bluuebunny/crossref_metadata_2025 huggingface dataset:
An In-Vitro Cell Model of Intracellular Protein Aggregation Provides Insights into RPE Stress Associated with Retinopathy
Authors: Keeling Eloise , Culling Annabelle J. , Johnston David A. , Chatelet David S. , Page Anton , Tumbarello David A. , Lotery Andrew J. , Ratnayaka J. Arjuna
Published: September 2020

Impaired cargo trafficking and the aggregation of intracellular macromolecules are key features of neurodegeneration, and a hallmark of aged as well as diseased retinal pigment epithelial (RPE) cells in the eye. Here, photoreceptor outer segments (POS), which are internalized daily by RPE cells, were modified by UV-irradiation to create oxidatively modified POS (OxPOS). Oxidative modification was quantified by a protein carbonyl content assay. Human ARPE-19 cells were synchronously pulsed with POS or OxPOS to study whether oxidatively modified cargos can recapitulate features of RPE pathology associated with blinding diseases. Confocal immunofluorescence microscopy analysis showed that OxPOS was trafficked to LAMP1, LAMP2 lysosomes and to LC3b autophagy vacuoles. Whilst POS were eventually degraded, OxPOS cargos were sequestered in late compartments. Co-localization of OxPOS was also associated with swollen autolysosomes. Ultrastructural analysis revealed the presence of electron-dense OxPOS aggregates in RPE cells, which appeared to be largely resistant to degradation. Measurement of cellular autofluorescence, using parameters used to assess fundus autofluorescence (FAF) in age-related macular disease (AMD) patients, revealed that OxPOS contributed significantly to a key feature of aged and diseased RPE. This in vitro cell model therefore represents a versatile tool to study disease pathways linked with RPE damage and sight-loss.
Identification of Gastritis Subtypes by Convolutional Neuronal Networks on Histological Images of Antrum and Corpus Biopsies
Authors: Steinbuss Georg , Kriegsmann Katharina , Kriegsmann Mark
Published: September 2020

Background: Gastritis is a prevalent disease and commonly classified into autoimmune (A), bacterial (B), and chemical (C) type gastritis. While the former two subtypes are associated with an increased risk of developing gastric intestinal adenocarcinoma, the latter subtype is not. In this study, we evaluated the capability to classify common gastritis subtypes using convolutional neuronal networks on a small dataset of antrum and corpus biopsies. Methods: 1230 representative 500 × 500 µm images of 135 patients with type A, type B, and type C gastritis were extracted from scanned histological slides. Patients were allocated randomly into a training set (60%), a validation set (20%), and a test set (20%). One classifier for antrum and one classifier for corpus were trained and optimized. After optimization, the test set was analyzed using a joint result from both classifiers. Results: Overall accuracy in the test set was 84% and was particularly high for type B gastritis with a sensitivity of 100% and a specificity of 93%. Conclusions: Classification of gastritis subtypes is possible using convolutional neural networks on a small dataset of histopathological images of antrum and corpus biopsies. Deep learning strategies to support routine diagnostic pathology merit further evaluation.
The brlA Gene Deletion Reveals That Patulin Biosynthesis Is Not Related to Conidiation in Penicillium expansum
Authors: Zetina-Serrano Chrystian , Rocher Ophélie , Naylies Claire , Lippi Yannick , Oswald Isabelle P. , Lorber Sophie , Puel Olivier
Published: September 2020

Dissemination and survival of ascomycetes is through asexual spores. The brlA gene encodes a C2H2-type zinc-finger transcription factor, which is essential for asexual development. Penicillium expansum causes blue mold disease and is the main source of patulin, a mycotoxin that contaminates apple-based food. A P. expansum PeΔbrlA deficient strain was generated by homologous recombination. In vivo, suppression of brlA completely blocked the development of conidiophores that takes place after the formation of coremia/synnemata, a required step for the perforation of the apple epicarp. Metabolome analysis displayed that patulin production was enhanced by brlA suppression, explaining a higher in vivo aggressiveness compared to the wild type (WT) strain. No patulin was detected in the synnemata, suggesting that patulin biosynthesis stopped when the fungus exited the apple. In vitro transcriptome analysis of PeΔbrlA unveiled an up-regulated biosynthetic gene cluster (PEXP_073960-PEXP_074060) that shares high similarity with the chaetoglobosin gene cluster of Chaetomium globosum. Metabolome analysis of PeΔbrlA confirmed these observations by unveiling a greater diversity of chaetoglobosin derivatives. We observed that chaetoglobosins A and C were found only in the synnemata, located outside of the apple, whereas other chaetoglobosins were detected in apple flesh, suggesting a spatial-temporal organization of the chaetoglobosin biosynthesis pathway.
Hedgehog Signaling in Skeletal Development: Roles of Indian Hedgehog and the Mode of Its Action
Authors: Ohba Shinsuke
Published: September 2020

Hedgehog (Hh) signaling is highly conserved among species and plays indispensable roles in various developmental processes. There are three Hh members in mammals; one of them, Indian hedgehog (Ihh), is expressed in prehypertrophic and hypertrophic chondrocytes during endochondral ossification. Based on mouse genetic studies, three major functions of Ihh have been proposed: (1) Regulation of chondrocyte differentiation via a negative feedback loop formed together with parathyroid hormone-related protein (PTHrP), (2) promotion of chondrocyte proliferation, and (3) specification of bone-forming osteoblasts. Gli transcription factors mediate the major aspect of Hh signaling in this context. Gli3 has dominant roles in the growth plate chondrocytes, whereas Gli1, Gli2, and Gli3 collectively mediate biological functions of Hh signaling in osteoblast specification. Recent studies have also highlighted postnatal roles of the signaling in maintenance and repair of skeletal tissues.
TGSim Plus™—Real-Time Dynamic Simulation Suite of Gas Turbine Systems for the MATLAB®/Simulink® Environment
Authors: Brighenti Attilio , Duranti Davide , Quintabà Debora
Published: September 2020

