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Abstract The record-breaking temperatures in Europe during the 2022 summer were associated with over 60,000 heat-related deaths. By combining epidemiological models with detection and attribution techniques, we attribute half of this mortality burden (~56% [95% CI 39–77%]) to anthropogenic warming. Likewise, this applies to all sexes, ages, and heat-related mortality burdens during previous years (2015–2021). Our results urgently call for increasing ambition in adaptation and mitigation.

Abstract Human-wildlife interactions are situated within dynamic systems, characterized by social and ecological complexity. Human-wildlife coexistence research, however, typically focuses on one component of these systems in isolation. We inadvertently followed this norm while carrying out semi-structured interviews of livestock-owners in Northern Tanzania. As existing literature highlighted that this area was a hotspot for livestock depredation, our research questions focused on human interactions with carnivores. Interestingly, almost three quarters (72%, n = 72 of 100) of study participants independently raised African elephants (Loxodonta africana) as presenting the greatest impediments to coexistence. By centering our interviews on carnivores, we omitted vital components of this complex system. To counteract the effects of this oversimplification, we changed our intended analytical process after data collection. Instead of conducting a quantitative analysis of rates of livestock depredation and perceptions of risk posed by a suite of sympatric carnivores, we applied a grounded theory approach to assess interactions across multiple dimensions of this complex system. Through this transparent effort to realign our approaches with the complexity of the study system, we highlight the importance of designing research approaches that effectively reflect the complexities inherent to human-wildlife coexistence.

Free-space optical communications in the mid-infrared transparency windows (4–5 and 8–14 μm wavelength regions) is emerging as a viable solution for high bitrate data transmission. Unipolar quantum optoelectronics is the technology of choice for data communication in this wavelength region, thanks to the high frequency response of detectors and modulators. In this work, it is demonstrated that the performances of these devices can be substantially enhanced by embedding them into metamaterials. It is also shown that metamaterials have to be engineered differently in detectors than in modulators, as the role of light–matter interaction must be tuned adequately in the two devices. Metamaterial-enhanced performances allow the realization of data transmission with a record rate of 68 Gbit/s, while ensuring robustness and consistency, as it should be for real-world applications. These findings underscore the promising role of metamaterial-enhanced unipolar devices in advancing free-space optical communication systems.

Background: Current segmentation approaches for radiation treatment planning in head and neck cancer patients (HNCP) typically consider the entire mandible as an organ at risk, whereas segmentation of the maxilla remains uncommon. Accurate risk assessment for osteoradionecrosis (ORN) or implant-based dental rehabilitation after radiation therapy may require a nuanced analysis of dose distribution in specific mandibular and maxillary segments. Manual segmentation is time-consuming and inconsistent, and there is no definition of jaw subsections. Materials and methods: The mandible and maxilla were divided into 12 substructures. The model was developed from 82 computed tomography (CT) scans of HNCP and adopts an encoder-decoder three-dimensional (3D) U-Net structure. The efficiency and accuracy of the automated method were compared against manual segmentation on an additional set of 20 independent CT scans. The evaluation metrics used were the Dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), and surface DSC (sDSC). Results: Automated segmentations were performed in a median of 86 s, compared to manual segmentations, which took a median of 53.5 min. The median DSC per substructure ranged from 0.81 to 0.91, and the median HD95 ranged from 1.61 to 4.22. The number of artifacts did not affect these scores. The maxillary substructures showed lower metrics than the mandibular substructures. Conclusions: The jaw substructure segmentation demonstrated high accuracy, time efficiency, and promising results in CT scans with and without metal artifacts. This novel model could provide further investigation into dose relationships with ORN or dental implant failure in normal tissue complication prediction models.

Background: Traumatic brain injuries (TBIs) are a common consequence of experiencing intimate partner violence (IPV). IPV-related TBI contributes to adverse health outcomes among women, but it is unknown whether a history of IPV-related TBI negatively impacts safety outcomes following healthcare-based interventions for IPV. Methods: Using data from a larger randomized clinical trial, we explored the impact of IPV-related TBI status on safety-related outcomes in two healthcare-based IPV interventions. At baseline, 35% (n = 21) of the sample screened positive for IPV-related TBI history. We used repeated measures ANOVAs to examine differences in safety outcomes at post-treatment and 1-month follow-up based on treatment condition and IPV-related TBI status. Results: Significant interaction effects were found for safety outcomes, such that women with IPV-related TBI history experienced larger reductions in the frequency of physical IPV and similar reductions in sexual IPV across both treatment conditions compared to women without IPV-TBI (F(2, 102) = 10.88, p < 0.001; F(2, 98) = 3.93, p = 0.036). Conclusions: Findings suggest that brief healthcare-based IPV interventions may result in improvements in safety outcomes for women with a history of IPV-TBI. This highlights the continued need for implementation of promising IPV-focused interventions to promote safety and protect women from experiencing further IPV.

