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BACKGROUND AND OBJECTIVES: 3-Dimensional (3D) printing has become a common tool to aid implant molding for cranioplastic surgery of large skull defects. Until now, 3D printing of cranial implants itself has not been used, mainly because of medicolegal concerns. With a 3D printer developed for printing medical applications and with implant-grade polyetheretherketone (PEEK) filament available, we established a workflow (in compliance with medical device regulations) to 3D print cranial implants for cranioplastic surgery directly at the point of care (POC). Here, we describe the implementation of 3D printing these PEEK implants for cranioplastic surgery at our academic hospital. METHODS: A thorough design and 3D printing process, in accordance with local medical device regulations, was developed. Implants are digitally designed based upon pre- and post-craniectomy cranial computed tomography scans by trained 3D printing experts from the department of medical engineering at our institution. Implants are then produced on a medical 3D printer with implant-grade PEEK filament using the fused filament fabrication process. After postprocessing and steam sterilization, implantation for reconstruction of the skull can be performed. RESULTS: Cranioplastic surgery with a 3D-printed PEEK implant was performed at our institution in a patient with a large frontotemporoparietal skull defect after traumatic brain injury with consecutive decompressive craniectomy. No intra- or post-operative complications occurred. Postoperative cranial computed tomography scans showed perfect reconstruction of precraniectomy skull shape. The aesthetic result was promising and satisfactory to the patient. CONCLUSION: This novel 3D printing workflow enables the production of patient-specific cranial implants from PEEK, to reconstruct large skull defects directly at the POC in accordance with the European Medical Device Regulation. This marks an unprecedented technological and legal advancement, enabling the hospital infrastructure not only to deliver the cranioplastic surgery itself, but also additive manufacturing of the implant directly at the POC.

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INTRODUCTION: The vertebral cartilage endplate (CEP), crucial for intervertebral disc health, is prone to degeneration linked to chronic low back pain, disc degeneration, and Modic changes (MC). While it is known that disc cells express toll-like receptors (TLRs) that recognize pathogen- and damage-associated molecular patterns (PAMPs and DAMPs), it is unclear if CEP cells (CEPCs) share this trait. The CEP has a higher cell density than the disc, making CEPCs an important contributor. This study aimed to identify TLRs on CEPCs and their role in pro-inflammatory and catabolic gene expression. METHODS: Gene expression of TLR1-10 was measured in human CEPs and expanded CEPCs using quantitative polymerase chain reaction. Additionally, surface TLR expression was measured in CEPs grouped into non-MC and MC. CEPCs were stimulated with tumor necrosis factor alpha, interleukin 1 beta, small-molecule TLR agonists, or the 30 kDa N-terminal fibronectin fragment. TLR2 signaling was inhibited with TL2-C29, and TLR2 protein expression was measured with flow cytometry. RESULTS: Ex vivo analysis found all 10 TLRs expressed, while cultured CEPCs lost TLR8 and TLR9 expression. TLR2 expression was significantly increased in MC1 CEPCs, and its expression increased significantly after pro-inflammatory stimulation. Stimulation of the TLR2/6 heterodimer upregulated TLR2 protein expression. The TLR2/1 and TLR2/6 ligands upregulated pro-inflammatory genes and matrix metalloproteases (MMP1, MMP3, and MMP13), and TLR2 inhibition inhibited their upregulation. Endplate resorptive capacity of TLR2 activation was confirmed in a CEP explant model. CONCLUSIONS: The expression of TLR1-10 in CEPCs suggests that the CEP is susceptible to PAMP and DAMP stimulation. Enhanced TLR2 expression in MC1, and generally in CEPCs under inflammatory conditions, has pro-inflammatory and pro-catabolic effects, suggesting a potential role in disc degeneration and MC.

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Despite its ubiquitous nature, the atomic structure of water in its liquid state is still controversially debated. We use a combination of X-ray Raman scattering spectroscopy in conjunction with ab initio and path integral molecular dynamics simulations to study the local atomic and electronic structure of water under high pressure conditions. Systematically increasing fingerprints of non-hydrogen-bonded H[Formula: see text]O molecules in the first hydration shell are identified in the experimental and computational oxygen K-edge excitation spectra. This provides evidence for a compaction mechanism in terms of a continuous collapse of the second hydration shell with increasing pressure via generation of interstitial water within locally tetrahedral hydrogen-bonding environments.

