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Malignant nasopharyngeal tumors account for approximately 4% of ENT malignant tumor pathology and 1% of all cancers. The diagnosis of nasopharyngeal tumors is often late, the reason being the location in a silent anatomical region in terms of symptomatology and accessibility. Thus, approximately 70% of newly diagnosed patients with nasopharyngeal carcinoma unfortunately present with the condition in an advanced local stage. The early signs and symptoms are varied (nasal obstruction, hearing loss, otalgia, headache) and are usually ignored by the patient and even by the doctor in the initial stage of nasopharyngeal tumor evolution. Approximately 5% of patients have systemic metastases at presentation, the most common location being bone. Latent Epstein-Barr virus infection appears to be involved in the pathogenesis of nasopharyngeal carcinoma. There is no exact evidence of how often a nasopharynx tumor’s first sign is unilateral hearing loss. Thus, further work is required to determine that exactly to help patients get diagnosed faster and therefore improving their therapeutical options. This study aims to explore which symptoms are most common as the first indication of NPC, as well as how these symptoms compare to each other in terms of frequency and likelihood of occurrence.

Managing anticoagulation therapy in individuals with atrial fibrillation who also have liver disease is highly challenging due to altered blood clotting processes and the risk of bleeding due to liver dysfunction. The literature highlights the complex nature of anticoagulant therapy in these patients, emphasizing the need for personalized treatment methods that take into account both thrombosis and bleeding risks. Research has shown a higher occurrence of atrial fibrillation in people with cirrhosis, highlighting the need to find the best anticoagulation methods based on the severity of liver disease and patient-specific factors. The debate over the safety and effectiveness of direct oral anticoagulants compared to traditional drugs like warfarin in cirrhotic patients with atrial fibrillation is still ongoing. Collaborative initiatives between experts in hepatology and cardiology are needed to address the complicated interplay between liver disease and atrial fibrillation, promoting interdisciplinary care models that enhance patient safety and treatment effectiveness. By prioritizing a patient-centered approach guided by extensive research, future directions in the hemostatic management of cirrhotic patients with atrial fibrillation may improve clinical decision-making and therapeutic outcomes.

The development of the optic nerve and its surrounding tissues during the early fetal period is a convoluted period because it spans both the organogenesis period and the fetal period. This study details the microscopic anatomy and histoembryology of the optic nerve in embryos during the early fetal period, including the second half of the first trimester of pregnancy. Serial sections through the orbit of variously aged embryos allowed us to analyze the nerve in both longitudinal and transverse aspects. A histological assessment and description of the structures surrounding and inside the nerve were performed, highlighting the cellular subtypes involved. By employing immunohistochemical techniques, we could characterize the presence and distribution of astrocytes within the optic nerve. Our findings suggest that by the 8th gestational week (WG) the structures are homologs to all the adult ones but with an early appearance so that maturation processes take place afterward. By this age, the axons forming the nerve are definitive adult axons. The glial cells do not yet exhibit adult phenotype, but their aspect becomes adult toward the 13th week. During its development the optic nerve increases in size then, at 14 weeks, it shrinks considerably, possibly through its neural maturation process. The morphological primordium of the blood–nerve barrier can be first noted at 10 WG and at 13 WG the morphological blood–nerve barrier is definitive. The meningeal primordium can be first noted as a layer of agglomerated fibroblasts, later toward 13 WG splitting in pachymeninx and leptomeninges and leaving space for intrinsic blood vessels.

Objectives. Colorectal cancer is responsible for more than two million cases diagnosed annually. Despite early diagnosis through screening programs and adequate treatment, 25% of cases are diagnosed with metastatic disease while up to 50% of patients diagnosed early progress to metastatic disease. Materials and Methods. The study of 40 patients aims to identify the role of placental growth factor and heparin-binding growth factor as prognostic tools for current treatments involving resistance to bevacizumab in metastatic colorectal cancer. Results. Our results suggested that overall survival was influenced by serum fibroblast growth factor 1 levels. A cut-off value of 260.71 pg/ml was considered predictive of a disease-free survival/DFS of 6 months to 1 year, while a cut-off value of 117.51 pg/ml was considered predictive of a better DFS. Regarding placental growth factor involvement, a serum level of 13.75 pg/ml as a first determination and 11.48 pg/ml after 8 months of chemotherapy and anti-vascular endothelial growth factor therapy were considered cut-off values for 1- to 3-year overall survival/OS, while 6.45 pg/ml and 8.12 pg/ml levels were considered cut-off levels for 3- to 5-year OS. Conclusions. The results of the current study detected cutoff levels that may better predict treatment resistance in advanced-stage colorectal cancer and poor OS and DFS rates. Serum levels of placental growth factor and fibroblast growth factor 1 at diagnosis become important prognostic factors predicting resistance to bevacizumab in metastatic colorectal cancer.

