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Rapid individual cognitive phenotyping holds the potential to revolutionize domains as wide-ranging as personalized learning, employment practices, and precision psychiatry. Going beyond limitations imposed by traditional lab-based experiments, new efforts have been underway towards greater ecological validity and participant diversity to capture the full range of individual differences in cognitive abilities and behaviors across the general population. Building on this, we developed Skill Lab, a novel game-based tool that simultaneously assesses a broad suite of cognitive abilities while providing an engaging narrative. Skill Lab consists of six mini-games as well as 14 established cognitive ability tasks. Using a popular citizen science platform (N = 10725), we conducted a comprehensive validation in the wild of a game-based cognitive assessment suite. Based on the game and validation task data, we constructed reliable models to simultaneously predict eight cognitive abilities based on the users' in-game behavior. Follow-'-up validation tests revealed that the models can discriminate nuances contained within each separate cognitive ability as well as capture a shared main factor of generalized cognitive ability. Our game-based measures are five times faster to complete than the equivalent task-based measures and replicate previous findings on the decline of certain cognitive abilities with age in our large cross-sectional population sample (N = 6369). Taken together, our results demonstrate the feasibility of rapid in-the-wild systematic assessment of cognitive abilities as a promising first step towards population-scale benchmarking and individualized mental health diagnostics., 24 pages, 8 figures, and 4 tables. Supplementary Information: osf.io/pnw5z//

Convolutional neural networks (CNNs) lack robustness to test image corruptions that are not seen during training. In this paper, we propose a new layer for CNNs that increases their robustness to several types of corruptions of the input images. We call it a ‘push–pull’ layer and compute its response as the combination of two half-wave rectified convolutions, with kernels of different size and opposite polarity. Its implementation is based on a biologically motivated model of certain neurons in the visual system that exhibit response suppression, known as push–pull inhibition. We validate our method by replacing the first convolutional layer of the LeNet, ResNet and DenseNet architectures with our push–pull layer. We train the networks on original training images from the MNIST and CIFAR data sets and test them on images with several corruptions, of different types and severities, that are unseen by the training process. We experiment with various configurations of the ResNet and DenseNet models on a benchmark test set with typical image corruptions constructed on the CIFAR test images. We demonstrate that our push–pull layer contributes to a considerable improvement in robustness of classification of corrupted images, while maintaining state-of-the-art performance on the original image classification task. We released the code and trained models at the url http://github.com/nicstrisc/Push-Pull-CNN-layer.

Background The lack of visualization of the spinal cord hinders the evaluation of [18F]Fluoro-deoxy-glucose (FDG) uptake of the spinal cord in PET/CT. By exploiting the capability of MRI to precisely outline the spinal cord, we performed a retrospective study aimed to define normal pattern of spinal cord [18F]FDG uptake in PET/MRI. Methods Forty-one patients with lymphoma without clinical or MRI signs of spinal cord or bone marrow involvement underwent simultaneous PET and MRI acquisition using Siemens Biograph mMR after injection of 3.5 MBq/kg body weight of [18F]FDG for staging purposes. Using a custom-made software, we placed ROIs of 3 and 9 mm in diameter in the spinal cord, lumbar CSF, and vertebral marrow that were identified on MRI at 5 levels (C2, C5, T6, T12, and L3). The SUVmax, SUVmean, and the SUVmax and SUVmean normalized (NSUVmax and NSUVmean) to the liver were measured. For comparison, the same ROIs were placed in PET-CT images obtained immediately before the PET-MRI acquisition following the same tracer injection. Results On PET/MRI using the 3 mm ROI, the following average (all level excluding L3) spinal cord median (1st and 3rd quartile) values were measured: SUVmean, 1.68 (1.39 and 1.83); SUVmax, 1.92 (1.60 and 2.14); NSUVmean, 1.18 (0.93 and 1.36); and NSUVmax, 1.27 (1.01 and 1.33). Using the 9 mm ROI, the corresponding values were SUVmean, 1.41 (1.25–1.55); SUVmax, 2.41 (2.08 and 2.61); NSUVmean, 0.93 (0.79 and 1.04); and NSUVmax, 1.28 (1.02 and 1.39). Using the 3 mm ROI, the highest values of PET-MRI SUVmax, SUVmean, NSUVmax, and NSUVmean were consistently observed at C5 and the lowest at T6. Using a 9 mm ROI, the highest values were consistently observed at C5 and the lowest at T12 or T6. The spinal cord [18F]FDG-uptake values correlated with the bone marrow uptake at the same level, especially in case of NSUVmax. Comparison with PET-CT data revealed that the average SUVmax and SUVmean of the spinal cord were similar in PET-MRI and PET-CT. However, the average NSUVmax and NSUVmean of the spinal cord were higher (range 21–47%) in PET-MRI than in PET-CT. Conclusions Using a whole-body protocol, we defined the maximum and mean [18F]FDG uptake of the normal spinal cord in PET/MRI. While the observed values show the expected longitudinal distribution, they appear to be higher than those measured in PET/CT. Normalization of the SUVmax and SUVmean of the spinal cord to the liver radiotracer uptake could help in multi-institutional comparisons and studies.

Aims 18F-FDG PET/CT is the most accurate imaging modality in differentiated thyroid cancer (DTC) patients with either an aggressive histology, an absence of radioiodine uptake in neoplastic foci, or in the absence of imaging abnormalities in patients with an elevated serum thyroglobulin (Tg) level that progresses with time. We evaluated the diagnostic performance of FDG PET/MR in comparison with that of PET/CT. Methods and results Following the injection of a single 18F-FDG activity, PET/MR and PET/CT were sequentially performed in 40 consecutive patients with DTC previously treated with total thyroidectomy and radioiodine ablation. All patients were then followed up for at least 6 months. PET/MR was positive in 11 patients and PET/CT in 10. PET/MR detected 33 tumor foci and PET/CT 30. During the follow-up of the 12 patients with negative initial PET studies and with a detectable serum Tg, only one patient had a neck recurrence and the administration of an empiric high activity of 131I in the other 11 patients did not reveal any tumor focus. In the 17 patients with an initial serum Tg level < 2 ng/mL, no recurrence occurred. Conclusion This study confirms the high diagnostic accuracy of FDG PET studies in DTC patients with elevated serum Tg levels and shows that PET/MR brings similar information as compared to PET/CT imaging.

Customized solutions for replacement of the temporomandibular joint (TMJ) along with surgical guides enable precise and fast transfer of the virtual plan to the patient. However, these guides lack information on screw vectors and length, and well-defined borders for bony resections towards the medial skull base. This retrospective study was performed to investigate the feasibility and benefit of real-time navigation and intraoperative three-dimensional imaging during total TMJ replacement (TJR), as well as patient clinical outcomes. Between 2016 and 2020, 26 customized prostheses were implanted in 21 patients either with or without real-time navigation and instrument tracking. The clinical, surgical, radiological, and navigational data were analysed. The accuracy of navigation registration with instrument tracking, precision of screw insertion, and implant and screw positions were analysed by fusion of the virtual plan and surgical outcome. Real-time navigation aided orientation during lateral skull base dissection and resection. However, the results of real-time navigation-aided drilling were inconclusive regarding vector and length control. At a mean 15.3±3.0 months of follow-up, average mouth opening had improved from 21.69±2.80mm to 36.40±1.25mm; the average pain score decreased from 6.18±0.74 to 1.06±0.52. Thus, intraoperative real-time navigation for TJR assists lateral skull base dissection and resection.

The u-serrated immunodeposition pattern in direct immunofluorescence (DIF) microscopy is a recognizable feature and confirmative for the diagnosis of epidermolysis bullosa acquisita (EBA). Due to unfamiliarity with serrated patterns, serration pattern recognition is still of limited use in routine DIF microscopy. The objective of this study was to investigate the feasibility of using convolutional neural networks (CNNs) for the recognition of u-serrated patterns that can assist in the diagnosis of EBA. The nine most commonly used CNNs were trained and validated by using 220,800 manually delineated DIF image patches from 106 images of 46 different patients. The data set was split into 10 subsets: nine training subsets from 42 patients to train CNNs and the last subset from the remaining four patients for a validation data set of diagnostic accuracy. This process was repeated 10 times with a different subset used for validation. The best-performing CNN achieved a specificity of 89.3% and a corresponding sensitivity of 89.3% in the classification of u-serrated DIF image patches, an expert level of diagnostic accuracy. Experiments and results show the effectiveness of CNN approaches for u-serrated pattern recognition with a high accuracy. The proposed approach can assist clinicians and pathologists in recognition of u-serrated patterns in DIF images and facilitate the diagnosis of EBA.

