Architecture-Promoted Biomechanical Performance-Tuning of Tissue-Engineered Constructs for Biological Intervertebral Disc Replacement

Background: Biological approaches to intervertebral disc (IVD) restoration and/or regeneration have become of increasing interest. However, the IVD comprises a viscoelastic system whose biological replacement remains challenging. The present study sought to design load-sharing two-component model systems of circular, nested, concentric elements reflecting the nucleus pulposus and annulus fibrosus. Specifically, we wanted to investigate the effect of architectural design variations on (1) model system failure loads when testing the individual materials either separately or homogeneously mixed, and (2) also evaluate the potential of modulating other mechanical properties of the model systems. Methods: Two sets of softer and harder biomaterials, 0.5% and 5% agarose vs. 0.5% agarose and gelatin, were used for fabrication. Architectural design variations were realized by varying ring geometries and amounts while keeping the material composition across designs comparable. Results: Variations in the architectural design, such as lamellar width, number, and order, combined with choosing specific biomaterial properties, strongly influenced the biomechanical performance of IVD constructs. Biomechanical characterization revealed that the single most important parameter, in which the model systems vastly exceeded those of the individual materials, was failure load. The model system failure loads were 32.21- and 84.11-fold higher than those of the agarose materials and 55.03- and 2.14-fold higher than those of the agarose and gelatin materials used for system fabrication. The compressive strength, dynamic stiffness, and viscoelasticity of the model systems were always in the range of the individual materials. Conclusions: Relevant architecture-promoted biomechanical performance-tuning of tissue-engineered constructs for biological IVD replacement can be realized by slight modifications in the design of constructs while preserving the materials’ compositions. Minimal variations in the architectural design can be used to precisely control structure–function relations for IVD constructs rather than choosing different materials. These fundamental findings have important implications for efficient tissue-engineering of IVDs and other load-bearing tissues, as potential implants need to withstand high in situ loads

Decompressive craniectomy plus best medical treatment versus best medical treatment alone for spontaneous severe deep supratentorial intracerebral haemorrhage:a randomised controlled clinical trial

BACKGROUND: It is unknown whether decompressive craniectomy improves clinical outcome for people with spontaneous severe deep intracerebral haemorrhage. The SWITCH trial aimed to assess whether decompressive craniectomy plus best medical treatment in these patients improves outcome at 6 months compared to best medical treatment alone.METHODS: In this multicentre, randomised, open-label, assessor-blinded trial conducted in 42 stroke centres in Austria, Belgium, Finland, France, Germany, the Netherlands, Spain, Sweden, and Switzerland, adults (18-75 years) with a severe intracerebral haemorrhage involving the basal ganglia or thalamus were randomly assigned to receive either decompressive craniectomy plus best medical treatment or best medical treatment alone. The primary outcome was a score of 5-6 on the modified Rankin Scale (mRS) at 180 days, analysed in the intention-to-treat population. This trial is registered with ClincalTrials.gov, NCT02258919, and is completed.FINDINGS: SWITCH had to be stopped early due to lack of funding. Between Oct 6, 2014, and April 4, 2023, 201 individuals were randomly assigned and 197 gave delayed informed consent (96 decompressive craniectomy plus best medical treatment, 101 best medical treatment). 63 (32%) were women and 134 (68%) men, the median age was 61 years (IQR 51-68), and the median haematoma volume 57 mL (IQR 44-74). 42 (44%) of 95 participants assigned to decompressive craniectomy plus best medical treatment and 55 (58%) assigned to best medical treatment alone had an mRS of 5-6 at 180 days (adjusted risk ratio [aRR] 0·77, 95% CI 0·59 to 1·01, adjusted risk difference [aRD] -13%, 95% CI -26 to 0, p=0·057). In the per-protocol analysis, 36 (47%) of 77 participants in the decompressive craniectomy plus best medical treatment group and 44 (60%) of 73 in the best medical treatment alone group had an mRS of 5-6 (aRR 0·76, 95% CI 0·58 to 1·00, aRD -15%, 95% CI -28 to 0). Severe adverse events occurred in 42 (41%) of 103 participants receiving decompressive craniectomy plus best medical treatment and 41 (44%) of 94 receiving best medical treatment.INTERPRETATION: SWITCH provides weak evidence that decompressive craniectomy plus best medical treatment might be superior to best medical treatment alone in people with severe deep intracerebral haemorrhage. The results do not apply to intracerebral haemorrhage in other locations, and survival is associated with severe disability in both groups.FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Inselspital Stiftung, and Boehringer Ingelheim.</p

Decompressive craniectomy plus best medical treatment versus best medical treatment alone for spontaneous severe deep supratentorial intracerebral haemorrhage: a randomised controlled clinical trial

