Search

Abstract Osteogenesis imperfecta (OI) is a genetically and clinically heterogeneous disorder characterized by bone fragility and reduced bone mass generally caused by defects in type I collagen structure or defects in proteins interacting with collagen processing. We identified a homozygous missense mutation in SEC16B in a child with vertebral fractures, leg bowing, short stature, muscular hypotonia, and bone densitometric and histomorphometric features in keeping with OI with distinct ultrastructural features. In line with the putative function of SEC16B as a regulator of trafficking between the ER and the Golgi complex, we showed that patient fibroblasts accumulated type I procollagen in the ER and exhibited a general trafficking defect at the level of the ER. Consequently, patient fibroblasts exhibited ER stress, enhanced autophagosome formation, and higher levels of apoptosis. Transfection of wild‐type SEC16B into patient cells rescued the collagen trafficking. Mechanistically, we show that the defect is a consequence of reduced SEC16B expression, rather than due to alterations in protein function. These data suggest SEC16B as a recessive candidate gene for OI.

Aeromonas salmonicida and Yersinia ruckeri are common pathogenic bacteria that impact salmonid aquaculture. Although vaccinations are available against both organisms, large-scale vaccination efforts can be expensive, cumbersome, and are not always reliable. Alternatively, these pathogens have been effectively inactivated using UV radiation from mercury-based systems. These systems are energy intensive and fragile which currently limits their use to closed and semi-closed production systems. UV light emitting diodes (UV LEDs) have recently emerged as a novel alternative to traditional mercury-based treatment. UV LEDs have durable housing, a relatively low energy draw, can be powered by a battery source and are adaptable to challenging environments. This study examined the effectiveness of three UV LED wavelengths for disinfection of A. salmonicida and Y. ruckeri in pure culture and resuspended in a wastewater matrix. All tested UV LEDs were effective in disinfecting both organisms. 267 and 279 nm wavelengths outperformed 255 nm disinfection in both test matrices. Particulate matter from wastewater reduced the upper limit of treatment for A. salmonicida but results still indicated that all wavelengths were effective for disinfection in a challenging matrix. This study represents the first use of UV LEDs for disinfection of A. salmonicida and Y. ruckeri and provides impact to aquaculture producers looking to implement novel technologies for disease control. [ABSTRACT FROM AUTHOR]

Purpose: Small cell lung cancer (SCLC) is a highly aggressive tumor with neuroendocrine origin. Although SCLC frequently express somatostatin receptor type 2 (SSTR2), a significant clinical benefit of SSTR2-targeted radionuclide therapies of SCLC was not observed so far. We hypothesize that combination treatment with a PARP inhibitor (PARPi) could lead to radiosensitization and increase the effectiveness of SSTR2-targeted therapy in SCLC. Methods: SSTR2-ligand uptake of the SCLC cell lines H69 and H446 was evaluated in vitro using flow cytometry, and in vivo using SPECT imaging and cut-and-count biodistribution. Single-agent (Olaparib, Rucaparib, [177Lu]Lu-DOTA-TOC) and combination treatment responses were determined in vitro via cell viability, clonogenic survival and γH2AX DNA damage assays. In vivo, we treated athymic nude mice bearing H69 or H446 xenografts with Olaparib, Rucaparib, or [177Lu]Lu-DOTA-TOC alone or with combination treatment regimens to assess the impact on tumor growth and survival of the treated mice. Results: H446 and H69 cells exhibited low SSTR2 expression, i.e. 60 to 90% lower uptake of SSTR2-ligands compared to AR42J cells. In vitro, combination treatment of [177Lu]Lu-DOTA-TOC with PARPi resulted in 2.9- to 67-fold increased potency relative to [177Lu]Lu-DOTA-TOC alone. We observed decreased clonogenic survival and higher amounts of persistent DNA damage compared to single-agent treatment for both Olaparib and Rucaparib. In vivo, tumor doubling times increased to 1.6-fold (H446) and 2.2-fold (H69) under combination treatment, and 1.0 to 1.1-fold (H446) and 1.1 to 1.7-fold (H69) in monotherapies compared to untreated animals. Concurrently, median survival was higher in the combination treatment groups in both models compared to monotherapy and untreated mice. Fractionating the PRRT dose did not lead to further improvement of therapeutic outcome. Conclusion: The addition of PARPi can markedly improve the potency of SSTR2-targeted PRRT in SCLC models in SSTR2 low-expressing tumors. Further evaluation in humans seems justified based on the results as novel treatment options for SCLC are urgently needed. [ABSTRACT FROM AUTHOR]

Copyright of Notfall & Rettungsmedizin is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and objectives: Although rare, complications like skin dehiscence and necrosis after neurosurgery pose significant challenges by increasing the risk of infections spreading to the epidural, subdural, or intracerebral spaces. This retrospective, single-center study aims to assess the prior clinical courses, neuroplastic repair, and outcomes of patients with skin defects following cranial neurosurgical procedures, and to outline our interdisciplinary reconstructive protocol. Methods: A retrospective analysis was performed on cranial surgeries conducted at the Department of Neurosurgery, spanning from 2017 to 2023. Patients with skin defects requiring the combined expertise of neurosurgery and plastic surgery for effective treatment were included. The sizes of the skin defects were measured using intraoperative photographs analyzed with the freeware ImageJ software, version 2018. All patients provided informed consent for the surgeries. If informed consent was not possible due to neurological deterioration, consent was sought from adult representatives or next of kin except for acute circumstances. All patients admitted to our hospital agree to the pseudonymized use of their medical data and tissue specimens for research purposes in their treatment contract. Results: A cohort of 24 patients experiencing wound healing complications after neurosurgical procedures underwent a total of 29 interdisciplinary surgeries for the reconstruction of skin, dural, and bone defects. After the neuroplastic surgery, 8 out of 24 patients (33.3%) developed surgical complications, with 6 of these requiring revision surgeries due to persistent cranial infection. In all cases, permanent wound closure was successfully achieved following adherence to the proposed treatment algorithm. Conclusions: Our study underscores the necessity of an integrated neurosurgical and plastic surgical approach to effectively manage wound healing complications in a single stage surgery. Key interventions include differentiation between necrosis and gaping lesions, alongside precise management of neurosurgical issues like cerebrospinal fluid fistulas and hydrocephalus. Plastic surgical expertise in assessing the possibilities and limitations of both local and free flap surgeries is essential. [ABSTRACT FROM AUTHOR]