Although the Prostate Imaging-Reporting and Data System™ version 2 (PI-RADS™ v2) is a reliable diagnostic tool for significant prostate cancer, less is known about the prognostic significance of the structured reporting scheme for estimating oncologic outcomes after treatment. We aimed to synthesize the available evidence regarding the association of PI-RADS v2 score and risk of biochemical recurrence (BCR) among patients undergoing primary definitive treatment for prostate cancer.We systematically queried the PubMed® and Web of Science™ databases to identify studies addressing the association between the PI-RADS v2 and treatment outcomes. We included studies through November 2020 that assessed the independent prognostic significance of PI-RADS v2. After assessing risk of bias and quality, we conducted a formal meta-analysis to estimate the pooled effects of prostate magnetic resonance imaging (MRI) classification on the risk of BCR.We identified 9 and 7 eligible studies including 2,274 and 1,215 patients for the systematic review and meta-analysis, respectively. Eight were conducted in the context of radical prostatectomy and 1 post-radiation. Among patients treated with radical prostatectomy, higher PI-RADS v2 scores were significantly associated with risk of BCR (pooled HR 3.06, 95% CI 2.16-4.33; p0.01). There was no significant heterogeneity among studies. For all studies, PI-RADS v2 score remained significantly associated with BCR (pooled HR 3.19, 95% CI 2.28-4.45; p0.01).Prostate MRI findings assessed with the PI-RADS v2 classification were independently associated with risk of BCR after definitive local therapy, primarily based on data from radical prostatectomy. These findings support the prognostic significance of MRI, in addition to its role in prostate cancer diagnosis.

Deep and complete reconstruction of the orbital cavity has been shown to be essential for preventing enophthalmos and hypoglobus in patients with orbital defects or deformities. Additively manufactured patient-specific titanium implants provide unlimited options in design. However, implant malpositioning can still occur, even when intraoperative imaging and navigation are used. In this study, we investigated novel orbital implants containing features facilitating self-centering. Accuracy of implant placement and reconstruction of the orbital dimensions were compared retrospectively between self-centering second-generation patient-specific functionalized orbital implants (study group) and CAD-based individualized implants (control group). Design features of implants in the study group included functionalization with navigation tracks, a preventive design, and flanges - so called stabilizers - towards opposite orbital walls. Implant position was evaluated by fusion of preoperative virtual plans and the post-therapeutic imaging. Aberrances were quantified by 3D heatmap analysis. 31 patients were assigned to the study group and 50 to the control group, respectively. In the study group, most implants were designed with either one (n = 18, 58.06%) or two (n = 10, 32.26%) stabilizers. Twice (6.45%), one stabilizer had to be shortened intraoperatively. Implant fit analysis revealed a significantly more precise (p 0.001) positioning in the study group (n = 22/31) than in the control group (n = 42/50). Self-centering second-generation patient-specific functionalized orbital implants showed significantly more accurate implant positioning, facilitating the transformation of virtual plans into patient's anatomy. The presented design provides an additional instrument for intraoperative quality control besides intraoperative imaging and navigation.

Increased attenuation of pericoronary adipose tissue (PCAT) around the right coronary artery (RCA) derived from coronary CTA might detect coronary inflammation. We investigated a potential association between RCA PCAT attenuation and serum levels of atherosclerosis-relevant cytokines and MACE (coronary revascularization, myocardial infarction and/or cardiac death).Blood samples of 293 clinically stable individuals (59.0 ​± ​9.8 years, 69% males) were analyzed for atherosclerosis-relevant cytokines including interleukin (IL)-2, IL- 4, IL-6, IL-7, IL-8, IL-10, IL-13, IL-15, IL-17, TNF-a, IP-10, CRP, MCP-1, MIP-1a, Eotaxin and GM-CSF. Subjects also underwent coronary calcium scoring (CCS) followed by CTA. PCAT CT attenuation was measured around the RCA using semi-automated software. Increased RCA PCAT attenuation was defined as PCAT attenuation above the 75th percentile (-73.5 HU). To assess MACE, 232 individuals were followed for a mean duration of 9.6 ​± ​2.1 years.In patients with increased RCA PCAT attenuation the serum levels of MCP-1 were increased (p ​ ​0.01), whereas levels of anti-inflammatory mediators IL-4 and -13 were significantly reduced (each p ​ ​0.05). Adipocytokine MCP-1 (r ​= ​0.23, p ​ ​0.01) and pro-inflammatory mediator IL-7 (r ​= ​0.12, p ​= ​0.04) showed a mild positive correlation with RCA PCAT attenuation, whereas anti-inflammatory mediators Il-4, -10 and -13 correlated inversely (each r-0.12, each p ​ ​0.05). 40/232 patients experienced MACE during follow-up. In multivariable Cox regression analysis increased RCA PCAT attenuation was shown to be an independent predictor of MACE (HR 2.01, p ​= ​0.044).Increased RCA PCAT CT attenuation shows a weak association with serum levels of selected atherosclerosis-relevant inflammatory biomarkers. Increased RCA PCAT attenuation is an independent predictor of MACE and may potentially guide future prevention strategies in stable patients.

Hormone and human epidermal growth factor receptor 2 (HER2/neu) receptor status is prognostic and predictive in breast cancer (BC) and guides the choice of therapy. However, owing to receptor conversion, the receptor status can differ in metastases compared with that of the primary tumor. The aim of the present study was to analyze the prognostic value of receptor status, receptor conversion, and clinical parameters in patients with resected BC brain metastases (BMs).Patients with BCBMs treated at our institution from July 2007 to December 2019 were eligible for the present study. The receptor status of the BC and corresponding BMs and the occurrence of receptor conversion were separately recorded for 3 common receptors: HER2/neu, estrogen receptor, and progesterone receptor. The association between the receptor status or receptor conversion and clinical parameters was adjusted for outcome-relevant patient and tumor characteristics.The final analysis included 78 patients. HER2/neu receptor status in BMs was associated with overall survival (P = 0.033). Receptor conversion was identified in 39 patients (50.0%): HER2/neu, n = 9 (11.5%); estrogen receptor, n = 22 (28.2%); and progesterone receptor, n = 25 (32.1%). In the final multivariate Cox regression analysis, HER2/neu receptor conversion (adjusted hazard ratio [aHR], 3.58; P = 0.006), Karnofsky performance status score70% (aHR, 3.11; P = 0.048), infratentorial BM location (aHR, 2.49; P = 0.007), and age ≥55 years at BM diagnosis (aHR, 2.20; P = 0.046) were independently associated with poorer survival.Of the 3 common BC receptors, only HER2/neu receptor conversion was strongly associated with the prognosis of patients with surgically treated BCBMs. The clinical relevance of the reevaluation of receptor status in BMs favors surgical treatment of patients with noneloquent BCBMs.

Objective This pilot study aimed to assess the feasibility of intraoperative assessment of safe margins with Confocal Laser Endomicroscopy (CLE) during planned partial or total laryngectomy. Methods Eight patients with confirmed larynx squamous cell carcinoma (SCC) and planned partial or total laryngectomy were included in this study in March 2020. Two head and neck surgeons and one pathologist were asked to classify carcinoma or healthy epithelium in a sample of 94 representative sequences (5.640 images), blinded to the histological results (H&E staining). Results Healthy mucosa areas showed epithelium with cells of uniform size and shape with distinct cytoplasmic membranes and regular vessel architecture. CLE optical biopsy of SCC demonstrated a disorganized arrangement of variable cellular morphology. We calculated an accuracy, sensitivity, specificity, PPV, and NPV of 80.1%, 72.3%, 87.9%, 85.7%, and 76.1%, respectively. A distinct transition between healthy appearing tissue and suspicious lesions could also be detected. Conclusion CLE can be easily integrated into the intraoperative setting, generate real-time, in-vivo microscopic images of the larynx for evaluation and demarcation of cancer. If validated in further studies, CLE could eventually contribute to a less radical approach by enabling a more precise evaluation of the cancer margin.

Severe burn injuries are associated with high morbidity and mortality. Well-implemented scoring systems for patients with major burns exist in the literature. A major disadvantage of these scores is the partial non-consideration of patient-related comorbidities. Published data on this matter is limited to small study cohorts and/or single center studies. Further, the effect of comorbidities on clinical outcome of patients with severe burn injuries has not yet been examined nationwide in a large cohort in Germany. Hence, the aim of this study was to examine the influence of comorbidities on clinical outcome of these patients based on data from the national registry.Anonymized data from a total of 3455 patients with documented burns of 1% or more Total Burn Surface Area (TBSA) and over 16 years of age included in the German Burn Registry between 2017 and 2018 were analyzed retrospectively. Data included burn extent, body weight, age, burn depth, inhalation injury, comorbidities, mortality, number of operations and length of hospital stay (LOS).In the logistic regression analysis age (OR 1.07 [1.06-1.09], p 0.001), TBSA (OR 1.09 [1.08-1.11], p 0.001), IHT (OR 2.15 [1.44-3.20], p 0001), third degree burn (OR 2.08 [1.39-3.11], p 0.001), Chronic Obstructive Pulmonary Disease (COPD) (OR 2.45 [1.38-4.35], p = 0.002) and renal insufficiency (OR 2.02 [1.13-3.59], p = 0.017) influenced mortality significantly. If a patient had more than one comorbidity, mortality was higher and in-hospital length of stay (LOS) longer. Renal insufficiency was significantly (p 0.001) associated with the most prolonged LOS by 11.44 days. TBSA (p 0.001), Abbreviated Burn Severity Index (ABSI)3 (p 0.001) and IHT (p = 0.001) correlated with the amount of required surgeries and significantly predicted the need for intubation. Patients with arrhythmia significantly required more surgeries (p = 0.041), whereas patients with COPD required significantly less surgical interventions (p = 0.013).Preexisting comorbidities have a significant impact on the clinical outcome of patients with severe burn injuries. Further investigation is warranted in order to supplement existing prognostic scores with new mortality-associated parameters.

