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This study investigates the recent evolution of corn yield, with a special focus on the tradeoff between corn profitability and risk. The analysis relies on time-series data from Wisconsin experimental farms at the edge of the Corn Belt. An econometric model of corn yield, corn grain moisture, and corn profitability is specified. Both conditional means and conditional variances are estimated for different sites in Wisconsin. The empirical analysis shows the changes in corn yield and profit over time and across space. The evidence suggests that yield trends are due mostly to technical progress, with smaller effects generated by climate change. On average, corn yield and profitability have improved faster in northern Wisconsin than in the Corn Belt. However, risk has also increased faster. Results show that the choice of corn hybrid maturity makes it easier to manage risk in the Corn Belt than in northern Wisconsin.

Background: Autologous bone grafts are essential in reconstructive oral and maxillofacial surgery, and depending on the donor site, they can be associated with specific harvesting morbidities. One of the most commonly applied bone grafts is the iliac crest bone graft, irrespective of other grafts, which might be associated with an easier surgical procedure or the possibility of harvesting them under local anaesthesia. Objective of the study is the clinical evaluation of proximal tibia bone grafts regarding their eligibility for maxillofacial bone grafting., Methods: In this retrospective study, proximal tibia bone grafts were examined with regard to associated donor and recipient site morbidity and their suitability for alveolar ridge augmentation and rhinoplasty., Results: In total, 21 tibia grafts were included. Fifty-seven percent of the bone grafts were used for alveolar ridge reconstruction, and 43% were used for augmentative rhinoplasty. No significant complications occurred during or after harvesting, but in 14.3% of the patients, minor wound healing disorders were recorded at the donor site, and in 19% of the patients, they were recorded at the recipient site. Statistically, patient sex, age, nicotine and alcohol abuse and metabolic diseases had no significant influence on the complication rate. Graft harvesting under local anaesthesia and at summer temperatures was associated with significantly more complications at the harvesting site (p < 0.05). In cases of dental implant insertion into augmented sites, the implants (n = 31) were followed up for a median period of 40.5 months, during this time 86.7% of the implants survived., Conclusion: The proximal tibia is a suitable donor site for harvesting autologous bone grafts for alveolar ridge augmentation or rhinoplasty because the donor site morbidity is low, and in contrast to iliac crest bone grafts, they can be harvested under local anaesthesia, which might be advantageous for outpatient surgeries., (© 2024. The Author(s).)

Background: With the rise of new 3D printers, assessing accuracy is crucial for obtaining the best results in patient care. Previous studies have shown that the highest accuracy is achieved with SLS printing technology; however, SLA printing technology has made significant improvements in recent years. Methods: In this study, a realistic anatomical model of a mandible and skull, a cutting guide for mandibular osteotomy, and a splint for orthognathic surgery were replicated five times each using two different 3D printing technologies: SLA and SLS. Results: The SLA group had a median trueness RMS value of 0.148 mm and a precision RMS value of 0.117 mm. The SLS group had a median trueness RMS value of 0.144 mm and a precision RMS value of 0.096 mm. There was no statistically significant difference in RMS values between SLS and SLA technologies regarding trueness. Regarding precision, however, the RMS values for SLS technology were significantly lower in the splint and cutting guide applications than those printed with SLA technology. Conclusions: Both 3D printing technologies produce modern models and applications with equally high dimensional accuracy. Considering current cost pressures experienced by hospitals, the lower-cost SLA 3D printer is a reliable choice for point-of-care 3D printing.

The mandible plays an essential part in human life and, thus, defects in this structure can dramatically impair the quality of life in patients. Axolotls, unlike humans, are capable of regenerating their lower jaws; however, the underlying mechanisms and their similarities to those in limb regeneration are unknown. In this work, we used morphological, histological and transcriptomic approaches to analyze the regeneration of lateral resection defects in the axolotl mandible. We found that this structure can regenerate all missing tissues in 90 days through gap minimization, blastema formation and, finally, tissue growth, differentiation and integration. Moreover, transcriptomic comparisons of regenerating mandibles and limbs showed that they share molecular phases of regeneration, that these similarities peak during blastema stages and that mandible regeneration occurs at a slower pace. Altogether, our study demonstrates the existence of a shared regenerative program used in two different regenerating body structures with different embryonic origins in the axolotl and contributes to our understanding of the minimum requirements for a successful regeneration in vertebrates, bringing us closer to understand similar lesions in human mandibles., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Background: Long-term outcomes of tenofovir-containing antiretroviral therapy (ART) for hepatitis B virus (HBV)/human immunodeficiency virus (HIV) coinfection were evaluated in Zambia., Methods: A prospective cohort of adults with HIV and hepatitis B surface antigen (HBsAg)-positivity was enrolled at ART initiation. On tenofovir-containing ART, we ascertained HBV viral load (VL) non-suppression, alanine aminotransferase (ALT) elevation, serologic end-points, progression of liver fibrosis based on elastography, and hepatocellular carcinoma (HCC) incidence. We also described a subgroup (low HBV VL and no/minimal fibrosis at baseline) that, under current international guidelines, would not have been treated in the absence of their HIV infection., Results: Among 289 participants at ART start, median age was 34 years, 40.1% were women, median CD4 count was 191 cells/mm3, 44.2% were hepatitis B e antigen-positive, and 28.4% had liver fibrosis/cirrhosis. Over median 5.91 years of ART, 13.6% developed HBV viral non-suppression, which was associated with advanced HIV disease. ALT elevation on ART was linked with HBV VL non-suppression. Regression of fibrosis and cirrhosis were common, progression to cirrhosis was absent, and no cases of HCC were ascertained. HBsAg seroclearance was 9.4% at 2 and 15.4% at 5 years, with higher rates among patients with low baseline HBV replication markers., Conclusions: Reassuring long-term liver outcomes were ascertained during tenofovir-based ART for HBV/HIV coinfection in Zambia. Higher than expected HBsAg seroclearance during ART underscores the need to include people with HIV in HBV cure research., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Postmortem computed tomography (pmCT) prior to forensic autopsy has become increasingly important in recent decades, especially in forensic documentation of single injuries, injury patterns, and causes of death. Postmortem decomposition gas formation can also be detected in pmCT scans, which might affect cochlear implant research in postmortem human temporal bones (TBs)., Material and Methods: Fifty non-putrefied hanging fatalities within a 2-year period (January 2017 to December 2019) were included with 100 TBs. Each body underwent whole-body pmCT prior to forensic autopsy. PmCT scans were analyzed with respect to the presence of intracochlear gas despite the lack of putrefaction at autopsy by an experienced fellow neurotologist., Results: PmCT revealed gas formation in two individuals despite the lack of head trauma and putrefaction at postmortem examination and autopsy. Both individuals showed enclosed gas in the vestibule and the cochlea on both sides., Discussion: Intracochlear gas formation, most likely related to decomposition, may occur despite the lack of putrefaction at postmortem examination and autopsy and can be detected by pmCT. This finding seems to be rather rare in non-traumatic death cases but might affect cochlear pressure research in postmortem human TB., 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., (© 2024 Mittmann, Ernst, Seidl, Lauer, Gölz, Mutze, Windgassen and Buschmann.)

