of treatment in outpatient orthopaedic and trauma patients., Materials and Methods: Within an ex ante study design, 40 patients with an orthopaedic clinical picture for trauma surgery with elective, urgent or emergency indication were selected from consultation hours. A short questionnaire was filled in based on the information provided and a medical colleague simulated a movement sequence based on the patient information. After modification to the "red flags" and "yellow flags" established in spinal orthopaedics, nine short questions were recorded, which inquire about the urgency of a medical consultation. The video-based movement sequence is based on a 60 s long instruction video in which motor tests and movement sequences are demonstrated: Cervical spine movement in all levels, elevation of the upper extremity, test of the finger-floor distance when "bending forward over-bending", possibility of crouching from standing and getting up again, standing on heels and toes., Results: In 91.1% (n = 328) of the cases, the diagnosis was associated with the same joint or the same pathological entity. In 37.5% (n = 135) of the cases an emergency indication was seen, in 10.8% (n = 39) of the cases an urgent indication and in 51.6% (n = 186) of the cases it was seen to offer an elective indication. 12.5% (n = 45) of the cases were evaluated as "false positives" with regard to an emergency or urgent presentation. This means that the test persons were classified as "emergency" or "urgent", although there was no preventable dangerous course or medical emergency. 18 cases (5%) were evaluated as "false negative"., Discussion: The screening questionnaire presented and the short video assessment are technically feasible and practicable method for the initial evaluation in video-based online medical consultation. In addition, the questionnaire presented in combination with the short video assessment was suitable as an instrument for assessing the urgency of the consultation and selecting preventable dangerous processes and acute emergencies., Conclusion: The questionnaire, in combination with the short video assessment, is a suitable method for the social distancing requirements during limited accessibility of the medical system. Nevertheless, a false negative rate of 5% is too high to implement the questionnaire presented into daily clinics without further optimisation., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Objectives: the aim of the present study is to investigate the associations between syncope and subsequent diagnoses of brain tumor, cardiac arrhythmia, stroke/transient ischemic attack (TIA), epilepsy, and anxiety disorder in a large outpatient population in Germany., Methods: This retrospective cohort study uses data from the Disease Analyzer database (IQVIA). Adults who received syncope diagnosis from one of 1284 general practices between January 2005 and December 2021 (index date) were included and matched (1:1) to individuals without syncope diagnosis using a propensity score based on age, sex, the number of consultations during the follow-up period (up to 6 months), and defined co-diagnoses documented within 12 months prior to and on the index date. Finally, associations between syncope and subsequent outcome diagnoses were investigated using multivariable logistic regression models., Results: Data related to 64,016 patients with and 64,016 patients without syncope (mean age 54.5 years, 56.5% female) were available. In total, 6.43% of syncope patients and 2.14% of non-syncope patients were diagnosed with one of the five outcome diagnoses within 6 months of the index date. There was a positive and significant association between syncope and incidences of ischemic stroke/TIA (OR = 2.83, 95% CI = 2.41-3.32), arrhythmia (OR = 3.81, 95% CI = 3.44-4.18), brain tumor (OR = 4.24, 95% CI = 2.50-7.19), epilepsy (OR = 5.52, 95% CI = 4.27-7.14), and anxiety disorder (OR = 1.99, 95% CI = 1.79-2.21)., Conclusions: Syncope is significantly associated with an increased risk of subsequent ischemic stroke/TIA, cardiac arrhythmia, brain tumor, epilepsy, and anxiety disorder. Nevertheless, the cumulative incidences for all five diagnoses are very low.