Despite continuous investigations in the diagnosis and treatment of severe acute pancreatitis (SAP), this disease still remains a critical condition with a mortality rate of up to 35%. The pathophysiology of SAP involves an important inflammatory reaction of the pancreas (mediated by inflammatory cytokines and immune system activation), causing severe local tissue damage as well as important systemic imbalances. IL-17 is an inflammatory mediator that have a pivotal role in SAP evolution, generating multiple interactions between inflammatory cytokines and significantly influencing the immune system response. Consequently, continuous renal replacement therapy/CRRT was added to the conventional therapy, leading to improved treatment results. This review aims to evaluate the involvement of Interleukin 17 in the diagnosis, pathogenesis and evolution of SAP, as well as the role of CRRT in reducing elevated serum levels of IL-17. As a conclusion, CRRT is a promising method to eliminate cytokine mediators from the blood, thus leading to a reduction of both pancreatic/peripancreatic tissue damage and systemic imbalances in severe acute pancreatitis, being strongly correlated with better therapeutic outcomes.

Abstract Background To investigate the potential of combining compressed sensing (CS) and artificial intelligence (AI), in particular deep learning (DL), for accelerating three-dimensional (3D) magnetic resonance imaging (MRI) sequences of the knee. Methods Twenty healthy volunteers were examined using a 3-T scanner with a fat-saturated 3D proton density sequence with four different acceleration levels (10, 13, 15, and 17). All sequences were accelerated with CS and reconstructed using the conventional and a new DL-based algorithm (CS-AI). Subjective image quality was evaluated by two blinded readers using seven criteria on a 5-point-Likert-scale (overall impression, artifacts, delineation of the anterior cruciate ligament, posterior cruciate ligament, menisci, cartilage, and bone). Using mixed models, all CS-AI sequences were compared to the clinical standard (sense sequence with an acceleration factor of 2) and CS sequences with the same acceleration factor. Results 3D sequences reconstructed with CS-AI achieved significantly better values for subjective image quality compared to sequences reconstructed with CS with the same acceleration factor (p ≤ 0.001). The images reconstructed with CS-AI showed that tenfold acceleration may be feasible without significant loss of quality when compared to the reference sequence (p ≥ 0.999). Conclusions For 3-T 3D-MRI of the knee, a DL-based algorithm allowed for additional acceleration of acquisition times compared to the conventional approach. This study, however, is limited by its small sample size and inclusion of only healthy volunteers, indicating the need for further research with a more diverse and larger sample. Trial registration DRKS00024156. Relevance statement Using a DL-based algorithm, 54% faster image acquisition (178 s versus 384 s) for 3D-sequences may be possible for 3-T MRI of the knee. Key points • Combination of compressed sensing and DL improved image quality and allows for significant acceleration of 3D knee MRI. • DL-based algorithm achieved better subjective image quality than conventional compressed sensing. • For 3D knee MRI at 3 T, 54% faster image acquisition may be possible. Graphical Abstract

Abstract There are several overlapping clinical practice guidelines in acute pancreatitis (AP), however, none of them contains suggestions on patient discharge. The Hungarian Pancreatic Study Group (HPSG) has recently developed a laboratory data and symptom-based discharge protocol which needs to be validated. (1) A survey was conducted involving all members of the International Association of Pancreatology (IAP) to understand the characteristics of international discharge protocols. (2) We investigated the safety and effectiveness of the HPSG-discharge protocol. According to our international survey, 87.5% (49/56) of the centres had no discharge protocol. Patients discharged based on protocols have a significantly shorter median length of hospitalization (LOH) (7 (5;10) days vs. 8 (5;12) days) p

Mangalia balneary resort is situated in the south of the Black Sea and uses sulphurous water springs for rehabilitation therapy. The purpose of this study is to demonstrate the effectiveness of Mangalia sulphurous water on Helicobacter Pylori (H. Pylori) infection. Considering that sulfurous water has a bacteriostatic effect and that most gastritis are caused by H. Pylori infection, we propose that a group of 27 H. Pylori positive patients with or without digestive symptoms ingest sulfurous water daily, for a few days. At the end of the study, 15 of the patients tested negative for H pylori antigen. The curative effects are due to the bacteriostatic effect of sulfurous water and its stimulating action on the digestive tube.