The ring-shaped chaperonin T-complex protein ring complex (TRiC; also known as chaperonin containing TCP-1, CCT) is an ATP-driven protein-folding machine that is essential for maintenance of cellular homeostasis 1,2 . Its dysfunction is related to cancer and neurodegenerative disease 3,4 . Despite its importance, how TRiC works in the cell remains unclear. Here we structurally analysed the architecture, conformational dynamics and spatial organization of the chaperonin TRiC in human cells using cryo-electron tomography. We resolved distinctive open, closed, substrate-bound and prefoldin-associated states of TRiC, and reconstructed its duty cycle in situ. The substrate-bound open and symmetrically closed TRiC states were equally abundant. Closed TRiC containing substrate forms distinctive clusters, indicative of spatial organization. Translation inhibition did not fundamentally change the distribution of duty cycle intermediates, but reduced substrate binding for all states as well as cluster formation. From our in-cell structures, we identified the programmed cell death protein 5 (PDCD5) as an interactor that specifically binds to almost all open but not closed TRiC, in a position that is compatible with both substrate and prefoldin binding. Our data support a model in which TRiC functions at near full occupancy to fold newly synthesized proteins inside cells. Defining the TRiC cycle and function inside cells lays the foundation to understand its dysfunction during cancer and neurodegeneration., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Due to the widespread use of high-resolution sonography, numerous thyroid nodules are diagnosed, often as incidental findings. The challenge lies in evaluating various criteria such as size, shape, and echogenicity to assess the nodules' malignancy risk. Risk stratification systems have been developed to enable systematic assessment as well as to avoid unnecessary medical interventions and malignant findings being overlooked. This article provides an overview of the current diagnostic standards in primary assessment of thyroid nodules., Competing Interests: Einhaltung ethischer Richtlinien Interessenkonflikt Gemäß den Richtlinien des Springer Medizin Verlags werden Autoren und Wissenschaftliche Leitung im Rahmen der Manuskripterstellung und Manuskriptfreigabe aufgefordert, eine vollständige Erklärung zu ihren finanziellen und nichtfinanziellen Interessen abzugeben. Autoren D. Richter: A. Finanzielle Interessen: D. Richter gibt an, dass kein finanzieller Interessenkonflikt besteht. – B. Nichtfinanzielle Interessen: Assistenzarzt an der HNO-Klinik Erlangen. Keine nebenberuflichen Tätigkeiten. M. Beck: A. Finanzielle Interessen: Honorar für Referententätigkeit von Ipsen Pharma GmbH, Reisekostenerstattung von Ipsen Pharma GmbH und Novartis Radiopharmaceuticals/AAA; Übernachtungskostenerstattung + Tätigkeit Advisory Board Novartis Radiopharmaceuticals/AAA. – B. Nichtfinanzielle Interessen: Oberarzt/Nuklearmedizinische Klinik/Universitätsklinikum Erlangen | Mitgliedschaften: Deutsche Gesellschaft für Nuklearmedizin, Berufsverband Deutscher Nuklearmediziner, European Association of Nuclear Medicine and Molecular Imaging. S.K. Müller: A. Finanzielle Interessen: S.K. Müller gibt an, dass kein finanzieller Interessenkonflikt besteht. – B. Nichtfinanzielle Interessen: Geschäftsführende Oberärztin an der HNO-Klinik Erlangen. Keine nebenberuflichen Tätigkeiten | Mitgliedschaft: Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e. V. H. Iro: A. Finanzielle Interessen: H. Iro gibt an, dass kein finanzieller Interessenkonflikt besteht. – B. Nichtfinanzielle Interessen: Ärztlicher Direktor der HNO Klinik Erlangen. Keine Nebenberufliche Tätigkeiten. | Mitgliedschaft: Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e. V. M. Koch: A. Finanzielle Interessen: M. Koch gibt an, dass kein finanzieller Interessenkonflikt besteht. – B. Nichtfinanzielle Interessen: Oberarzt an der HNO Klinik Erlangen. Keine nebenberuflichen Tätigkeiten. M. Sievert: A. Finanzielle Interessen: M. Sievert gibt an, dass kein finanzieller Interessenkonflikt besteht. – B. Nichtfinanzielle Interessen: Oberarzt Abteilung für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie, Universität Erlangen-Nürnberg, Waldstraße 1, 91054 Erlangen, Deutschland. | DEGUM-Kursleiter Sektion Kopf-Hals und Veranstalter von DEGUM-zertifizierten Kursen. Wissenschaftliche Leitung Die vollständige Erklärung zum Interessenkonflikt der Wissenschaftlichen Leitung finden Sie am Kurs der zertifizierten Fortbildung auf www.springermedizin.de/cme. Der Verlag erklärt, dass für die Publikation dieser CME-Fortbildung keine Sponsorengelder an den Verlag fließen.Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objective: Despite numerous studies addressing the impact of p16 INK4a in oral squamous cell carcinoma (OSCC), consistent data regarding survival and tumor proliferation behavior are lacking. Although some authors investigate both p16 INK4a and Mib/Ki-67 in their cohorts, direct correlations are consistently missing. The aim of this study was to investigate the combined influence of p16 INK4a and Mib/Ki-67 status on prognosis in OSCC., Materials and Methods: Clinical data of all patients diagnosed with OSCC and treated curatively between 2005 and 2011 were collected retrospectively. Tissue microarrays of formalin-fixed paraffin-embedded specimens were stained for p16 INK4a and Mib/Ki-67 using the CINtec Histology V-Kit or MIB-1 antibody and correlated with the clinical outcome., Results: A total of 316 patients, with a mean age of 61.7 years were included. Tumor tissues that were tested p16 INK4a positive with low Mib/Ki-67 expression demonstrated a remarkable 5-year survival rate of 83% with an improved RFS compared to all other subgroups (p=0.034; p=0.017; p=0.026) and an improved OS compared to those with high Mib/Ki-67 expression (p=0.026; p=0.020). Cox regression identified the combined p16 INK4a and Mib/Ki-67 status as a risk factor on OS (HR 6.25; CI1.26-31.0; p=0.025) and RFS (HR 5.88; CI1.19-29.20; p=0.030)., Conclusion: These results underscore the importance of a combined assessment of p16 INK4a and Mib/Ki-67 in evaluating the prognosis of OSCC, leading to the identification of distinct subgroups that may serve as risk factors for treatment stratification., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Richter, Doll, Mrosk, Hofmann, Koerdt, Heiland, Neumann, Beck, Dommerich, Jöhrens and Raguse.)