Distraction osteogenesis (DO) is a valuable surgical method for limb lengthening and bone defect correction, but its lengthy consolidation phase presents challenges. The accordion technique (AT), involving compression and distraction of bone segments, has shown potential for enhancing healing. This study aimed to investigate the effectiveness of the AT conducted at three different time points (distraction phase, early consolidation phase, or late consolidation phase) compared to conventional DO in a mouse osteotomy model. Healing was evaluated using in vivo microCT, histology, and computational modeling. Results showed that bridging frequency, BV, and callus tissue composition were similar between conventional DO and late consolidation AT. In contrast, distraction phase AT led to delayed healing at day 15 with a 72% reduction in BV compared to DO, but no significant differences by the endpoint. Early consolidation AT showed significantly impaired healing compared to DO, with only 29% of mice achieving bony bridging, and significantly reduced bone marrow area of the endpoint callus. In silico modeling was generally predictive of in vivo findings and suggested that application of the AT during early consolidation results in destruction of newly-formed vascular tissue. Overall, no benefit was observed for the AT compared to conventional DO with the parameters employed in this study. [ABSTRACT FROM AUTHOR]

Vbfnlo is a flexible parton level Monte Carlo program for the simulation of vector boson fusion (VBF), QCD-induced single and double vector boson production plus two jets, and double and triple vector boson production (plus jet) in hadronic collisions at next-to-leading order (NLO) in the strong coupling constant, as well as Higgs boson plus two and three jet production via gluon fusion at the one-loop level. For the new version – Version 3.0 – several major enhancements have been included. An interface according to the Binoth Les Houches Accord (BLHA) has been added for all VBF and di/tri-boson processes including fully leptonic decays. For all dimension-8 operators affecting vector boson scattering (VBS) processes, a modified T-matrix unitarization procedure has been implemented. Several new production processes have been added, namely the VBS Z γ j j and γ γ j j processes at NLO, γ γ j j , WWj and ZZj production at NLO including the loop-induced gluon-fusion contributions and the gluon-fusion one-loop induced Φ j j j (Φ is a CP-even or CP-odd scalar boson) process at LO, retaining the full top-mass dependence. Finally, the code has been parallelized using Openmpi. [ABSTRACT FROM AUTHOR]

Acute intoxications and poisonings are a relevant cause for ICU admission of critically ill patients. This study aimed to determine the characteristics of intoxicated patients in a tertiary center medical ICU in Austria over time and to investigate parameters associated with ICU mortality. This study was a retrospective data analysis including adult ICU patients from the years 2007 to 2021. In addition to ICU documentation, pre-hospital, and emergency department documents as well as autopsy reports were utilized. In an exploratory subanalysis, we compared these findings to a historical dataset from our facility from 1992 to 1996. We identified 581 cases admitted to the medical ICU because of acute poisoning (2007–2021), of which 45% were female and 46.6% were mixed intoxications. Suicidal intent was the primary cause of intoxication (48.2%) and ICU length of stay was median 1.2 days. The majority of deceased patients received pre-hospital mechanical CPR. Primary and secondary poison/toxin removal modalities were used in 29.9% and 11.7% of cases, whereas antidotes were administered in 54.4%. Comparing the data with a historical cohort (n = 168), we found a shift in primary detoxification away from gastric lavage and an increase in alternative secondary poison/toxin removal techniques. The ICU mortality was 4.1% and 4.2% in the present and historic cohort, respectively. Pre-existing psychiatric illnesses increased from 49% in the historic to 69% in the present cohort. Psychiatric illness predisposes patients to severe intoxications necessitating ICU care, thus increasing prevention measures seems warranted. Females did present with a different spectrum of intoxications compared to males. ICU mortality remained low over time and most deceased patients had a grim prognosis already on ICU arrival. [ABSTRACT FROM AUTHOR]

Purpose: The thalamo-mesencephalic (TM) branches of the posterior cerebral artery (PCA) supply critical structures. Previous descriptions of these vessels are inconsistent and almost exclusively rely on cadaver studies. We aimed to provide a neuroradiological description of TM vessels in vivo based on routine 3D rotational angiographies (3D-RA). Methods: We analyzed 3D-RAs of 58 patients with pathologies remote from the PCA. PCA-origins were considered. Delineation, origin and number of branches of the collicular artery (CA), the accessory CA (ACA), the posterior thalamoperforating artery (PTA), the thalamogeniculate artery (TGA), and the posterior medial (PMCA) and lateral (PCLA) choroid arteries were assessed. The PTAs were categorized based on Percheron's suggested classification. Results: A CA was identified in 84%, an ACA in 20%. The PTA was delineated in 100%. In 27%, PTA anatomy had features of several Percheron types (n = 7) or vessels emanating from a net like origin (n = 9). 26% had a type IIb PTA. A fetal type PCA origin with hypoplastic ipsilateral P1 was observed in 5 cases with type IIa (n = 2) or type IIb (n = 3) PTAs originating from contralateral P1. The TGA was identified in 85% of patients, with ≥ 2 branches in 67%. The PMCA was delineable in 41%, the PLCA in 100%. Conclusion: The prevalence of a proper "Artery of Percheron" type IIb PTA seems to be higher than previously reported. A fetal type P1-origin may be predictive of a type IIa/b PTA emanating from contralateral P1. 3D-RA may be useful for planning PCA interventions, as impairment of TM branches is a severe risk. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review aims to provide a comprehensive overview of the current understanding of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), including its incidence, risk factors, clinical presentation, and diagnostic criteria. The aim is to enhance awareness among healthcare professionals and patients about BIA-ALCL, its management strategies, and the importance of surveillance in individuals with breast implants. Recent Findings: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare form of T cell lymphoma characterized by the presence of the CD30 biomarker. Although BIA-ALCL is more prevalent than other primary breast lymphomas, its incidence rate is extremely low. Textured implants have been associated with nearly all instances of BIA-ALCL. A significant proportion of BIA-ALCL patients exhibit an excellent prognosis after the extraction of the implants and capsules. Unfavorable outcomes are seen in instances of tumor bulk and implant capsule invasion. Summary: This review provides an in-depth understanding of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), focusing on its incidence, risk factors, clinical presentation, diagnostic criteria, and imaging evaluation. BIA-ALCL management techniques, treatment modalities, effectiveness, and outcomes are examined to improve patient care and awareness. [ABSTRACT FROM AUTHOR]

Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility and fractures, short stature, dental abnormalities, hearing loss, scoliosis, and chronic pain. Despite a growing literature on the functional outcomes of OI, limited research has explicitly examined the psychosocial outcomes of pain within OI. Adults with OI (N = 15) were interviewed to understand pain-related experiences through a thematic analysis of semi-structured interview data. Research team members, genetic research experts, and OI clinicians developed an interview guide focused on topics related to pain and mental health challenges. Participants' transcripts were coded by two independent coders; codes were then merged across coders and quotation outputs were subsequently abstracted (paraphrased then thematically classified) to identify common themes. Themes related to pain management variability regarding pain type, pain risk management and accessibility, pain outcomes (e.g., behavior, cognitive, affective), and pain exacerbating factors (e.g., individual, contextual) were identified. Participants reported chronic and acute pain, and despite the inaccessibility and stigmatization of pain medications (e.g., opioids), pharmacological treatments were the most common pain management approach. Participants reported negative pain outcomes, such as limited daily functioning and activity participation, fear, anger, anxiety, depression, and difficulty concentrating. Lastly, participants suggested that lack of physician and community knowledge on chronic pain in OI indirectly exacerbates both subjective pain intensity and outcomes. Although limited by a small, nondiverse sample, the current study provides valuable exploration of the unique pain experiences of adults with OI that may have implications for proactive management, treatment development, and clinician training. [ABSTRACT FROM AUTHOR]

This article explores the challenges and solutions in the physical characterization of materials at the microscale using robotized systems, with a specific focus on manipulating and characterizing micrometer-sized particles with different and complex 3D shapes and internal sub-micrometer structures. In this paper, the studied particles are Molybdenum diSulfide (MoS2) based materials generated within the contact interface during friction.These particles are being studied because they offer a particularly promising solution for reducing mechanical friction and the associated high energy losses. However, they are distributed randomly within the contact area and possess intricate sub-micrometer structures. Characterization demands precise manipulation techniques in an in-situ Scanning Electron Microscope(SEM) environment. To address these challenges, existing commercial micro and nanomanipulation tools are integrated within a vacuum SEM chamber, and robotics strategies are investigated to enable the whole process from particle preparation, and manipulation setup definition, to effective MoS 2 particle characterization all in-situ SEM. A set of several complementary experimental investigations are done and involve force measurement and deformation estimation studies, leading to the first qualitative results on MoS 2 based particles directly from the friction track. The work contributes to advancements in both microscale manipulation and characterization. It also has implications for lubrication research. [ABSTRACT FROM AUTHOR]

Copyright of HNO is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: The rate of depression among college students has increased significantly, reducing vitality and ability to flourish. Mindfulness interventions delivered via technological platforms offer great promise for reducing depression symptoms and supporting positive wellbeing outcomes for college students. The present study aimed to understand the broader positive wellbeing outcomes that accompany a reduction in psychological distress following use of a technology-delivered mindfulness intervention. Methods: Using a randomized controlled treatment design, this study evaluated the benefits of a mindfulness-based mobile application (app), Headspace, on various aspects of wellbeing in depressed college students. Students (n = 145) were randomly assigned to 2 months of app-based intervention or to a waitlist control. Participants completed self-report surveys assessing mental health and wellbeing at pre-intervention, midpoint (1 month), post-intervention (2 months), and follow-up (3 months). Results: Using intent-to-treat analysis, those randomized to use the app, compared to those on the waitlist, demonstrated a reduction in depression symptoms, and in other indicators of psychological distress (e.g., anxiety, stress, negative affect), over time. Self-reported positive wellbeing outcomes included an increase in positive affect and happiness, enhanced capacity to savor the moment, enhanced compassion, self-regulation, and trait mindfulness. These statistically significant benefits were medium to large in size and lasted into the 1-month follow-up period. Further, students' patterns of app use point to the critical gap that evidence-based technology-delivered interventions can fill. Conclusions: Building on previous research, the present study illustrated that a technology-delivered mindfulness intervention comprehensively improved aspects of psychological distress and positive wellbeing in a sustained manner in college students. Preregistration: This study was registered at OSF, https://osf.io/3trzk. [ABSTRACT FROM AUTHOR]

Objectives: Bitewing radiography is considered to be of high diagnostic value in caries detection, but owing to projections, lesions may remain undetected. The novel bitewing plus (BW +) technology enables scrolling through radiographs in different directions and angles. The present study aimed at comparing BW + with other 2D and 3D imaging methods in terms of sensitivity, specificity, and user reliability. Materials and methods: Five human cadavers were used in this study. In three cadavers, natural teeth were transplanted post-mortem. BW + , two-dimensional (digital sensors, imaging plates, 2D and 3D bitewing radiographs) and 3D methods (high and low dose CBCT) were taken. Carious lesions were evaluated on 96 teeth at three positions (mesial, distal, and occlusal) and scored according to their level of demineralization by ten observers, resulting in 35,799 possible lesions across all observers and settings. For reference, µCT scans of all teeth were performed. Results: Overall, radiographic evaluations showed a high rate of false-negative diagnoses, with around 70% of lesions remaining undetected, especially enamel lesions. BW + showed the highest sensitivity for dentinal caries and had comparatively high specificity overall. Conclusions: Within the limits of the study, BW + showed great potential for added diagnostic value, especially for dentinal caries. However, the tradeoff of diagnostic benefit and radiation exposure must be considered according to each patient's age and risk. [ABSTRACT FROM AUTHOR]

Introduction: Heart failure represents a major challenge for healthcare systems worldwide. Rehabilitation is recommended as an important pillar of therapy for these patients, especially for those with reduced left ventricular ejection fraction (HFrEF: heart failure with reduced ejection fraction). Methods: The data collected in this multi-center project provide information on the rates of patients with HFrEF who were treated in five German rehabilitation facilities and whether the patients adhered to drug therapy at 3-/6-month follow-up. The project was supported by an unrestricted grant from Novartis-Pharma-GmbH. Results: The mean age of the 234 patients included was 63.4 ± 10.6 years and 78% were male. The mean LVEF was 31 ± 8% at admission and 36 ± 10% at discharge. Only 20.6% of the patients were assigned to rehabilitation with the main indication HF. The most frequent main indication was acute coronary syndrome (46.6%). A high proportion of patients was already on the recommended drug therapy upon admission (94% beta blockers, 100% angiotensin-effective drugs, 70% mineralocorticoid receptor antagonists, etc.). This was optimized, in particular by a higher proportion of patients treated with sodium-glucose cotransporter-2 inhibitors (35% admission vs. 45% discharge) and sacubitril/valsartan (49% admission vs. 64% discharge), which was further optimized during the 6-month follow-up (e.g., 50% SGLT2 inhibitors, 67% sacubitril/valsartan). Discussion: These data illustrate the effect of rehabilitation in terms of optimizing drug therapy, which stabilized over the course of 6 months. Furthermore, only a few patients with the main diagnosis HFrEF are referred for cardiac rehabilitation, although it is an essential part of guideline-based therapy. [ABSTRACT FROM AUTHOR]