Background It is unknown whether decompressive craniectomy improves clinical outcome for people with spontaneous severe deep intracerebral haemorrhage. The SWITCH trial aimed to assess whether decompressive craniectomy plus best medical treatment in these patients improves outcome at 6 months compared to best medical treatment alone. Methods In this multicentre, randomised, open-label, assessor-blinded trial conducted in 42 stroke centres in Austria, Belgium, Finland, France, Germany, the Netherlands, Spain, Sweden, and Switzerland, adults (18–75 years) with a severe intracerebral haemorrhage involving the basal ganglia or thalamus were randomly assigned to receive either decompressive craniectomy plus best medical treatment or best medical treatment alone. The primary outcome was a score of 5–6 on the modified Rankin Scale (mRS) at 180 days, analysed in the intention-to-treat population. This trial is registered with ClincalTrials.gov , NCT02258919 , and is completed. Findings SWITCH had to be stopped early due to lack of funding. Between Oct 6, 2014, and April 4, 2023, 201 individuals were randomly assigned and 197 gave delayed informed consent (96 decompressive craniectomy plus best medical treatment, 101 best medical treatment). 63 (32%) were women and 134 (68%) men, the median age was 61 years (IQR 51–68), and the median haematoma volume 57 mL (IQR 44–74). 42 (44%) of 95 participants assigned to decompressive craniectomy plus best medical treatment and 55 (58%) assigned to best medical treatment alone had an mRS of 5–6 at 180 days (adjusted risk ratio [aRR] 0·77, 95% CI 0·59 to 1·01, adjusted risk difference [aRD] −13%, 95% CI −26 to 0, p=0·057). In the per-protocol analysis, 36 (47%) of 77 participants in the decompressive craniectomy plus best medical treatment group and 44 (60%) of 73 in the best medical treatment alone group had an mRS of 5–6 (aRR 0·76, 95% CI 0·58 to 1·00, aRD −15%, 95% CI −28 to 0). Severe adverse events occurred in 42 (41%) of 103 participants receiving decompressive craniectomy plus best medical treatment and 41 (44%) of 94 receiving best medical treatment. Interpretation SWITCH provides weak evidence that decompressive craniectomy plus best medical treatment might be superior to best medical treatment alone in people with severe deep intracerebral haemorrhage. The results do not apply to intracerebral haemorrhage in other locations, and survival is associated with severe disability in both groups. Funding Swiss National Science Foundation, Swiss Heart Foundation, Inselspital Stiftung, and Boehringer Ingelheim

Periodontal health and gingival diseases and conditions on an intact and a reduced periodontium::Consensus report of workgroup 1 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions

Periodontal health is defined by absence of clinically detectable inflammation. There is a biological level of immune surveillance that is consistent with clinical gingival health and homeostasis. Clinical gingival health may be found in a periodontium that is intact, i.e. without clinical attachment loss or bone loss, and on a reduced periodontium in either a non-periodontitis patient (e.g. in patients with some form of gingival recession or following crown lengthening surgery) or in a patient with a history of periodontitis who is currently periodontally stable. Clinical gingival health can be restored following treatment of gingivitis and periodontitis. However, the treated and stable periodontitis patient with current gingival health remains at increased risk of recurrent periodontitis, and accordingly, must be closely monitored. Two broad categories of gingival diseases include non-dental plaque biofilm-induced gingival diseases and dental plaque-induced gingivitis. Non-dental plaque biofilm-induced gingival diseases include a variety of conditions that are not caused by plaque and usually do not resolve following plaque removal. Such lesions may be manifestations of a systemic condition or may be localized to the oral cavity. Dental plaque-induced gingivitis has a variety of clinical signs and symptoms, and both local predisposing factors and systemic modifying factors can affect its extent, severity, and progression. Dental plaque-induced gingivitis may arise on an intact periodontium or on a reduced periodontium in either a non-periodontitis patient or in a currently stable "periodontitis patient" i.e. successfully treated, in whom clinical inflammation has been eliminated (or substantially reduced). A periodontitis patient with gingival inflammation remains a periodontitis patient (Figure 1), and comprehensive risk assessment and management are imperative to ensure early prevention and/or treatment of recurrent/progressive periodontitis. Precision dental medicine defines a patient-centered approach to care, and therefore, creates differences in the way in which a "case" of gingival health or gingivitis is defined for clinical practice as opposed to epidemiologically in population prevalence surveys. Thus, case definitions of gingival health and gingivitis are presented for both purposes. While gingival health and gingivitis have many clinical features, case definitions are primarily predicated on presence or absence of bleeding on probing. Here we classify gingival health and gingival diseases/conditions, along with a summary table of diagnostic features for defining health and gingivitis in various clinical situations

A Spatial Interpretation of the Persistency of China's Provincial Inequality

China's rapid economic growth in recent decades has not led to balanced income distribution: inter- and intra-provincial income inequality have been increasing and their respective contribution to the total income inequality remains relatively stable. Based on a new set of prefectural database during a relatively longer period from 1994 to 2008 on Chinese economic development, this paper investigates the nexus between the spatial dependence and income inequality in China on a prefectural level. Using the decomposition results of the inequality and spatial dependence of inter- and intra-provincial groups, and also the choropleth maps of clusters in China, this paper reaches the conclusion that clusters of prefectures and provinces with high positive spatial association are persistent over years in China, and the resulting highly correlated income disparity on both inter- and intra-provincial levels might be lasting for a relatively longer period, implying that spatial dependence is a contributing factor to the regional income inequality in a spatial context