Objectives: In this paper, we use a UK case study to explore how the COVID-19 pandemic affected the mental health (emotional, psychological, social wellbeing) of farmers. We outline the drivers of poor farming mental health, the manifold impacts of the pandemic at a time of policy and environmental change, and identify lessons that can be learned to develop resilience in farming communities against future shocks., Methods: We undertook a survey answered by 207 farmers across the UK, focusing on drivers of poor mental health and the effect of the COVID-19 pandemic. We also conducted 22 in-depth interviews with individuals in England, Scotland and Wales who provide mental health support to farmers. These explored how and why the COVID-19 pandemic affected the mental health of farmers. These interviews were supplemented by 93 survey responses from a similar group of support providers (UK-wide)., Results: We found that the pandemic exacerbated underlying drivers of poor mental health and wellbeing in farming communities. 67% of farmers surveyed reported feeling more stressed, 63% felt more anxious, 38% felt more depressed, and 12% felt more suicidal. The primary drivers of poor mental health identified by farmers during the pandemic included decreased social contact and loneliness, issues with the general public on private land, and moving online for social events. Support providers also highlighted relationship and financial issues, illness, and government inspections as drivers of poor mental health. Some farmers, conversely, outlined positive impacts of the pandemic., Conclusion: The COVID-19 pandemic is just one of many potential stressors associated with poor farming mental health and its impacts are likely to be long-lasting and delayed. Multiple stressors affecting farmers at the same time can create a tipping point. Therefore, there is a need for long-term support and ongoing evaluation of the drivers of poor mental health in farming families.

Hypoxia contributes to numerous pathophysiological conditions including inflammation-associated diseases. We characterized the impact of hypoxia on the immunometabolic cross-talk between cholesterol and interferon (IFN) responses. Specifically, hypoxia reduced cholesterol biosynthesis flux and provoked a compensatory activation of sterol regulatory element-binding protein 2 (SREBP2) in monocytes. Concomitantly, a broad range of interferon-stimulated genes (ISGs) increased under hypoxia in the absence of an inflammatory stimulus. While changes in cholesterol biosynthesis intermediates and SREBP2 activity did not contribute to hypoxic ISG induction, intracellular cholesterol distribution appeared critical to enhance hypoxic expression of chemokine ISGs. Importantly, hypoxia further boosted chemokine ISG expression in monocytes upon infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Mechanistically, hypoxia sensitized toll-like receptor 4 (TLR4) signaling to activation by SARS-CoV-2 spike protein, which emerged as a major signaling hub to enhance chemokine ISG induction following SARS-CoV-2 infection of hypoxic monocytes. These data depict a hypoxia-regulated immunometabolic mechanism with implications for the development of systemic inflammatory responses in severe cases of coronavirus disease-2019 (COVID-19)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bauer, Meyer, Raue, Palmer, Guerrero Ruiz, Cardamone, Rösser, Heffels, Roesmann, Wilhelm, Lütjohann, Zarnack, Fuhrmann, Widera, Schmid and Brüne.)

Objective: Treatment of chronic periprosthetic joint infection of the knee requires the removal of the implant and thorough debridement, with reimplantation in a second stage surgery. Intramedullary spacers can be helpful during the interval between explantation and reimplantation and provide a temporary arthrodesis which fixes the knee in extension preserving leg length and administers local antibiotic therapy., Indications: Periprosthetic joint infection of the knee with large bony defects and severe infection of the native joint with advanced destruction/infiltration of the cartilage and bone and/or ligament insufficiency., Contraindications: Suspected antibiotic resistance of the microbiological pathogen to local antibiotic drugs, incompliant patient, and known allergy to bone cement or antibiotic., Surgical Technique: After implant removal, suitable metal rods are coated