Purpose: Our aim was to investigate the course of the hearing capacity of the better-hearing ear in single-sided deafness (SSD) and asymmetric hearing loss (AHL) over time, in a multicenter study. Methods: We included 2086 pure-tone audiograms from 323 patients with SSD and AHL from four hospitals and 156 private practice otorhinolaryngologists. We collected: age, gender, etiology, duration of deafness, treatment with CI, number and monosyllabic speech recognition, numerical rating scale (NRS) of tinnitus intensity, and the tinnitus questionnaire according to Goebel and Hiller. We compared the pure tone audiogram of the better-hearing ear in patients with SSD with age- and gender-controlled hearing thresholds from ISO 7029:2017. Results: First, individuals with SSD showed a significantly higher hearing threshold from 0.125 to 8 kHz in the better-hearing ear compared to the ISO 7029:2017. The duration of deafness of the poorer-hearing ear showed no relationship with the hearing threshold of the better-hearing ear. The hearing threshold was significantly higher in typically bilaterally presenting etiologies (chronic otitis media, otosclerosis, and congenital hearing loss), except for Menière's disease. Second, subjects that developed AHL did so in 5.19 ± 5.91 years and showed significant reduction in monosyllabic word and number recognition. Conclusions: Individuals with SSD show significantly poorer hearing in the better-hearing ear than individuals with NH from the ISO 7029:2017. In clinical practice, we should, therefore, inform our SSD patients that their disease is accompanied by a reduced hearing capacity on the contralateral side, especially in certain etiologies. [ABSTRACT FROM AUTHOR]

Besides the need for more advanced predictive methods, there is increasing demand for easily interpretable results. Couples of enhanced association rules (a generalization of association rules/apriori/frequent itemsets) are excellent candidates for this task. They can be interpreted in various ways, subgroup discovery being an example. A typical result in rule mining is that there are too low or too many rules in the resulting ruleset. Analysts must usually iterate 5–15 times to get a reasonable number of rules. Inspired by research in a similar area of frequent itemsets to simplify input and parameter-free frequent itemsets, we have proposed a novel algorithm that finds rules based not on parameters like support and confidence but the best rules by a given range of required rule count in output. We propose this algorithm for couples of rules – SD4ft-Miner procedure and benefits from a brand new implementation of methods of mechanizing hypothesis formation in Python called Cleverminer that allows easy implementation of this algorithm. We have verified the algorithm by several applications on eight public data sets. Our original case was a case study, and it was also the reason why we developed the algorithm. However, implementation is in Python, and the algorithm itself can be used on a broader class of methods in any language. The algorithm iterates quickly, in all experiments we needed a maximum of 10 iterations. Possible enhancements to this algorithm are also outlined. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Anaesthesia / Journal Canadien d'Anesthésie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of e & i Elektrotechnik und Informationstechnik is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Dealing with a mass casualty incident presents many challenges in the clinical and preclinical situation. There are various systems and structures to address this problem. In the present work, the management of the train accident near Garmisch-Partenkirchen on 3 June 2022 is evaluated with the aid of the recommendations of the Federal Office for Civil Protection and Disaster Relief for hospital alarm and deployment planning as well as the recommendations from the terror and disaster surgical care training of the German Academy of Trauma Surgery and the findings are presented from the perspective of a regional trauma center. It also discusses which key factors in the present case have proved to be successful and in which areas there is still a need for improvement. [ABSTRACT FROM AUTHOR]

Objectives: The influence of cochlear morphology and electrode array design on scalar position and dislocation rates is of great interest in CI surgery. The aim of this study is to evaluate scalar position and specific points of dislocation in relation to cochlear morphology in patients implanted with a new slim perimodiolar electrode array. Materials and methods: Patients were implanted using the slim modiolar electrode array (= SMA) (= 532/632 electrode array of Cochlear™). Postoperative imaging was performed via cone beam computed tomography (CBCT) and the scans were analyzed regarding cochlear morphology (distances A and B and cochlear height), scalar location of the electrode array, basal insertion depth and apical insertion angle. Furthermore, electrode array design and surgical protocols were evaluated. Results: 81 ears implanted with the SMA were retrospectively included. We evaluated 3 electrode array tip fold over intraoperatively via X-ray imaging and performed revision during the same surgery. The CBCT scans showed 76 initial scala tympani (ST) insertions without dislocation. Two ears showed a dislocated array, one at 77° and the other at 163°. Three arrays were inserted into scala vestibuli (SV) via cochleostomy. These patients showed no signs of obliteration. Cochlear morphology showed no influence on angular insertion depth and scalar position. Conclusions: The SMA showed a very low rate of scalar dislocations due to its slim electrode array design (2.7%). We could find a learning curve regarding the handling and the risk of dislocation and tip fold over with this electrode array. The rate of intraoperative tip fold over detection via X-ray imaging was 3.7%. Therefore, we highly recommend X-ray imaging and transimpedance matrix measurements within the surgery protocol. Scala vestibuli insertions happened in patients with cochleostomy only. We could identify two specific points of dislocation depending on electrode array design. [ABSTRACT FROM AUTHOR]

Copyright of HNO is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

SNURPORTIN-1, encoded by SNUPN, plays a central role in the nuclear import of spliceosomal small nuclear ribonucleoproteins. However, its physiological function remains unexplored. In this study, we investigate 18 children from 15 unrelated families who present with atypical muscular dystrophy and neurological defects. Nine hypomorphic SNUPN biallelic variants, predominantly clustered in the last coding exon, are ascertained to segregate with the disease. We demonstrate that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients' primary fibroblasts and CRISPR/Cas9-mediated mutant cell lines. Additionally, mutant nuclei exhibit defective spliceosomal maturation and breakdown of Cajal bodies. Transcriptome analyses reveal splicing and mRNA expression dysregulation, particularly in sarcolemmal components, causing disruption of cytoskeletal organization in mutant cells and patient muscle tissues. Our findings establish SNUPN deficiency as the genetic etiology of a previously unrecognized subtype of muscular dystrophy and provide robust evidence of the role of SPN1 for muscle homeostasis. SNURPORTIN-1, encoded by the SNUPN gene, plays a key role in the nuclear import of spliceosomal small nuclear ribonucleoproteins, however its physiological function remains unclear. Here the authors report that recessive SNUPN mutations cause a distinct subtype of childhood muscular dystrophy and reveal SNURPORTIN-1's role in muscle homeostasis, offering insights for new therapeutic strategies. [ABSTRACT FROM AUTHOR]