Purpose: This study aims to measure the cortical and cancellous bone thickness in the upper and lower jaws, serving as a data template for developing pre-defined calcium phosphate cement primary implant forms. These measurements are crucial for creating a biphasic scaffold., Methods: Forty complete jaws were assessed for cortical bone shape and thickness using statistical analysis and specific software tools. Sex and age were considered, and four groups were created., Results: The cumulative thickness of the cortical layer varied from region to region. In both the upper and lower jaws, the cortical layer in the molar region was significantly thicker than in the frontal region. Within the alveolar process, cortical thickness increases with distance from the alveolar crest on both sides. The oral side of the lower jaw is significantly thicker than the vestibular side. For the upper jaw, no significant differences between the oral and vestibular sides were found in this study. Additionally, it is noteworthy that men have a significantly thicker cortical layer than women. Regarding age, no significant overall differences were found., Conclusion: Mathematical analysis of anatomical forms using polynomial functions improves understanding of jaw anatomy. This approach facilitates the design of patient-specific scaffold structures, minimizing the need for costly and time-consuming planning and enabling more efficient implementation of optimal therapy., 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 GmbH.. All rights reserved.)

Fractures of the mandibular condyle account for a significant proportion of mandibular fractures. The specific functional loads require particular specifications for the implant design used for open reduction and internal fixation of such fractures. The clinical and radiographic outcomes in patients treated using a single rhombic 3D condylar fracture plate for open reduction and internal fixation at a single institution, and who fulfilled the inclusion and exclusion criteria, are presented. The primary outcome variables were: occlusion, maximum interincisal distance and mandibular excursion at 1, 3, and 6 months postoperatively, and radiographic measurements for mandibular height and gonion angle. In total, 263 patients were included, of whom 173 (65.8%) were male and 90 (34.2%) female. The mean age was 40.4 ± 18.9 years. There was satisfactory occlusion in 98.9% of patients at the 6-month follow-up, and a significant improvement in all parameters for mandibular excursion (p < 0.001), with a reduced ramus height and an increase in the gonion angle on the fractured side. Excellent clinical and radiographic results were achieved using the rhombic-shaped implant, deeming it appropriate for the osteosynthesis of mandibular condyle fractures., Competing Interests: Declaration of competing interest The authors have no direct or indirect interests relating to the work submitted for publication, including any financial or non-financial interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A promising therapeutic option for the treatment of critical-size mandibular defects is the implantation of biodegradable, porous structures that are produced patient-specifically by using additive manufacturing techniques. In this work, degradable poly(DL-lactide) polymer (PDLLA) was blended with different mineral phases with the aim of buffering its acidic degradation products, which can cause inflammation and stimulate bone regeneration. Microparticles of CaCO 3 , SrCO 3 , tricalcium phosphates (α-TCP, β-TCP), or strontium-modified hydroxyapatite (SrHAp) were mixed with the polymer powder following processing the blends into scaffolds with the Arburg Plastic Freeforming 3D-printing method. An in vitro degradation study over 24 weeks revealed a buffer effect for all mineral phases, with the buffering capacity of CaCO 3 and SrCO 3 being the highest. Analysis of conductivity, swelling, microstructure, viscosity, and glass transition temperature evidenced that the mineral phases influence the degradation behavior of the scaffolds. Cytocompatibility of all polymer blends was proven in cell experiments with SaOS-2 cells. Patient-specific implants consisting of PDLLA + CaCO 3 , which were tested in a pilot in vivo study in a segmental mandibular defect in minipigs, exhibited strong swelling. Based on these results, an in vitro swelling prediction model was developed that simulates the conditions of anisotropic swelling after implantation.