The study of the visual system of the brain has attracted the attention and interest of many neuro-scientists, that derived computational models of some types of neuron that compose it. These findings inspired researchers in image processing and computer vision to deploy such models to solve problems of visual data processing.In this paper, we review approaches for image processing and computer vision, the design of which is based on neuro-scientific findings about the functions of some neurons in the visual cortex. Furthermore, we analyze the connection between the hierarchical organization of the visual system of the brain and the structure of Convolutional Networks (ConvNets). We pay particular attention to the mechanisms of inhibition of the responses of some neurons, which provide the visual system with improved stability to changing input stimuli, and discuss their implementation in image processing operators and in ConvNets.

Aims/hypothesis Metabolic effects of intermittent unhealthy lifestyle in young adults are poorly studied. We investigated the gluco-metabolic and hepatic effects of participation in Roskilde Festival (1 week of binge drinking and junk food consumption) in young, healthy males. Methods Fourteen festival participants (FP) were studied before, during and after 1 week’s participation in Roskilde Festival. Fourteen matched controls (CTRL) who did not participate in Roskilde Festival or change their lifestyle in other ways were investigated along a similar timeline. Results The FP group consumed more alcohol compared to their standard living conditions (2.0 ± 3.9 vs 16.3 ± 8.3 units/day, P < 0.001). CTRLs did not change their alcohol consumption. AUC for glucose during OGTT did not change in either group. C-peptide responses increased in the FP group (206 ± 24 vs 236 ± 17 min × nmol/L, P = 0.052) and the Matsuda index of insulin sensitivity decreased (6.2 ± 2.4 vs 4.7 ± 1.4, P = 0.054). AUC for glucagon during oral glucose tolerance test (OGTT) increased in the FP group (1037 ± 90 vs 1562 ± 195 min × pmol/L, P = 0.003) together with fasting fibroblast growth factor 21 (FGF21) (62 ± 30 vs 132 ± 72 pmol/L, P < 0.001), growth differentiation factor 15 (GDF5) (276 ± 78 vs 330 ± 83 pg/mL, P = 0.009) and aspartate aminotransferase (AST) levels (37.6 ± 6.8 vs 42.4 ± 11 U/L, P = 0.043). Four participants (29%) developed ultrasound-detectable steatosis and a mean strain elastography-assessed liver stiffness increased (P = 0.026) in the FP group. Conclusions/Interpretation Participation in Roskilde Festival did not affect oral glucose tolerance but was associated with a reduction in insulin sensitivity, increases in glucagon, FGF21, GDF15 and AST and lead to increased liver stiffness and, in 29% of the participants, ultrasound-detectable hepatic steatosis.

Resumen Objetivo El objetivo de este estudio fue investigar la precision diagnostica de la PET/TC con 18F-FDG en la estadificacion del cancer de laringe, comparar estos resultados con las tecnicas de imagen convencional ( C I) y evaluar los parametros metabolicos para predecir la supervivencia. Metodos Estudio retrospectivo que incluye cincuenta y cuatro pacientes con cancer escamoso de laringe que acudieron para realizacion de estadificacion mediante PET/TC con 18F-FDG. Las imagenes PET se analizaron visualmente y semicuantitativamente midiendo varios parametros metabolicos. Se tomo como estandar de referencia el seguimiento clinico, por imagen y/o histopatologia. Se calculo el tiempo libre de enfermedad y la supervivencia mediante curvas de Kaplan-Meier. Resultados Todos los tumores fueron identificados por las CI y 52/54 por la PET/TC con 18F-FDG, con sensibilidad del 96,3%. La sensibilidad, especificidad, valor predictivo positivo, valor predictivo negativo y precision, basada en el analisis por paciente para la deteccion de enfermedad ganglionar fue del: 100%, 85,7%, 94,6%, 100% y 95,9% para la PET/TC con 18F-FDG y del 91,4%, 85,7%, 94,1%, 80% y 89,9% para las CI. El rendimiento diagnostico de la PET/TC y las CI no fue significativamente diferente ni en analisis por paciente, ni en el de la lateralizacion ni el de los niveles ganglionares. La PET/TC con 18F-FDG detecto metastasis a distancia en 7 pacientes que permitieron una estadificacion superior. En una mediana de seguimiento de 27 meses, la recaida/progresion de la enfermedad ocurrio en 31 pacientes y muerte en 32. El volumen metabolico tumoral (VMT) y la glucolisis total (TLG) de la lesion primaria se mostraron como factores pronosticos independientes para el tiempo libre de enfermedad. Conclusiones Tanto las CI como la PET/TC con 18F-FDG mostraron resultados diagosticos en la estadificacion del cancer de laringe. Los parametros metabolicos basales (MTV y TLG) mostraron valor pronostico en la evaluacion del tiempo libre de enfermedad.

The transmission of Plasmodium spp. sporozoites to the mammalian host is the first step in the initiation of the mosquito-borne disease known as malaria. The exact route of transmission from the bloodstream to the liver is still not clearly elucidated, and identification of the host glycan structures bound by the sporozoites may inform as to which host cells are involved. Here, we provide a comprehensive analysis of the glycan structures that sporozoites from the human pathogen, P. falciparum, and the rodent pathogen, P. yoelii, recognize and bind. Glycan array analysis was used to profile the glycans bound by the sporozoites, and the binding affinities of these sporozoite-glycan interactions were then determined by surface plasmon resonance. Data showed that the different Plasmodium spp. bind different classes of glycans. P. falciparum was observed to bind to glycans with terminal N-acetylgalactosamine (GalNAc) or Galactose (Gal) linked to a GalNAc, and the highest-affinity observed was with the GalNAc monosaccharide (12.5 nM). P. yoelii bound glycosaminoglycans, mannosyl glycans, Gal linked to N-acetylglucosamine structures, and the αGal epitope. The highest-affinity interaction for P. yoelii was with the αGal epitope (31.4 nM). This is the first study to identify the key host glycan structures recognized by human and rodent Plasmodium spp. sporozoites. An understanding of how Plasmodium sporozoites interact with the specific glycan structures identified here may provide further insight into this infectious disease that could help direct the design of an effective therapeutic.

Background There is growing evidence that upper airway symptoms coexist with lower airway symptoms in COPD. Still, the prevalence and impact of upper airway disease on the nature and course of COPD remain unclear. We aimed to describe this in a cross-sectional study. Methods We examined a cohort of COPD patients with pulmonary function tests, induced sputum, blood eosinophils, atopy tests and computed tomography (CT) of the paranasal sinuses. Lower airway symptoms were assessed using the COPD Assessment Test (CAT), and upper airway symptoms were assessed using the nasal subdomain of the 22-item Sino Nasal Outcome Test (SNOT22nasal). We recruited patients from five sites in Denmark and Sweden. We excluded patients with a history of asthma. Findings In total, 180 patients (female 55%, age 67±8 years, forced expiratory volume in 1 s (FEV1 %) 52.4±16.6, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage: A: 18%, B: 54%, C: 3%, D: 25%) were included in the study. Seventy-four patients (41%) reported high upper airway symptoms (UAS, defined as SNOT22nasal≥6) with a median score of 10 (IQR 8–13). Patients with high UAS reported higher CAT scores (17.4±7.5 versus 14.9±6.6, p, Upper airway symptoms are common in COPD, and are associated with elevated CAT scores and more pronounced systemic and airway eosinophilia https://bit.ly/3iIKBUS

Background and aim Genetic markers are established as predictive of type 1 diabetes, but unknown early life environment is believed to be involved. Umbilical cord blood may reflect perinatal metabolism and exposures. We studied whether selected polar metabolites in cord blood contribute to prediction of type 1 diabetes. Methods Using a targeted UHPLC-QQQ-MS platform, we quantified 27 low-molecular-weight metabolites (including amino acids, small organic acids, and bile acids) in 166 children, who later developed type 1 diabetes, and 177 random control children in the Norwegian Mother, Father, and Child cohort. We analyzed the data using logistic regression (estimating odds ratios per SD [adjusted odds ratio (aOR)]), area under the receiver operating characteristic curve (AUC), and k-means clustering. Metabolites were compared to a genetic risk score based on 51 established non-HLA single-nucleotide polymorphisms, and a 4-category HLA risk group. Results The strongest associations for metabolites were aminoadipic acid (aOR = 1.23; 95% CI, 0.97-1.55), indoxyl sulfate (aOR = 1.15; 95% CI, 0.87-1.51), and tryptophan (aOR = 0.84; 95% CI, 0.65-1.10), with other aORs close to 1.0, and none significantly associated with type 1 diabetes. K-means clustering identified 6 clusters, none of which were associated with type 1 diabetes. Cross-validated AUC showed no predictive value of metabolites (AUC 0.49), whereas the non-HLA genetic risk score AUC was 0.56 and the HLA risk group AUC was 0.78. Conclusions In this large study, we found no support of a predictive role of cord blood concentrations of selected bile acids and other small polar metabolites in the development of type 1 diabetes.