Background and Purpose: With standard radiotherapy protocols after R0 resection of advanced local oral squamous cell carcinoma (OSCC) and primary reconstruction of segmental defects, a high radiation dose is applied to healthy tissue in autologous microvascular free flaps. Considering the potential consequences of flap complications and associated surgeries for patients, data is lacking on whether postoperative radiotherapy (PORT) of the flap volume is indicated at all., Materials and Methods: Patients with segmental mandibular resection and immediate reconstruction with osseous free flaps due to advanced OSCC between 2012 and 2022 were analyzed retrospectively regarding overall (OS), disease-free survival (DFS), local failure-free survival (LFFS), the need for secondary surgeries as well as flap complications and compared between patients with and without PORT in a matched-pair approach with occurrence of flap complications as a primary endpoint., Results: 105 patients matched the inclusion criteria. The maximum follow-up period was 60 months. 68 patients received PORT. 74 patients were included in the final analysis. No case of disease recurrence inside the free flap was recorded. There were no significant differences in DFS (p = 0.21), OS (p = 0.33) and LFFS (p = 0.6) between both cohorts. Occurrence of osteoradionecrosis (p = 0.03) and bone exposure (p = 0.003) was higher in irradiated flaps. In patients with PORT, the demand for secondary surgeries due to flap complications was significantly higher (p = 0.009). Radiation doses were not increased in patients with flap ORN., Conclusion: PORT is associated with higher flap complications and need for secondary surgeries in advanced stage OSCC. Given a recurrence rate of zero inside the flap without PORT and the improbability of recurrence within healthy transplanted tissue, the usefulness of applying high radiation doses to this vulnerable tissue is questioned. Further refinements of RT planning should be evaluated and tested in a RCT trial., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Regulatory T (Treg) cells are pivotal in immune tolerance to allergens. Low-dose IL-2 (IL-2 LD ) activates Treg cells., Objective: Our aim was to assess IL-2 LD efficacy for controlling clinical responses to allergen exposures., Methods: RHINIL-2 was a phase-2a, randomized, double-blind, placebo-controlled trial. Patients with allergic rhinitis to birch pollen (BP) were included; 66% of them had concomitant asthma. All had a total nasal symptom score (TNSS) of 5 or more following nasal exposure to BP in an environmental exposure chamber. Patients received 1 MUI per day of IL-2 (n = 12) or placebo (n = 12) for 5 days, followed by weekly injections for 4 weeks. Clinical responses to subsequent BP exposures in the environmental exposure chamber were evaluated by using TNSS, the rhinitis visual analog scale (VAS), and spirometry. The primary efficacy end point was the difference in TNSS area under the curve (AUC) between inclusion and day 40., Results: IL-2 LD treatment induced a significant expansion of Treg cells. The difference in TNSS AUC between inclusion and day 40 AUC in the IL-2 and placebo groups was not significant. TNSS and visual analog scale AUCs were significantly reduced from baseline to day 40 in the IL-2 LD group only (P = .04 and P = .01, respectively). The ratio of FEV 1 to forced vital capacity (FEV 1P ) and the forced midexpiratory flow (FEF 25%-75% ) showed improvement in the IL-2 LD -treated versus in the groups given placebo at day 40 (P = .04 and P = .04, respectively). However, the short treatment duration used in this study could not have effects on specific IgE or IgG4 levels given their half-life. There were no severe treatment-related adverse events., Conclusion: IL-2 LD is well tolerated in patients with allergy, even in those with asthma, thus clearing the path for further therapeutic development. Our work suggests that Treg cells can safely attenuate an ongoing allergic response. It paves the way for larger studies with longer treatment periods, which are needed to properly evaluate the therapeutic potential of IL-2 in allergy., Competing Interests: Disclosure statement Supported by the Programme Hospitalier de Recherche Clinique, No. P160936J. The Assistance Publique-Hôpitaux de Paris sponsored the study, and ILTOO pharma provided the treatments. Disclosure of potential conflict of interest: M. Rosenzwajg, R. Lorenzon, B. Bellier, and D. Klatzmann are inventors on patent applications related to the therapeutic use of IL-2(LD), which belongs to their academic institutions and has been licensed to ILTOO Pharma. M. Rosenzwajg, B. Bellier, and D. Klatzmann hold shares in ILTOO Pharma. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background and Purpose: Metaphyseal-stabilised short stems rely on sufficient metaphyseal fixation and are inserted by following the medial cortex. This type of stem is used extensively in our institution, and we observed on occasion unintended implant positioning with an increased distance between the implant and the medial cortex. A bony structure within the proximal femur which was first described in 1874 and named the calcar femorale, coincides with this phenomenon.The aim of this study was to investigate the impact of the calcar femorale on the position of a metaphyseal-stabilised short stem., Patients and Methods: The frequency of cases with an increased distance between medial cortex and the implanted short stem was analysed in 52 consecutive patients. Additionally, we performed an anatomical CT study with 60 cadaveric femora to obtain more detailed information on the anatomy of the calcar femorale. Detailed measurements regarding the calcar femorale and its relationship to the proximal femur were obtained. From this, we derived implications for the implantation of a short stem prosthesis., Results: In 50% of all cases, we found an increased gap between the stem and the medial cortex. An increased gap did not significantly affect stem size, position, or subsidence rate, but in cases with an increased gap we found fewer stems with a radiologically optimum fit. The calcar could be identified in all 60 cadavers. The calcar femorale angle showed a high correlation with the mechanical antetorsion (0.87, p  = 0.02) and the functional antetorsion (0.86, p  = 0.05) of the femur., Conclusions: The calcar femorale is a consistent anatomical structure which may be the cause for an increased gap medial to the short stem in 50% of our cases. It limits the intramedullary space and influences both stem size and orientation. The CF angle which correlates with femoral antetorsion may influence the anteversion of the stem., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Mucopolysaccharidosis II (MPS II, Hunter syndrome) is a rare, X-linked lysosomal storage disease caused by reduced activity of iduronate-2-sulfatase (I2S), with subsequent cellular accumulation of the glycosaminoglycans (GAGs), heparan sulfate, and dermatan sulfate (DS). DS is a major component of the extracellular matrix of heart valves, which can be affected in MPS II. We investigated the natural history of valve disease in MPS II and the impact of long-term intravenous enzyme replacement therapy (ERT) with recombinant I2S (idursulfase). In total, 604 cardiac examinations were assessed from serial follow-up of 80 male patients (49 neuronopathic). Valve disease was classified according to standard practice from hemodynamic features evident from echocardiography. The natural history group comprised 48 patients (up to 14.8 years of follow-up; median, 2.6 years; 24 patients started ERT during the study); 56 patients were treated (up to 14.2 years of follow-up; median, 6.2 years). Lifetime GAG burden (calculated from urinary GAG measurements) correlated significantly with the degree of valve disease. Onset of moderate-to-severe valve disease was significantly delayed in treated (median age at onset, 29.1 ± 2 [95% CI: 25.2-32.9] years; Kaplan-Meier estimation) versus untreated patients (17.6 ± 1 [95% Cl: 15.8-19.4] years; p < 0.0001). Cox regression modeling found that long-term ERT reduced the probability of developing severe valve disease (χ 2 , 32.736; significant after 5 years of ERT). Overall, this study found that valve disease severity in MPS II correlates with GAG burden and that progression is delayed by long-term ERT., (© 2024 The Author(s). Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

The CHILD Cohort Study is an active multi-center longitudinal, prospective, population pregnancy cohort study following Canadian infants from fetal life until adulthood. We hypothesized that early life physical and psychosocial environments interact with biological factors (e.g. immunologic, genetic, physiologic, and metabolic) influencing burdensome non-communicable disease outcomes, including asthma and allergic disorders, growth and development, cardio-metabolic health, and neurodevelopmental outcomes that manifest during the life-course. Detailed clinical and physiologic phenotyping at strategic intervals was complemented by environmental sampling, actigraphy and global positioning system measures, biological sampling including gut, breastmilk and nasal microbiome, nutritional studies, genetics, and epigenetic profiling. Of 3,454 families recruited from 2008 to 2012, study retention was 96.0% at 1-year, 93.2% at 5-years and 90.7% at 8-years. Data collection during the SARS-2 COVID-19 pandemic was partially completed via virtual visits. A sub-cohort was implemented, capturing detailed information on the prevalence and predictors of SARS-CoV-2 infection and the health and psychosocial impact of the pandemic on Canadian families. The 13-year clinical assessment launched in 2022 will be completed in 2025. Ultimately, the CHILD Cohort Study provides a data science platform designed to enable a deep understanding of early life factors associated with the development of chronic non-communicable diseases and multimorbidity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Issues Addressed: Evidence on how COVID-19 lockdowns impacted physical activity (PA) is mixed. This study explores changes in PA following initial mobility restrictions, and their subsequent relaxation, in a sample of Sydney (Australia) residents using a natural experiment methodology., Methods: Participants' health and travel behaviours were collected pre-pandemic in late 2019 (n = 1937), with follow-up waves during the pandemic in 2020 (n = 1706) and 2021 (n = 1514). Linear mixed-effects models were used to analyse changes in weekly duration of PA between the three waves., Results: Compared with pre-pandemic, average weekly PA increased in 2021 by 42.6 min total PA (p = .001), 16 min walking PA (p = .02), and 26.4 min moderate-vigorous PA (MVPA) (p = .003). However, average weekly sessions of PA decreased in 2020 and remained lower in 2021. For participants who were sufficiently active in 2019, weekly total PA (-66.3 min) MVPA (-43.8 min) decreased in 2020 compared to pre-pandemic. Conversely, among participants who were insufficiently active in 2019, average weekly PA increased in both 2020 (total PA, +99.1 min; walking PA, +46.4 min; MVPA +52.8 min) and 2021 (total PA, +117.8 min; walking PA, +58.4 min; MVPA +59.2 min), compared to 2019. Participants who did more work from home increased their average weekly total PA in 2021 compared to pre-pandemic (+45.3 min)., Conclusion: These findings reveal the complex variability in PA behaviour brought about by the pandemic. SO WHAT?: Strategies to support the population in achieving sufficient PA must focus on maintaining an appetite for PA as we move out of the pandemic and on promoting more frequent PA sessions., (© 2024 The Authors. Health Promotion Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of Australian Health Promotion Association.)