In 2018, American developer Riot Games introduced their new musical venture – K-pop virtual band K/DA – through a live augmented reality performance opening the League of Legends World Championship Finals. The band’s first single – POP/STARS – quickly became a hit even outside of gaming circles, leading the developers to stage a follow-up in 2020, when the band released a full EP titled ALL OUT. This article examines the evolution of the virtual band and its members as virtual characters, personas, and performers, at the intersection of discourses surrounding popular music, videogames, and hallyu.

Abstract Background To investigate the potential of combining compressed sensing (CS) and deep learning (DL) for accelerated two-dimensional (2D) and three-dimensional (3D) magnetic resonance imaging (MRI) of the shoulder. Methods Twenty healthy volunteers were examined using at 3-T scanner with a fat-saturated, coronal, 2D proton density-weighted sequence with four acceleration levels (2.3, 4, 6, and 8) and a 3D sequence with three acceleration levels (8, 10, and 13), all accelerated with CS and reconstructed using the conventional algorithm and a new DL-based algorithm (CS-AI). Subjective image quality was evaluated by two blinded readers using 6 criteria on a 5-point Likert scale (overall impression, artifacts, and delineation of the subscapularis tendon, bone, acromioclavicular joint, and glenoid labrum). Objective image quality was measured by calculating signal-to-noise-ratio, contrast-to-noise-ratio, and a structural similarity index measure. All reconstructions were compared to the clinical standard (CS 2D acceleration factor 2.3; CS 3D acceleration factor 8). Additionally, subjective and objective image quality were compared between CS and CS-AI with the same acceleration levels. Results Both 2D and 3D sequences reconstructed with CS-AI achieved on average significantly better subjective and objective image quality compared to sequences reconstructed with CS with the same acceleration factor (p ≤ 0.011). Comparing CS-AI to the reference sequences showed that 4-fold acceleration for 2D sequences and 13-fold acceleration for 3D sequences without significant loss of quality (p ≥ 0.058). Conclusions For MRI of the shoulder at 3 T, a DL-based algorithm allowed additional acceleration of acquisition times compared to the conventional approach. Relevance statement The combination of deep-learning and compressed sensing hold the potential for further scan time reduction in 2D and 3D imaging of the shoulder while providing overall better objective and subjective image quality compared to the conventional approach. Trial registration DRKS00024156. Key points • Combination of compressed sensing and deep learning improved image quality and allows for significant acceleration of shoulder MRI. • Deep learning-based algorithm achieved better subjective and objective image quality than conventional compressed sensing. • For shoulder MRI at 3 T, 40% faster image acquisition for 2D sequences and 38% faster image acquisition for 3D sequences may be possible. Graphical Abstract

ABSTRACT: Background: Diagnosing myocarditis relies on multimodal data, including cardiovascular magnetic resonance (CMR), clinical symptoms, and blood values. The correct interpretation and integration of CMR findings require radiological expertise and knowledge. We aimed to investigate the performance of Generative Pre-trained Transformer 4 (GPT-4), a large language model, for report-based medical decision-making in the context of cardiac MRI for suspected myocarditis. Methods: This retrospective study includes CMR reports from 396 patients with suspected myocarditis and eight centers, respectively. CMR reports and patient data including blood values, age, and further clinical information were provided to GPT-4 and radiologists with 1 (resident 1), 2 (resident 2), and 4 years (resident 3) of experience in CMR and knowledge of the 2018 Lake Louise Criteria. The final impression of the report regarding the radiological assessment of whether myocarditis is present or not was not provided. The performance of Generative pre-trained transformer 4 (GPT-4) and the human readers were compared to a consensus reading (two board-certified radiologists with 8 and 10 years of experience in CMR). Sensitivity, specificity, and accuracy were calculated. Results: GPT-4 yielded an accuracy of 83%, sensitivity of 90%, and specificity of 78%, which was comparable to the physician with 1 year of experience (R1: 86%, 90%, 84%, p = 0.14) and lower than that of more experienced physicians (R2: 89%, 86%, 91%, p = 0.007 and R3: 91%, 85%, 96%, p