Cytochrome c nitrite reductases (CcNIR or NrfA) play important roles in the global nitrogen cycle by conserving the usable nitrogen in the soil. Here, the electron storage and distribution properties within the pentaheme scaffold of Geobacter lovleyi NrfA were investigated via electron paramagnetic resonance (EPR) spectroscopy coupled with chemical titration experiments. Initially, a chemical reduction method was established to sequentially add electrons to the fully oxidized protein, 1 equiv at a time. The step-by-step reduction of the hemes was then followed using ultraviolet-visible absorption and EPR spectroscopy. EPR spectral simulations were used to elucidate the sequence of heme reduction within the pentaheme scaffold of NrfA and identify the signals of all five hemes in the EPR spectra. Electrochemical experiments ascertain the reduction potentials for each heme, observed in a narrow range from +10 mV (heme 5) to -226 mV (heme 3) (vs the standard hydrogen electrode). On the basis of quantitative analysis and simulation of the EPR data, we demonstrate that hemes 4 and 5 are reduced first (before the active site heme 1) and serve the purpose of an electron storage unit within the protein. To probe the role of the central heme 3, an H108M NrfA variant was generated where the reduction potential of heme 3 is shifted positively (from -226 to +48 mV). The H108M mutation significantly impacts the distribution of electrons within the pentaheme scaffold and the reduction potentials of the hemes, reducing the catalytic activity of the enzyme to 1% compared to that of the wild type. We propose that this is due to heme 3's important role as an electron gateway in the wild-type enzyme.

Objectives Few data exist on perioperative three-dimensional–derived right ventricular strain. The authors aimed to describe the perioperative course of three-dimensional–derived right ventricular strain in coronary artery bypass graft (CABG) surgery patients. Design Prospective, observational, pilot trial. Setting Single university hospital. Participants: The study comprised 40 patients with preserved left ventricular and right ventricular (RV) function undergoing isolated on-pump CABG surgery. Interventions: Three-dimensional strain analysis and standard echocardiographic evaluation of RV function were performed preoperatively (T1) and postoperatively (T4) with transthoracic echocardiography (TTE) and intraoperatively before sternotomy (T2) and after sternotomy (T3) with transesophageal echocardiography (TEE). All echocardiographic measurements were performed under stable hemodynamic conditions and predefined fluid management without any vasoactive support. Measurements and Main Results The measurements of three-dimensional–derived RV free-wall strain (3D-RV FWS) and RV ejection fraction were performed using TomTec 4D RV-Function 2.0 software. Philips QLAB 10.8 was used to analyze tissue velocity of the tricuspid annulus, tricuspid annular systolic excursion, and RV fractional area change. There were no significant differences (median [interquartile range {IQR}]) between preoperative TTE and intraoperative TEE measurements for 3D-RV FWS (T1 v T2: –22.35 [IQR –17.70 to –27.22] v –24.35 [IQR –20.63 to –29.88]; not significant). 3D-RV FWS remained unchanged after sternotomy (T2 v T3: –24.35 [IQR –20.63 to –29.88] v –23.75 [IQR –20.25 to –29.28]; not significant) but deteriorated significantly after CABG (T1 v T4: –22.35 [IQR –17.70 to –27.22] v –18.5 [IQR –16.90 to –21.65]; p = 0.004). Conclusion In patients undergoing on-pump CABG, 3D-RV FWS values for awake, spontaneously breathing patients measured with TTE and values assessed in patients under general anesthesia with TEE did not significantly differ. Three-dimensional RV FWS did not change after sternotomy but deteriorated after on-pump CABG.

Sodium-glucose transporter-2 inhibitors (SGLT2i) lower blood glucose and are used for treatment of type-2-diabetes. However, SGLT2i have been associated with increases in endogenous glucose production (EGP) by mechanisms that have been proposed to result from SGLT2i-mediated increases in circulating glucagon concentrations, but the relative importance of this effect is debated, and mechanisms possibly coupling SGLT2i to increased plasma glucagon are unclear. A direct effect on alpha-cell activity has been proposed, but data on alpha-cell SGLT2 expression are inconsistent, and studies investigating direct effects of SGLT2 inhibition on glucagon secretion are conflicting. In contrast, alpha-cell SGLT1 expression has been found more consistently and seems to be more prominent, pointing to an underappreciated role for this transporter. Nevertheless, the selectivity of most SGLT2i does not support interference with SGLT1 during therapy. Paracrine effects mediated by secretion of glucagonotropic/-static molecules from beta- and/or delta-cells have also been suggested to be involved in SGLT2i-induced increase in plasma glucagon, but studies are few and arrive at different conclusions. It is also possible that the effect on glucagon is secondary to drug-induced increases in urinary glucose excretion and lowering of blood glucose, as demonstrated in experiments with glucose clamping where SGLT2i-associated increases in plasma glucagon is are prevented. However, regardless of the mechanisms involved, the current balance of evidence does, not support that SGLT2 plays a crucial role for alpha-cell physiology or that SGLT2i-induced glucagon secretion is important for the associated increased EGP, particularly since the increase in EGP occurs before any rise in plasma glucagon. This article is protected by copyright. All rights reserved.

Follistatin is secreted from the liver and is involved in the regulation of muscle mass and insulin sensitivity via inhibition of activin A in humans. The secretion of follistatin seems to be stimulated by glucagon and inhibited by insulin, but only limited knowledge on the postprandial regulation of follistatin exists. Moreover, results on postoperative changes after Roux-en-Y gastric bypass (RYGB) are conflicting with reports of increased, unaltered, and lowered fasting concentrations of follistatin. In this study, we investigated postprandial follistatin and activin A concentrations after intake of isocaloric amounts of protein, fat, or glucose in subjects with obesity with and without previous RYGB to explore the regulation of follistatin by the individual macronutrients. Protein intake enhanced follistatin concentrations similarly in the two groups, whereas glucose and fat ingestion did not change postprandial follistatin concentrations. Concentrations of activin A were lower after protein intake compared with glucose intake in RYGB. Glucagon concentrations were also particularly enhanced by protein intake and tended to correlate with follistatin in RYGB. In conclusion, we demonstrated that protein intake, but not glucose or fat, is a strong stimulus for follistatin secretion in subjects with obesity and that this regulation is maintained after RYGB surgery.

Highlights • Local ablative radiotherapy is associated with high rates of local control. • Prognosis in oligometastatic disease may be improved by metastases-directed therapy. • OLIGOMA assesses the role of radiotherapy in oligometastatic breast cancer patients., Background Several recent randomized therapeutic exploratory trials demonstrated improvement of progression-free survival and in some even overall survival using stereotactic body radiotherapy in patients with oligometastatic disease. However, only very few patients enrolled in these trials had breast cancer, and results from confirmatory trials are lacking. Methods/design The OLIGOMA-trial is a randomized controlled multi-national multi-center therapeutic confirmatory trial studying the role of local ablative radiotherapy as an additive treatment in patients with oligometastatic breast cancer receiving standard systemic therapy. Patients will be randomized 1:1 to standard systemic therapy according to national guidelines with or without radiotherapy to all metastatic sites. Randomization will be stratified according to type and line of systemic therapy, which has to be determined by a multidisciplinary tumor board before enrollment. Patients with up to five metastatic lesions are eligible, including patients with up to three brain metastases (only in case of extracranial disease) and with locoregional recurrence (only in case of additional metastatic lesions). In the standard arm, palliative radiotherapy to symptomatic metastases is permitted if at least one lesion remains untreated. The co-primary endpoints are progression-free survival and quality of life. The primary hypothesis is that progression-free survival in the experimental arm will be superior to the standard arm while simultaneously demonstrating non-inferiority of quality of life at 12 weeks after randomization. Secondary endpoints are feasibility, overall survival, toxicity, quality of life and patient satisfaction. A translational sub-study with collection of ctDNA will be conducted. Discussion The OLIGOMA-trial will provide high level evidence on the use of and benefit from local ablative radiotherapy for patients with oligometastatic breast cancer. Trial registration The OLIGOMA-trial is registered at clinicialtrials.gov under the identification NCT04495309. The related information was first posted on July 31st 2020.