Purpose: Following the introduction of the Regulation (EU) 2017/745 by the European Parliament, any bioactive substance or surgical implant introduced into the human body must be documented. The regulation requires any implant to be traced back to the manufacturer. Lot numbers need to be available for every single medical implant. Also, the manufacturer is required by law to provide implants individually packaged and sterilized. Previously, model tray systems (MOS tray) were used for osteosynthesis in oral and maxillofacial surgery, in which the individual implants could not be registered separately. The new regulation made it impossible to use such processes during surgery anymore and a need for a change in the medical practice surged. We examined a possible solution for the new legislation. The aim of this prospective cohort study is to analyze the MOS tray systems to osteosynthesis materials prepackaged in sets. We record and evaluate parameters such as surgical time and documentation time. We perform a short cost analysis of our clinic. The primary aim is to determine how much time is gained or lost by the mandatory increased patient safety. The secondary aim is to describe change in costs., Methods: Patients that underwent standard surgical procedures in the clinic of oral and maxillofacial surgery of the faculty hospital Carl Gustav Carus in Dresden were included. We chose open reduction and internal fixation (ORIF) of anterior mandibular corpus fractures as well as mandibular advancement by means of bilateral sagittal split osteotomies (BSSO) as standardized procedures. Both of these procedures require two osteosynthesis plates and at least four screws for each plate. MOS trays were compared to prepackaged sterilized sets. The sets include a drill bit, two plates, and eight 5-mm screws. A total number of 40 patients were examined. We allocated 20 patients to the ORIF group and the other 20 patients to the BSSO group. Each group was evenly subdivided into a MOS tray group and a prepackaged group. Parameters such as the incision-suture time (IST) as well as the documentation time (DT) by the operating room (OR) staff to complete documentation for the implants are the main focus of investigation., Results: For open reduction, the incision-suture time was significantly different in favor of the MOS tray (p < 0.05). There was no difference in the BSSO groups. However, we observed a significantly different (p < 0.01) documentation time advantage for the prepackaged sets in both the ORIF and BSSO groups. On top of that, we find that by using the prepackaged kits, we are able to reduce sterilization costs by €11.53 per size-reduced container. Also, there is also a total cut of costs of €38.90 and €43.70, respectively, per standardized procedure for implant material., Conclusions: By law, a change in the method of approaching surgery is necessary. For standardized procedures, the right choice of implants can lead to a reduction of documentation time and costs for implant material, sterilization, as well as utilizing less instruments. This in turn leads to lower costs for perioperative processing as well as provision of state-of-the-art implant quality implementing higher patient security., (© 2022. The Author(s).)

Purpose: The aim of this study is to develop a test bench, which integrates different complexity levels and enables in that way a flexible and dynamic testing for mid and long term intervals as well as testing of maximum loads till implant failure of different osteosynthesis systems on the mandible. Material and Methods: For this purpose, an analysis of the state of the art regarding existing test benches was combined with interviews of clinical experts to acquire a list of requirements. Based on these requirements a design for a modular test bench was developed. During the implementation of the test stand, functional tests were continuously carried out and improvements made. Depending on the level of complexity, the test bench can be used either as an incorporated variant or as a standalone solution. In order to verify the performance and the degree of fulfilment of the requirements of these two variants of the test bench, preliminary studies were carried out for all levels of complexity. In these preliminary studies, commercially available osteosynthesis and reconstruction plates were investigated for their biomechanical behaviour and compared with data from the literature. Results: In total, fourteen test runs were performed for the different levels of complexity. Firstly, five test runs were executed to test the simplified load scenario in the incorporated variant of the test bench. High forces could be transmitted without failure of the miniplates. Secondly a quasi-static test scenario was examined using the incorporated variant with simplified load insertion. Five experiments with a number of cycles between 40,896 and 100,000 cycles were carried out. In one case the quasi-static testing resulted in a fracture of the tested reconstruction plate with a failure mode similar to the clinical observations of failure. The last four test runs were carried out using the standalone variant of the test bench simulating complex load patterns via the insertion of forces through imitated muscles. During the test runs joint forces were measured and the amplitude and vector of the resulting joint forces were calculated for both temporomandibular joints. Differences in the force transmission depending on the implant system in comparison to the zero sample could be observed. Conclusion: The presented modular test bench showed to be applicable for examination of the biomechanical behavior of the mandible. It is characterized by the adjustability of the complexity regarding the load patterns and enables the subsequent integration of further sensor technologies. Follow-up studies are necessary to further qualify and optimize the test bench., 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 Ben Achour, Apfeld, Lauer, Bräuer, Leonhardt, Franke, Lipphaus, Teicher, Witzel and Schröder.)

Neurotransmitters are important signaling molecules in the brain and are relevant in many diseases. Measuring them with high spatial and temporal resolutions in biological systems is challenging. Here, we develop a ratiometric fluorescent sensor/probe for catecholamine neurotransmitters on the basis of near-infrared (NIR) semiconducting single wall carbon nanotubes (SWCNTs). Phenylboronic acid (PBA)-based quantum defects are incorporated into them to interact selectively with catechol moieties. These PBA-SWCNTs are further modified with poly(ethylene glycol) phospholipids (PEG-PL) for biocompatibility. Catecholamines, including dopamine, do not affect the intrinsic E 11 fluorescence (990 nm) of these (PEG-PL-PBA-SWCNT) sensors. In contrast, the defect-related E 11 * emission (1130 nm) decreases by up to 35%. Furthermore, this dual functionalization allows tuning selectivity by changing the charge of the PEG polymer. These sensors are not taken up by cells, which is beneficial for extracellular imaging, and they are functional in brain slices. In summary, we use dual functionalization of SWCNTs to create a ratiometric biosensor for dopamine.

In Lusaka, Zambia, we introduced liver fine needle aspiration (FNA) into a research cohort of adults with treatment-naïve chronic hepatitis B virus (HBV) infection, with and without HIV coinfection, as well as with acute HBV infection. Over 117 enrollment and 47 longitudinal FNAs (at 1 year follow-up), we established participant acceptability and safety. We also demonstrated the quality of the material through single cell RNA sequencing of selected enrollment FNAs, which revealed a range of immune cells. This approach can drive new insights into HBV immunology, informing cure strategies, and can improve our understanding of HBV natural history in Africa., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: The long-term preservation of residual hearing after cochlear implantation has become a major goal over the past few years. The aim of the present study was to evaluate residual hearing in the long-term follow-up using mid-scala electrodes., Methods: In this retrospective, single-center study, we collected data from 27 patients who were implanted between 2014 and 2015 with residual hearing in the low-frequency range using a mid-scala electrode. Measurements of the hearing thresholds were carried out directly postoperatively (day 1 after surgery) and in the long-term follow-up 43.7 ± 6.9 months. The calculation of the extent of audiological hearing preservation was determined using the HEARRING group formula by Skarsynski., Results: Postoperative preservation of residual hearing was achieved in 69.2% of the cases in the low-frequency range between 250 Hz and 1 kHz, of which 89.5% of the patients had frequencies that suggested using electroacoustic stimulation (EAS). In the long-term follow-up, 30.8% of the patients showed residual hearing; however, 57.1% had apparently benefited from EAS., Conclusion: Preservation of residual hearing is feasible in the long term using mid-scala electrodes. Postoperatively, there is over the half of patients who benefit from an EAS strategy. The long-term follow-up shows a certain decrease in residual hearing. However, these results are comparable to studies relating to other types of electrodes. Further research should be conducted in future to better evaluate hearing loss in long-term follow-up, compared to direct postoperative audiological results., 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.