with antibiotic-loaded bone cement and inserted into the cleaned intramedullary canals of femur and tibia. Rods are joined at the joint line with a connector and joint space is filled with more bone cement to achieve temporary and very stable arthrodesis., Postoperative Management: Partial weight-bearing and no flexion/extension while spacer is in place; second stage reimplantation as soon as infection is controlled., Results: Complications related to the spacer were rare (5.3%). Reimplantation of an implant was possible in 95 of 113 patients (84%), of those, 23 (20%) received an arthrodesis. Of the 95 patients that were reimplanted, 14 showed signs of recurrent infection. Mean time to last follow-up was 15.6 months post reimplantation. Mean knee pain was 2.9/10; overall function was good; 6 patients had an extension lag; mean total range of motion was 88°., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: Hypnosis is useful for diminishing distress during medical procedures. This study investigated the efficacy of virtually augmented self-hypnosis as an adjunctive non-pharmacological method for procedural pain and anxiety relief during endovascular interventions (EVI)., Methods: We compared an immersive distraction experience (clinicaltrials.gov identifier NCT04561596) featuring virtual reality (VR) using a head-mounted display versus treatment as usual (TAU). Patients followed the "Aqua" module (Oncomfort™) consisting of a scuba dive and breathing exercises. They experienced a self-induced dissociative state similar to clinical hypnosis without direct intervention of a professional. Enrollment followed a 1:1 randomized open study (VR or TAU). Patients' feelings were evaluated just before and after the procedure, and 3 months following intervention. Anxiety was evaluated using the State Trait Anxiety Inventory (STAI) and pain (sensory, emotional, and memory) with a visual analogue scale (VAS)., Results: This study included 100 patients. Mean anxiety (pre-post) was significantly reduced within groups and between groups (difference of 4.2 points, p = 0.016). The percentage of responders to anxiety lowering were 76 and 46% for VR and TAU, respectively (p = 0.004). The two groups did not significantly differ in mean sensory-intensity and affective emotional pain (pre-post) using VAS, in negative memories concerning remembered pain at 3 months (difference > 1 from immediate post-procedural reported pain intensity), mean procedural time, or the need for analgesic or sedative drugs., Conclusions: VR self-hypnosis has the potential to improve the management of patients' distress during radiological procedures. It is safe and effective for reducing anxiety during EVI., (© 2023. The Author(s).)

Introduction: 5α-reductase inhibitors (5ARI) are commonly prescribed medications. There is ongoing controversy about the adverse events of these medications. The aim of this study is to characterize lawsuits in Canada involving medical complications of 5ARIs use., Materials and Methods: Legal cases were queried from CanLII. Cases were included if they involved a party taking a 5ARI who alleged an adverse event. Relevant full cases were retained, and pertinent characteristics were extracted with the help of a legal expert., Results: Our deduplicated search yielded 67 unique legal documents from December 2013 to February 2019. Twelve of these documents met the inclusion criteria (representing 3 cases, considering each case had several hearings). The medical complaints filed by the plaintiffs were all related to medication side effects (n = 3, 100%). The plaintiffs were commonly patients themselves. Defendants were exclusively pharmaceutical companies. Persistent erectile dysfunction after stopping the medication was cited as a side effect in all complaints. The prescriptions were made for male pattern hair loss (n = 3, 100%) in all cases. All cases represent class actions brought by the plaintiffs, and they have been certified by their respective court. However, the cases are still ongoing., Conclusion: While 5ARI use has been linked to undesired sexual side effects, there have been few litigations on this issue in Canada. Persisting sexual dysfunction after stopping the medication is the only complaint presented in legal action. To date, no judgment against a physician or pharmaceutical company was identified. Cases are still ongoing.