The aim of this study was to analyze the current situation of trainees in OMFS in a nationwide survey at German universities and teaching hospitals. A questionnaire about their training in OMFS and discrimination, gender (in-)equality, and reconcilability of work and family life was sent to many OMFS residents in Germany. Seventy-five questionnaires were included. The average age of the participants was 32.15 years (± 0.75 years); 47 participants were male, 22 female, and 3 "diverse". The participants' overall satisfaction rate was good. Training concepts existed in most of the teaching hospitals (54.67%). 8.11% of the participants stated discrimination existed against men while, 24.32% agreed that discrimination existed against women. Stating that discrimination against women exists, it was associated with female gender (p 0.001), being married (p = 0.042), and not aiming for further academic degrees (p = 0.009). Overall, the training situation in Germany seems structured in most teaching hospitals. Apart from the residents' general satisfaction with the training concepts, there seems to be a matter of concern regarding discrimination especially against women and the reconcilability of work and family life in OMFS training. Furthering the establishment of structured training concepts might be useful to overcome these issues in the course of training in OMFS.

Quando è indicato un approccio chirurgico multidisciplinare nei tumori naso-sinusali con estensione cranica?I tumouri nasosinusali includono un ampio spettro di neoplasie caratterizzate da un comportamento biologico eterogeneo e dalla localizzazione in un distretto anatomico critico. Diverse discipline mediche sono coinvolte nella diagnosi e nel trattamento di tali tumori. Una revisione narrativa della letteratura è stata condotta per identificare i ruoli delle specialità chirurgiche che appartengono al gruppo multidisciplinare. La diagnosi e la stadiazione dei tumori nasosinusali richiede la collaborazione tra chirurghi, radiologi e patologi. L’identificazione delle estensioni tumorali critiche è fondamentale per un corretto trattamento. L’intervento chirurgico necessario per la maggior parte dei tumori nasosinusali avanzati può essere eseguito da un team otorinolaringoiatrico con adeguato training. Il contributo di neurochirurghi e di specialisti in chirurgia orbitaria è necessario in scenari selezionati. Nei casi di difetti chirurgici complessi possono essere necessarie strategie ricostruttive multidisciplinari. La collaborazione chirurgica multidisciplinare è essenziale per la gestione delle complicanze nel periodo perioperatorio. Nonostante la chirurgia rimanga il trattamento principale, si sta affermando una vasta gamma di trattamenti non-chirurgici, adiuvanti o esclusivi.The term “sinonasal tumours” includes a large spectrum of diseases, which are characterized by heterogeneous biological behavior and prognosis, and located in a critical anatomic area. Diagnosis and treatment of sinonasal tumours require the contribution of different disciplines. A narrative review was performed to highlight the role of surgeons in contributing to a multidisciplinary approach to sinonasal tumours. Diagnosis and staging of sinonasal tumours is challenging and requires collaboration between surgeons, radiologists, and pathologists. The identification and management of critical extensions (orbital or intracranial encroachment, vascular abutment or encasement) is fundamental for successful treatment. Most cases of advanced sinonasal tumours can undergo surgical intervention by an adequately trained otorhinolaryngological team. The contribution of neurosurgeons and oculoplastic surgeons is required in selected scenarios. In rare circumstances, multidisciplinary reconstructive strategies can be indicated for complex tissue defects. Furthermore, a multidisciplinary approach is pivotal in the management of perioperative complications. While surgery remains the mainstay of treatment, the role of non-surgical adjuvant or even exclusive treatments is constantly expanding.

Introduction New-onset atrial fibrillation (NOAF) is frequently observed in critically ill patients and may be associated with prolonged hospital stay and increased mortality. Considerable variation exists in the reported frequencies of NOAF due to the lack of a standardised definition and detection method. Importantly, there are limited data on NOAF in the intensive care unit (ICU). Thus, we aim to provide contemporary epidemiological data on NOAF in the ICU.Methods and Analysis We have designed an international inception cohort study including at least 1,000 consecutive adult patients acutely admitted to the ICU without prior history of persistent or permanent AF. We will present data on the incidence, risk factors, used management strategies and outcomes of NOAF. We will register data daily during stay in the ICU for a maximum of 90 days after admission. The incidence of NOAF and management strategies used will be presented descriptively, and we will use Cox regression analyses including competing risk analyses to assess risk factors for NOAF and any association with 90-day mortality.Conclusion The outlined international AFIB-ICU inception cohort study will provide contemporary data on the incidence, risk factors, used management strategies and outcomes of NOAF in adult ICU patients.Ethics and dissemination This observational study poses no risk to the included patients. All participating sites will obtain relevant approvals according to national laws before patient enrollment. Funding sources will have no influence on data handling, analyses or writing of the manuscript. The study report(s) will be submitted to an international peer-reviewed journal.

ZusammenfassungBei vielen Patienten, die an einem Malignom erkranken, ist die Familienplanung noch nicht abgeschlossen, sodass für den Erhalt des fertilen Potenzials Maßnahmen der Fertilitätsprotektion sinnvoll sind. Durch eine Polychemotherapie, unabhängig ob im neoadjuvanten oder adjuvanten Setting, Molekular- oder Immuntherapien kann es zu einer irreversiblen Schädigung der Follikel bzw. Spermatogenese kommen, was u. U. zu einer permanenten Infertilität führen kann. Abhängig von der verwendeten Therapie und der altersabhängigen Ovarialreserve der Frau muss das gonadotoxische Risiko als niedrig, mittel oder hoch eingeschätzt werden. Möglichkeiten des Fertilitäserhalts sind: a) die Kryokonservierung von fertilisierten oder unfertilisierten Oozyten. Hierbei werden nach ovarieller Hyperstimulation reife Oozyten mittels transvaginaler Follikelaspiration gewonnen und im Anschluss entweder unfertilisiert oder nach erfolgter IVF- oder ICSI-Behandlung kryokonserviert. Bei b) der Kryokonservierung von Ovarialgewebe wird mithilfe eines laparoskopischen Eingriffs etwa 50 % des Ovarkortex eines Ovars reseziert und kryokonserviert. Die Verwendung von c) GnRH-Agonisten als medikamentöse Therapieoption unternimmt den Versuch einer endokrinen Ovarialsuppression, um Oozyten, Granulosa- und Thekazellen vor dem zytotoxischen Einfluss der jeweiligen Therapie zu schützen. Bei männlichen Patienten können Spermien vor Therapiebeginn kryokonserviert werden.

INTRODUCTION: Immunosuppressant drugs are increasingly being used in the reproductive years. Theoretically, such medications could affect fetal health either through changes in the sperm DNA or through fetal exposure caused by a presence in the seminal fluid. This systematic overview summarizes existing literature on the spermatotoxic and genotoxic potentials of methotrexate (MTX), a drug widely used to treat rheumatic and dermatologic diseases, and mycophenolate mofetil (MMF), which alone or supplemented with ganciclovir (GCV) may be crucial for the survival of organ transplants.MATERIAL AND METHODS: The systematic overview was performed in accordance with the PRISMA guidelines: A systematic literature search of the MEDLINE and Embase databases was done using a combination of relevant terms to search for studies on spermatotoxic or genotoxic changes related to treatment with MTX, GCV or MMF. The search was restricted to English language literature, and to in vivo animal studies (mammalian species) and clinical human studies.RESULTS: A total of 102 studies were identified, hereof 25 human and 77 animal studies. For MTX, human studies of immunosuppressive dosages show transient effect on sperm quality parameters, which return to reference values within 3 months. No human studies have investigated the sperm DNA damaging effect of MTX, but in other organs the genotoxic effects of immunosuppressive doses of MTX are fluctuating. In animals, immunosuppressive and cytotoxic doses of MTX adversely affect sperm quality parameters and show widespread genotoxic damages in various organs. Cytotoxic doses transiently change the DNA material in all cell stages of spermatogenesis in rodents. For GCV and MMF, data are limited and the results are indeterminate, for which reason spermatotoxic and genotoxic potentials cannot be excluded.CONCLUSIONS: Data from human and animal studies indicate transient spermatotoxic and genotoxic potentials of immunosuppressive and cytotoxic doses of MTX. There are a limited number of studies investigating GCV and MMF.

Background and Study Aims/Object Despite the relevance of molecular criteria for brain tumor diagnosis and prognosis, meningioma grading is still solely based on histologic features. Atypical meningiomas (AMs; WHO grade II) display a great histologic heterogeneity and individual courses of disease can differ significantly. This study aimed to identify clinically aggressive AMs that are prone to early recurrence after gross total resection (GTR) by assessing a specific histologic score. Patients and Methods A retrospective analysis of 28 consecutive patients (17 females and 11 males; mean age of 62 years [range: 35–88 years]) treated in our institution between January 2006 and December 2015 was performed. Basic demographic and clinical characteristics were assessed. A scoring scale was designed to address the histologic diversity by summing up the individual histologic features in every tumor sample. According to that, points were awarded as follows: major AM defining criterion (3 points) and minor criterion (1 point). Results The subclassification based on our specific histologic score revealed no significant difference in frequency of one (46.4%) or two (42.9%) AM defining features; three criteria were less frequently seen (10.7%). Mean follow-up was 61.89 ± 9.03 months. Local recurrence occurred in 35.7% after a mean time of 37.4 ± 22.6 months after primary surgery. Age > 60 years was significantly associated with a shorter progression-free survival (PFS). There was a trend toward shorter PFS with increasing scores, tantamount with the presence of several AM defining histologic criteria in one sample. No tumor relapse was seen when diagnosis was based only on minor criteria. Conclusion AMs display a histologic diversity. There is a trend toward shorter PFS with increasing numbers of AM defining histologic features. The inclusion of this score in the decision algorithm regarding further treatment for patients >60 years after GTR might be helpful and should be evaluated in further studies.