(1) Background: This study aims to highlight differences in the etiology and fitting of low vision aids in visually impaired children and adolescents in comparison to adults. (2) Methods: A retrospective data collection from visually impaired patients presenting to obtain assistive devices from 1 January 2016 to 30 April 2020 was conducted. A total of 502 patients were included. Inclusion criteria were a minimum age of 4 years and the chart notation of a best-corrected distance visual acuity in the patient record prior to the fitting of magnifying visual aids. (3) Results: Of the 502 patients, 147 (29.3%) were children under the age of 18 years. The most common cause of visual impairment in children was albinism, and in adults, it was age-related macular degeneration (AMD). Children showed better distance visual acuity, with a median of 0.88 logMAR (Logarithm of the Minimum Angle of Resolution) compared to 1.0 in adults ( p = 0.001). Near visual acuity was also significantly better, with a median of 0.54 logMAR in children compared to 0.9 in adults ( p < 0.001). Near and distance visual acuity were significantly improved by fitting magnifying visual aids ( p < 0.001). After fitting, near visual acuity averaged 0.3 logMAR, and distance visual acuity, 0.7. The most commonly prescribed aids were optical vision aids, which 68.5% of the patients received; 43.8% received electronic aids. In children, optical aids were more frequently prescribed, and in adults, electronic and acoustic aids ( p < 0.001). (4) Conclusion: Visually impaired patients can regain the ability to read and improve distance vision by using individually adapted and tested magnifying vision aids, often with optical aids alone. Differences between children and adults could be discovered in the etiology and severity of visual impairment, as well as in the provision type of low vision aids.

Background: To inform novel therapies, a more nuanced understanding of HIV's impact on hepatitis B virus (HBV) natural history is needed, particularly in high burden countries., Methods: In Lusaka, Zambia, we compared prospectively recruited adults (18+ years) with chronic HBV infection, with and without HIV. We excluded those with prior antiviral treatment experience or HBV diagnosis due to clinical suspicion (rather than routine testing). We assessed HBV DNA levels, hepatitis B e antigen (HBeAg), CD4 + (if HIV coinfection), and liver disease (transient elastography, serum alanine aminotransferase). In multivariable analyses, we evaluated the association of HIV overall and by level of CD4 + count on these markers., Results: Among 713 adults analyzed, median age was 33 years, 63% were male, and 433 had HBV/HIV coinfection. Median CD4 + count was 200 cells/μl. HBV DNA was greater than 2000 IU/ml for 311 (51.0%) and 227 (32.5%) were HBeAg-positive. 15.5% had advanced fibrosis or cirrhosis. HIV coinfection was associated with five-fold increased HBV DNA levels [adjusted geometric mean ratio, 5.78; 95% confidence interval (CI), 2.29-14.62] and two times the odds of HBeAg-positivity (adjusted odds ratio, 2.54; 95% CI, 1.59-4.08). These associations were significant only at CD4 + counts 100-350 and <100 cells/μl. HIV was not associated with markers of fibrosis or ALT., Discussion: HIV's impact on HBV natural history likely depends on the degree and duration of immune suppression. There is strong rationale to monitor HBV DNA in people with HBV/HIV coinfection and immune suppression. A better understanding is needed of mechanisms of increased liver-related mortality in people with HBV/HIV coinfection., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Reconstruction of continuity defects following osteonecrosis in multimorbid patients is challenging. In all cases of the predescribed palliative treatment method for alloplastic mandible reconstruction, plate fractures were detected in follow-up. We hypothesized that a modification could avoid these fractures, leading to stable long-term results., Methods: This retrospective study compares the original method with a modification using single, laser-sintered CAD-CAM plates instead of manually bent miniplates. The predescribed shuttering technique was used to reconstruct the mandible in its original shape with bone cement., Results: Uneventful wound healing was observed in 86% of the cases after modification of the method. No implant or plate fracture occurred., Conclusions: The presented method should be considered as a treatment option for mandible reconstruction in elderly, multimorbid patients in palliative situations. The results of this study suggest that the modification of the method leads to significantly improved long-term stability. Donor site morbidity is avoided with this method of palliative surgery., (© 2023 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Objectives: Symmetry is essential for computer-aided surgical (CAS) procedures in oral and maxillofacial surgery (OMFS). A critical step for successful CAS is mirroring the unaffected side to create a template for the virtual reconstruction of the injured anatomical structure. The aim was to identify specific anatomical landmarks of the midfacial skeleton, to evaluate the symmetry in a group of the real-world Central European population, and to use these landmarks to assess midfacial symmetry in CT scans., Material and Methods: The retrospective cross-sectional study defined landmarks of the midface's bony contour using viscerocranial CT data. The distances of the skeletal landmarks (e.g., the frontozygomatic suture and temporozygomatic suture) of the left and right sides from the midline were measured and statistically compared. Midfacial symmetry for reference points was defined as a difference within 0 mm and their mean difference plus one standard deviation., Results: We examined a total of 101 CT scans. 75% of our population shows symmetrical proportions of the midface. The means of the differences for the left and right sides ranged from 0.8 to 1.3 mm, averaging 1.1 ± 0.2 mm for all skeletal landmarks. The standard deviations ranged from 0.6 to 1.4 mm, with a computed mean of 0.9 ± 0.3 mm., Conclusion: We established a methodology to assess the symmetry of the bony midface. If the determined differences were equal to or lower than 2.5 mm in the mentioned midfacial skeletal landmarks, then the symmetry of the bony midface was considered present, and symmetry-based methods for CAS procedures are applicable., Clinical Relevance: Many CAS procedures require facial symmetry. We provide an easy-to-apply method to probe for symmetry of the midface. The method may be used for population-based research, to check for proper reduction of fractures after reposition or to screen for symmetry prior to CAS planning., (© 2023. The Author(s).)