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Successful navigation to spatial locations relies on lasting memories from previous experiences. Spatial navigation undergoes profound maturational changes during childhood. It is unclear how well children can consolidate navigation-based spatial memories and if age-related variations in navigation during training predict spatial memory. The present study examined the immediate and long-delay (after a 2-week period) consolidation of navigation-based spatial memories in 6- to 8-year-old children (n = 33, 18 female/15 male, Mage = 7.61, SDage = 0.71), 9- to 11-year-old children (n = 32, 13 female/19 male, Mage = 9.90, SDage = 0.59), and 20- to 30-year-old adults (n = 31, 15 female/16 male, Mage = 23.71, SDage = 2.87). Our results showed that, with age, participants navigated more efficiently during training and formed better immediate spatial memories. Long-delay spatial memory retention after 2 weeks was comparable between children and adults, indicating robust consolidation even in children. Interestingly, while children successfully distinguished between perceptually detailed landmarks after 2 weeks, their abstract knowledge of spatial boundaries and cognitive map of landmark relations was poor. Developmental trajectories were similar for egocentric and allocentric spatial memory. Age-related variations in initial navigation were predictive of spatial memory, that is, children with a more mature initial navigation were more likely to find and remember spatial locations immediately and after a 2-week delay. Taken together, our results show an overall robust spatial memory consolidation in mid and late childhood that can be predicted by initial navigation behavior, coupled with nuanced age differences in the recall of spatial boundaries and cognitive maps. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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Ventriculoperitoneal (VP) shunt placement, essential for managing hydrocephalus, often risks catheter malpositioning, especially in patients with small ventricles. We present a novel technique combining neuronavigation with intraoperative cone-beam computed tomography using the BrainLab system and Loop-X mobile imaging unit. This approach enables real-time verification of catheter placement by integrating preoperative MRI data with intraoperative CT imaging. In a 12-year-old boy with therapy-refractory idiopathic intracranial hypertension, neuronavigation was guided by the BrainLab Skull Fix and Cushing canula, ensuring precise catheter insertion into the right frontal horn. Post-placement, Loop-X facilitated immediate verification of the catheter's trajectory and positioning, corroborated by postoperative MRI. This technique demonstrated high precision and minimized radiation exposure, emphasizing its utility in reducing revision rates due to suboptimal catheter placement.

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PURPOSE: To assess whether the Modified 5 (mFI-5) and 11 (mFI-11) Factor Frailty Indices associate with postoperative mortality, complications, and functional benefit in supratentorial meningioma patients aged over 80 years. METHODS: Baseline characteristics were collected from eight centers. Based on the patients' preoperative status and comorbidities, frailty was assessed by the mFI-5 and mFI-11. The collected scores were categorized as "robust (mFI=0)", "pre-frail (mFI=1)", "frail (mFI=2)", and "significantly frail (mFI≥3)". Outcome was assessed by the Karnofsky Performance Scale (KPS); functional benefit was defined as improved KPS score. Additionally, we evaluated the patients' functional independence (KPS≥70) after surgery. RESULTS: The study population consisted of 262 patients (median age 83 years) with a median preoperative KPS of 70 (range 20 to 100). The 90-day and 1-year mortality were 9.0% and 13.2%; we recorded surgery-associated complications in 111 (42.4%) patients. At last follow-up within the postoperative first year, 101 (38.5%) patients showed an improved KPS, and 183 (69.8%) either gained or maintained functional independence. "Severely frail" patients were at an increased risk of death at 90 days (OR 16.3 (CI95% 1.7-158.7)) and one year (OR 11.7 (CI95% 1.9-71.7)); nine (42.9%) of severely frail patients died within the first year after surgery. The "severely frail" cohort had increased odds of suffering from surgery-associated complications (OR 3.9 (CI 95%) 1.3-11.3)), but also had a high chance for postoperative functional improvements by KPS≥20 (OR 6.6 (CI95% 1.2-36.2)). CONCLUSION: The mFI-5 and mFI-11 associate with postoperative mortality, complications, and functional benefit. Even though "severely frail" patients had the highest risk morbidity and mortality, they had the highest chance for functional improvement.

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Atherosclerosis is a lipid-driven chronic inflammatory disease that is modulated by innate and adaptive immunity including humoral immunity. Importantly, antibody alterations achieved by genetic means or active and passive immunization strategies in preclinical studies can improve or aggravate atherosclerosis. Additionally, a wide range of epidemiological data demonstrate not only an association between the total levels of different antibody isotypes but also antibody levels targeting specific antigens with atherosclerotic cardiovascular disease. Here, we discuss the potential role of atherogenic dyslipidemia on the antibody repertoire and review potential antibody-mediated effector mechanisms involved in atherosclerosis development highlighting the major atherosclerosis-associated antigens that trigger antibody responses.