Post-partum depression is one of the most severe types of depression and can be developed at any age, no matter of cultural of social status. Objectives. To determine the factors associated with the psychological impact of pregnancy and to emphasize the psychological and psychiatric risks after giving birth for a woman. Materials and Methods. The study enrolled 35 patients diagnosed with postpartum depression that have been hospitalized in a tertiary-care center for psychiatric disorders between 2016 and 2020. Data were collected from patients’ observation charts. Results. The incidence of postpartum depression is higher in the age range 30-45 years old for primiparous women who are from urban areas, unemployed and not integrated in a family (unbalanced families or single parents), with medium level of education (high school) and alcohol addiction. One of 35 patients committed infanticide. Conclusions. Even if the postpartum depression is known worldwide it is still underdiagnosed, with certain factors concurring to that. Postpartum depression requires the identification of risk conditions in pregnant women and individualized therapy in a patient-centered, holistic manner.

Despite neutrophil involvement in inflammation and tissue repair, little is understood about their inflammatory status in acute coronary syndrome (ACS) patients with poor outcomes. Hence, we investigated the potential correlation between neutrophil inflammatory markers and the prognosis of ACS patients with/without diabetes and explored whether neutrophils demonstrate a unique inflammatory phenotype in patients experiencing an adverse in-hospital outcome. The study enrolled 229 ACS patients with or without diabetes. Poor evolution was defined as either death, left ventricular ejection fraction (LVEF) CCL3, IL-1β, interleukin-18 (IL-18), S100A9, intracellular cell adhesion molecule-1 (ICAM-1), matrix metalloprotease (MMP-9), of molecules essential in reactive oxygen species (ROS) production p22phox and Nox2, and increased capacity to form neutrophil extracellular traps. Inflammation is associated with adverse short-term prognosis in acute ACS, and inflammatory biomarkers exhibit greater specificity in predicting short-term outcomes in diabetics. Moreover, neutrophils from patients with unfavorable evolution exhibit distinct inflammatory patterns, suggesting that alterations in the innate immune response in this subgroup may exert detrimental effects on disease progression.

Objectives. The objective of this study was to evaluate the potential use of Prostate Imaging – Reporting and Data System version 2 (PI-RADS) in combination with Glutathione S-transferase P1 (GST-P1) expression for an improved diagnosis of prostate cancer, in patients with inconclusive values of prostate-specific antigen (PSA). Materials and Methods. The study was conducted on 80 patients for whom PSA values were evaluated and were found to be inconclusive (4-10 ng/ml). These patients underwent imagistic evaluation (PI-RADS), followed by transurethral prostate biopsy, with the evaluation of GST-P1 expression and histopathological examination (for diagnosis confirmation). Results. By combining the results of PI-RADS and GST-P1 the capacity of the tests to correctly identify healthy subjects, with an area under curve of 0,832 (95% CI 0.732–0.907), with a sensitivity of 73,25% and a specificity of 77,78%. Conclusions. PI-RADS lesions and GST-P1 methylation testing when PSA levels are in a “grey zone”, provide a better specificity and sensitivity by comparison through single testing. Testing patients with inconclusive PSA levels allows for a more accurate diagnosis and less over-diagnosis by non-invasive procedures, such as repeated biopsies.

Predictive justice is one of the newest directions of law evolution, being at the same time an expression of its digitalization. Modern society places great emphasis on interdisciplinarity, so that law and IT technologies are models in this direction. The paper aims to study this new phenomenon, identify the principles according to which it works, as well as present, respectively analyze predictive justice models already implemented in countries such as the United States or France. At the same time, we aim to highlight the functions that predictive justice can perform, in the sense that such a high-tech legal approach can be an aid in decision-making or can even be the main tool in decision-making. Can human resources be replaced by an algorithm in the administration of justice? A proposed result, following the research undertaken, is the drawing up of a predictive justice model that can be implemented in the national law system. The research methods used are literature review, epistemological method and comparative method.