Skeletal muscle has fiber architectures ranging from simple to complex, alongside variations in fiber-type and neuro-anatomical compartmentalization. However, the functional implications of muscle subdivision into discrete functional units remain poorly understood. The rat medial gastrocnemius has well-characterized regions with distinct architectures and fiber type composition. Here, force-length and force-velocity contractions were performed for two stimulation intensities (supramaximal and submaximal) and for three structural units (whole muscle belly, proximal region, and distal region) to assess the effect of muscle compartmentalization on contractile force-length-velocity relationships and optimal speed for power production. Additionally, fiber strain, fiber rotation, pennation, and architectural gearing were quantified. Our results suggest that the proximal and distal muscle regions have fundamentally different physiological function. During supramaximal activation, the proximal region has shorter (8.4 ± 0.8 mm versus 10.9 ± 0.7 mm) fibers and steeper (28.7 ± 11.0° versus 19.6 ± 6.3°) fiber angles at optimum length, and operates over a larger (17.9 ± 3.8% versus 12.6 ± 2.7%) range of its force-length curve. The proximal region also exhibits larger changes in pennation angle (5.6 ± 2.2°/mm versus 2.4 ± 1.5°/mm muscle shortening) and architectural gearing (1.82 ± 0.53 versus 1.25 ± 0.24), whereas the distal region exhibits greater peak shortening speed (96.0 mm/s versus 81.3 mm/s) and 18-27% greater optimal speed. Overall, similar patterns were observed during submaximal activation. These regional differences in physiological function with respect to the whole muscle highlight how variation in motor recruitment could fundamentally shift regional functional patterns within a single muscle, which likely has important implications for whole muscle force and work output in vivo. NEW & NOTEWORTHY We show that muscle compartmentalization can influence whole muscle contractile properties, with slower-fibered proximal rat medial gastrocnemius undergoing larger changes in pennation angle and architectural gearing, whereas the faster-fibered distal region achieves greater peak and optimal shortening velocity, and power output. Consequently, regional variation in motor recruitment can fundamentally influence functional patterns within a single muscle.

Objective: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of mortality worldwide and it remains under-diagnosed. Unrecognized somatic disease contributes significantly to the observed increased mortality rate in patients with psychiatric diseases.Aims: To investigate whether screening with spirometry and simple questions on respiratory symptoms were efficacious in identifying previously unknown cases of COPD and/or asthma in patients admitted to psychiatric wards.Methods: In this observational cohort study, we included hospitalized psychiatric patients in2013. All were assessed with handheld spirometry, medical history and completion of a simple, short questionnaire on respiratory symptoms, the COPD assessment test (CAT questionnaire).Results: In total, 106 patients were screened and 45 patients (age: median 45, range 19-75, 43% female gender) were included whereas 61 patients (age: median 42, range 19-73) 34% female gender) were excluded. Prior to screening three patients (6.5%) reported having a diagnosis of COPD whereas eight patients (17%) reported having a diagnosis of asthma. Six new cases were diagnosed with COPD and four new cases with asthma. The number needed to screen to find one new case was 3.4 (total cohort 4.5).Conclusion: We present a simple study where the patients are screened for obstructive lung disease with a handheld spirometry and a questionnaire on respiratory symptoms. Number needed to screen is low at 3.4-4.5. In all, 10 new cases of obstructive lung disease were diagnosed. This study illustrates that screening for COPD and asthma is feasible even in a psychiatric population.

In this report, we describe the fluorescent labeling of bacterial polysaccharides (Escherichia coli O86:B7, Escherichia coli O19ab, Pseudomonas aeruginosa O10a10b, and Shigella flexneri 2b) at the “natural” amino group of their phosphoethanolamine moiety. Two protocols for labeling are compared: 1) on a scale of a few mg of the polysaccharide, with a dialysis procedure for purification from excessive reagents; and 2) on a scale of 0.1 mg of the polysaccharide, with a simple precipitation procedure instead of dialysis. The microscale version is sufficient for comfortable cytofluorometric analysis. The resulting probes were found to specifically bind to human dendritic cells in a dose-dependent manner. The used limited set of polysaccharides did not allow us even to get close to understanding which dendritic cell-associated lectins and which cognate polysaccharide epitopes are involved in recognition, but the proposed microscale protocol allows to generate a library of fluorescent probes for further mapping of the polysaccharide specificity of the dendritic cells.

The Palaeotropical genus Antirhea (Guettardeae, Rubiaceae) currently comprises 37 dioecious species classified into three subgenera, Antirhea, Mesocarpa and Guettardella. It has a complex taxonomic history with varying generic delineation and variable application of species names. Recent phylogenetic studies have indicated the non-monophyly of Antirhea, but the limited sampling does not allow resolution of its circumscription or nomenclatural changes to be proposed. Here, we reconcile the generic boundaries of Antirhea based on phylogenetic analyses of two nuclear (ETS, ITS) and three plastid loci (atpB-rbcL, rps16, trnT-F) using Bayesian, maximum likelihood and parsimony methods. Our results show that Antirhea in its current circumscription is highly polyphyletic, whereas its three subgenera are retrieved as well-supported independent clades. A new generic framework is proposed based on phylogenetic results and supported by morphological evidence. We intend to restrict Antirhea to species native to the Mascarene Islands and Madagascar, to reinstate the genus Guettardella with emended diagnostic features and to describe the new genus Achilleanthus to accommodate the species of subgenus Mesocarpa plus Guettarda glabrescens, G. hypoplasia and G. ngoyensis. As a consequence, seven new combinations in Achilleanthus and 17 new combinations in Guettardella are made.

OBJECTIVES Machine learning (ML) has experienced a revolutionary decade with advances across many disciplines. We seek to understand how recent advances in ML are going to specifically influence the practice of surgery in the future with a particular focus on thoracic surgery. METHODS Review of relevant literature in both technical and clinical domains. RESULTS ML is a revolutionary technology that promises to change the way that surgery is practiced in the near future. Spurred by an advance in computing power and the volume of data produced in healthcare, ML has shown remarkable ability to master tasks that had once been reserved for physicians. Supervised learning, unsupervised learning and reinforcement learning are all important techniques that can be leveraged to improve care. Five key applications of ML to cardiac surgery include diagnostics, surgical skill assessment, postoperative prognostication, augmenting intraoperative performance and accelerating translational research. Some key limitations of ML include lack of interpretability, low quality and volumes of relevant clinical data, ethical limitations and difficulties with clinical implementation. CONCLUSIONS In the future, the practice of cardiac surgery will be greatly augmented by ML technologies, ultimately leading to improved surgical performance and better patient outcomes.

ZusammenfassungDie Verwendung von patientenspezifischen Implantaten zur Rekonstruktion von Defekten des Schädels und der Kiefer hat sich in den letzten Jahren als Standard in der Mund-, Kiefer- und Gesichtschirurgie etabliert. Anfänglich wurden die zum Einsatz kommenden Implantate intraoperativ direkt an die Defektsituation angepasst. Mit dem Fortschritt in der 3-dimensionalen Bildgebung und im Zuge der zunehmenden Digitalisierung wurden zunächst patientenspezifische 3-D-gedruckte Biomodelle zur direkten Anpassung konfektionierter Implantate im Operationssaal verwendet. Heute kommen vermehrt Implantate zum Einsatz, die im Rahmen eines computerassistierten Designprozesses (CAD) und einer anschließenden computerassistierten Herstellung (CAM) vollständig digital geplant werden. Anfangs war die Verwendung dieser CAD/CAM-gefertigten Implantate auf Defekte mit einfachen Geometrien, wie die Rekonstruktion des Schädeldachs, beschränkt. Durch Fortschritte in der digitalen Planung und der digital gestützten Herstellung können CAD/CAM-gefertigte patientenspezifische Implantate heute auch zur Versorgung komplexer Defektsituationen im präventiven und funktionalisierten Design verwendet werden. Neben der Orbitarekonstruktion und der alloplastischen Rekonstruktion des Unterkiefers kommen individualisierte Implantate auch zur komplexen dentalen Rehabilitation und funktionellen Wiederherstellung der Kiefergelenke zum Einsatz.