Background: The present study aims to investigate the feasibility of labeling ligaments using ultrasound-guided injections. On formalin-fixed cadavers, the anterolateral ligament was selected and targeted for demonstration. The development of portable ultrasound machines and the ability to connect them to tablets via Bluetooth or WLAN makes it an accessible tool to implement into the anatomical dissection courses in order to associate medical imaging (MRI and ultrasound), anatomical structures and their subsequent dissection., Methods: 8 formalin fixed human cadavers were used for the ultrasound-guided injections of 1 mL of blue latex into the anterolateral ligament. 8 cadavers were not injected with latex for comparative purposes. The injections were performed by an experienced ultra-sonographer. After approximately 10 months, five dissections were carried out by students during the dissection course and three specimens were dissected by anatomists., Results: The anterolateral ligament was successfully marked and demonstrated in 7 out of 8 cases. In 4 out of 5 cases, the dissection was primarily conducted by students, while in 3 out of 3 cases, it was performed by anatomists. The accuracy was 80 % and 100 %, respectively., Conclusion: The present study demonstrated that labeling obscure ligaments, such as the anterolateral ligament, using ultrasound guidance is feasible on formalin-fixed cadavers. It also showed that students can successfully perform the dissections as the structure is highlighted and that the time between injection and dissection (approximately 10 months) has little impact on the outcome. The use of ultrasound in dissection courses should be further encouraged., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Introduction: A femoral head fracture (Pipkin fracture) is a rare but severe injury. The optimal treatment is controversial, and there is a lack of research focusing on treatment strategies. The study aimed to analyze the treatment strategies in comparison to the outcome in patients after traumatic hip joint dislocation (THD) with concomitant femoral head fractures., Materials and Methods: A retrospective multicenter study at three Level I Trauma Centers was performed over a 12 year period from January 2009 to January 2021. Epidemiological data, associated injuries, and treatment were recorded. Patients were followed up for further treatment, re-operations, complications, and long-term functional outcomes using patient-reported outcome measures (PROMs), specifically the modified Harris Hip Score (mHHS) and the Tegner Activity Scale (TAS)., Results: 45 patients with a mean age of 44 ± 16.11 years were finally evaluated. The majority of 38 patients (84%) were treated surgically. The mean follow-up time was 5.75 years (range 2-12 years). 8 patients (31%) developed post-traumatic osteoarthritis and 4 patients (15%) developed osteonecrosis of the femoral head. 7 patients (27%) underwent total hip arthroplasty (THA). Fixation of the Pipkin fracture was more common in younger patients but had no statistically significant impact on PROMs. Patients with a higher BMI were significantly less likely to undergo fragment fixation (p < 0.05). TAS was significantly worse in patients who underwent THA (p < 0.05)., Conclusions: A femoral head fracture is a severe injury with overall limitations in activities of daily living and a high rate of post-traumatic osteoarthritis and osteonecrosis of the femoral head. Fragment fixation had no statistically significant impact on the outcome and PROMs. Treatment strategies should be guided by the fracture type, the patient's condition, and associated injuries. However, concomitant and life-threatening injuries may affect the treatment and limit the outcome., Competing Interests: Declarations Conflict of interest The authors declare that they have no conflict of interest related to the publication of this manuscript. Ethical approval This Work submitted to Archives of Orthopaedic and Trauma Surgery is complied with the principles laid down in the Declaration of Helsinki. The study was approved by the local medical ethics committee (IRB No. S-211/2021) and all participants gave written consent before the follow-up., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Enhanced recovery after surgery programs with median postoperative hospitalization of 2 days improve outcomes after lung cancer surgery. This article explores nursing care practices for patients with lung cancer who remain hospitalized despite having recovered somatically. Qualitative focus group interviews were conducted with 16 nurses. Ricoeur's phenomenological hermeneutics underpins the methodology applied in this study, and we relied on Benner and Wrubel's theory. The nurses emphasized that the thoughts of patients with a recent lung cancer diagnosis revolve around more than the surgery. Nursing comprises not only practicalities but also attending to patients' stress and their coping with being struck with lung cancer and having undergone surgery. A counterculture emerged to counteract the logic of productivity, indicating that caring as a worthy end in itself may be underestimated in protocol-driven care. Prolonging hospitalization largely depends on clinical judgment. The nurses' aim is not to keep patients in the hospital but to avoid any needless suffering, allowing them to reclaim the primacy of caring., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aging is a consequence of complex molecular changes, but whether a single microRNA (miRNA) can drive aging remains unclear. A miRNA known to be upregulated during both normal and premature aging is miR-29. We find miR-29 to also be among the top miRNAs predicted to drive aging-related gene expression changes. We show that partial loss of miR-29 extends the lifespan of Zmpste24 -/- mice, an established model of progeria, indicating that miR-29 is functionally important in this accelerated aging model. To examine whether miR-29 alone is sufficient to promote aging-related phenotypes, we generated mice in which miR-29 can be conditionally overexpressed (miR-29TG). miR-29 overexpression is sufficient to drive many aging-related phenotypes and led to early lethality. Transcriptomic analysis of both young miR-29TG and old WT mice reveals shared downregulation of genes associated with extracellular matrix organization and fatty acid metabolism, and shared upregulation of genes in pathways linked to inflammation. These results highlight the functional importance of miR-29 in controlling a gene expression program that drives aging-related phenotypes., (© 2024. The Author(s).)