The stability of Reissner–Nördstrom black holes with an extremal mass–charge relation was determined by calculating the propagation speed of gravitational waves on this background in an effective field theory (EFT) of gravity. New results for metric components are shown, along with the corresponding new extremal relation, part of which differs by a global factor of 2 from the past published work. This new relation further develops the existing constraints on EFT parameters. The radial propagation speed for gravitational waves in the Regge–Wheeler gauge was calculated linearly for all perturbations, yielding exact luminality for all dimension-4 operators. The dimension-6 radial speed modifications introduce no constraints on the sign of the modified theory parameters from causality arguments, while the deviation from classical theories vanishes at both horizons. The angular speed was found to be altered for the dimension-4 operators, with possible new constraints on the modified theory being suggested from causality arguments. Results are consistent with existing literature on Schwarzschild black hole backgrounds, with some EFT terms becoming active only in non-vacuum spacetimes such as Reissner–Nördstrom black holes. [ABSTRACT FROM AUTHOR]

Copyright of Datenschutz und Datensicherheit - DuD is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This works presents a methodology, along with its software implementation called "Design 2 Cost", for evaluating the manufacturing cost and complexity of a part built by a subtractive (e.g. milling) or additive (e.g. laser metal deposition, Selective laser melting, wire-arc additive manufacturing) process. The overall manufacturing complexity is calculated as a weighted average of morphological and material criteria, which are defined either locally or globally. The local morphological criteria are calculated over the leaf nodes of an octree representation of the part using a raycasting technique. This allows to efficiently probe the local geometry of the part and compare it with manufacturing constraints emanating from the manufacturing process and its associated effector. This algorithm yields a cartography of the local complexity criteria that helps visualizing the problematic regions for the processes under consideration. The software is accompanied by a database that feeds the required material and process properties needed for the calculation of the manufacturing complexity and cost. The proposed methodology therefore permits a technical and economic comparison of manufacturing processes for a given geometry and material, as well as a comparison of various part geometries and materials for a given manufacturing process. [ABSTRACT FROM AUTHOR]

Background: Breast cancer patients with residual disease after neoadjuvant systemic treatment (NAST) have a worse prognosis compared with those achieving a pathologic complete response (pCR). Earlier identification of these patients might allow timely, extended neoadjuvant treatment strategies. We explored the feasibility of a vacuum-assisted biopsy (VAB) after NAST to identify patients with residual disease (ypT+ or ypN+) prior to surgery. Methods: We used data from a multicenter trial, collected at 21 study sites (NCT02948764). The trial included women with cT1-3, cN0/+ breast cancer undergoing routine post-neoadjuvant imaging (ultrasound, MRI, mammography) and VAB prior to surgery. We compared the findings of VAB and routine imaging with the histopathologic evaluation of the surgical specimen. Results: Of 398 patients, 34 patients with missing ypN status and 127 patients with luminal tumors were excluded. Among the remaining 237 patients, tumor cells in the VAB indicated a surgical non-pCR in all patients (73/73, positive predictive value [PPV] 100%), whereas PPV of routine imaging after NAST was 56.0% (75/134). Sensitivity of the VAB was 72.3% (73/101), and 74.3% for sensitivity of imaging (75/101). Conclusion: Residual cancer found in a VAB specimen after NAST always corresponds to non-pCR. Residual cancer assumed on routine imaging after NAST corresponds to actual residual cancer in about half of patients. Response assessment by VAB is not safe for the exclusion of residual cancer. Response assessment by biopsies after NAST may allow studying the new concept of extended neoadjuvant treatment for patients with residual disease in future trials. [ABSTRACT FROM AUTHOR]

Enhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis, which is characterized by increased bone resorption and inadequate bone formation. As novel antiosteoporotic therapeutics are needed, understanding the genetic regulation of human osteoclastogenesis could help identify potential treatment targets. This study aimed to provide an overview of transcriptional reprogramming during human osteoclast differentiation. Osteoclasts were differentiated from CD14+ monocytes from eight female donors. RNA sequencing during differentiation revealed 8 980 differentially expressed genes grouped into eight temporal patterns conserved across donors. These patterns revealed distinct molecular functions associated with postmenopausal osteoporosis susceptibility genes based on RNA from iliac crest biopsies and bone mineral density SNPs. Network analyses revealed mutual dependencies between temporal expression patterns and provided insight into subtype-specific transcriptional networks. The donor-specific expression patterns revealed genes at the monocyte stage, such as filamin B (FLNB) and oxidized low-density lipoprotein receptor 1 (OLR1, encoding LOX-1), that are predictive of the resorptive activity of mature osteoclasts. The expression of differentially expressed G-protein coupled receptors was strong during osteoclast differentiation, and these receptors are associated with bone mineral density SNPs, suggesting that they play a pivotal role in osteoclast differentiation and activity. The regulatory effects of three differentially expressed G-protein coupled receptors were exemplified by in vitro pharmacological modulation of complement 5 A receptor 1 (C5AR1), somatostatin receptor 2 (SSTR2), and free fatty acid receptor 4 (FFAR4/GPR120). Activating C5AR1 enhanced osteoclast formation, while activating SSTR2 decreased the resorptive activity of mature osteoclasts, and activating FFAR4 decreased both the number and resorptive activity of mature osteoclasts. In conclusion, we report the occurrence of transcriptional reprogramming during human osteoclast differentiation and identified SSTR2 and FFAR4 as antiresorptive G-protein coupled receptors and FLNB and LOX-1 as potential molecular markers of osteoclast activity. These data can help future investigations identify molecular regulators of osteoclast differentiation and activity and provide the basis for novel antiosteoporotic targets. [ABSTRACT FROM AUTHOR]

Stabilization and solidification (S/S) is known to improve the structural properties of sediment and reduce contaminant mobility, enabling the utilization of dredged contaminated sediment. Further reduction of contaminants (e.g., tributyltin (TBT) and metals) can be done using electrochemical treatment prior to S/S and could potentially minimize contaminant leaching. This is the first study on how electrochemical pretreatment affects the strength and leaching properties of stabilized sediments. It also investigates how salinity and organic carbon in the curing liquid affect the stabilized sediment. The results showed that the electrolysis reduced the content of TBT by 22% and zinc by 44% in the sediment. The electrolyzed stabilized samples met the requirements for compression strength and had a reduced surface leaching of zinc. Curing in saline water was beneficial for strength development and reduced the leaching of TBT compared to curing in fresh water. The results indicate that pretreatment prior to stabilization could be beneficial in reducing contaminant leaching and recovering metals from the sediment. The conclusion is that a better understanding of the changes in the sediment caused by electrochemical treatment and how these changes interact with stabilization reactions is needed. In addition, it is recommended to investigate the strength and leaching behavior in environments similar to the intended in situ conditions. [ABSTRACT FROM AUTHOR]