BACKGROUND Community-acquired pneumonia (CAP) represents one of the most common infectious diseases among children. Diagnosis of CAP is mainly clinical. Chest X-ray (CXR) remains the gold standard for the diagnosis in severe or controversial conditions. Recently, some authors have focused on the application of ultrasound in lung diseases but the role of lung ultrasound (LUS) in the diagnosis of CAP is still debated. We aimed to study the concordance between LUS and CXR in evaluating specific signs of CAP. As a secondary aim, we sought to determine the sensitivity and specificity of LUS in CAP diagnosis compared with CXR. Finally, we evaluated the role of LUS during the follow up. METHODS We enrolled 68 children (

Purpose The human antibody repertoire forms in response to infections, the microbiome, vaccinations, and environmental exposures. The specificity of such antibody responses was compared among a cohort of toddlers to identify differences between seropositive versus seronegative responses. Methods An assessment of the serum IgM and IgG antibody reactivities in 197 toddlers of 1- and 2-years of age was performed with a microfluidic array containing 110 distinct antigens. Longitudinal profiling was done from years 1 to 2. Seropositivity to RNA and DNA viruses; bacteria; live attenuated, inactive, and subunit vaccines; and autoantigens was compared. A stratification was developed based on quantitative variations in the IgG responses. Clinical presentations and previously known genetic risk alleles for various immune system conditions were investigated in relation to IgG responses. Results IgG reactivities stratified toddlers into low, moderate, and high responder groups. The high group (17%) had elevated IgG responses to multiple RNA and DNA viruses (e.g., respiratory syncytial virus, Epstein-Barr virus, adenovirus, Coxsackievirus) and this correlated with increased responses to live attenuated viral vaccines and certain autoantigens. This high group was more likely to be associated with gestational diabetes and an older age. Genetic analyses identified polymorphisms in the IL2RB, TNFSF4, and INS genes in two high responder individuals that were associated with their elevated cytokine levels and clinical history of eczema and asthma. Conclusion Serum IgG profiling of toddlers reveals correlations between the magnitude of the antibody responses towards viruses, live attenuated vaccines, and certain autoantigens. A low responder group had much weaker responses overall, including against vaccines. The serum antibody screen also identifies individuals with IgG responses to less common infections (West Nile virus, parvovirus, tuberculosis). The characterization of the antibody responses in combination with the identification of genetic risk alleles provides an opportunity to identify children with increased risk of clinical disease. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-021-00993-w.

Introduction: Incidental finding of mass lesion in the choroid represents a very challenging situation for the ophthalmologist. We describe a case of an incidental, computed tomography (CT)-hyperintense, choroidal lesion in a patient with parotid malignancy and renal failure, and how multimodal imaging helped us reaching the correct diagnosis. Case description: A 63-year-old man with parotid gland malignancy was brought to our attention because preoperative staging CT showed a hyperintense choroidal lesion of the right eye. Fundus examination showed a yellow elevated lesion near the superior temporal branch retinal artery. Enhanced depth imaging optical coherence tomography (EDI-OCT), A- and B-scan ultrasonography, and Indocyanine Green Angiography (ICGA) allowed us to exclude a malignant lesion and to diagnose a sclerochoroidal calcification. Conclusion: Multimodal imaging can guide the clinician to choose the appropriate therapeutic approach even in case of uncommon conditions like sclerochoroidal calcification.

Background Enhanced Recovery After Surgery (ERAS) protocols reduce length of stay, complications and costs for a large number of elective surgical procedures. A similar, structured approach appears to improve outcomes, including mortality, for patients undergoing high-risk emergency general surgery, and specifically emergency laparotomy. These are the first consensus guidelines for optimal care of these patients using an ERAS approach. Methods Experts in aspects of management of the high-risk and emergency general surgical patient were invited to contribute by the International ERAS® Society. Pubmed, Cochrane, Embase, and MEDLINE database searches on English language publications were performed for ERAS elements and relevant specific topics. Studies on each item were selected with particular attention to randomized controlled trials, systematic reviews, meta-analyses and large cohort studies, and reviewed and graded using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Recommendations were made on the best level of evidence, or extrapolation from studies on non-emergency patients when appropriate. The Delphi method was used to validate final recommendations. The guideline has been divided into two parts: Part 1—Preoperative Care and Part 2—Intraoperative and Postoperative management. This paper provides guidelines for Part 1. Results Twelve components of preoperative care were considered. Consensus was reached after three rounds. Conclusions These guidelines are based on the best available evidence for an ERAS approach to patients undergoing emergency laparotomy. Initial management is particularly important for patients with sepsis and physiological derangement. These guidelines should be used to improve outcomes for these high-risk patients.

Background The Coronavirus disease 2019 (COVID‐19) pandemic is having a major global impact, and the resultant response in the development of new diagnostics is unprecedented. The detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has a role in managing the pandemic. We evaluated the feasibility of using SARS‐CoV‐2 peptide Kode Technology‐modified red cells (C19‐kodecytes) to develop an assay compatible with existing routine serologic platforms. Study Design and Methods A panel of eight unique red cells modified using Kode Technology function‐spacer‐lipid constructs and bearing short SARS‐CoV‐2 peptides was developed (C19‐kodecyte assay). Kodecytes were tested against undiluted expected antibody‐negative and ‐positive plasma samples in manual tube and three column agglutination technology (CAT) platforms. Parallel analysis with the same peptides in solid phase by enzyme immunoassays was performed. Evaluation samples included >120 expected negative blood donor samples and >140 COVID‐19 convalescent plasma samples, with independent serologic analysis from two centers. Results Specificity (negative reaction rate against expected negative samples) in three different CAT platforms against novel C19‐kodecytes was >91%, which correlated with published literature. Sensitivity (positive reaction rate against expected positive convalescent, PCR‐confirmed samples) ranged from 82% to 97% compared to 77% with the Abbott Architect SARS‐CoV‐2 IgG assay. Manual tube serology was less sensitive than CAT. Enzyme immunoassay results with some Kode Technology constructs also had high sensitivity. Conclusions C19‐kodecytes are viable for use as serologic reagent red cells for the detection of SARS‐CoV‐2 antibody with routine blood antibody screening equipment.

Many viruses, beside binding to their main cell target, interact with other molecules that promote virus adhesion to the cell; often, these additional targets are glycans. The main receptor for SARS-CoV-2 is a peptide motif in the ACE2 protein. We studied interaction of the recombinant SARS-CoV-2 spike (S) protein with an array of glycoconjugates, including various sialylated, sulfated, and other glycans, and found that the S protein binds some (but not all) glycans of the lactosamine family. We suggest that parallel influenza infection will promote SARS-CoV-2 adhesion to the respiratory epithelial cells due to the unmasking of lactosamine chains by the influenza virus neuraminidase. Electronic supplementary material Supplementary material is available in the online version of this article at 10.1134/S0006297921030019 and on the journal website (http://protein.bio.msu.ru/biokhimiya).

Trotz bahnbrechender Erfolge in der Organtransplantation stellen die Transplantatabstosung und immunsuppressivainduzierte Komplikationen nach wie vor eine grose Herausforderung dar. Neuere Studien legen nahe, dass das Darmmikrobiom das Transplantations-Outcome und die Patientengesundheit nachhaltig beeinflussen kann. Nach wegweisenden Erkenntnissen auf dem Gebiet der hamatopoetischen Stammzelltransplantation (HSZT) wird die hier beschriebene Bedeutung des Mikrobioms auch in der Organtransplantation immer deutlicher. Der derzeitige Wissenstand uber den Einfluss des Mikrobioms auf transplantationsassoziierte Komplikationen wie z. B. Transplantatabstosung und sein potenzieller Einfluss auf die immunsuppressive Behandlung bildet den Schwerpunkt dieses Ubersichtsartikels. Insbesondere beschreiben wir das Potenzial des Mikrobioms als diagnostischen Biomarker und fur therapeutische Interventionsansatze. Das Darmmikrobiom birgt unzahlige klinische Anwendungsmoglichkeiten und verspricht, die Transplantationsmedizin nachhaltig zu beeinflussen.

As the population ages, loss of autonomy is becoming a priority public health issue. "Atout Age Mobility" prevention interventions for seniors aim to limit frailty, which is a predictive and reversible factor in the loss of autonomy and disability.The objective of this study is to describe the impact of these interventions on the physical performance and quality of life of a pilot sample of participants.We conducted a prospective study named 5P PILOT with 3 months of follow up.Subjects were recruited by convenience sampling from participants in the "Atout Age Mobility" workshops at Saint Joseph from 04/09/2017 to 29/01/2019.Retired people over 55 years old with no contraindications to physical activity recruited from participants in the "Atout Age Mobility" workshops in Saint Joseph. Intervention(s) (for clinical trials) or Exposure(s) (for observational studies): All participants completed 12 weeks of physical exercise called the "Atout Age Mobility" workshop, which lasted 60 minutes each week and was supervised by physical activity coaches. Main Outcome(s) and Measure(s): Physical performance was assessed by Short physical performance battery (SPPB), 10-m gait speed and grip strength measurement. Quality of life through the SF-36 test.Ninety-six patients were included and 55 (57.3%) completed the study. There was a significant improvement in gait speed (1.35±0.26m/s vs. 1.27±0.24m/s; p=0.008). There was no significant change in SF-36, grip strength dominant arm and SPPB at the 0.01 significance level.The "Atout Ages Mobility" workshops seem to significantly improve gait speed but not other aspects of physical performance or quality of life.