Introduction: Glyphosate-based herbicides (GBHs) have been shown to have significant neurotoxic effects, affecting both the structure and function of the brain, and potentially contributing to the development of neurodegenerative disorders. Despite the known importance of glycosylation in disease progression, the glycome profile of systems exposed to GBH has not been thoroughly investigated., Methods: In this study, we conducted a comprehensive glycomic profiling using LC-MS/MS, on the hippocampus and prefrontal cortex (PFC) of juvenile rats exposed to GBH orally, aiming to identify glyco-signature aberrations after herbicide exposure., Results: We observed changes in the glycome profile, particularly in fucosylated, high mannose, and sialofucosylated N-glycans, which may be triggered by GBH exposure. Moreover, we found major significant differences in the N-glycan profiles between the GBH-exposed group and the control group when analyzing each gender independently, in contrast to the analysis that included both genders. Notably, gender differences in the behavioral test of object recognition showed a decreased performance in female animals exposed to GBH compared to controls ( p  < 0.05), while normal behavior was recorded in GBH-exposed male rats ( p  > 0.05)., Conclusion: These findings suggest that glycans may play a role in the neurotoxic effect caused by GBH. The result suggests that gender variation may influence the response to GBH exposure, with potential implications for disease progression and specifically the neurotoxic effects of GBHs. Understanding these gender-specific responses could enhance knowledge of the mechanisms underlying GBH-induced toxicity and its impact on brain health. Overall, our study represents the first detailed analysis of N-glycome profiles in the hippocampus and PFC of rats chronically exposed to GBH. The observed alterations in the expression of N-glycan structures suggest a potential neurotoxic effect associated with chronic GBH exposure, highlighting the importance of further research in this area., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Solomon, Gutierrez-Reyes, Chávez-Reyes, Onigbinde, Marichal-Cancino, López-Lariz, Beck and Mechref.)

Arthritis affects many individuals and can cause pain and limit physical functioning. Exercise is an important treatment option for individuals with arthritis; however, adherence to exercise programs can be challenging. A new initiative in Denmark has introduced nature-based exercises for patients with arthritis. This qualitative study aimed to explore the experiences of the individuals who participated in those exercises. The study used a hermeneutic-phenomenological approach and conducted along-side interviews with 12 women and three men who participated in nature-based exercise programs for arthritis. Analysis of the data revealed two main themes. The first theme highlighted the positive effects of being in nature, such as increased vitality, reduced pain, and a sense of well-being. The second theme emphasized the social benefits of participating in these exercises, including a sense of connection and community with others. Overall, this study suggests that incorporating nature-based exercises in treatment programs for arthritis could have significant benefits for individuals with this condition., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: STS is associate editor of the Journal of Orthopaedic and Sports Physical Therapy, has received personal fees from Munksgaard, TrustMe-Ed, and Nestlé Health Science, outside the submitted work, and is co-founder of GLA:D®, a not-for-profit initiative hosted at the University of Southern Denmark aimed at implementing clinical guidelines for osteoarthritis in clinical practice. The authors have no other potential conflicts to disclose.

Background: PSMA-PET is increasingly used for staging prostate cancer (PCA) patients. However, it is not clear if quantitative imaging parameters of positron emission tomography (PET) have an impact on disease progression and are thus important for the prognosis of localized PCA., Methods: This is a monocenter retrospective analysis of 86 consecutive patients with localized intermediate or high-risk PCA and PSMA-PET before treatment The quantitative PET parameters maximum standardized uptake value (SUV max ), tumor asphericity (ASP), PSMA tumor volume (PSMA-TV), and PSMA total lesion uptake (PSMA-TLU = PSMA-TV × SUV mean ) were assessed for their prognostic significance in patients with radiotherapy or surgery. Cox regression analyses were performed for biochemical recurrence-free survival, overall survival (OS), local control, and loco-regional control (LRC)., Results: 67% of patients had high-risk disease, 51 patients were treated with radiotherapy, and 35 with surgery. Analysis of metric PET parameters in the whole cohort revealed a significant association of PSMA-TV (p = 0.003), PSMA-TLU (p = 0.004), and ASP (p < 0.001) with OS. Upon binarization of PET parameters, several other parameters showed a significant association with clinical outcome. When analyzing high-risk patients according to the primary treatment approach, a previously published cut-off for SUV max (8.6) showed a significant association with LRC in surgically treated (p = 0.048), but not in primary irradiated (p = 0.34) patients. In addition, PSMA-TLU (p = 0.016) seemed to be a very promising biomarker to stratify surgical patients., Conclusion: Our data confirm one previous publication on the prognostic impact of SUV max in surgically treated patients with high-risk PCA. Our exploratory analysis indicates that PSMA-TLU might be even better suited. The missing association with primary irradiated patients needs prospective validation with a larger sample size to conclude a predictive potential. Trial registration Due to the retrospective nature of this research, no registration was carried out., (© 2024. The Author(s).)