Background: The active transcutaneous, partially implantable osseointegrated bone conduction system Cochlear™ Osia® (Cochlear, Sydney, Australia) has been approved for use in German-speaking countries since April 2021. The Osia is indicated for patients either having conductive (CHL) or mixed hearing loss (MHL) with an average bone conduction (BC) hearing loss of 55 dB HL or less, or having single-sided deafness (SSD). Objectives: The aim of this retrospective study was to investigate the prediction of postoperative speech recognition with Osia® and to evaluate the speech recognition of patients with MHL and in particular an aided dynamic range of less than 30 dB with Osia®. Materials and methods: Between 2017 and 2022, 29 adult patients were fitted with the Osia®, 10 patients (11 ears) with CHL and 19 patients (25 ears) with MHL. MHL was subdivided into two groups: MHL‑I with four-frequency pure-tone average in BC (BC-4PTA) ≥ 20 dB HL and < 40 dB HL (n = 15 patients; 20 ears) vs. MHL-II with BC-4PTA ≥ 40 dB HL (n = 4 patients; 5 ears). All patients tested a bone conduction hearing device on a softband preoperatively. Speech intelligibility in quiet was assessed preoperatively using the Freiburg monosyllabic test in unaided condition, with the trial BCHD preoperatively and with Osia® postoperatively with Osia®. The maximum word recognition score (mWRS) unaided and the word recognition score (WRS) with the test system at 65 dB SPL were correlated with the postoperative WRS with Osia® at 65 dB SPL. Results: Preoperative prediction of postoperative outcome with Osia® was better using the mWRS than by the WRS at 65 dB SPL with the test device on the softband. Postoperative WRS was most predictive for patients with CHL and less predictable for patients with mixed hearing loss with BC-4PTA ≥ 40 dB HL. For the test device on a softband, the achievable outcome tended to a minimum, with the mWRS tending to predict the realistically achievable outcome. Conclusion: Osia® can be used for the treatment of CHL and MHL within the indication limits. The average preoperative bone conduction hearing threshold also provides an approximate estimate of the postoperative WRS with Osia®, for which the most accurate prediction is obtained using the preoperative mWRS. Prediction accuracy decreases from a BC-4PTA of ≥ 40 dB HL. [ABSTRACT FROM AUTHOR]

Despite the availability of live-attenuated oral vaccines, rotavirus remains a major cause of severe childhood diarrhea worldwide. Due to the growing demand for parenteral rotavirus vaccines, we developed mRNA-based vaccine candidates targeting the viral spike protein VP8*. Our monomeric P2 (universal T cell epitope)-VP8* mRNA design is equivalent to a protein vaccine currently in clinical development, while LS (lumazine synthase)-P2-VP8* was designed to form nanoparticles. Cyro-electron microscopy and western blotting-based data presented here suggest that proteins derived from LS-P2-VP8* mRNA are secreted in vitro and self-assemble into 60-mer nanoparticles displaying VP8*. mRNA encoded VP8* was immunogenic in rodents and introduced both humoral and cellular responses. LS-P2-VP8* induced superior humoral responses to P2-VP8* in guinea pigs, both as monovalent and trivalent vaccines, with encouraging responses detected against the most prevalent P genotypes. Overall, our data provide evidence that trivalent LS-P2-VP8* represents a promising mRNA-based next-generation rotavirus vaccine candidate. [ABSTRACT FROM AUTHOR]

Purpose: The number of homeless people in Germany is steadily increasing. Due to their often precarious living conditions, this specific population may be increasingly exposed to ectoparasites that can transmit various pathogens. To assess the prevalence and thus the risk of such infections, we analyzed the seropositivity of rickettsiosis, Q fever, tularemia and bartonellosis in homeless individuals. Methods: A total of 147 homeless adults from nine shelters in Hamburg, Germany, were included. The individuals underwent questionnaire-based interviewing, physical examination, and venous blood was drawn between May and June 2020. Blood samples were analyzed for antibodies against rickettsiae (Rickettsia typhi and R. conorii), Coxiella burnetii, Francisella tularensis and bartonellae. Results and conclusion: A very low seroprevalence of R. typhi and F. tularensis infection was found (0–1%), while antibodies against R. conorii and C. burnetii were more common (7% each), followed by a relatively high seroprevalence of 14% for bartonellosis. Q fever seroprevalence was associated with the country of origin, whereas bartonellosis seroprevalence was associated with the duration of homelessness. Preventive measures targeting ectoparasites, especially body lice, should be put in place continuously. [ABSTRACT FROM AUTHOR]

Copyright of Die Kardiologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: To investigate Martens hardness parameters of splint materials after storage in liquids and toothbrush simulation. Materials and methods: Ten specimens per material and group were fabricated (hand-cast CAST, thermoformed TF, CAD/CAM-milled CAM, 3D-printed PS, PL, PK, PV), stored in air, water, coffee, red wine, and cleaning tablets and investigated after fabrication, 24 h, 2- and 4-week storage or toothbrushing. Martens hardness (HM), indentation hardness (HIT), indentation modulus (EIT), the elastic part of indentation work (ηIT), and indentation creep (CIT) were calculated (ISO 14577-1). Statistics: ANOVA, Bonferroni post hoc test, between-subjects effects, Pearson correlation (α = 0.05). Results: HM varied between 30.8 N/mm2 for PS (water 4 weeks) and 164.0 N/mm2 for CAM (toothbrush). HIT values between 34.9 N/mm2 for PS (water 4 weeks) and 238.9 N/mm2 for CAM (toothbrush) were found. EIT varied between 4.3 kN/mm2 for CAM (toothbrush) and 1.8 kN/mm2 for PK (water 2 weeks). ηIT was found to vary between 16.9% for PS (water 4 weeks) and 42.8% for PL (toothbrush). CIT varied between 2.5% for PL (toothbrush) and 11.4% for PS (water 4 weeks). The highest impact was identified for the material (p ≤ 0.001). Conclusions: Storage and toothbrushing influenced Martens parameters. The properties of splints can be influenced by the choice of materials, based on different elastic and viscoelastic parameters. High HM and EIT and low CIT might be beneficial for splint applications. Clinical relevance: Martens parameters HM, EIT, and CIT might help to evaluate clinically relevant splint properties such as hardness, elasticity, and creep. [ABSTRACT FROM AUTHOR]