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INTRODUCTION: Thrombectomy complications remain poorly explored. This study aims to characterize periprocedural intracranial vessel perforation including the effect of thrombolysis on patient outcomes. PATIENTS AND METHODS: In this multicenter retrospective cohort study, consecutive patients with vessel perforation during thrombectomy between January 2015 and April 2023 were included. Vessel perforation was defined as active extravasation on digital subtraction angiography. The primary outcome was modified Rankin Scale (mRS) at 90 days. Factors associated with the primary outcome were assessed using proportional odds models. RESULTS: 459 patients with vessel perforation were included (mean age 72.5 ± 13.6 years, 59% female, 41% received thrombolysis). Mortality at 90 days was 51.9% and 16.3% of patients reached mRS 0-2 at 90 days. Thrombolysis was not associated with worse outcome at 90 days. Perforation of a large vessel (LV) as opposed to medium/distal vessel perforation was independently associated with worse outcome at 90 days (aOR 1.709, p = 0.04) and LV perforation was associated with poorer survival probability (HR 1.389, p = 0.021). Patients with active bleeding >20 min had worse survival probability, too (HR 1.797, p = 0.009). Thrombolysis was not associated with longer bleeding duration. Bleeding cessation was achieved faster by permanent vessel occlusion compared to temporary measures (median difference: 4 min, p < 0.001). DISCUSSION AND CONCLUSION: Vessel perforation during thrombectomy is a severe and frequently fatal complication. This study does not suggest that thrombolysis significantly attributes to worse prognosis. Prompt cessation of active bleeding within 20 min is critical, emphasizing the need for interventionalists to be trained in complication management.

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PURPOSE: Superficial surgical site infection (SSSI) is a prominent problem in spine surgery. Intracutaneous sutures and staple-assisted closure are two widely used surgical techniques for skin closure. Yet, their comparative impact on wound healing and infection rates is underexplored. Our goal was to address this gap and compare wound healing between these two techniques. METHODS: This study was a multicenter international prospective randomized trial. Patient data were prospectively collected at three large academic centers, patients who underwent non-instrumented lumbar primary spine surgery were included. Patients were intraoperatively randomized to either intracutaneous suture or staple-assisted closure cohorts. The primary endpoint was SSSI within 30 days after surgery according to the wound infection Centers for Disease Control and Prevention (CDC) classification system. RESULTS: Of 207 patients, 110 were randomized to intracutaneous sutures and 97 to staple-assisted closure. Both groups were homogenous with respect to epidemiological as well as surgical parameters. Two patients (one of each group) suffered from an A1 wound infection at the 30-day follow up. Median skin closure time was faster in the staple-assisted closure group (198 s vs. 13 s, p < 0,001). CONCLUSION: This study showed an overall low superficial surgical site infection rate in both patient cohorts in primary non instrumented spine surgery.

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Light management (LM) is the key to the encapsulation of high-performance silicon (Si) photovoltaic devices (PVs). In this work, simulation analyses provide meaningful insights into optical losses and guide the improvement of the PV performance of the encapsulated silicon solar cells (Encap-Si SCs). An antireflective layer, textured polydimethylsiloxane (PDMS), is designed to reduce reflection losses, especially at a lower illumination intensity, thereby achieving an improvement of 10.89% in the short-current density (JSC) and hence 12.67% in the power conversion efficiency (PCE) when illuminated at an incident angle of 60°. Subsequently, a luminescence down-shifting material, lead-free Cs2AgxNa1-xBiyIn1-yCl6 (CANBIC) double perovskite phosphor, is incorporated into the PDMS film to further enhance the energy yield in the ultraviolet (UV) region. The textured PDMS film with an optimized CANBIC content ultimately achieves a significant improvement in PCE from 21.770 to 23.136%. This enhancement is attributed to the increase in JSC by 2.381 mA/cm2 due to the reduced reflection losses (by antireflective PDMS) and down-converted UV energy (by CANBIC), providing a remarkable advance in LM toward highly efficient encapsulated PVs.