Dynamic simulation of turbomachinery by Hardware in the Loop (HIL) real-time systems has become an essential practice, due to the high cost of real equipment testing and the need to verify the control and diagnostic systems’ reaction to emergency situations. The authors developed a full model of a power generation Gas Turbine Plant, including liquid and gaseous auxiliaries, and the electrical generator and starter motor, integrated in a MATLAB®/Simulink® simulation suite: TGSim Plus™. This allows assembling models of various gas turbine (GT) architectures by customised Simulink® library blocks and simulating steady state and transient conditions, such as complete start-up and shutdown operations as well as emergency, contingent operations and artificially injected fault scenarios. The model solver runs real-time steps at milliseconds scale. The paper describes the main modelling characteristics and typical results of steady state and transient simulations of a heavy-duty gas turbine under development by Doosan Heavy Industries and Construction (Changwon, South Korea). Comparison with benchmark design simulations obtained by a reference non real-time software shows a good match between the two environments, duly taking into account some differences in the GT models setting affecting parts of the sequence. The paper discusses also the bleed streams warm-up influence on GT performance and the start-up states trajectories dependency on control logic and on the starter helper motor torque envelope.
Population Dynamics of Drosophila suzukii in Coastal and Mainland Sweet Cherry Orchards of Greece
Authors: Papanastasiou Stella A. , Rodovitis Vasilis G. , Bataka Evmorfia P. , Verykouki Eleni , Papadopoulos Nikos T.
Published: September 2020

Despite the recent invasion and wide spread of Drosophila suzukii Matsumura (Diptera: Drosophilidae) in Europe, little is known regarding its population trends in coastal areas of the southern Mediterranean countries. Using adult trapping and fruit sampling, we studied the population dynamics of D. suzukii in coastal and mainland (semi-highland) cherry orchards of Greece, from 2018 to 2020. Adults were captured in traps baited with apple cider vinegar, placed in conventional and unmanaged sweet-cherry orchards, and in neighbouring wild growing hosts. Sampling of sweet-cherry fruit to assess infestation levels was conducted from early and late-ripening cherry cultivars in both areas. Adults were captured throughout the year in the coastal area with two peaks registered in spring and late-autumn. Captures were nearly zero during the hot summer months. Flight activity exhibited only one peak in autumn at the mainland area, and ceased during winter and spring. Captures in wild hosts were lower during the sweet-cherry ripening period than later in the season. Higher sweet-cherry infestation levels were recorded in the coastal than in the mainland area and in unmanaged than in commercial orchards. Both early and late-ripening cultivars were highly susceptible to D. suzukii infestation in the coastal area. Infestation rates were higher in late-ripening cultivars than in early-ripening ones in the mainland area. We conclude that D. suzukii has well adapted to the Mediterranean climate of Greece, and is able to progressively exploit several crops and wild hosts of mainland and coastal areas.
Necrobia rufipes (De Geer) Infestation in Pet Food Packaging and Setup of a Monitoring Trap
Authors: Savoldelli Sara , Jucker Costanza , Peri Ezio , Arif Mokhtar Abdulsattar , Guarino Salvatore
Published: September 2020

Necrobia rufipes (De Geer) (Coleoptera: Cleridae), also known as the red-legged ham beetle, is a newly emerging pest of pet food stores, causing apprehension among producers worldwide. Concerns about this pest are exacerbated by the lack of information about infestation modalities in pet food, while specific monitoring tools are missing. Considering that adequate pet food packaging could limit N. rufipes infestations, information about the penetration modalities in commonly used pet food packaging is needed. Moreover, the development of appropriate monitoring instruments is urgent to detect pest presence early and to reduce chemical treatments for its control. In this paper, the adults’ and larvae’s ability to enter into pet food packaging was evaluated. Furthermore, to develop monitoring traps, behavioral bioassays were done: (1) testing two different commercial adhesive surfaces, one generally used in mouse glue traps (MG), and the other used in cockroach glue traps (CG), to evaluate their different abilities in avoiding insects’ escape; (2) screening different molecules, typical of the substrates attacked by N. rufipes, as candidate food attractants for this pest: methyl cyclopentenolone (MCP), squalene (SQ), and stearic acid (SA). The results show that N. rufipes adults and larvae enter into packaging through the air vent valves on the bottom, suggesting that a way to improve the packaging to prevent insect infestation would be to modify these points of weakness. Laboratory tests show that the different bioassayed glues have strong differences in the ability to retain the caught insects, with MG being more effective than CG. The behavioral bioassay indicated that MCP and SQ attract N. rufipes adults in olfactometer. Finally, the results of dual-choice arena bioassays show that among the candidate attractant tested, a mixture of pet food (PF) and MCP elicited the strongest attraction in N. rufipes adults. These results encourage further experiments with the use of an MG adhesive trap loaded with a mixture of PF+MCP to test the effectiveness of such a tool for monitoring N.rufipes in pet food industries and warehouses.
A Meta-Analysis Shows That Screen Bottom Boards Can Significantly Reduce Varroa destructor Population
Authors: Liu Fang , Xu Xinjian , Zhang Yuan , Zhao Hongxia , Huang Zachary Y.
Published: September 2020