Purpose: Despite extensive research on cancer and work-related outcomes, evidence from longitudinal cohort studies is limited, especially in young women with breast cancer (BC). We aimed to investigate employment trajectories in young BC survivors and to identify potential factors associated with changes in work activity. Methods: The HOHO European prospective multicenter cohort study enrolled 300 young women (≤ 40 years) with newly diagnosed BC. Women completed surveys at baseline and every 6 months for 3 years, then yearly for up to 10 years to assess, among other variables, employment status, sociodemographic, medical, and treatment data. Symptoms were assessed by the Breast Cancer Prevention Trial symptom scales and single items from the Cancer Rehabilitation Evaluation System. Univariable and multivariable multinomial logistic regression analyses identified factors associated with changes in employment status. Results: Among the 245 women included in this analysis, 85% were employed at the last individual post-baseline assessment (1 to 10 years). At 5 years, women had a 29.4% probability (95% CI: 23.6–35.5) of experiencing any reduction and a 14.9% probability (95% CI: 10.6–19.9) of experiencing any increase in work activities. Being enrolled in Switzerland (vs. Italy) and reporting more trouble in performing daily activities were significantly associated with work reduction. Conclusion: Our results suggest that most young BC survivors remain employed in the long-term. Implications for Cancer Survivors: Regular evaluation of symptoms which may interfere with daily life and identification of financial discomfort is critical in providing timely and individually tailored interventions and in limiting unwanted reductions in work activities. [ABSTRACT FROM AUTHOR]

Purpose: Sociodemographic and structural conditions have consequences for the labor market participation of young persons with disabilities (YPWD) in vocational rehabilitation (VR). As the type of program determines the labor market chances, we analyze the processes of selecting active labor market programs (ALMP) in VR. Which factors determine the allocation to (1) programs in general and (2) moreover, the allocation to specific programs? Materials and methods: We conduct logistic (1) and multinomial regression (2) using register data of the German Federal Employment Agency. Besides variables on the micro level, we control for a wide range of structural and organizational influences. The sample comprises VR and employment biographies of 255,009 YPWD accepted to VR between 2010 and 2015. Program participation is restricted to start 180 days after VR acceptance. Results: Sociodemographic factors, like age and the status before entering VR as well as the local apprenticeship market as a structural condition, highly influence the general allocation to ALMP. For the allocation to specific ALMP, sociodemographics (age, education, type of disability, status before entering VR) are highly relevant. Furthermore, structural conditions (regional structure of subsidized vocational training and of the apprenticeship market as well as local work possibilities on a special labor market for PWD) and – to a lesser extent - re-organization processes at the FEA (NEO, VR cohort) are important determinants. Conclusion: (Automatic) paths into VR programs for especially persons with mental disabilities in sheltered workshop are clearly shown. Furthermore, it is somewhat questionable that YPWD participate more often in sheltered workshops in regions where sheltered work possibilities are more common, as well as where NEO was implemented locally; and participate more often in company-external vocational training where VR service providers are commissioned to a greater extent. [ABSTRACT FROM AUTHOR]

Purpose: Obese patients exhibit an overall increased platelet reactivity and a reduced sensitivity to antiplatelet therapy. The aim of this study is to evaluate the platelet reactivity measured by impedance aggregometry in overweight and obese patients and chronic coronary syndrome (CCS) that were treated with dual antiplatelet therapy (DAPT). Methods: Platelet aggregation was assessed by impedance aggregometry in patients with CCS receiving DAPT (aspirin plus clopidogrel). We compared the platelet reactivity in patients with a normal weight versus overweight or obese patients. Furthermore, the correlation between the body mass index (BMI) and adenosine diphosphate- (ADP-) or thrombin receptor-activating peptide- (TRAP-) dependent platelet aggregation was analyzed. Results: 64 patients were included in the study of which 35.9% were patients with normal weight. A higher ADP- and TRAP-dependent platelet reactivity was observed in overweight and obese patients (ADP: median 27 units (U) [IQR 13–39.5] vs. 7 U [6–15], p < 0.001 and TRAP: 97 U [73–118.5] vs. 85 U [36–103], p = 0.035). Significant positive correlations were observed between agonist-induced platelet reactivity and BMI. Conclusion: Despite the use of DAPT, a higher platelet reactivity was found in overweight and obese patients with CCS. If these patients will benefit from treatment with more potent platelet inhibitors, it needs to be evaluated in future clinical trials. [ABSTRACT FROM AUTHOR]

RAF kinases play major roles in cancer. BRAFV600E mutants drive ~6% of human cancers. Potent kinase inhibitors exist but show variable effects in different cancer types, sometimes even inducing paradoxical RAF kinase activation. Both paradoxical activation and drug resistance are frequently due to enhanced dimerization between RAF1 and BRAF, which maintains or restores the activity of the downstream MEK-ERK pathway. Here, using quantitative proteomics we mapped the interactomes of RAF1 monomers, RAF1-BRAF and RAF1-BRAFV600E dimers identifying and quantifying >1,000 proteins. In addition, we examined the effects of vemurafenib and sorafenib, two different types of clinically used RAF inhibitors. Using regression analysis to compare different conditions we found a large overlapping core interactome but also distinct condition specific differences. Given that RAF proteins have kinase independent functions such dynamic interactome changes could contribute to their functional diversification. Analysing this dataset may provide a deeper understanding of RAF signalling and mechanisms of resistance to RAF inhibitors. [ABSTRACT FROM AUTHOR]

Although a myriad of studies have been conducted on player behavior in football, in-depth studies with structured theory are rare due to the difficulty in quantifying individual player skills and team strategies. We propose a physics-based mathematical model that describes football players' movements during dribbling situations, parameterized by the attacker aggressiveness, the defender hesitance and the top speed of both players. These player- and situation-specific parameters are extracted by fitting the model to real player trajectories from Major League Soccer games, and enable the quantification of player dribbling attributes and decisions beyond classical statistics. We show that the model captures the essential dribbling dynamics, and analyze how differences between parameters in varying game situations provide valuable insights into players' behavior. Lastly, we quantitatively study how changes in the player's parameters impact dribbling performance, enabling the model to provide scientific guidance to player training, scouting and game strategy development. [ABSTRACT FROM AUTHOR]