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Fenton-like processes using persulfate for oxidative water treatment and contaminant removal can be enhanced by the addition of redox-active biochar, which accelerates the reduction of Fe(III) to Fe(II) and increases the yield of reactive species that react with organic contaminants. However, available data on the formation of non-radical or radical species in the biochar/Fe(III)/persulfate system are inconsistent, which limits the evaluation of treatment efficiency and applicability in different water matrices. Based on competition kinetics calculations, we employed different scavengers and probe compounds to systematically evaluate the effect of chloride in presence of organic matter on the formation of major reactive species in the biochar/Fe(III)/persulfate system for the transformation of the model compound N,N­diethyl-m-toluamide (DEET) at pH 2.5. We show that the transformation of methyl phenyl sulfoxide (PMSO) to methyl phenyl sulfone (PMSO2) cannot serve as a reliable indicator for Fe(IV), as previously suggested, because sulfate radicals also induce PMSO2 formation. Although the formation of Fe(IV) cannot be completely excluded, sulfate radicals were identified as the major reactive species in the biochar/Fe(III)/persulfate system in pure water. In the presence of dissolved organic matter, low chloride concentrations (0.1 mM) shifted the major reactive species likely to hydroxyl radicals. Higher chloride concentrations (1 mM), as present in a mining-impacted acidic surface water, resulted in the formation of another reactive species, possibly Cl2•-, and efficient DEET degradation. To tailor the application of this oxidation process, the water matrix must be considered as a decisive factor for reactive species formation and contaminant removal.

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In an aging society, unveiling new anti-aging strategies to prevent and combat aging-related diseases is of utmost importance. Mitochondria are the primary ATP production sites and key regulators of programmed cell death. Consequently, these highly dynamic organelles play a central role in maintaining tissue function, and mitochondrial dysfunction is a pivotal factor in the progressive age-related decline in cellular homeostasis and organ function. The current review examines recent advances in understanding the interplay between mitochondrial dysfunction and organ-specific aging. Thereby, we dissect molecular mechanisms underlying mitochondrial impairment associated with the deterioration of organ function, exploring the role of mitochondrial DNA, reactive oxygen species homeostasis, metabolic activity, damage-associated molecular patterns, biogenesis, turnover, and dynamics. We also highlight emerging therapeutic strategies in preclinical and clinical tests that are supposed to rejuvenate mitochondrial function, such as antioxidants, mitochondrial biogenesis stimulators, and modulators of mitochondrial turnover and dynamics. Furthermore, we discuss potential benefits and challenges associated with the use of these interventions, emphasizing the need for organ-specific approaches given the unique mitochondrial characteristics of different tissues. In conclusion, this review highlights the therapeutic potential of addressing mitochondrial dysfunction to mitigate organ-specific aging, focusing on the skin, liver, lung, brain, skeletal muscle, and lung, as well as on the reproductive, immune, and cardiovascular systems. Based on a comprehensive understanding of the multifaceted roles of mitochondria, innovative therapeutic strategies may be developed and optimized to combat biological aging and promote healthy aging across diverse organ systems.

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BACKGROUND: Anterior cervical discectomy and fusion (ACDF) for the surgical treatment of cervical degenerative disease often includes an intervertebral cage, which restores disc height and lordosis while promoting fusion . Cage materials include titanium (TTN) or polyetheretherketone (PEEK). Controversy in material selection stems from higher fusion rates with TNN, despite a higher subsidence rate, while PEEK cages demonstrate superior preservation of interspace height. Combining the advantages of both materials, TTN-coated PEEK (TCPEEK) cages were developed, featuring a PEEK core with similar stiffness to the bone, enveloped with a TTN coat, improving osteointegration. However, the potential superiority of TCPEEK over TTN cages has not been investigated. This study aimed to compare clinical and radiographic outcomes following single- or double-level ACDF using either TTN or TCPEEK cages. METHODS: This retrospective single-center study included patients undergoing single- or double-level ACDF between 2017 and 2019. Clinical outcomes included the Neck Disability Index and revision surgery incidence. Radiographic parameters included cervical and segmental lordosis, C2 to C7 sagittal vertical axis, fusion, subsidence, and adjacent segment degeneration at a minimum 12-month follow-up. RESULTS: A total of 45 patients (16 TTN; 29 TCPEEK) and 58 cervical levels (21 TTN; 37 TCPEEK) were included. Both cages significantly improved Neck Disability Index scores (TTN -10.0; TCPEEK -14.1) without significant differences. Two single-level TCPEEK patients required revision surgery due to non-union. In the radiological assessments, no significant difference was found for subsidence rates (TTN 52.4%; TCPEEK 56.8%), adjacent segment degeneration, cervical and segmental lordosis, and changes in C2 to C7 sagittal vertical axis. Though not statistically significant, fusion rates trended slightly higher with TTN (90.5%) vs TCPEEK cages (86.5%). CONCLUSION: TTN and TCPEEK cages achieve satisfactory clinical and radiological outcomes in single- or double-level ACDF. This finding suggests that the choice between them can be based on other factors, such as surgeon preference or availability, rather than specific material properties. CLINICAL RELEVANCE: This study found that the selection of ACDF cage material did not affect clinical outcomes.