Embedded Interests and the Managerial Local State: Methanol Fuel-Switching in China

This paper analyzes the determinants of alternative automobile fuel regulation and development support with a particular focus on methanol fuel. We find that embedded interests, bureaucratic reforms, and political circumstances in the Chinese national, provincial, and municipal governments have all shaped policy outcomes in this area. The paper seeks to explain why at, the national level, support for alternative fuels has waned and finds that the concerns of state oil majors and disorganization during the process of national bureaucratic restructuring have been the deciding factors. Interestingly, at the sub-national level promotion of methanol continues unabated in some places. At the local level, business relationships as well as the embedded economic and personal interests of local leaders help to explain managerial local government behavior and sheds light on why government officials actively create and manage methanol fuel business opportunities through local standardization, subsidies, and hands-on management of SOE opposition. The switch towards methanol fuel was more successful in localities where individuals, either government officials or enterprise managers, formed an alliance and made this their 'pet projects'. The analysis draws on 55 interviews conducted between June and October 2010 in Shanxi, a major coal-producing province which has supported methanol fuel-switching programs for over ten years. The findings contribute to debates about the condition of the local state in China. The argument put forward in this paper is that because of limited state capacity at the central level and insufficient concerns for the development of alternative fuels in the short-term, some sub-national governments with strong embedded interests promote certain alternative fuels by taking on active managerial roles, adopting creative and ad-hoc strategies to fill in the national level policy gap at the local level

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Assessing the Role of Facial Symmetry and Asymmetry between Partners in Predicting Relationship Duration: A Pilot Deep Learning Analysis of Celebrity Couples

Prevailing studies on romantic relationships often emphasize facial symmetry as a factor in partner selection and marital satisfaction. This study aims to explore the inverse of this hypothesis—the relationship between facial dissimilarity and partnership duration among celebrity couples. Utilizing the CELEB-A dataset, which includes 202,599 images of 10,177 celebrities, we conducted an in-depth analysis using advanced artificial intelligence-based techniques. Deep learning and machine learning methods were employed to process and evaluate facial images, focusing on dissimilarity across various facial regions. Our sample comprised 1822 celebrity couples. The predictive analysis, incorporating models like Linear Regression, Ridge Regression, Random Forest, Support Vector Machine, and a Neural Network, revealed varying degrees of effectiveness in estimating partnership duration based on facial features and partnership status. However, the most notable performance was observed in Ridge Regression (Mean R2 = 0.0623 for whole face), indicating a moderate predictive capability. The study found no significant correlation between facial dissimilarity and partnership duration. These findings emphasize the complexity of predicting relationship outcomes based solely on facial attributes and suggest that other nuanced factors might play a more critical role in determining relationship dynamics. This study contributes to the understanding of the intricate nature of partnership dynamics and the limitations of facial attributes as predictors

Artificial Intelligence-Based Prediction of Oroantral Communication after Tooth Extraction Utilizing Preoperative Panoramic Radiography

Oroantral communication (OAC) is a common complication after tooth extraction of upper molars. Profound preoperative panoramic radiography analysis might potentially help predict OAC following tooth extraction. In this exploratory study, we evaluated n = 300 consecutive cases (100 OAC and 200 controls) and trained five machine learning algorithms (VGG16, InceptionV3, MobileNetV2, EfficientNet, and ResNet50) to predict OAC versus non-OAC (binary classification task) from the input images. Further, four oral and maxillofacial experts evaluated the respective panoramic radiography and determined performance metrics (accuracy, area under the curve (AUC), precision, recall, F1-score, and receiver operating characteristics curve) of all diagnostic approaches. Cohen&rsquo;s kappa was used to evaluate the agreement between expert evaluations. The deep learning algorithms reached high specificity (highest specificity 100% for InceptionV3) but low sensitivity (highest sensitivity 42.86% for MobileNetV2). The AUCs from VGG16, InceptionV3, MobileNetV2, EfficientNet, and ResNet50 were 0.53, 0.60, 0.67, 0.51, and 0.56, respectively. Expert 1&ndash;4 reached an AUC of 0.550, 0.629, 0.500, and 0.579, respectively. The specificity of the expert evaluations ranged from 51.74% to 95.02%, whereas sensitivity ranged from 14.14% to 59.60%. Cohen&rsquo;s kappa revealed a poor agreement for the oral and maxillofacial expert evaluations (Cohen&rsquo;s kappa: 0.1285). Overall, present data indicate that OAC cannot be sufficiently predicted from preoperative panoramic radiography. The false-negative rate, i.e., the rate of positive cases (OAC) missed by the deep learning algorithms, ranged from 57.14% to 95.24%. Surgeons should not solely rely on panoramic radiography when evaluating the probability of OAC occurrence. Clinical testing of OAC is warranted after each upper-molar tooth extraction