Demand for mass surveillance during peak times of the SARS-CoV-2 pandemic caused high workload for clinical laboratories. Efficient and cost conserving testing designs by means of group testing can substantially reduce resources during possible future emergency situations. The novel hypercube algorithm proposed by Mutesa et al. 2021 published in Nature provides methodological proof of concept and points out the applicability to epidemiological testing. In this work, the algorithm is explored and expanded for settings with high group prevalence. Numerical studies investigate the limits of the adapted hypercube methodology, allowing to optimize pooling designs for specific requirements (i.e. number of samples and group prevalence). Hyperparameter optimization is performed to maximize test-reduction. Standard deviation is examined to investigate resilience and precision. Moreover, empirical validation was performed by elaborately pooling SARS-CoV-2 virus samples according to numerically optimized pooling designs. Laboratory experiments with SARS-CoV-2 sample groups, ranging from 50 to 200 items, characterized by group prevalence up to 10%, are successfully processed and analysed. Test-reductions from 50 to 72.5% were achieved in the experimental setups when compared to individual testing. Higher theoretical test-reduction is possible, depending on the number of samples and the group prevalence, indicated by simulation results. [ABSTRACT FROM AUTHOR]

Copyright of Wissen Kompakt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: COVID-19 is associated with a prothrombotic state. Current guidelines recommend prophylactic anticoagulation upon hospitalization. Methods: COVID-PREVENT, an open-label, multicenter, randomized, clinical trial enrolled patients (≥ 18 years) with moderate to severe COVID-19 and age-adjusted d-dimers > 1.5 upper limit of normal (ULN). The participants were randomly assigned (1:1) to receive either therapeutic anticoagulation with rivaroxaban 20 mg once daily or thromboprophylaxis with a heparin (SOC) for at least 7 days followed by prophylactic anticoagulation with rivaroxaban 10 mg once daily for 28 days or no thromboprophylaxis. The primary efficacy outcome was the d-dimer level and the co-primary efficacy outcome the 7-category ordinal COVID-19 scale by WHO at 7 days post randomization. The secondary outcome was time to the composite event of either venous or arterial thromboembolism, new myocardial infarction, non-hemorrhagic stroke, all-cause death or progression to intubation and invasive ventilation up to 35 days post randomization. Results: The primary efficacy outcome d-dimer at 7 days was not different between patients assigned to therapeutic (n = 55) or prophylactic anticoagulation (n = 56) (1.21 mg/L [0.79, 1.86] vs 1.27 mg/L [0.79, 2.04], p = 0.78). In the whole study population d-dimer was significantly lower at 7 days compared to baseline (1.05 mg/L [0.75, 1.48] vs 1.57 mg/L [1.13, 2.19], p < 0.0001). Therapy with rivaroxaban compared to SOC was not associated an improvement on the WHO 7-category ordinal scale at 7 days (p = 0.085). Rivaroxaban improved the clinical outcome measured by the score in patients with a higher baseline d-dimer > 2.0 ULN (exploratory analysis; 0.632 [0.516, 0.748], p = 0.026). The secondary endpoint occurred in 6 patients (10.9%) in the rivaroxaban group and in 12 (21.4%) in the SOC group (time-to-first occurrence of the components of the secondary outcome: HR 0.5; 95% CI 0.15–1.67; p = 0.264). There was no difference in fatal or non-fatal major or clinically relevant non-major bleeding between the groups. Conclusions: Therapeutic anticoagulation with rivaroxaban compared to prophylactic anticoagulation with a heparin did not improve surrogates of clinical outcome in patients with moderate to severe COVID-19. Whether initial rivaroxaban at therapeutic doses might be superior to thromboprophylaxis in patients with COVID-19 and a high risk as defined by d-dimer > 2 ULN needs confirmation in further studies. [ABSTRACT FROM AUTHOR]

Aims: Sphingosine-1-phosphate (S1P) is a signaling lipid, which is involved in several cellular processes including cell growth, proliferation, migration and apoptosis. The associations of serum S1P levels with cardiac geometry and function are still not clear. We investigated the associations of S1P with cardiac structure and systolic function in a population-based sample. Methods and results: We performed cross-sectional analyses of 858 subjects (467 men; 54.4%), aged 22 to 81 years, from a sub-sample of the population-based Study of Health in Pomerania (SHIP-TREND-0). We analyzed the associations of serum S1P with structural and systolic function left ventricular (LV) and left atrial (LA) parameters as determined by magnetic resonance imaging (MRI) using sex-stratified multivariable-adjusted linear regression models. In men, MRI data showed that a 1 µmol/L lower S1P concentration was associated with an 18.1 mL (95% confidence interval [CI] 3.66–32.6; p = 0.014) larger LV end-diastolic volume (LVEDV), a 0.46 mm (95% CI 0.04–0.89; p = 0.034) greater LV wall thickness (LVWT) and a 16.3 g (95% CI 6.55–26.1; p = 0.001) higher LV mass (LVM). S1P was also associated with a 13.3 mL/beat (95% CI 4.49–22.1; p = 0.003) greater LV stroke volume (LVSV), an 18.7 cJ (95% CI 6.43–30.9; p = 0.003) greater LV stroke work (LVSW) and a 12.6 mL (95% CI 1.03–24.3; p = 0.033) larger LA end-diastolic volume (LAEDV). We did not find any significant associations in women. Conclusions: In this population-based sample, lower levels of S1P were associated with higher LV wall thickness and mass, larger LV and LA chamber sizes and greater stroke volume and work of the LV in men, but not in women. Our results indicate that lower levels of S1P were associated with parameters related with cardiac geometry and systolic function in men, but not in women. [ABSTRACT FROM AUTHOR]

Objective: Thus far, there is very limited knowledge regarding homeless individuals during the COVID-19 pandemic, particularly related to the health-related quality of life (HRQoL). Thus, our aim was to evaluate HRQoL and to clarify the determinants of HRQoL among homeless individuals during the COVID-19 pandemic in Germany. Methods: Data were taken from the national survey on psychiatric and somatic health of homeless individuals during the COVID-19 pandemic—NAPSHI (n = 616). The established EQ-5D-5L was used to quantify problems in five health dimensions, and its visual analogue scale (EQ-VAS) was used to record self-rated health status. Sociodemographic factors were included in regression analysis. Results: Pain/discomfort was the most frequently reported problem (45.3%), thereafter anxiety/depression (35.9%), mobility (25.4%), usual activities (18.5%) and self-care (11.4%). Average EQ-VAS score was 68.97 (SD: 23.83), and the mean EQ-5D-5L index was 0.85 (SD: 0.24). Regressions showed that higher age and having a health insurance were associated with several problem dimensions. Being married was associated with higher EQ-VAS scores. Conclusions: Overall, our study findings showed a quite high HRQoL among homeless individuals during the COVID-19 pandemic in Germany. Some important determinants of HRQoL were identified (e.g., age or marital status). Longitudinal studies are required to confirm our findings. [ABSTRACT FROM AUTHOR]