Background: Periprosthetic joint infection remains a common and serious complication after hip arthroplasty. To improve function and patient comfort after joint removal in two-stage revision, commercially manufactured spacers for the hip joint allow retention of the anatomical joint geometry thereby limiting soft tissue contraction and allow mobilization., Indications: Periprosthetic joint infection of the hip, septic arthritis with severe destruction of the hip cartilage and/or bone requiring arthroplasty., Contraindications: Allergies to polymethylmethacrylate (PMMA) or antibiotics, severe hip dysplasia with insufficient cranial support, incompliant patient, large osseous defect of the acetabulum, insufficient metaphyseal/diaphyseal support of the femoral bone, resistance of the microbiological pathogen to spacer-inert antibiotic medication, inability to perform primary wound closure requiring temporary open-wound therapy., Surgical Technique: Preoperative templating on radiograph; removal of joint prosthesis and thorough debridement with removal of all foreign material; trial spacer selection and insertion and trial reduction of the joint, fixing the spacer with PMMA to the proximal femur, final reduction, radiograph and stability test., Results: Data were analyzed from patients treated between 2016 and 2021. In all, 20 patients were treated with preformed spacers and 16 with custom-made spacers. Pathogens were detected in 23 of the 36 cases (64%). Polymicrobial infections were present in 8 of 36 cases (22%). In patients who received preformed spacers, there were 6 cases of spacer-related complications (30%). Of the 36 patients (83%), 30 were reimplanted with a new implant; 3 patients died due to septic or other complications before reimplantation (8%). Average follow-up was 20.2 months after reimplantation. There were no major differences between the two groups of spacers. Patient comfort was not measured., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objective: Mobile knee spacers can be utilized in the first stage of a two-stage exchange in periprosthetic joint infection or septic arthritis of the knee to prevent soft tissue contraction, enable local antibiotic elution, and improve patient mobility. Commercially made moulds enable the surgeon to prepare a reproducible spacer design and match the preparation of the arthroplasty, which will be carried out in a second step., Indications: Periprosthetic joint infection of the knee and severe cases of septic arthritis of the knee with advanced destruction/infiltration of the cartilage., Contraindications: Antibiotic resistance of the microbiological pathogen to available antibiotic agents, incompliant patient, large osseous defect preventing proper fixation, known allergy to polymethylmethacrylate (PMMA) or antibiotic, severe soft tissue damage with high ligament instability, especially deterioration of extensor mechanism and insufficient patella/quadricep tendon., Surgical Technique: After thorough debridement and removal of all foreign material, cutting blocks are used to shape femur and tibia to the implant design required. Using a silicone mould, PMMA with suitable antibiotics is moulded into the shape of the future implant. After polymerization, the implants are fixed onto the bone with additional PMMA without pressurize for the sake of easy removal., Postoperative Management: Partial weight bearing with no restriction of flexion/extension while spacer is in place; second stage reimplantation as soon as infection is controlled., Results: In all, 22 cases were treated, mostly with a PMMA spacer containing gentamicin and vancomycin. Pathogens were detected in 13 of 22 cases (59%). We observed two complications (9%). Twenty of 22 patients (86%) were reimplanted with a new arthroplasty; 16 of the 20 patients remained revision-free and infection-free at the last follow-up (average time to follow-up 13 months, range 1-46 months). Average range of motion in flexion and extension at follow-up was 98°., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: Epileptic seizures can cause multiple shoulder injuries, the most common of which are dislocations, recurrent instability, fractures, and isolated lesions of the rotator cuff. Currently, only limited literature exists which describes the frequency and types of lesions in cohorts of epileptic patients and the corresponding treatment outcome. This study aims to document the occurrence of shoulder lesions in patients affected by seizures and to provide detailed information on trauma dynamics, specific lesion characteristics and treatment complications., Methods: All patients referring to a tertiary epilepsy center were screened for shoulder injuries and the clinical records of those sustaining them during a seizure were reviewed. Demographic information, lesions' characteristics and trauma dynamics were analysed, as wells as-when carried out-the type of surgical intervention and any postoperative complications., Results: The average age at the time of injury of 106 included patients was 39.7 ± 17.5 years and a male predominance was recorded (65%). Bilateral injuries occurred in 29 patients, simultaneously in 17 cases. A younger age, bilateral shoulder injuries and shoulder dislocations were significantly associated with the occurrence of a shoulder injury solely by muscular activation (p = 0.0054, p = 0.011, p < 0.0001). The complication rate in 57 surgically treated patients with follow-up data was 38.7%, with recurring instability being the most frequently reported complication (62.5%)., Conclusions: Uncontrolled muscle activation during a seizure is a distinctive but not exclusive dynamic of injury in epileptic patients, accounting for more than the half of all shoulder lesions, especially in the younger. This can lead both to anterior and posterior dislocations or fracture-dislocations and is frequently cause of bilateral lesions and of instability recurrence after surgery. The high complication rates after surgical treatment in this selected subgroup of patients require that appropriate preventative measures are taken to increase the probability of treatment success., Level of Evidence: Cohort study, level III., (© 2022. The Author(s).)