Purpose: 68 Ga-labeled fibroblast activation protein inhibitor (FAPI) is a novel PET tracer with great potential for staging pancreatic cancer. Data on locally advanced or recurrent disease is sparse, especially on tracer uptake before and after high dose chemoradiotherapy (CRT). The aim of this study was to evaluate [ 68 Ga]Ga-FAPI-46 PET/CT staging in this setting. Methods: Twenty-seven patients with locally recurrent or locally advanced pancreatic adenocarcinoma (LRPAC n = 15, LAPAC n = 12) in stable disease or partial remission after chemotherapy underwent FAPI PET/CT and received consolidation CRT in stage M0 with follow-up FAPI PET/CT every three months until systemic progression. Quantitative PET parameters SUV max , SUV mean FAPI PET/CT modified staging compared to ceCT alone in 23 of 27 patients in baseline, resulting in major treatment alterations in 52% of all patients (30%: target volume adjustment due to N downstaging, 15%: switch to palliative systemic chemotherapy only due to diffuse metastases, 7%: abortion of radiotherapy due to other reasons). Regarding follow-up scans, major treatment alterations after performing FAPI PET/CT were noted in eleven of 24 follow-up scans (46%) with switch to systemic chemotherapy or best supportive care due to M upstaging and ablative radiotherapy of distant lymph node and oligometastasis. Unexpectedly, in more than 90 % of the follow-up scans, radiotherapy did not induce local fibrosis related FAPI uptake. During the first follow-up, all quantitative PET metrics decreased, and irradiated lesions showed significantly lower FAPI uptake in locally controlled disease (SUV Results: FAPI PET/CT modified staging compared to ceCT alone in 23 of 27 patients in baseline, resulting in major treatment alterations in 52% of all patients (30%: target volume adjustment due to N downstaging, 15%: switch to palliative systemic chemotherapy only due to diffuse metastases, 7%: abortion of radiotherapy due to other reasons). Regarding follow-up scans, major treatment alterations after performing FAPI PET/CT were noted in eleven of 24 follow-up scans (46%) with switch to systemic chemotherapy or best supportive care due to M upstaging and ablative radiotherapy of distant lymph node and oligometastasis. Unexpectedly, in more than 90 % of the follow-up scans, radiotherapy did not induce local fibrosis related FAPI uptake. During the first follow-up, all quantitative PET metrics decreased, and irradiated lesions showed significantly lower FAPI uptake in locally controlled disease (SUV max p = 0.047, SUV mean p = 0.0092) compared to local failure. Conclusion: Compared to ceCT, FAPI PET/CT led to major therapeutic alterations in patients with LRPAC and LAPAC prior to and after radiotherapy, which might help identify patients benefiting from adjustments in every treatment stage. FAPI PET/CT should be considered a useful diagnostic tool in LRPAC or LAPAC before and after CRT., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: This scoping review aims to identify and map interventions and/or strategies used to support the initiation and continuation of breastfeeding for women at risk of delaying initiation, early cessation, or not breastfeeding due to low levels of education, psychosocial problems, and/or socioeconomic challenges in high-income countries., Introduction: While breastfeeding has lifelong beneficial health effects for women and infants, there is a risk of delaying initiation, early cessation, or not initiating breastfeeding at all due to factors related to health inequalities, such as low levels of education, psychosocial problems, and/or socioeconomic constraints., Inclusion Criteria: This review will include eligible quantitative, qualitative, and mixed methods studies, as well as systematic reviews and gray literature. We will encompass studies conducted in high-income countries, focusing on interventions and/or strategies to support women with low levels of education, psychosocial problems, and/or socioeconomic constraints in the initiation and continuation of breastfeeding for up to 6 months postpartum., Methods: This review will follow the JBI methodology for scoping reviews, using the Participants, Concept, and Context framework. The primary search will be performed in the following databases: MEDLINE (PubMed), PsycINFO (EBSCOhost), Embase (Ovid), and CINAHL (EBSCOhost). We will include publications in English, Swedish, Norwegian, Danish, German, Bulgarian, Arabic, and Spanish, published from 1991 until the present. A data charting form will be developed and applied to all the included articles., Review Registration: The study is registered in Open Science Framework, DOI 10.17605/OSF.IO/TMP4V., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 JBI.)

Purpose: The effects of physical activity on health are well-established for chronic diseases such as multiple sclerosis (MS), Alzheimer's disease (AD), and ischaemic heart disease (IHD). However, sustaining physical activity in everyday life is difficult. Lifeworld knowledge can help qualify interventions aimed at resolving this public health issue, but there is a gap in regard to synthesized research on peoples' experiences with integrating and sustaining physical activity. Hence, the purpose of this review is to explore and present the available evidence on experiences with integrating and sustaining physical activity in a lived life with MS, AD, and IHD., Methods: We conducted a scoping review with qualitative analysis and narrative syntheses in accordance with PRISMA-ScR. Based on SPIDER we ran a systematic search in Cinahl, Embase, Medline, and PsychInfo for primary qualitative research papers published until December 2022., Results: 43 papers were included. A thematic content analysis found that individuals who have MS, AD or IHD find integrating and sustaining physical activity in everyday life meaningful on several levels: Physical activity can facilitate meaningful movement with outcomes of physical, psychosocial, and existential importance., Conclusion: The research literature presents a meaning to physical activity that extends the idea of physical fitness to one of existential movement and personal growth. In addition, our review finds that people are more likely to integrate and sustain physical activity if they feel acknowledged, supported and believe that physical activity has a meaningful purpose reflecting their sense of self. Taking a more person-centred approach in rehabilitative care might help qualify the content of physical activity in terms of integration into everyday life, but more research is needed on how to implement a person-centred approach in practice.

How do we explore the meaningfulness of others' experiences? What means do we have to access their experiencing of the world? How do we express our understandings of others' experiences of body and place without reducing them to objectification? In this methodological paper, we reflect on how we can gain valuable insights into the lived experiences of others through research activities that are conducted 'alongside' participants. Phenomenological concepts of intentionality and embodiment are considered as we draw on an empirical example of exploring the experiences of hospitalized patients with neurological diseases through observations and interviews. The aim is to unfold alongside as an epistemological stance to explore the meaning of another's lifeworld. We strive to show that personal presence and engagement within this approach contains relational, existential, and aesthetic dimensions worth considering., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Michael van Manen is a Deputy Editor of Qualitative Health Research. He was not involved in any part of the peer review process and the manuscript was subject to the same standard of peer-review as others submitted to the journal. This includes the input of two or more independent peer-reviewers who were blinded to the author’s editorial association with Qualitative Health Research.

Background: Minimizing patient falls and fall-related injuries within organizational constraints is a high priority for nurse leaders. The Centers for Medicare & Medicaid Services do not reimburse hospitals for fall-related expenditures. In-person sitters are used to prevent falls but are resource intensive and costly. Remote patient monitoring (RPM) may offer alternatives to in-person sitters to reduce fall-related harm., Purpose: The efficacy of RPM to reduce patient falls and fall-related injuries was explored., Methods: Electronic health record data were extracted from a 13-hospital integrated health care system. Incidence rate ratios were used to analyze the impact of RPM technology on falls and fall-related injuries., Results: When used in conjunction with standard fall precautions, RPM reduced falls 33.7% and fall-related injuries 47.4%. Fall-related expenditures decreased $304 400 with a combined estimated savings systemwide of $2 089 600 annually., Conclusions: RPM technology minimized falls and associated harm and improved patient safety, positively impacting hospital expenditures., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The emergence of artificial intelligence (AI) is catching the interest of hospital pharmacists. A massive collection of health data is now available to train AI models and hold the promise of disrupting codes and practices. The objective of this systematic review was to examine the state of the art of machine learning or deep learning models that detect inappropriate hospital medication orders., Methods: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. MEDLINE and Embase databases were searched from inception to May 2023. Studies were included if they reported and described an AI model intended for use by clinical pharmacists in hospitals. Risk of bias was assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST)., Results: 13 articles were selected after review: 12 studies were judged to have high risk of bias; 11 studies were published between 2020 and 2023; 8 were conducted in North America and Asia; 6 analysed orders and detected inappropriate prescriptions according to patient profiles and medication orders; and 7 detected specific inappropriate prescriptions, such as detecting antibiotic resistance, dosage abnormality in prescriptions, high alert drugs errors from prescriptions or predicting the risk of adverse drug events. Various AI models were used, mainly supervised learning techniques. The training datasets used were very heterogeneous; the length of study varied from 2 weeks to 7 years and the number of prescription orders analysed went from 31 to 5 804 192., Conclusions: This systematic review points out that, to date, few original research studies report AI tools based on machine or deep learning in the field of hospital clinical pharmacy. However, these original articles, while preliminary, highlighted the potential value of integrating AI into clinical hospital pharmacy practice., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Ameloblastoma, a benign yet aggressive odontogenic tumor known for its recurrence and the severe morbidity from radical surgeries, may benefit from advancements in targeted therapy. We present a case of a 15-year-old girl with ameloblastoma successfully treated with targeted therapy and review the literature with this question: Is anti-MAPK targeted therapy safe and effective for treating ameloblastoma? This systematic review was registered in PROSPERO, adhered to PRISMA guidelines, and searched multiple databases up to December 2023, identifying 13 relevant studies out of 647 records, covering 23 patients treated with MAPK inhibitor therapies. The results were promising as nearly all patients showed a positive treatment response, with four achieving complete radiological remission and others showing substantial reductions in primary, recurrent, and metastatic ameloblastoma sizes. Side effects were mostly mild to moderate. This study presents anti-MAPK therapy as a significant shift from invasive surgical treatments, potentially enhancing life quality and clinical outcomes by offering a less invasive yet effective treatment alternative. This approach could signify a breakthrough in managing this challenging tumor, emphasizing the need for further research into molecular-targeted therapies., Competing Interests: The authors declare no conflicts of interest.