The surgical options for patients with single-sided Menière's disease and functional deafness are challenging. Our case series reports the outcomes of surgical treatments of patients with single-sided Menière's disease and functional deafness. These patients have undergone a one-staged occlusion of all semi-circular canals and cochlear implantation. Five patients (four female and one male; 62 ± 8.2 years with a range from 50 to 72 years) with single-sided Menière's disease and functional deafness were included in this study. In all cases, the patients suffered from frequent rotational vertigo episodes for many years. Other treatment options (e.g., medication) had not yet been successful. Preoperatively, the Dizziness Handicap Inventory (DHI) of all patients indicated severe emotional, physical, and functional deficits. Patients showed a functional (near-total) deafness of the affected ear in all cases. All patients were supplied with cochlear implants in combination with a triple occlusion of all semi-circular canals in a one-stage procedure. After a short period of increased dizziness following surgery and after the activation of the cochlear implant and CI rehabilitation (auditory-verbal therapy), vertigo control and an adequate audiological outcome were achieved. The DHI showed a constant decrease after surgery. The combination of a triple semi-circular canal occlusion and cochlear implantation can be an efficient treatment for patients with single-sided Menière's disease.

Malignant transformation of oral lichen planus (OLP) into oral squamous cell carcinoma is considered as one of the most serious complications of OLP. For the early detection of oral cancer in OLP follow-up, accurate localization of the OLP center is still difficult but often required for confirmatory biopsy with histopathological examination. Optical coherence tomography (OCT) offers the potential for more reliable biopsy sampling in the oral cavity as it is capable of non-invasively imaging the degenerated oral layer structure. In this case-series study with 15 patients, features of clinically classified forms of OLP in OCT cross-sections were registered and correlated with available histologic sections. Besides patients with reticular, atrophic, erosive and plaque-like OLP, two patients with leukoplakia were included for differentiation. The results show that OCT yields information about the epithelial surface, thickness and reflectivity, as well as the identifiability of the basement membrane and the vessel network, which could be used to complement the visual clinical appearance of OLP variants and allow a more accurate localization of the OLP center. This forms the basis for further studies on OCT-assisted non-invasive clinical classification of OLP, with the aim of enabling decision support for biopsy sampling in the future.

Their excellent mechanical properties, degradability and suitability for processing by 3D printing technologies make the thermoplastic polylactic acid and its derivatives favourable candidates for biomaterial-based bone regeneration therapies. In this study, we investigated whether bioactive mineral fillers, which are known to promote bone healing based on their dissolution products, can be integrated into a poly(L-lactic- co -glycolic) acid (PLLA-PGA) matrix and how key characteristics of degradation and cytocompatibility are influenced. The polymer powder was mixed with particles of CaCO 3 , SrCO 3 , strontium-modified hydroxyapatite (SrHAp) or tricalcium phosphates (α-TCP, β-TCP) in a mass ratio of 90 : 10; the resulting composite materials have been successfully processed into scaffolds by the additive manufacturing method Arburg Plastic Freeforming (APF). Degradation of the composite scaffolds was investigated in terms of dimensional change, bioactivity, ion (calcium, phosphate, strontium) release/uptake and pH development during long-term (70 days) incubation. The mineral fillers influenced the degradation behavior of the scaffolds to varying degrees, with the calcium phosphate phases showing a clear buffer effect and an acceptable dimensional increase. The amount of 10 wt% SrCO 3 or SrHAp particles did not appear to be appropriate to release a sufficient amount of strontium ions to exert a biological effect in vitro . Cell culture experiments with the human osteosarcoma cell line SAOS-2 and human dental pulp stem cells (hDPSC) indicated the high cytocompatibility of the composites: For all material groups cell spreading and complete colonization of the scaffolds over the culture period of 14 days as well as an increase of the specific alkaline phosphatase activity, typical for osteogenic differentiation, were observed.

Background: Education of undergraduates in implant dentistry has been extended. In order to assess the correct implant position, the accuracy of implant insertion using templates for pilot-drill guided and full-guided implant insertion was examined in a laboratory set-up in a cohort of undergraduates., Methods: After three-dimensional planning of the implant position in partially edentulous mandibular models, individual templates for the pilot-drill guided or full-guided implant insertion in the region of the first premolar were produced. A total of 108 dental implants were inserted. The results of the radiographic evaluation of the three-dimensional accuracy were statistically analyzed. Furthermore, the participants completed a questionnaire., Results: The deviation of the three-dimensional angle of the implants inserted fully guided was 2.74 ± 1.49 degrees compared to 4.59 ± 2.70 degrees for pilot-drill guided. The difference was statistically significant (p < 0.01). The returned questionnaires revealed a high interest in oral implantology and a positive evaluation of the hands-on course., Conclusions: In this study, the undergraduates benefited from applying full-guided implant insertion considering the accuracy in this laboratory examination. However, the clinical effects are not clear as the differences are within a small range. Based on the returned questionnaires, the implementation of practical courses in the undergraduate curriculum should be encouraged., Competing Interests: Conflict of interest statement Matthias C. Schulz, Marc Tokarski, Johann Jacoby, Andreas Naros, Christina Weise, Eve Tausche, Günter Lauer and Dominik Haim declare that they have no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces B and T cell responses, contributing to virus neutralization. In a cohort of 2,911 young adults, we identified 65 individuals who had an asymptomatic or mildly symptomatic SARS-CoV-2 infection and characterized their humoral and T cell responses to the Spike (S), Nucleocapsid (N) and Membrane (M) proteins. We found that previous infection induced CD4 T cells that vigorously responded to pools of peptides derived from the S and N proteins. By using statistical and machine learning models, we observed that the T cell response highly correlated with a compound titer of antibodies against the Receptor Binding Domain (RBD), S and N. However, while serum antibodies decayed over time, the cellular phenotype of these individuals remained stable over four months. Our computational analysis demonstrates that in young adults, asymptomatic and paucisymptomatic SARS-CoV-2 infections can induce robust and long-lasting CD4 T cell responses that exhibit slower decays than antibody titers. These observations imply that next-generation COVID-19 vaccines should be designed to induce stronger cellular responses to sustain the generation of potent neutralizing antibodies., Competing Interests: CD, MSc, BS, PZ, FH, AR, Y-JH, GL, and HB are employees of Miltenyi Biotec B.V. & Co. KG. LP is an employee of Humabs BioMed SA, a subsidiary of Vir Biotechnology. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Marcinkevics, Silva, Hankele, Dörnte, Kadelka, Csik, Godbersen, Goga, Hasenöhrl, Hirschi, Kabakci, LaPierre, Mayrhofer, Title, Shu, Baiioud, Bernal, Dassisti, Saenz-de-Juano, Schmidhauser, Silvestrelli, Ulbrich, Ulbrich, Wyss, Stekhoven, Al-Quaddoomi, Yu, Binder, Schultheiβ, Zindel, Kolling, Goldhahn, Seighalani, Zjablovskaja, Hardung, Schuster, Richter, Huang, Lauer, Baurmann, Low, Vaqueirinho, Jovic, Piccoli, Ciesek, Vogt, Sallusto, Stoffel and Ulbrich.)