Purpose: To evaluate local control and longitudinal endocrine data in monorchid patients treated with testicular-sparing surgery and adjuvant radiotherapy (RT) for seminomatous germ-cell tumors. Methods: We searched our database established in 2009 for patients with seminoma who received testis irradiation following partial orchiectomy up to 2018. Eleven patients were identified. All had associated germ cell neoplasia in situ (GCNIS) in surrounding parenchyma. Analysis focused on local control and testosterone levels preservation after RT. We considered age, baseline (pre-RT) testosterone and luteinizing hormone (LH) levels, residual testicular volume, tumor size, and testosterone and LH levels trend over time in order to identify any association with endocrine impairment leading to hormonal replacement need. Results: After a median follow-up of 21 months, no local or distant relapses were observed and hormonal function was maintained in 54.5% of patients (6/11). No significant interactions were observed for the investigated covariates. Notably, we observed an association between higher baseline testosterone levels and a decreased risk of exogenous androgen replacement (hazard ratio [HR] 0.409, 95% confidence interval [CI] 0.161–1.039, p = 0.060), whereas tumor size was associated with an increased risk of exogenous androgen replacement (HR 1.847, 95% CI 0.940–3.627, p = 0.075). Conclusions: Radiotherapy after testicular sparing surgery is effective in preventing local disease relapse in presence of GCNIS in the medium term. This strategy allows a preservation of adequate endocrine function in about half of patients. More patients and longer follow-up are needed to confirm these findings.

Background Nomograms applying the 8th edition of the TNM staging system aimed at predicting overall (OS), disease-specific (DSS), locoregional recurrence-free (LRRFS) and distant recurrence-free survivals (DRFS) for oral tongue squamous cell carcinoma (OTSCC) are still lacking. Methods A training cohort of 438 patients with OTSCC was retrospectively enrolled from a single institution. An external validation set of 287 patients was retrieved from two independent institutions. Results Internal validation of the multivariable models for OS, DSS, DRFS and LRRFS showed a good calibration and discrimination results with optimism-corrected c-indices of 0.74, 0.75, 0.77 and 0.70, respectively. The external validation confirmed the good performance of OS, DSS and DRFS models (c-index 0.73 and 0.77, and 0.73, respectively) and a fair performance of the LRRFS model (c-index 0.58). Conclusions The nomograms herein presented can be implemented as useful tools for prediction of OS, DSS, DRFS and LRRFS in OTSCC.

Objective Glucagon and glucagon-like peptide-1 (GLP-1) originate from the common precursor, proglucagon, and their plasma concentrations have been reported to be increased during inflammatory conditions. Increased blood glucose levels are frequently observed in septic patients, and therefore we hypothesized that glucagon, but not GLP-1, is increased in individuals with inflammation. Design Prospective longitudinal cohort study. Materials and methods We measured glucagon and GLP-1 in plasma sampled consecutively in three cohorts consisting of patients with infective endocarditis (n = 16), urosepsis (n = 28) and post-operative inflammation following percutaneous aortic valve implantation or thoracic endovascular aortic repair (n = 5). Correlations between C-reactive protein (CRP), a marker of systemic inflammation, and glucagon and GLP-1 concentrations were investigated. Additionally, glucagon and GLP-1 concentrations were measured after a bolus infusion of lipopolysaccharide (LPS, 1 ng/kg) in nine healthy young males. Results Glucagon and CRP were positively and significantly correlated (r = 0.27; P = 0.0003), whereas no significant association between GLP-1 and CRP was found (r = 0.08, P = 0.30). LPS infusion resulted in acute systemic inflammation reflected by increased temperature, pulse, tumor necrosis factor-α (TNFα), interleukin-6 (IL-6) and concomitantly increased concentrations of glucagon (P < 0.05) but not GLP-1. Conclusions Systemic inflammation caused by bacterial infections or developed as a non-infected condition is associated with increased plasma concentration of glucagon, but not GLP-1. Hyperglucagonemia may contribute to the impaired glucose control in patients with systemic inflammatory diseases.

To compare the accuracy of contrast-enhanced MRI using established dimensional and morphological criteria versus integrated [18F]FDG PET/MRI in identifying regional lymph node metastases in patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC). For this purpose, we compare MRI and PET/MRI using the histopathological findings in dissected lymph nodes as the gold standard. We retrospectively reviewed 26 patients with histologically proven HNSCC who underwent gadolinium-enhanced [18F]FDG PET/MRI as part of their staging. All neck lymph nodes were classified on MRI using dimensional and/or morphological criteria. Then, they were jointly assessed by a nuclear medicine physician and a radiologist using integrated [18F]PET/MR images. ROC curves were obtained to compare the techniques. Lymph node histopathology was considered as the reference standard. Out of 865 lymph nodes, 35 were malignant at histopathology (3 with micro-metastases). Sensitivity and specificity were 48.6% and 99.5% for MRI using dimensional criteria; 60.0% and 99.6% for MRI using morphological criteria; 60.0% and 99.4% for MRI using both; and 74.3% and 97.6% for PET using MR as anatomic localization. The area under the ROC curve was higher for PET and MRI localization (0.859) than for MRI using dimensional (0.740; p

During the preclinical period of medical school, the clinical relevance of theoretical knowledge is given little attention. Medical students of the second year were invited to participate in an interdisciplinary congress for robot-assisted and digital surgery. The students had to evaluate the impact of the congress on their learning motivation, decision-making for a career in surgery, and relevance for their educational curriculum. Participation in the congress increased their learning motivation for preclinical subjects, and significantly increased their interest in a surgical career. Most students considered active involvement in medical congresses a valuable supplement to the medical curriculum. Congress participation during the preclinical period was ranked positively by medical students. Greater learning motivation and enthusiasm for the pilot teaching project as well as for surgical disciplines were registered. Thus, early involvement of medical students in scientific congresses should be an integral part of their educational curriculum.In den vorklinischen Semestern des Medizinstudiums wird der klinischen Relevanz oft wenig Aufmerksamkeit geschenkt. Medizinstudierende des zweiten Studienjahres wurden eingeladen, an einem interdisziplinären Kongress für robotergestützte und digitale Chirurgie teilzunehmen. Im Anschluss sollten die Studierenden den Einfluss des Kongresses auf ihre Lernmotivation, die Entscheidungsfindung für eine Karriere in einem chirurgischen Fach und die Relevanz für das Curriculum bewerten. Durch die Kongressteilnahme steigerte sich die Lernmotivation für vorklinische Fächer, und das Interesse an einer chirurgischen Laufbahn nahm erheblich zu. Die meisten Studierenden betrachteten die aktive Teilnahme an medizinischen Kongressen als wertvolle Ergänzung des Lehrplans für das Studium. Die Kongressteilnahme während der Vorklinik wurde sehr positiv bewertet. Es wurde eine größere Lernmotivation für das Medizinstudium sowie eine Begeisterung für das Pilot-Lehrprojekt und für die chirurgischen Disziplinen registriert. Daher sollte die frühzeitige Einbindung der Medizinstudenten in wissenschaftliche Kongresse ein integraler Bestandteil ihres Curriculums werden.

Polyacrylamide conjugates of glycans have long been widely used in many research areas of glycobiology, mainly for immobilizing glycans in solid-phase assays and as multivalent inhibitors. Pending biotin tag allows immobilizing Glyc-PAA quantitatively on any surface, and acts as a tracer for detection of carbohydrate-binding proteins. However, the scope of already realized capabilities of these probes is immeasurably richer than those listed above. This review is not so much about routine as about less common, but not less significant applications. Also, the data on the glycopolymers themselves, their molecular weight, size and polymer chain flexibility are presented, as well as the methods of synthesis, clusterisation and entropy factor in their interaction with proteins.

Waterbodies such as lakes and ponds are fragile environments affected by human influences. Suitable conditions can result in massive growth of phototrophs, commonly referred to as phytoplankton blooms. Such events benefit heterotrophic bacteria able to use compounds secreted by phototrophs or their biomass as major nutrient source. One example of such bacteria are Planctomycetes, which are abundant on the surfaces of marine macroscopic phototrophs; however, less data are available on their ecological roles in limnic environments. In this study, we followed a cultivation-independent deep sequencing approach to study the bacterial community composition during a cyanobacterial bloom event in a municipal duck pond. In addition to cyanobacteria, which caused the bloom event, members of the phylum Planctomycetes were significantly enriched in the cyanobacteria-attached fraction compared to the free-living fraction. Separate datasets based on isolated DNA and RNA point towards considerable differences in the abundance and activity of planctomycetal families, indicating different activity peaks of these families during the cyanobacterial bloom. Motivated by the finding that the sampling location harbours untapped bacterial diversity, we included a complementary cultivation-dependent approach and isolated and characterized three novel limnic strains belonging to the phylum Planctomycetes.