Ribosomes translate the genetic code into proteins. Recent technical advances have facilitated in situ structural analyses of ribosome functional states inside eukaryotic cells and the minimal bacterium Mycoplasma. However, such analyses of Gram-negative bacteria are lacking, despite their ribosomes being major antimicrobial drug targets. Here we compare two E. coli strains, a lab E. coli K-12 and human gut isolate E. coli ED1a, for which tetracycline exhibits bacteriostatic and bactericidal action, respectively. Using our approach for close-to-native E. coli sample preparation, we assess the two strains by cryo-ET and visualize their ribosomes at high resolution in situ. Upon tetracycline treatment, these exhibit virtually identical drug binding sites, yet the conformation distribution of ribosomal complexes differs. While K-12 retains ribosomes in a translation-competent state, tRNAs are lost in the vast majority of ED1a ribosomes. These structural findings together with the proteome-wide abundance and thermal stability assessments indicate that antibiotic responses are complex in cells and can differ between different strains of a single species, thus arguing that all relevant bacterial strains should be analyzed in situ when addressing antibiotic mode of action., (© 2024. The Author(s).)

In this work, poly(lactide) nanoparticles were equipped with a bioinspired coating layer based on poly[2-(methacryloyloxy)ethyl phosphorylcholine] and then evaluated when administered to the lungs and after intravenous injection. Compared to the plain counterparts, the chosen zwitterionic polymer shell prevented the coated colloidal formulation from aggregation and conditioned it for lower cytotoxicity, protein adsorption, complement activation and phagocytic cell uptake. Consequently, no interference with the biophysical function of the lung surfactant system could be detected accompanied by negligible protein and cell influx into the bronchoalveolar space after intratracheal administration. When injected into the central compartment, the coated formulation showed a prolonged circulation half-life and a delayed biodistribution to the liver. Taken together, colloidal drug delivery vehicles would clearly benefit from the investigated poly[2-(methacryloyloxy)ethyl phosphorylcholine]-based polymer coatings., Competing Interests: Declaration of Competing Interest The author discloses authors declare that they have no conflicting known competing financial interests associated with or personal relationships that could have appeared to influence the work reported in this manuscript paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: The aim of this work was to assess the current state of digitalization in radiation oncology departments in Germany, Austria, and Switzerland., Methods: A comprehensive survey was conducted in a digital format, consisting of 53 questions that covered various aspects of digitalization including patient workflow, departmental organization, radiotherapy planning, and employee-related aspects., Results: Overall, 120 forms were eligible for evaluation. Participants were mainly physicians or medical physicists responsible for digitalization aspects in their departments. Nearly 70% of the institutions used electronic patient records, with 50% being completely paperless. However, the use of smartphone apps for electronic patient reported outcomes (ePROMs) and digital health applications (DIGA) was limited (9% and 4.9%, respectively). In total, 70.8% of the radio-oncology departments had interfaces with diagnostic departments, and 36% had digital interchanges with other clinics. Communication with external partners was realized mainly through fax (72%), e‑mails (55%), postal letters (63%), or other digital exchange formats (28%). Almost half of the institutions (49%) had dedicated IT staff for their operations., Conclusion: To the best of our knowledge, this survey is the first of its kind conducted in German-speaking radiation oncology departments within the medical field. The findings suggest that there is a varied level of digitalization implementation within these departments, with certain areas exhibiting lower rates of digitalization that could benefit from targeted improvement initiatives., (© 2023. The Author(s).)

Bullous pemphigoid is the most common autoimmune blistering disease induced by autoantibodies against basement membrane anchoring proteins (anti-BP-180 and anti-BP-230). The disease generally appears after the age of 70 and is associated with a 23.5% 1-year mortality, especially in diabetics, or in the presence of ischemic heart disease and high anti-BP-180. Treatment starts with topical steroids but some patients may require oral steroids and systemic immunosuppression. We, hereby, discuss a diabetic patient on chronic hemodialysis, with severely relapsed bullous pemphigoid under biotherapy with omalizumab, who was successfully treated with five sessions of double filtration plasmapheresis, thus avoiding the need for systemic steroids., (© 2024 The Author(s). Journal of Clinical Apheresis published by Wiley Periodicals LLC.)

The authors of this Comment are longstanding selenium investigators with a total of 200 or more published articles on selenium; the corresponding author (Margaret P [...].

Background: In intra-arterial chemotherapy for retinoblastoma, a backflow from unreachable external carotid artery branches in the ophthalmic artery can be challenging., Objective: To describe a new endovascular technique using Gelfoam pledgets to temporarily occlude distal branches of the external carotid artery to reverse the competitive backflow into the ophthalmic artery in order to perform intra-arterial chemotherapy via the ostium of the ophthalmic artery in selected cases., Methods: We queried our prospectively collected database of 327 consecutive patients treated for retinoblastoma by intra-arterial chemotherapy and identified those employing Gelfoam pledgets. We describe this new technique with emphasis on feasibility and safety., Results: We treated 11 eyes with 14 infusions of intra-arterial chemotherapy using Gelfoam pledgets to occlude the distal branches of the external carotid artery. We report no perioperative complications due to this occlusion technique. At the ophthalmologic follow-up 1 month after the injection of Gelfoam pledgets, all cases showed tumor regression or stable disease. Two injections into the same eye as the rescue intra-arterial chemotherapy infusion resulted in a transient exudative retinal detachment, and one injection in a heavily pretreated case was followed by iris neovascularization and retinal ischemia. None of the pledget injections led to irreversible vision-threatening intraocular complications., Conclusions: Intra-arterial chemotherapy in retinoblastoma using Gelfoam to transiently occlude the distal branches of the external carotid artery and reverse the backflow into the ophthalmic artery seems feasible and safe. Larges series will help to confirm the effectiveness of this new technique., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