Varroa destructor is by far the most serious threat to the western honey bee, Apis mellifera. A screen bottom board, a cultural method for mite control, is a modified bottom board with a screen that allows mites to fall onto a sticky board, or the grass or soil below the screen. Whether or not a screen bottom board can reduce varroa significantly has been controversial. Most studies show a trend of lower varroa populations in colonies with these boards, but the results are usually not statistically significant. To understand whether the negative results have been due to small sample sizes, or because the board is actually ineffective, we conducted a meta-analysis with seven published studies with a total of 145 colonies. Meta-analysis showed that the confidence intervals of the combined effect sizes were negative with a Hedges’ g of −1.09 (SE 0.39, 95% CI −2.0 to −0.19, p < 0.01), which suggests that the varroa population in colonies with screen bottom boards is significantly lower compared to those with traditional wooden floors. We thus conclude that the screen bottom board does have a significantly negative impact on the varroa population and can be part of tool kits for mite control.
Phylogeny and Density Dynamics of Wolbachia Infection of the Health Pest Paederus fuscipes Curtis (Coleoptera: Staphylinidae)
Authors: Ge Chen , Hu Jiayao , Zhao Zimiao , Hoffmann Ary A. , Ma Shuojia , Shen Li , Fang Jie , Zhu Jianqing , Yu Weidong , Jiang Weibin
Published: September 2020

The maternally inherited obligate intracellular bacteria Wolbachia infects the reproductive tissues of a wide range of arthropods and affects host reproduction. Wolbachia is a credible biocontrol agent for reducing the impact of diseases associated with arthropod vectors. Paederus fuscipes is a small staphylinid beetle that causes dermatitis linearis and conjunctivitis in humans when they come into contact with skin. Wolbachia occur in this beetle, but their relatedness to other Wolbachia, their infection dynamics, and their potential host effects remain unknown. In this study, we report the phylogenetic position and density dynamics of Wolbachia in P. fuscipes. The phylogeny of Wolbachia based on an analysis of MLST genotyping showed that the bacteria from P. fuscipes belong to supergroup B. Quantitative PCR indicated that the infection density in adults was higher than in any other life stage (egg, larva or pupa), and that reproductive tissue in adults had the highest infection densities, with similar densities in the sexes. These findings provide a starting point for understanding the Wolbachia infection dynamics in P. fuscipes, and interactions with other components of the microbiota.
Clinical Benefit of Tamsulosin and the Hexanic Extract of Serenoa Repens, in Combination or as Monotherapy, in Patients with Moderate/Severe LUTS-BPH: A Subset Analysis of the QUALIPROST Study
Authors: Alcaraz Antonio , Rodríguez-Antolín Alfredo , Carballido-Rodríguez Joaquín , Castro-Díaz David , Esteban-Fuertes Manuel , Cózar-Olmo José , Ficarra Vincenzo , Medina-López Rafael , Fernández-Gómez Jesús , Angulo Javier , Medina-Polo José , Brenes-Bermúdez Francisco , Molero-García José , Fernández-Pro-Ledesma Antonio , Manasanch José , on behalf of The QUALIPROST Study Group
Published: September 2020

To investigate whether tamsulosin (TAM) and the hexanic extract of Serenoa repens (HESr) are more effective in combination than as monotherapy in men with moderate-to-severe lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). Subset analysis of data from a 6-month, multicenter observational study. Patients received either tamsulosin (0.4 mg/day) or HESr (320 mg/day) alone or in combination. Primary endpoints were change in symptoms and quality of life. Tolerability was also assessed. Seven hundred and nine patients were available for intention to treat (ITT) analysis, 263 treated with tamsulosin, 262 with HESr, and 184 with TAM + HESr. After 6 months, International Prostate Symptom Score (IPSS) scores improved by a mean (standard deviation) of 7.2 (5.0) points in the TAM + HESr group compared to 5.7 (4.3) points with TAM alone and 5.4 (4.6) points with HESr (p < 0.001). Quality of life showed greatest improvement with combination therapy (p < 0.02). Adverse effects were reported by 1.9% of patients receiving HESr, 13.3% receiving TAM, and 12.0% receiving TAM + HESr (p < 0.001). In men with moderate/severe LUTS/BPH, combination treatment with TAM + HESr produced more effective symptom relief and greater improvement in quality of life than with either treatment alone, with acceptable tolerability.
Organ-Sparing Surgery in Testicular Tumor: Is This the Right Approach for Lesions ≤ 20 mm?
Authors: Staudacher Nina , Tulchiner Gennadi , Bates Katie , Ladurner Michael , Kafka Mona , Aigner Friedrich , Pichler Renate , Horninger Wolfgang
Published: September 2020