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Transmembrane transition metal transporter proteins are central gatekeepers in selectively controlling vectorial metal cargo uptake and extrusion across cellular membranes in all living organisms, thus playing key roles in essential and toxic metal homeostasis. Biochemical characterization of transporter-mediated translocation events and transport kinetics of redox-active metals, such as iron and copper, is challenged by the complexity in generating reconstituted systems in which vectorial metal transport can be studied in real time. We present fluorescence-based proteoliposome methods to monitor redox-active metal transmembrane translocation upon reconstitution of purified metal transporters in artificial lipid bilayers. By encapsulating turn-on/-off iron or copper-dependent sensors in the proteoliposome lumen and conducting real-time transport assays using small unilamellar vesicles (SUVs), in which selected purified Fe(II) and Cu(I) transmembrane importer and exporter proteins have been reconstituted, we provide a platform to monitor metal translocation events across lipid bilayers in real time. The strategy is modular and expandable toward the study of different transporter families featuring diverse metal substrate selectivity and promiscuity.

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The commercialization of single-cell protein (SCP) obtained from microbial fermentation in large-scale bioreactors emerged almost 50 years ago, with Pruteen marketed as animal feed in the 1970s and Quorn®, released for human nutrition in 1985. SCP holds great promises to feed the meanwhile doubled world population in a sustainable way, but its application is still limited by price and availability on scale. There is a need to optimize the underlying manufacturing processes with enhanced affordability and productivity. From the industrial perspective, it is crucial to identify key process components and prioritize innovations that best promote cost efficiency and large-scale production. Here, we present the state-of-art in SCP manufacturing and provide a comprehensive insight into recent techno-economic analyses and life-cycle assessments of different production scenarios. Thereby, we identified the most influential technical hotspots and challenges for each of the main production scenarios and evaluated the technological opportunities to overcome them.

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BACKGROUND: The M1 middle cerebral artery (MCA) commonly bifurcates into M2 superior and M2 inferior segments. However, MCA anatomy is highly variable rendering classification for mechanical thrombectomy trials difficult. This study explored safety and effectiveness of M2 MCA stroke thrombectomy stratified by M2 MCA anatomy. METHODS: Cases of large vessel occlusion strokes treated by mechanical thrombectomy between February 2016 and August 2022 were reviewed (N = 784). M1 (n = 431) and M2 (n = 118) MCA occlusions were assessed. Among M2 MCA occlusions, only prototypical MCA bifurcation anatomy cases were included (n = 99). Dominance was assessed based on angiography. Procedural and outcome data were compared between M1, M2 superior, and M2 inferior MCA occlusions. RESULTS: Baseline demographics and periprocedural criteria of M2 superior (n = 56) and M2 inferior (n = 43) occlusion mechanical thrombectomies were comparable. The occluded branch was dominant in 41/43 (95.3%) M2 inferior cases, but in only 37/56 (66.1%) M2 superior cases (P < 0.001). The 90-day favorable functional outcome (modified Rankin Scale score 0-2) and mortality (modified Rankin Scale score 6) rates were 60.0% and 8.9% in M2 superior, 42.9% and 32.6% in M2 inferior, and 44.1% and 26.0% in M1 (n = 431) cases. Compared with M2 superior cases, in M2 inferior cases, favorable outcome rates were lower (P = 0.094) and mortality rates were higher (P = 0.003) and resembled M1 rates (P = 0.750 and P = 0.355, respectively). CONCLUSIONS: In the setting of prototypical MCA bifurcation anatomy, thrombectomy of dominant M2 inferior occlusions had outcome rates similar to M1 occlusions. In contrast, M2 superior occlusions had significantly lower mortality rates and a trend toward better favorable functional outcome rates.

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