BACKGROUND: Alopecia areata (AA) is an autoimmune disease characterized by nonscarring hair loss. AA frequently co-occurs with other inflammatory autoimmune conditions, presenting a significant clinical burden. OBJECTIVE: To compare the burden of illness, direct and indirect costs in adult patients with AA vs atopic dermatitis (AD). METHODS: This retrospective cohort study used US administrative claims data from the Merative MarketScan Commercial Claims and Encounters Database to compare commercially insured adults with AA to those with AD. Patients with an AA diagnosis between January 2017 and September 2019 were propensity score matched to patients with AD. Comorbidity burden, medication use, health care resource utilization, health care costs, and indirect costs during a 12-month follow-up period were compared between cohorts. RESULTS: Overall, 25,446 adult patients with AA were selected for the matched analysis with the AD cohort. Patients with AA generally had lower comorbidity burden than patients with AD; mean Deyo-Charlson Comorbidity Index scores were 0.36 (SD = 0.99) and 0.39 (SD = 0.92), for AA and AD, respectively ( P = 0.007). Patients with AA had significantly lower proportions of allergic rhinitis, asthma, pruritus, skin infections, and urticaria, but higher proportions of thyroid disease, when compared with patients with AD (all P < 0.001). A smaller proportion of patients with AA had prescriptions for topical (45.3% vs 64.8%; P < 0.001) and oral (20.3% vs 29.6%; P < 0.001) corticosteroids and antianxiety and/or antidepressants (24.7% vs 29.7%; P < 0.001), but a significantly larger proportion for intralesional corticosteroids (triamcinolone) (49.6% vs 21.7%; P < 0.001), compared with patients with AD. Despite a lower comorbidity burden and generally less medication usage in patients with AA, total all-cause health care costs did not significantly differ between the AA and AD cohorts ($10,705 vs $10,816; P = 0.712), and outpatient costs were higher in patients with AA ($6,297 vs $5,859; P = 0.014). Female patients with AA had significantly greater costs for both outpatient and outpatient pharmacy when compared with female patients with AD. Patients with AA were more likely to have a claim for long-term disability (0.6% vs 0.3%; P = 0.001) and higher long-term disability-associated indirect costs ($73 [SD = $1,442] vs $25 [SD = $774]; P = 0.004) compared with patients with AD. CONCLUSIONS: We found similar total health care costs in patients with AA and AD, despite a lower proportion of comorbidities and prescription use in patients with AA. Outpatient costs were also significantly higher overall in patients with AA. Although often dismissed as a cosmetic condition, AA, an autoimmune disease, has a similar level of medical expenditure as AD. DISCLOSURES: This study was funded by Eli Lilly and Company. Mr Fenske and Drs Ding, Morrow, and Smith are employed by Eli Lilly and Company. Drs Manjelievskaia, Moynihan, and Silver are employed by Merative. Drs Manjelievskaia, Moynihan, and Silver were employed by IBM Watson Health at the time of study completion. IBM Watson Health received funding from Eli Lilly and Company to conduct this study.