Background: This study was conducted in order to analyze factors predicting malignancy in patients undergoing organ-sparing surgery (OSS) for small testicular lesions. Methods: Patients with small (≤20 mm) marker-negative clinical stage I testicular tumors were managed by OSS with tumor enucleation and frozen section examination (FSE) for the past 15 years at our institution. Benign and malignant cases were compared, focusing on preoperative and postoperative lesion sizes. Results: Eighty-nine patients were enrolled in this retrospective study. Ten (11.2%) of them were treated for synchronous bilateral tumors. Sixty-seven (67.7%) of ninety-nine lesions were benign, confirming a high concordance rate (98%) between FSE and final histology. Patients with benign tumors were significantly older than patients with malignant tumors (p = 0.026), and benign tumors were detected more frequently during urologic work-up of hormone disorders (p = 0.001). Preoperative tumor size was a strong predictor of malignancy (area under the curve (AUC) = 0.726; p < 0.001). According to the Youden index, the best cutoff to predict tumor dignity was 13.5 mm, resulting in a sensitivity and specificity of 53% and 85%, respectively. No cases of local recurrence or distant metastasis were confirmed after a median follow-up of 42 months. Conclusion: Our findings are consistent with previous reports, supporting an OSS approach in small testicular tumors whenever possible. Most tumors ≤ 20 mm were benign, and in the case of malignancy, OSS with FSE and consecutive orchiectomy is oncologically safe due to the high concordance rate of FSE and final histology, thus preventing a two-stage procedure.
Didactic Benefits of Surgery on Body Donors during Live Surgery Events in Minimally Invasive Surgery
Authors: Ackermann Johannes , Wedel Thilo , Holthaus Bernd , Bojahr Bernd , Hackethal Andreas , Brucker Sara , Biebl Matthias , Westermann Martina , Günther Veronika , Krüger Magret , Maass Nicolai , Mettler Liselotte , Peters Göntje , Alkatout Ibrahim
Published: September 2020

Background: Live surgery events serve as a valuable tool for surgical education, but also raise ethical concerns about patient safety and professional performance. In the present study, we evaluate the technical feasibility and didactic benefits of live surgery on body donors compared to real patients. Methods: A live surgery session performed on a body donor’s cadaver embalmed in ethanol–glycerol–lysoformin was integrated into the live surgery program presented at a major gynecological convention of minimally invasive surgery. Surgical procedures carried out in real patients were paralleled in the body donor, including the dissection and illustration of surgically relevant anatomical landmarks. A standardized questionnaire was filled by the participants (n = 208) to evaluate the appropriateness, effectiveness, and benefits of this novel concept. Results: The live surgery event was appreciated as a useful educational tool. With regard to the use of body donors, authenticity was rated high (85.5%), and the overall value of body donors for surgical education and training was rated very high (95.0%). The didactic benefit of simultaneous operations performed on body donors and real patients was considered particularly useful (95.5%), whereas complete replacement of real patients by body donors was not favored (14.5%). Conclusions: The study demonstrated both the technical feasibility and didactic benefits of performing minimally invasive surgery in body donors as part of live surgery events. This novel concept has the potential to enhance anatomical knowledge, providing insights into complex surgical procedures, and may serve to overcome yet unresolved ethical concerns related to live surgery events.
Melatonin Improves Mitochondrial Dynamics and Function in the Kidney of Zücker Diabetic Fatty Rats
Authors: Agil Ahmad , Chayah Meriem , Visiedo Lucia , Navarro-Alarcon Miguel , Rodríguez Ferrer José Manuel , Tassi Mohamed , Reiter Russel J. , Fernández-Vázquez Gumersindo
Published: September 2020

Obesity and associated diabetes (diabesity) impair kidney mitochondrial dynamics by augmenting fission and diminishing fusion, which results in mitochondrial and renal dysfunction. Based on available evidence, the antioxidant activities of melatonin may improve impaired renal mitochondrial function in obese diabetic animals by restoring the imbalanced dynamics through inhibiting fission and promoting fusion. Male Zücker diabetic fatty (ZDF) rats and lean littermates (ZL) were orally treated either with melatonin (10 mg/kg BW/day) (M-ZDF and M-ZL) or vehicle (C-ZDF and C-ZL) for 17 weeks. Kidney function was evaluated by measurement of total urine volume, proteinuria, creatinine clearance, and assessment of kidney mitochondrial dynamics and function. C-ZDF exhibited impaired dynamics and function of kidney mitochondria in comparison to C-ZL. Melatonin improved nephropathy of ZDF rats and modulated their mitochondrial dynamics by reducing expression of Drp1 fission marker and increasing that of fusion markers, Mfn2 and Opa1. Furthermore, melatonin ameliorated mitochondrial dysfunction by increasing respiratory control index and electron transfer chain complex IV activity. In addition, it lowered mitochondrial oxidative status. Our findings show that melatonin supplementation improves nephropathy likely via modulation of the mitochondrial fission/fusion balance and function in ZDF rats.
New Developments in Emotion-Focused Therapy for Social Anxiety Disorder
Authors: Shahar Ben
Published: September 2020

Social anxiety disorder (SAD) is a highly complex, chronic, disabling and costly anxiety disorder. Although cognitive-behavioral therapy (CBT) is effective for many patients, many others do not respond to CBT or remain considerably symptomatic at the end of treatment. Pharmacological effects are also modest. More empirically-supported treatment options are needed in order to increase patient access to effective treatment. Emotion-focused therapy (EFT) shows great promise in treating SAD effectively and is particularly suitable for treating SAD because pervasive emotional avoidance, difficulties with emotional differentiation, and high levels of self-criticism, which are central psychopathological processes in SAD, are also primary therapeutic targets in EFT. EFT is based on the assumption that the most efficient way to change a maladaptive emotion is not through reason or skill learning, but through the activation of other, more adaptive emotions. EFT aims to access shame-based emotional memories that underlie SAD, and transform them by exposing them to new adaptive emotional experiences, such as empowering assertive anger, grief, and self-compassion. In this paper, the core features of EFT for SAD are presented, as well as the EFT view of dysfunction in SAD and EFT change processes. Research findings regarding the effectiveness of EFT for SAD are presented together with initial findings regarding mechanisms of change occurring during treatment.
Physical Activity Practice and Optimal Development of Postural Control in School Children: Are They Related?
Authors: García-Soidán Jose L. , García-Liñeira Jesús , Leirós-Rodríguez Raquel , Soto-Rodríguez Anxela
Published: September 2020