This retrospective multicenter study examines therapy-induced orbital and ocular MRI findings in retinoblastoma patients following selective intra-arterial chemotherapy (SIAC) and quantifies the impact of SIAC on ocular and optic nerve growth. Patients were selected based on medical chart review, with inclusion criteria requiring the availability of posttreatment MR imaging encompassing T2-weighted and T1-weighted images (pre- and post-intravenous gadolinium administration). Qualitative features and quantitative measurements were independently scored by experienced radiologists, with deep learning segmentation aiding total eye volume assessment. Eyes were categorized into three groups: eyes receiving SIAC (Rb-SIAC), eyes treated with other eye-saving methods (Rb-control), and healthy eyes. The most prevalent adverse effects post-SIAC were inflammatory and vascular features, with therapy-induced contrast enhancement observed in the intraorbital optic nerve segment in 6% of patients. Quantitative analysis revealed significant growth arrest in Rb-SIAC eyes, particularly when treatment commenced ≤ 12 months of age. Optic nerve atrophy was a significant complication in Rb-SIAC eyes. In conclusion, this study highlights the vascular and inflammatory adverse effects observed post-SIAC in retinoblastoma patients and demonstrates a negative impact on eye and optic nerve growth, particularly in children treated ≤ 12 months of age, providing crucial insights for clinical management and future research.

Visual proteomics attempts to build atlases of the molecular content of cells but the automated annotation of cryo electron tomograms remains challenging. Template matching (TM) and methods based on machine learning detect structural signatures of macromolecules. However, their applicability remains limited in terms of both the abundance and size of the molecular targets. Here we show that the performance of TM is greatly improved by using template-specific search parameter optimization and by including higher-resolution information. We establish a TM pipeline with systematically tuned parameters for the automated, objective and comprehensive identification of structures with confidence 10 to 100-fold above the noise level. We demonstrate high-fidelity and high-confidence localizations of nuclear pore complexes, vaults, ribosomes, proteasomes, fatty acid synthases, lipid membranes and microtubules, and individual subunits inside crowded eukaryotic cells. We provide software tools for the generic implementation of our method that is broadly applicable towards realizing visual proteomics., (© 2024. The Author(s).)

Play has positive effects on children's well-being and development. Play heroes, in Danish, called "Legeheltene", have worked, for the last 7 years, to improve play and movement for hospitalized children in Danish hospitals. However, the significance of this novel Danish intervention is insufficiently researched. This phenomenological-hermeneutic study explored how children experience interacting with a play hero when hospitalized at a Danish paediatric unit. Combined observations and interviews were performed with children from two paediatric departments. Data were analyzed with inspiration from the French philosopher Paul Ricoeur. Three themes were identified: "A sense of familiarity," "From loneliness to connectedness," and "Becoming more powerful." Children experience that interaction with play heroes is existentially meaningful. Through playful activities, children experience that they are connected to their daily lives outside the hospital and their true selves. Bridges to children's everyday lives are built, leading to an improved sense of freedom, security, and the ability to manage difficult aspects of their hospital stay. Engagement with play heroes provides children with an experience of well-being and can be a positive direction in care provided to hospitalized children., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Accounting for more than 60% of cancer survivors, older (≥65 years) cancer survivors have a 2- to 5-fold risk of physical function impairment, compared to cancer-free peers. One strategy to improve physical function is dietary and resistance training interventions, which improve muscle strength and mass by stimulating muscle protein synthesis. The E-PROOF (E-intervention for Protein Intake and Resistance Training to Optimize Function) study will examine the feasibility, acceptability, and preliminary efficacy of a 12-week randomized controlled trial of an online, tailored nutritional and resistance training education and counseling intervention to improve physical function and associated health outcomes (muscle strength, health-related quality of life (HRQoL), self-efficacy, and weight management)., Methods: In this study, 70 older cancer survivors will be randomized to one of two groups: experimental (receiving remote behavioral counseling and evidence-based education and resources), and control (general survivorship education). We will examine the intervention effects on physical function, muscle strength, HRQoL, self-efficacy, weight, and waist circumference during a 12-week period between the experimental and control groups. Three months following the end of the intervention, we will conduct a follow-up assessment to measure physical function, muscle strength, and HRQoL., Significance and Impact: This study is the first synchronous, online protein-focused diet and resistance training intervention among older cancer survivors. This novel study advances science by promoting independent health behaviors among older cancer survivors to improve health outcomes, and provide foundational knowledge to further address this growing problem on a wider scale through online platforms., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Krok-Schoen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: In advanced oral squamous cell carcinoma (OSCC), adjuvant therapy (AT) is an important part of the treatment to ensure extended locoregional control after primary surgical resection. The impact of the time interval between surgery and AT on the oncological prognosis remains unclear, particularly in high-risk constellations. The aim of this study is to categorize treatment delays and to determine their impact on the oncological prognosis within the context of the histopathological risk parameters of patients with advanced OSCC., Methods: In this single-institutional retrospective cohort study, all patients treated for OSCC between 2016 and 2021 and who received postoperative chemoradiation (POCRT) were included. Patients were divided into two groups: Group I: ≤ 6 weeks between surgery and POCRT; and Group II: > 6 weeks between surgery and POCRT., Results: Overall, 202 patients were included (Group I: 156 (77.2%) vs. Group II: 46 (22.8%)). There were no statistically significant differences in epidemiological aspects and histopathological risk factors between the two groups. The maximum time to initiation of POCRT was 11 weeks. Delayed POCRT initiation had no statistically significant influence on the 5-year OS (61.6% vs. 57.3%, p = 0.89), locoregional control rate (38.6% vs. 43.3%, p = 0.57), and RFS (32.3% vs. 30.4%, p = 0.21). On multivariate analysis, extracapsular spread (HR: 2.21, 95% CI: 1.21 - 4.04, p = 0.01) and incomplete surgical resection (HR: 2.01, 95% CI: 1.10 - 3.69, p = 0.02) were significantly correlated with OS. For RFS, ECS (HR: 1.82, 95% CI: 1.15 - 2.86, p = 0.01), incomplete resection (HR: 1.67, 95% CI: 1.04 - 2.71, p = 0.04), and vascular infiltration of the tumor (V-stage; HR: 2.15, 95% CI: 1.08 - 4.27, p = 0.03) were significant risk predictors., Conclusion: Delays in POCRT initiation up to 11 weeks after surgical resection for advanced OSCC were not statistically significantly associated with impaired survival. In cases of prolonged surgical treatment due to management of complications, a small delay in AT beyond the recommended time limit may be justified and AT should still be pursued., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mrosk, Absah, Richter, Sprünken, Doll, Kreutzer, Rendenbach, Beck, Klinghammer, Heiland and Koerdt.)