Objective: In the course of the corona pandemic, resource conservation and the protection of further infections have made it necessary to break new ground in the organisation of orthopaedic and trauma surgery consultations. One solution is consistent digitisation and the offer of video consultation hours. In this study, non-contact examination of patients with shoulder disorders is described and critically examined., Methods: Thirty patients who presented with pathologies of the shoulder joint in a university outpatient clinic were subjected to a physical examination in a conventional and contactless manner. The data obtained on mobility, function and provocation test of both examinations were compared to draw conclusions about the virtual feasibility., Results: 46% of the patients suffered from a traumatic shoulder lesion, and 54% showed degenerative lesions. The assessment of mobility showed a high correlation of 70 - 90% between the two examinations. Common tests to evaluate the supraspinatus, infraspinatus, subscapularis and the long head of the biceps could be adequately performed in a contactless version by more than three quarters of the patients, but with low-to-moderate performance values., Conclusion: Contact-less examination is particularly disadvantageous when evaluating stability criteria. For the medical history and functional test, there were no significant differences between the classic consultation and contactless consultation. Although virtual consultation is a widespread and valuable addition in pandemic times, it cannot replace a safe assessment and indication by personal examination., Competing Interests: The authors declare that they have no conflict of interest./Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Introduction: Acetabular defect recognition and classification remains a challenging field of practice for orthopedic surgeons. Recently, the Acetabular Defect Classification (ADC) has been introduced to provide a reliable, reproducible and intuitive classification system. In order to improve ease of use and efficiency of the ADC, a browser-based application has been created. We hypothesized that the ADC application can improve rating performance of non-specialists (medical students) to achieve good inter- and intra-rater agreement and will compare favorable to the results of specialists (experienced surgeons) without the help of the application., Materials and Methods: The ADC is based on the integrity of the acetabular rim and the supporting structures. It consists of four main types of defects ascending in severity. These defects are further subdivided in A-C, narrowing down defect location. 80 randomized radiographs were graded according to ADC by three non-specialists (medical students) with help of the ADC application and by three specialists (orthopedic surgeons) without help of the application to evaluate the difference in inter-rater agreement between groups. To account for intra-rater agreement, the rating process was repeated after a reasonable wash-out period., Results: Inter-rater and intra-rater agreement within the non-specialist group rated lower when compared to the specialist group while still falling into the good agreement range. The student group presented with k values of 0.61 for inter-rater agreement and 0.68 for intra-rater agreement, while the surgeon group displayed k values of 0.72 for inter-rater agreement and 0.83 for intra-rater agreement., Conclusion: The app-guided assessment of acetabular defects offers a promising innovative approach to simplify complex situations. It makes the challenging field of acetabular revision arthroplasty more approachable especially for less experienced surgeons and offers insight and guidance in the planning stage as well as intra-operative setting., (© 2021. The Author(s).)

Background: Surgical treatment of patients with osteoarthritis of the hip and persisting symptoms under conservative therapy has become increasingly important against the background of an aging population., Objectives: What are the physiological reactions in the interface between cementless implants and bone?, Methods: The literature is reviewed, expert opinions and animal models are analyzed and discussed., Results: Surface coating of implants with hydroxyapatite or titanium can have positive effects on osteointegration. Additional local application of mediators might be beneficial for osteointegration in the future., Conclusion: Early peri-implant bone healing directly after implantation and late remodeling of the bone-implant interface are essential for secondary implant stability., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Introduction: The complex field of femoral defects in revision hip arthroplasty displays a lack of standardized, intuitive pre- and intraoperative assessment. To address this issue, the femoral defect classification (FDC) is introduced to offer a reliable, reproducible and an intuitive classification system with a clear therapeutic guideline., Materials and Methods: The FDC is based on the integrity of the main femoral segments which determine function and structural support. It focuses on the femoral neck, the metaphysis consisting of the greater and lesser trochanter, and the femoral diaphysis. The four main categories determine the location of the defect while subcategories a, b and c are being used to classify the extent of damage in each location. In total, 218 preoperative radiographs were retrospectively graded according to FDC and compared to intraoperatively encountered bone defects. To account for inter-rater and intra-rater agreement, 5 different observers evaluated 80 randomized cases at different points in time., Results: A Cohens kappa of 0.832 ± 0.028 could be evaluated, accounting for excellent agreement between preoperative radiographs and intraoperative findings. To account for inter-rater reliability, 80 patients have been evaluated by 5 different observers. Testing for inter-rater reliability, a Fleiss Kappa of 0.688 could be evaluated falling into the good agreement range. When testing for intra-rater reliability, Cohens Kappa of each of the 5 raters has been analyzed and the mean was evaluated at 0.856 accounting for excellent agreement., Conclusion: The FDC is a reliable and reproducible classification system. It combines intuitive use and structured design and allows for consistent preoperative planning and intraoperative guidance. A therapeutic algorithm has been created according to current literature and expert opinion. Due to the combination of the FDC with the recently introduced Acetabular Defect Classification (ADC) a structured approach to the entire field of hip revision arthroplasty is now available., (© 2021. The Author(s).)