Background: This study aims to analyze the effect of physical activity practice on the postural control state of school children. If such an effect was detected, the second aim of the study was to identify which specific capacities of postural control benefited the most from physical activity. Methods: A cross-sectional study was performed using a convenience sample of 118 healthy children (54 girls) with a mean age of 10.3 ± 1.2 years. Their weight and height were measured. The accelerometric assessment of balance included four different tests in static balance and walking. Results: Physical activity habit prevalence was 38.9% in girls and 60.9% in boys, and its frequency was 2.3 days per week in girls and 2.8 days in boys. The active children obtained lower accelerations, but the active and sedentary girls showed lower accelerometric values than the active boys. The logistic regression analysis demonstrated the influence of sex on the accelerations of the body (p < 0.001), regardless of the habit of physical activity. Conclusions: Active children have better postural control than sedentary children, although sedentary girls have better balance than active boys. Therefore, physical activity practice seems to favor a more efficient development of postural control, but it cannot level or reverse the effect of the neurophysiological factors that are conditioned by sex.
Determinants of Sleep Quality in Inflammatory Bowel Diseases
Authors: Sochal Marcin , Małecka-Panas Ewa , Gabryelska Agata , Talar-Wojnarowska Renata , Szmyd Bartosz , Krzywdzińska Monika , Białasiewicz Piotr
Published: September 2020

The causes of disordered sleep, frequently reported by patients with inflammatory bowel diseases (IBD), are poorly understood. The study aimed to evaluate sleep quality in IBD patients and to identify factors affecting their sleep. IBD patients (n = 133) and healthy controls (HC; n = 57) were included in the study and completed sleep questionnaires (Pittsburgh Sleep Quality Index (PSQI), Athens insomnia scale (AIS), and Epworth sleepiness scale (ESS)), Beck Depression Inventory (BDI), and pain scales (Visual Analogue Scale and Laitinen Pain Scale). IBD patients attained higher scores in all sleep questionnaires compared to HC: PSQI, AIS, and ESS (all p < 0.001). They also had prolonged sleep latency (p < 0.001) with reduced sleep efficiency (p < 0.001). Patients in exacerbation of IBD had higher scores in PSQI (p = 0.008), ESS (p = 0.009), but not in AIS, compared to those in remission. Participants with comorbid chronic diseases had higher scores in PSQI and AIS, but not in ESS, compared to others. Multiple regression revealed that the sleep questionnaire results were significantly affected by mood level (BDI), but not by the aforementioned pain scales. Sleep impairment in IBD patients is a common problem that deserves attention in everyday clinical practice and mood level seems to be the main factor affecting the quality of sleep in IBD patients.
Treatment of Mandible Fractures Using a Miniplate System: A Retrospective Analysis
Authors: Bohner Lauren , Beiglboeck Fabian , Schwipper Stephanie , Lustosa Rômulo , Pieirna Marino Segura Carla , Kleinheinz Johannes , Jung Susanne
Published: September 2020

Three-dimensional (3D) mini plate systems are used in the treatment of mandibular fractures. The system is advantageous in comparison to conventional plates due to the stabilization of tension and compression areas, improved initial stability, and biomechanical behavior. The aim of this retrospective study was to evaluate the use of a 3D miniplate system for the treatment of patients with mandibular fractures. Patients with mandibular fractures treated with a 3D plate system at the Department of Oral and Maxillofacial Surgery, University Hospital Münster, during a period of 5 years, were included in this study. Mandibular fracture conditions and minor and major post-operative complications were reported. In total, 336 patients and 391 mandibular fractures were assessed. The most common fracture site was anterior mandible, and 155 cases involved a tooth-bearing area. Minor complications were seen in 8.03% of cases, whereas only 1.49% of patients suffered from major complications. The treatment of mandible fractures using 3D miniplates resulted in fracture reduction with a low complication rate.
Assessing Viral Shedding and Infectivity of Asymptomatic or Mildly Symptomatic Patients with COVID-19 in a Later Phase
Authors: Sohn Yujin , Jeong Su Jin , Chung Won Suk , Hyun Jong Hoon , Baek Yae Jee , Cho Yunsuk , Kim Jung Ho , Ahn Jin Young , Choi Jun Yong , Yeom Joon-Sup
Published: September 2020

Background: The coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a major global public health issue. SARS-CoV-2 infection is confirmed by the detection of viral RNA using reverse transcription polymerase chain reaction (RT-PCR). Prolonged viral shedding has been reported in patients with SARS-CoV-2 infection, but the presence of viral RNA does not always correlate with infectivity. Therefore, the present study aimed to confirm the presence of viable virus in asymptomatic or mildly symptomatic patients in the later phase of the disease, more than two weeks after diagnosis. Method: Asymptomatic or mildly symptomatic COVID-19 patients who had been diagnosed with the disease at least two weeks previously and admitted to a community treatment center (CTC) from 15 March to 10 April 2020 were enrolled in this study. Nasopharyngeal and salivary swab specimens were collected from each patient. Using these specimens, RT-PCR assay and viral culture were performed. Result: In total, 48 patients were enrolled in this study. There were no significant differences in baseline characteristics between the asymptomatic and mildly symptomatic patient groups. RT-PCR assay and viral culture of SARS-CoV-2 were performed using nasopharyngeal and salivary swabs. The results of RT-PCR performed using salivary swab specimens, in terms of cycle threshold (Ct) values, were similar to those of RT-PCR using nasopharyngeal swab specimens. In addition, no viable virus could be cultured from swab specimens collected from the late-phase COVID-19 patients with prolonged viral RNA shedding. Conclusions: In conclusion, our study suggests that even if viral shedding is sustained in asymptomatic or mildly symptomatic patients with later phase of COVID-19, it can be expected that the transmission risk of the virus is low. In addition, saliva can be used as a reliable specimen for the diagnosis of SARS-CoV-2 infection.
“eLoriCorps Immersive Body Rating Scale”: Exploring the Assessment of Body Image Disturbances from Allocentric and Egocentric Perspectives
Authors: Monthuy-Blanc Johana , Bouchard Stéphane , Ouellet Marilou , Corno Giulia , Iceta Sylvain , Rousseau Michel
Published: September 2020