Xerostomia is the phenomenon of dry mouth and is mostly caused by hypofunction of the salivary glands. This hypofunction can be caused by tumors, head and neck irradiation, hormonal changes, inflammation or autoimmune disease such as Sjögren's syndrome. It is associated with a tremendous decrease in health-related quality of life due to impairment of articulation, ingestion and oral immune defenses. Current treatment concepts mainly consist of saliva substitutes and parasympathomimetic drugs, but the outcome of these therapies is deficient. Regenerative medicine is a promising approach for the treatment of compromised tissue. For this purpose, stem cells can be utilized due to their ability to differentiate into various cell types. Dental pulp stem cells are adult stem cells that can be easily harvested from extracted teeth. They can form tissues of all three germ layers and are therefore becoming more and more popular for tissue engineering. Another potential benefit of these cells is their immunomodulatory effect. They suppress proinflammatory pathways of lymphocytes and could therefore probably be used for the treatment of chronic inflammation and autoimmune disease. These attributes make dental pulp stem cells an interesting tool for the regeneration of salivary glands and the treatment of xerostomia. Nevertheless, clinical studies are still missing. This review will highlight the current strategies for using dental pulp stem cells in the regeneration of salivary gland tissue.

Myelination of the neocortex of altricial species is mostly a postnatal event, and the appearance of myelin has been associated with the end of the critical period for ocular dominance plasticity in rodent visual cortex. Due to their precocality, ungulates may tell a different story. Here, we analyzed the development of PDGFRα positive oligodendrocyte precursor cells and expression of myelin proteins in the laminar compartments of fetal and postnatal porcine cortex from E45 onwards. Precursor cell density initially increased and then decreased but remained present at P90. MAG and MBP staining were detectable at E70 in subventricular zone and deep white matter, ascending into gyral white matter at E85, and into the gray matter and marginal zone at E100 (birth in pig at E114). Protein blots confirmed the declining expression of PDGFRα from E65 onwards, and the increase of MBP and MAG expression from E80 onwards. Somatosensory input elicited by spontaneous activity is considered important for the formation of the body representation. Indeed, PDGFRα, MBP and MAG expression started earlier in somatosensory than in visual cortex. Taken together, myelination proceeded in white and gray matter and marginal zone of pig cortex before birth with an areal-specific time course, and an almost mature pattern was present at P5 in visual cortex., (© 2023. The Author(s).)

Background: In health care research, patient-reported opinions are a critical element of personalized medicine and contribute to optimal health care delivery. The importance of integrating natural language processing (NLP) methods to extract patient-reported opinions has been gradually acknowledged over the past years. One form of NLP is sentiment analysis, which extracts and analyses information by detecting feelings (thoughts, emotions, attitudes, etc) behind words. Sentiment analysis has become particularly popular following the rise of digital interactions. However, NLP and sentiment analysis in the context of intrafamilial communication for genetic cancer risk is still unexplored. Due to privacy laws, intrafamilial communication is the main avenue to inform at-risk relatives about the pathogenic variant and the possibility of increased cancer risk., Objective: The study examined the role of sentiment in predicting openness of intrafamilial communication about genetic cancer risk associated with hereditary breast and ovarian cancer (HBOC) syndrome., Methods: We used narratives derived from 53 in-depth interviews with individuals from families that harbor pathogenic variants associated with HBOC: first, to quantify openness of communication about cancer risk, and second, to examine the role of sentiment in predicting openness of communication. The interviews were conducted between 2019 and 2021 in Switzerland and South Korea using the same interview guide. We used NLP to extract and quantify textual features to construct a handcrafted lexicon about interpersonal communication of genetic testing results and cancer risk associated with HBOC. Moreover, we examined the role of sentiment in predicting openness of communication using a stepwise linear regression model. To test model accuracy, we used a split-validation set. We measured the performance of the training and testing model using area under the curve, sensitivity, specificity, and root mean square error., Results: Higher "openness of communication" scores were associated with higher overall net sentiment score of the narrative, higher fear, being single, having nonacademic education, and higher informational support within the family. Our results demonstrate that NLP was highly effective in analyzing unstructured texts from individuals of different cultural and linguistic backgrounds and could also reliably predict a measure of "openness of communication" (area under the curve=0.72) in the context of genetic cancer risk associated with HBOC., Conclusions: Our study showed that NLP can facilitate assessment of openness of communication in individuals carrying a pathogenic variant associated with HBOC. Findings provided promising evidence that various features from narratives such as sentiment and fear are important predictors of interpersonal communication and self-disclosure in this context. Our approach is promising and can be expanded in the field of personalized medicine and technology-mediated communication., (©Vasiliki Baroutsou, Rodrigo Cerqueira Gonzalez Pena, Reka Schweighoffer, Maria Caiata-Zufferey, Sue Kim, Sharlene Hesse-Biber, Florina M Ciorba, Gerhard Lauer, Maria Katapodi, CASCADE Consortium. Originally published in JMIR Formative Research (https://formative.jmir.org), 19.01.2023.)