Glucose metabolism is dysregulated in Parkinson's disease (PD) causing a shift toward the metabolism of lipids. Carnitine palmitoyl-transferase 1A (CPT1A) regulates the key step in the metabolism of long-chain fatty acids. The aim of this study is to evaluate the effect of downregulating CPT1, either genetically with a Cpt1a P479L mutation or medicinally on PD using chronic rotenone mouse models using C57Bl/6J and Park2 knockout mice. We show that Cpt1a P479L mutant mice are resistant to rotenone-induced PD, and that inhibition of CPT1 is capable of restoring neurological function, normal glucose metabolism, and alleviate markers of PD in the midbrain. Furthermore, we show that downregulation of lipid metabolism via CPT1 alleviates pathological motor and non-motor behavior, oxidative stress, and disrupted glucose homeostasis in Park2 knockout mice. Finally, we confirm that rotenone induces gut dysbiosis in C57Bl/6J and, for the first time, in Park2 knockout mice. We show that this dysbiosis is alleviated by the downregulation of the lipid metabolism via CPT1., (© 2023. The Author(s).)

Background: Gliomas with FGFR3::TACC3 fusion mainly occur in adults, display pathological features of glioblastomas (GB) and are usually classified as glioblastoma, IDH-wildtype. However, cases demonstrating pathological features of low-grade glioma (LGG) lead to difficulties in classification and clinical management. We report a series of 8 GB and 14 LGG with FGFR3:TACC3 fusion in order to better characterize them., Methods: Centralized pathological examination, search for TERT promoter mutation and DNA-methylation profiling were performed in all cases. Search for prognostic factors was done by the Kaplan-Meir method., Results: TERT promoter mutation was recorded in all GB and 6/14 LGG. Among the 7 cases with a methylation score > 0.9 in the classifier (v12.5), 2 were classified as glioblastoma, 4 as ganglioglioma (GG) and 1 as dysembryoplastic neuroepithelial tumor (DNET). t-SNE analysis showed that the 22 cases clustered into three groups: one included 12 cases close to glioblastoma, IDH-wildtype methylation class (MC), 5 cases each clustered with GG or DNET MC but none with PLNTY MC. Unsupervised clustering analysis revealed four groups, two of them being clearly distinct: 5 cases shared age (< 40), pathological features of LGG, lack of TERT promoter mutation, FGFR3(Exon 17)::TACC3(Exon 10) fusion type and LGG MC. In contrast, 4 cases shared age (> 40), pathological features of glioblastoma, and were TERT-mutated. Relevant factors associated with a better prognosis were age < 40 and lack of TERT promoter mutation., Conclusion: Among gliomas with FGFR3::TACC3 fusion, age, TERT promoter mutation, pathological features, DNA-methylation profiling and fusion subtype are of interest to determine patients' risk., (© 2023. The Author(s).)