The first objective of this study was to test the convergent and discriminant validity between the “eLoriCorps Immersive Body Rating Scale” and the traditional paper-based figure rating scale (FRS). The second objective was to explore the contribution of the egocentric virtual reality (VR) perspective of eLoriCorps to understanding body image disturbances (BIDs). The sample consisted of 53 female and 13 male adults. Body size dissatisfaction, body size distortion, perceived body size, and ideal body size were assessed. Overall, outcomes showed good agreement between allocentric perspectives as measured via VR and the FRS. The egocentric VR perspective produced different results compared to both the allocentric VR perspective and the FRS. This difference revealed discriminant validity and suggested that eLoricorps’ egocentric VR perspective might assess something different from the traditional conception of body dissatisfaction, which an allocentric VR perspective generally assesses. Finally, the egocentric VR perspective in assessing BIDs deserves to be studied more extensively to explore the possibility of finding two types of body image distortion: (a) an egocentric perceptual body distortion, referring to internal body sensation affected by intra-individual changes, and (b) an allocentric perceptual body distortion, referring to external body benchmarks constructed by inter-individual comparison occurring in a given cultural context.
The Effects of Erector Spinae Plane Block in Terms of Postoperative Analgesia in Patients Undergoing Laparoscopic Cholecystectomy: A Meta-Analysis of Randomized Controlled Trials
Authors: Koo Chang-Hoon , Hwang Jin-Young , Shin Hyun-Jung , Ryu Jung-Hee
Published: September 2020

Ultrasound-guided erector spinae plane block (ESPB), a recent regional analgesic technique, has been used to manage acute pain after surgery. The aim of this meta-analysis is to identify the benefits of ESPB in patients undergoing laparoscopic cholecystectomy (LC). The authors searched PubMed, EMBASE, CENTRAL, CINAHL, and Web of Science to identify all randomized controlled trials (RCTs) evaluating the effects of ESPB on postoperative pain after LC. Primary outcome was defined as 24 h cumulative opioid consumption. Secondary outcomes were pain scores and the incidence of postoperative nausea and vomiting (PONV). We estimated mean differences (MD) and odds ratio (OR) using a random-effects model. A total of 8 RCTs, including 442 patients, were included in the final analysis. Postoperative opioid consumption was significantly lower in the ESPB group than in the control group (MD −4.72, 95% CI −6.00 to −3.44, p < 0.001). Compared with the control group, the ESPB group also showed significantly lower pain scores and incidence of PONV. A separate analysis of RCTs comparing ESPB with oblique subcostal transversus abdominis plane (OSTAP) block showed that the analgesic efficacy of ESPB was similar to that of OSTAP block. The results of this meta-analysis demonstrated that ESPB may provide effective postoperative analgesia in patients undergoing LC.
Proteomic Profiles of Exosomes of Septic Patients Presenting to the Emergency Department Compared to Healthy Controls
Authors: Morris Daniel C. , Jaehne Anja K. , Chopp Michael , Zhang Zhanggang , Poisson Laila , Chen Yalei , Datta Indrani , Rivers Emanuel P.
Published: September 2020

Background: Septic Emergency Department (ED) patients provide a unique opportunity to investigate early sepsis. Recent work focuses on exosomes, nanoparticle-sized lipid vesicles (30–130 nm) that are released into the bloodstream to transfer its contents (RNA, miRNA, DNA, protein) to other cells. Little is known about how early changes related to exosomes may contribute to the dysregulated inflammatory septic response that leads to multi-organ dysfunction. We aimed to evaluate proteomic profiles of plasma derived exosomes obtained from septic ED patients and healthy controls. Methods: This is a prospective observational pilot study evaluating a plasma proteomic exosome profile at an urban tertiary care hospital ED using a single venipuncture blood draw, collecting 40 cc Ethylenediaminetetraacetic acid (EDTA) blood. Measurements: We recruited seven patients in the ED within 6 h of their presentation and five healthy controls. Plasma exosomes were isolated using the Invitrogen Total Exosome Isolation Kit. Exosome proteomic profiles were analyzed using fusion mass spectroscopy and Proteome Discoverer. Principal component analysis (PCA) and differential expression analysis (DEA) for sepsis versus control was performed. Results: PCA of 261 proteins demonstrated septic patients and healthy controls were distributed in two groups. DEA revealed that 62 (23.8%) proteins differed between the exosomes of septic patients and healthy controls, p-value < 0.05. Adjustments using the False Discovery Rate (FDR) showed 23 proteins remained significantly different (FDR < 0.05) between sepsis and controls. Septic patients and controls were classified into two distinct groups by hierarchical clustering using the 62 nominally DE proteins. After adjustment multiple comparisons, three acute phase proteins remained significantly different between patients and controls: Serum amyloid A-1, C-reactive protein and Serum Amyloid A-2. Inflammatory response proteins immunoglobulin heavy constant Δ and Fc-fragment of IgG binding protein were increased. Conclusion: Exosome proteomic profiles of septic ED patients differ from their healthy counterparts with regard to acute phase response and inflammation.
Assessing the Relationship between Sense of Agency, the Bodily-Self and Stress: Four Virtual-Reality Experiments in Healthy Individuals
Authors: Stern Yonatan , Koren Danny , Moebus Renana , Panishev Gabriella , Salomon Roy
Published: September 2020