Background: The SARS-CoV-2 variant B.1.1.529 potentially escapes immunity from vaccination via a heavily mutated Spike protein. Here, we analyzed whether T cell memory towards the B.1.1.529 Spike protein is present in individuals who received two or three doses of vaccines designed against the original Wuhan strain of SARS-CoV-2., Methods: PBMCs were isolated from two- and three-times vaccinated study participants and incubated in vitro with peptide pools of the Spike protein derived from sequences of the original Wuhan or the B.1.1.529 strains of SARS-CoV-2. Activated antigen-specific T cells were detected by flow cytometry. In silico analyses with NetMHCpan and NetMHCIIpan were used to determine differences in MHC class presentation between the original strain and the B.1.1.529 strain for the most common MHCs in the European-Caucasian population., Results: Here we show, that both CD4 and CD8 responses to the B.1.1.529 Spike protein are marginally reduced compared to the ancestor protein and a robust T cell response is maintained. Epitope analyses reveal minor differences between the two SARS-CoV-2 strains in terms of MHC class presentations for the MHC-alleles being most common in the European-Caucasian population., Conclusions: The memory T cell response induced via first generation vaccination remains robust and is mostly unaffected by B.1.1.529 mutations. Correspondingly, in silico analyses of MHC presentation of epitopes derived from the B.1.1.529 Spike protein shows marginal differences compared to the ancestral SARS-CoV-2 strain., (© 2022. The Author(s).)

There have been unprecedented advances in the identification of new treatment targets for chronic hepatitis B that are being developed with the goal of achieving functional cure in patients who would otherwise require lifelong nucleoside analogue treatment. Many of the new investigational therapies either directly target the immune system or are anticipated to impact immunity indirectly through modulation of the viral lifecycle and antigen production. While new viral biomarkers (HBV RNA, HBcAg, small, middle, large HBs isoforms) are proceeding through validation steps in clinical studies, immunological biomarkers are non-existent outside of clinical assays for antibodies to HBs, HBc and HBe. To develop clinically applicable immunological biomarkers to measure mechanisms of action, inform logical combination strategies, and guide clinical management for use and discontinuation of immune-targeting drugs, immune assays must be incorporated into phase I/II clinical trials. This paper will discuss the importance of sample collection, the assays available for immunological analyses, their advantages/disadvantages and suggestions for their implementation in clinical trials. Careful consideration must be given to ensure appropriate immunological studies are included as a primary component of the trial with deeper immunological analysis provided by ancillary studies. Standardising immunological assays and data obtained from clinical trials will identify biomarkers that can be deployed in the clinic, independently of specialised immunology laboratories., Competing Interests: Conflict of interest Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Lysil oxidase like enzyme-2 (LOXL-2) and TNC-C play important roles in organ fibrosis. We assessed circulating LOXL-2 and TNC-C levels and their relationship to fibrosis severity in HIV- and/or HCV-infected individuals. Methods: Healthy controls (n = 22), HIV mono- (n = 15), HCV mono- (n = 52) and HCV/HIV-co-infected (n = 92) subjects were included. Results: LOXL-2 and TNC-C levels were significantly higher in HCV mono- and HCV/HIV-co-infected individuals with F0 compared to healthy controls. In addition, in HCV/HIV-co-infected individuals, LOXL-2 levels were higher in intermediate fibrosis compared to no/mild fibrosis. Conclusion: In HCV/HIV-co-infected study participants, both LOXL-2 and TNC-C were significantly higher in intermediate fibrosis compared to no/mild fibrosis, but did not further increase with advanced fibrosis. Furthermore, both markers were elevated among HCV/HIV-positive individuals with mild/no fibrosis.

Background: In reconstructive surgery, loss of a microvascular free flap due to perfusion disorders, especially thrombosis, is a serious complication. In recent years, viscoelastic testing (VET) has become increasingly important in point-of-care (POC) anticoagulation monitoring. This paper describes a protocol for enhanced anticoagulation monitoring during maxillofacial flap surgery., Objective: The aim of the study will be to evaluate, in a controlled setting, the predictive value of POC devices for the type of flap perfusion disorders due to thrombosis or bleeding. VET, Platelet monitoring (PM) and standard laboratory tests (SLT) are comparatively examined., Methods/design: This study is an investigator-initiated prospective trial in 100 patients undergoing maxillofacial surgery. Patients who undergo reconstructive surgery using microvascular-free flaps will be consecutively enrolled in the study. All patients provide blood samples for VET, PM and SLT at defined time points. The primary outcome is defined as free flap loss during the hospital stay. Statistical analyses will be performed using t-tests, including the Bonferroni adjustment for multiple comparisons., Discussion: This study will help clarify whether VET can improve individualized patient care in reconstruction surgery. A better understanding of coagulation in relation to flap perfusion disorders may allow real-time adaption of antithrombotic strategies and potentially prevent flap complications.