Prevalent narratives of agricultural innovation predict that we are once again on the cusp of a global agricultural revolution. According to these narratives, this so-called fourth agricultural revolution, or agriculture 4.0, is set to transform current agricultural practices around the world at a quick pace, making use of new sophisticated precision technologies. Often used as a rhetorical device, this narrative has a material effect on the trajectories of an inherently political and normative agricultural transition; with funding, other policy instruments, and research attention focusing on the design and development of new precision technologies. A growing critical social science literature interrogates the promises of revolution. Engagement with new technology is likely to be uneven, with benefits potentially favouring the already powerful and the costs falling hardest on the least powerful. If grand narratives of change remain unchallenged, we risk pursuing innovation trajectories that are exclusionary, failing to achieve responsible innovation. This study utilises a range of methodologies to explore everyday encounters between farmers and technology, with the aim of inspiring further work to compile the microhistories that can help to challenge robust grand narratives of change. We explore how farmers are engaging with technology in practice and show how these interactions problematise a simple, linear notion of innovation adoption and use. In doing so, we reflect upon the contribution that the study of everyday encounters can make in setting more inclusionary, responsible pathways towards sustainable agriculture., Competing Interests: Conflict of interestThe authors declared that they have no conflict of interest., (© The Author(s) 2022.)

Non-face (NF) emojis are increasingly used to complement or substitute words in digital marketing messages, yet the effects, mechanisms, and contingencies of this communication strategy remain underexplored. In a large-scale longitudinal study of Airbnb listings, we show that NF emojis (vs. simple text) lead to an increase in eWOM volume, an effect we replicate experimentally. This effect is qualified by important boundary conditions whose underlying mechanisms are investigated in two additional experimental studies. At the message level, using multiple substitutive (vs. complementary) NF emojis reduces message evaluations and eWOM volume due to reduced processing fluency. At the source level, seller quality further moderates the interaction between emoji function and emoji number: for premium sellers, using multiple NF emojis reduces message evaluations and eWOM volume irrespective of their function due to reduced perceptions of competence. We distill these findings into detailed managerial guidelines for using NF emojis in digital marketing., Supplementary Information: The online version contains supplementary material available at 10.1007/s11747-022-00917-z., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© Academy of Marketing Science 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Because of their individual vulnerabilities, treatment decisions for older patients can be difficult. Geriatric assessment (GA) may help to select patients for systemic treatment, but its value is still unproven. Older cancer patients (≥65 years of age) with and without complex GA followed by discussion in the geriatric-oncologic conference, who had been treated in palliative intention with standard combination chemotherapy at the Evang. Kliniken Essen-Mitte, were retrospectively evaluated. All patients had been orally informed about the treatment options and had chosen chemotherapy beside supportive care. To reduce selection bias, the method of propensity-score matching was performed. Patient groups treated in the years 2011-2013 (without GA, group 1) and in the years 2014-2015 (with GA, group 2) were compared regarding different toxicity endpoints. The primary endpoint of the study was defined as numbers of patients with unplanned admission to the hospital or death during first-line chemotherapy and GA should reduce these events by 15%. Overall, 114 patients were evaluated in both groups. The median age was 74 years. Patients suffered from gastrointestinal carcinomas (47%), lung cancer (28%), breast cancer (12%), and other cancer types (3%). Consequently, most patients were treated with platinum-based (41%), fluoropyrimidine-based (35%), or anthracycline-based (13%) combination chemotherapy. In group 2, the events were numerically lower for all toxicity endpoints. The need for a premature stop of treatment was 54.4% in group 1 compared to 29.8% in group 2 (p < 0.01) and also the treatment-related mortality was significantly lower in group 2 (17.5% vs. 5.3%; p = 0.04). The primary endpoint, the rate of unplanned hospital admission, and death was 49.1% versus 35.1% (difference 14.0%), which did not reach the predefined border of 15%. There was a nonsignificant overall survival benefit in the group with GA (22.6 vs. 18.4 months). GA appears useful to better select older patients with advanced cancer for combination chemotherapy. The significant reduction of mortality during chemotherapy justifies the efforts and costs which need to be expended. To evaluate the effect of GA on overall survival, prospective trials are required., (© 2023 S. Karger AG, Basel.)