The bodily-self, our experience of being a body, arises from the interaction of several processes. For example, embodied Sense of Agency (SoA), the feeling of controlling our body’s actions, is a fundamental facet of the bodily-self. SoA is disturbed in psychosis, with stress promoting its inception. However, there is little knowledge regarding the relationship between SoA, stress, and other facets of the bodily-self. In four experiments manipulating embodied SoA using a virtual hand (VH), we examined (1) How is embodied SoA related to other facets of the bodily-self?; and (2) How is SoA impacted by stress? We found that increased alteration of the VH significantly decreased subjective ratings of SoA and body ownership (Exp. 1), supporting the close relation between SoA and body ownership. Interoceptive accuracy and SoA were positively correlated (Exp. 3), connecting awareness to one’s actions and cardiac signals. Contrary to our expectations, SoA was not related to trait anxiety (Exp. 3), nor did induced stress impair SoA (Exp. 4). Finally, we found a negative correlation between self-reported prodromal symptoms and SoA. These results strongly support the connection between SoA and the bodily-self. Whereas, SoA was not impaired by stress, and weakly related to psychotic symptoms.
Six-Month Predictive Value of Diuretic Resistance Formulas in Discharged Heart Failure Patients after an Acute Decompensation
Authors: Feola Mauro , Rossi Arianna , Testa Marzia , Ferreri Cinzia , Palazzuoli Alberto , Pastorini Guido , Ruocco Gaetano
Published: September 2020

Background. The diuretic response has been shown to be a robust independent marker of cardiovascular outcomes in acute heart failure patients. The objectives of this clinical research are to analyze two different formulas (diuretic response (DR) or response to diuretic (R-to-D)) in predicting 6-month clinical outcomes. Methods: Consecutive patients discharged alive after an acute decompensated heart failure (ADHF) were enrolled. All patients underwent N-terminal-pro hormone BNP (NT-proBNP) and an echocardiogram together with DR and R-to-D calculation during diuretic administration. Death by any cause, cardiac transplantation and worsening heart failure (HF) requiring readmission to hospital were considered cardiovascular events. Results: 263 patients (62% male, age 78 years) were analyzed at 6-month follow-up. During the follow-up 58 (22.05%) events were scheduled. Patients who experienced CV-event had a worse renal function (p = 0.001), a higher NT-proBNP (p = 0.001), a lower left ventricular ejection fraction (p = 0.01), DR (p = 0.02) and R-to-D (p = 0.03). Spearman rho’s correlation coefficient showed a strong direct correlation between DR and R to D in all patients (r = 0.93; p < 0.001) and both in heart failure with reduced ejection fraction (HFrEF) (r = 0.94; p < 0.001) and HF preserved ejection fraction (HFpEF) (r = 0.91; p < 0.001). At multivariate analysis, a value of R-to-D <1.69 kg/40 mg, but only <0.67 kg/40 mg for DR were significantly related to poor 6-month outcome (p = 0.04 and p = 0.05, respectively). Receiver operating characteristic (ROC) curve analyses demonstrated that DR and R-to-D are equivalent in predicting prognosis (area under curve (AUC): 0.39 and 0.40, respectively). Only R-to-D was inversely related to in-hospital stay (r = −0.23; p = 0.01). Conclusion: Adding diuresis to DR seemed to provide a better risk assessment in alive HF patients discharged after an acute decompensation.
Shortcomings of Trials Assessing Antidepressants in the Management of Irritable Bowel Syndrome: A Critical Review
Authors: Oh Sun Jung , Takakura Will , Rezaie Ali
Published: September 2020

Irritable bowel syndrome (IBS) is a common disorder requiring complex, multidisciplinary management. Antidepressants are commonly used and recommended in guidelines for the treatment of patients with IBS. We assessed randomized controlled trials (RCTs) on antidepressants in patients with IBS, with specific attention to study design and data quality/reporting characteristics. Following a comprehensive search, data and RCT characteristics were systematically summarized. Fragility index, representing the number of positive “events” that the study relies on for its significance, was calculated. Eighteen RCTs were included. Overall, tricyclic antidepressants (TCAs), but not selective serotonin reuptake inhibitors (SSRIs), appeared to be efficacious in IBS. Eight studies reported on adverse events (AEs), which were significantly greater in patients receiving antidepressants versus placebo. The median (mean) fragility index of TCA trials was 0 (1.5). RCTs with positive results had significantly lower placebo rates (20.8%) versus negative studies (45.7%; p < 0.0001). RCTs exhibited limitations related to study design (sample size and blinding), data analysis (outcomes and placebo response), and data reporting (selective reporting of AEs and publication bias). Careful consideration of limitations of RCTs on antidepressants in IBS is warranted to formulate a safe and beneficial treatment regimen for patients with IBS.
Targeting PI3K/Akt/mTOR in AML: Rationale and Clinical Evidence
Authors: Darici Salihanur , Alkhaldi Hazem , Horne Gillian , Jørgensen Heather G. , Marmiroli Sandra , Huang Xu
Published: September 2020