Objective: In many countries the access to high quality medical service depends on socioeconomic factors. Therefore, these factors are associated with the treatment and prognosis of many diseases. In Germany health care is claimed to be independent from such factors due to obligatory health insurance and a well-developed medical infrastructure. Thus, socioeconomically caused health disparities should be absent. The aim of this study was to analyze the association between socioeconomic factors and the survival of oral cavity cancer in Germany., Patients and Methods: In this descriptive cohort study socioeconomic status related factors as well as demographic, tumor-specific, and comorbidity factors of 500 patients treated for oral cavity cancer were obtained in the university hospital of Dresden. Pearson correlation was used to describe associations between continuous variables. Associations between categorical variables were assessed using the chi-square test. Overall and recurrence-free survival were studied using the Kaplan-Meier method. Log-rank test was carried out to test between-group differences. Cox proportional hazard models were used to estimate the risk of death and the risk of recurrence., Results: Significant differences in overall survival were found between the different educational levels and sex. Seventy-nine percent of the patients did not have a university degree or master craftsman/craftswoman. Less discrepancy was observed according to the marital status (49.4% married/engaged vs. 47.8% single, divorced, or widowed). In the multivariable analysis only sex, age at diagnosis, the Charlson score, the number of positive lymph nodes, and the nodal status were identified as independent predictors for overall survival whereas sex and the age at diagnosis were identified as independent predictors for recurrence-free survival., Conclusion: Despite the equitable health system in Germany, significant associations between overall survival of oral cavity cancer and different socioeconomic factors could be found. For elimination of these disparities, health education programs should be established in socially deprived areas. Furthermore, clinicians should keep these factors in mind when determining recall periods for dental check-ups., (Copyright © 2022 Muallah, Matschke, Muallah, Klimova, Kroschwald, Schröder, Lauer and Haim.)

In the case of maxillary involution, augmentation is necessary for implant-supported prosthetics. The use of bone grafts is standard; customized allogeneic bone blocks may be a predictable alternative before dental implantation. For maxillary full-arch reconstruction, this case shows a horse-shoe augmentation by four allogeneic blocks, followed by guided dental implantation and fixed prosthetics after 6 months of healing. Using allogeneic blocks is an option for full-arch maxillary augmentation and comparable with autologous bone grafts. There is no donor site comorbidity. Bone height is stable for a minimum of 3 years after loading with resorption less than 10% in vertical, buccolingual, and mesiodistal directions. Short-implants allow for the long-term stability of prosthetic fixtures. Prefabricated customized allogeneic blocks for augmentation may increase the fitting accuracy of the graft, decrease morbidity, and lower operation time in maxillary full-arch reconstruction. The percentage of resorption after 3 years is comparable to the commonly used iliac crest., (© 2021. The Author(s).)

Knowledge on cortical development is based mainly on rodents besides primates and carnivores, all being altricial. Here, we analyzed a precocial animal, the pig, looking at dorsoparietal cortex from E45 to P90. At E45, most ionized calcium-binding adapter molecule 1-positive (Iba1+) cells had a macrophage-like morphology and resided in meninges and choroid plexus. Only a few cells were scattered in the ventricular and subventricular zone (VZ and SVZ). At E60/E70, all laminar compartments displayed microglia cells at a low-to-moderate density, being highest in VZ and SVZ followed by intermediate zone/white matter (IZ/WM). The cortical plate and marginal zone displayed only a few Iba1+ cells. Cells were intensely labeled, but still had poorly arborized somata and many resembled ameboid, macrophage-like microglia. Concurrent with a massive increase in cortical volume, microglia cell density increased until E85, and further until E100/E110 (birth at E114) to densities that resemble those seen postnatally. A fraction of microglia colabeled with Ki67 suggesting proliferation in all laminar compartments. Cell-to-cell distance decreased substantially during this time, and the fraction of microglia to all nuclei and to neurons increases in the laminar compartments. Eventually, of all cortical DAPI+ nuclei 7-12% were Iba1+ microglia. From E70 onwards, more and more cells with ramified processes were present in MZ down to IZ/WM, showing, for instance, a close association with NeuN+, NPY+, and GAD65/67+ somata and axon initial segments. These results suggested that the development of microglia cell density and morphology proceeds rapidly from mid-gestation onwards reaching near-adult status already before birth., (© 2021 The Authors. The Journal of Comparative Neurology published by Wiley Periodicals LLC.)

Cleft lip and palate belong to the most frequent craniofacial anomalies. Secondary osteoplasty is usually performed between 7 and 11 years with the closure of the osseus defect by autologous bone. Due to widespread occurrence of the defect in conjunction with its social significance due to possible esthetic impairments, the outcome of treatment is of substantial interest. The success of the treatment is determined by the precise rebuilding of the dental arch using autologous bone from the iliac crest. A detailed analysis of retrospective data disclosed a lack of essential and structured information to identify success factors for fast regeneration and specify the treatment. Moreover, according to the current status, no comparable process monitoring is possible during osteoplasty due to the lack of sensory systems. Therefore, a holistic approach was developed to determine the parameters for a successful treatment via the incorporation of patient data, the treatment sequences and sensor data gained by an attachable sensor module into a developed Dental Tech Space (DTS). This approach enables heterogeneous data sets to be linked inside of DTS, archiving and analysis, and is also for future considerations of respective patient-specific treatment plans.

Liver damage in hepatitis B is immune driven and correlates with inflammatory markers in patient serum. There is no comparison of these markers to determine if inflammatory profiles are distinct to different types of liver damage across patients at different stages of disease. We measured 25 inflammatory markers in patients with acute hepatitis B and chronic hepatitis B with hepatitis B e antigen seroconversion and chronic patients stopping nucleoside analogue therapy. Myeloid markers dominated the inflammatory profile in all stages of hepatitis B. More inflammatory markers were detectable in chronic patients, including elevated concentrations of cytotoxic effectors Fas ligand, TRAIL, and TNF-α., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Stories do not fossilize. Thus, exploring tales shared during prehistory, the longest part of human history inevitably becomes speculative. Nevertheless, various attempts have been made to find a more scientifically valid way into our deep human past of storytelling. Following the social brain hypothesis, we suggest including into the theory of human storytelling more fine-grained and evidence-based findings (from archaeology, the cognitive sciences, and evolutionary psychology) about the manifold exaptation and adaptation, genetic changes, and phenotypic plasticity in the deep human past, which all shaped the emergence of storytelling in hominins. We identify three preconditions for humans sharing stories: first, the long evolution of language in the different taxa as one of the preconditions of ostensive signaling; second, the pivotal role of childhood in the evolution of collaborative intentionality; and third, the role of fireside chats in the rise of elaborative (i.e., narrative) sharing of stories. We propose that humans, albeit perhaps no other hominins learned to understand others through sharing stories, not only as intentional agents, but also as mental ones., Competing Interests: The author declares 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 © 2022 Lauer.)