Acute myeloid leukemia (AML) is a highly heterogeneous hematopoietic malignancy characterized by excessive proliferation and accumulation of immature myeloid blasts in the bone marrow. AML has a very poor 5-year survival rate of just 16% in the UK; hence, more efficacious, tolerable, and targeted therapy is required. Persistent leukemia stem cell (LSC) populations underlie patient relapse and development of resistance to therapy. Identification of critical oncogenic signaling pathways in AML LSC may provide new avenues for novel therapeutic strategies. The phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) signaling pathway, is often hyperactivated in AML, required to sustain the oncogenic potential of LSCs. Growing evidence suggests that targeting key components of this pathway may represent an effective treatment to kill AML LSCs. Despite this, accruing significant body of scientific knowledge, PI3K/Akt/mTOR inhibitors have not translated into clinical practice. In this article, we review the laboratory-based evidence of the critical role of PI3K/Akt/mTOR pathway in AML, and outcomes from current clinical studies using PI3K/Akt/mTOR inhibitors. Based on these results, we discuss the putative mechanisms of resistance to PI3K/Akt/mTOR inhibition, offering rationale for potential candidate combination therapies incorporating PI3K/Akt/mTOR inhibitors for precision medicine in AML.
The Macrophage Migration Inhibitory Factor (MIF) Promoter Polymorphisms (rs3063368, rs755622) Predict Acute Kidney Injury and Death after Cardiac Surgery
Authors: Averdunk Luisa , Bernhagen Jürgen , Fehnle Karl , Surowy Harald , Lüdecke Hermann-Josef , Mucha Sören , Meybohm Patrick , Wieczorek Dagmar , Leng Lin , Marx Gernot , Leaf David , Zarbock Alexander , Zacharowski Kai ,   on behalf of the RIPHeart Study Collaborators, Bucala Richard , Stoppe Christian
Published: September 2020

Background: Macrophage Migration Inhibitory Factor (MIF) is highly elevated after cardiac surgery and impacts the postoperative inflammation. The aim of this study was to analyze whether the polymorphisms CATT5–7 (rs5844572/rs3063368,“-794”) and G>C single-nucleotide polymorphism (rs755622,-173) in the MIF gene promoter are related to postoperative outcome. Methods: In 1116 patients undergoing cardiac surgery, the MIF gene polymorphisms were analyzed and serum MIF was measured by ELISA in 100 patients. Results: Patients with at least one extended repeat allele (CATT7) had a significantly higher risk of acute kidney injury (AKI) compared to others (23% vs. 13%; OR 2.01 (1.40–2.88), p = 0.0001). Carriers of CATT7 were also at higher risk of death (1.8% vs. 0.4%; OR 5.12 (0.99–33.14), p = 0.026). The GC genotype was associated with AKI (20% vs. GG/CC:13%, OR 1.71 (1.20–2.43), p = 0.003). Multivariate analyses identified CATT7 predictive for AKI (OR 2.13 (1.46–3.09), p < 0.001) and death (OR 5.58 (1.29–24.04), p = 0.021). CATT7 was associated with higher serum MIF before surgery (79.2 vs. 50.4 ng/mL, p = 0.008). Conclusion: The CATT7 allele associates with a higher risk of AKI and death after cardiac surgery, which might be related to chronically elevated serum MIF. Polymorphisms in the MIF gene may constitute a predisposition for postoperative complications and the assessment may improve risk stratification and therapeutic guidance.
Autism and COVID-19: A Case Series in a Neurodevelopmental Unit
Authors: Nollace Leslie , Cravero Cora , Abbou Alice , Mazda-Walter Brice , Bleibtreu Alexandre , Pereirra Nathalie , Sainte-Marie Myriam , Cohen David , Giannitelli Marianna
Published: September 2020

Background: COVID-19 has become pandemic and can impact individuals with autism as well. Here, we report a case series admitted to a neurobehavioral unit dedicated to challenging behaviors in patients with autism. Methods: We describe 16 patients (mean age 20.8 years; range 12–43 years; 76% male) with autism hospitalized between March 2020 and mid-April 2020 for challenging behaviors, for which COVID-19 disease has been suspected and who needed both psychiatric and medical care. A close cooperation with the Infectious and Tropical Diseases Department was organized to limit viral spread and training sessions (e.g., hygiene, clinical COVID-19 monitoring, virus testing) were given to staff members. Results: Most patients had severe autism and severe/moderate intellectual disability. Eleven patients were already in the unit when it was hit by the pandemic, and five were admitted from the community. Based on a virus search via reverse transcriptase polymerase chain reaction (RT-PCR) or serology at the 2-month follow-up, we had 11 confirmed COVID-19 cases. The main COVID-19 symptoms included benign upper respiratory infection signs (N = 9, 81.8%), diarrhea (N = 7, 63.6%), fatigue (N = 7, 63.6%), and respiratory signs (N = 5, 45.5%), including one patient who needed oxygen therapy. Three patients remained asymptomatic and COVID-19-free (including two under immunosuppressive treatments). Among the symptomatic patients, five showed atypical behaviors that we understood as idiosyncratic manifestations (e.g., irrepressible licking behavior). On day 14, only one patient with respiratory dysfunction still had a positive RT-PCR SARS-CoV-2 test. Conclusions: Organizing a COVID+ unit for patients with autism is realistic and requires close collaboration with infectologists. We believe that this initiative should be promoted to limit both the spread of the virus and the ostracism of patients with autism and challenging behaviors.