Participatory scenario planning is a powerful approach to guide diverse stakeholders in creating and reflecting on visions of plausible and desired futures. However, this process requires tools to guide collective action to implement such visions within management agendas. This study develops, applies, and analyzes a novel visual tool within a virtual participatory scenario planning process about the Sierra de Guadarrama National Park (Madrid, Spain). Building on the identification of stakeholders who might engage in scenario strategies, the visual tool guided them in defining tasks to be developed and envisioning their willingness to collaborate in their implementation. We qualitatively analyzed data from recordings, online field observations, a post-survey from the scenario planning process, and a successive policy workshop. Our findings show that the visual tool fosters dialogue between stakeholders to redistribute tasks for working together on needed strategies in the protected area while promoting reflection on their willingness to collaborate as a group to implement them. The visual tool provided graphic outcomes for nine strategies corresponding to pictures of who may or may not be willing to engage in implementing such strategies. We argue that the visual tool is a robust method that can complement participatory scenario planning processes by providing a useful starting point for creating action networks to incorporate the resulting scenario strategies into management agendas. We deliberate on the nature of the visual tool as a boundary object and discuss its role as a decision-support tool. In particular, we reflect on the potential contributions and limitations of the visual tool to four dimensions of participatory conservation governance during participatory scenario planning processes: inclusivity, integration, adaptation, and pluralism. Our study provides a practical orientation to adapt the tool to other contexts and knowledge co-creation processes.

The phenomenon of homelessness can be written from key, worrying figures 580,000 homeless people in the United States in 2020 or an increase in the number of homeless people in 24 states of the 27 member states of the European Union (in a percentage from 16 to 389%). Emphasizing that the phenomenon we are focusing on is constantly growing, we propose through the study of comparative law to identify and analyze the following elements: the forms that the phenomenon takes homelessness, interpretation of recent public statistics, identification of causes leading to the phenomenon, proposals for amelioration and reduction of the phenomenon. The approached topic has a multidisciplinary character, being at the intersection of fields such as: law, sociology, economics, psychology, and the research, using the method of comparative law, will take the form of a comparative synthesis study.

It goes without saying that literary translators participate actively in the creative process of authors. They read the original work and try to understand the author’s perspective, so that they are able to communicate the message to those readers who do not understand the source text language. Therefore, translators act as mediators, that constantly struggle to surmount linguistic, stylistic or cultural difficulties, by using effective strategies. With regard to the retranslation theory, subsequent translations of the same literary work are susceptible to supplement previous versions, and to capture more of the original work. However, some researchers blame translation practices used nowadays of ‘too much’ invisibility, up to the point that the role of mediation is nullified. Therefore, this paper seeks to understand how the strategies of translation evolve over time, and what the predisposition of translators’ attitudes is nowadays. In order to obtain some conclusive answers to our questions, this research is based on a quantitative and qualitative analysis of three Romanian renditions of one of the stories in James Joyce’s Dubliners— “A little cloud”. The advantage of this study is that even though there is a fifty-one-year gap between the first Romanian version and the second, the last two translators belong to the same period of time and have similar education backgrounds, knowledge and skill in the field of specialty.

Prostate cancer represents the leading malignant tumor in men over 50 years of age with 400,000 new cases being diagnosed yearly in Europe. Even if the incidence rate is higher than the mortality rate, still there is an increasing trend when speaking of its mortality. The increasing incidence of the metabolic syndrome, the unhealthy lifestyle, the high lipid and Calcium intake, the high spread of infections with Human Papilloma Virus, Human Herpes Virus, the excess of androgen consumption and the longer life expectancy, are few of the main causes of prostate cancer increasing incidence. The new systemic therapies such as immunotherapy with Checkpoint Inhibitors or Poly, ADP-Ribose Polymerase inhibitors and local experimental procedures addressing tumor destruction, such as HighIntensity Focused Ultrasound, the Cryo and Focal Laser Ablation, provide good outcomes and become new promising tools for prostate cancer therapy. Physicians consider these methods worth using; the efficacy of some specific categories of patients being arguments for their use in the current protocols even though solid data regarding the improvement of global mortality rates are not yet published. The current article focuses on the newest systemic and local experimental treatment tools highlighting their benefits, especially for hormone-resistant prostate cancer.

As the pathophysiologic mechanisms of type 2 diabetes mellitus (T2DM) are discovered, there is a switch from glucocentric to a more comprehensive, patient-centered management. The holistic approach considers the interlink between T2DM and its complications, finding the best therapies for minimizing the cardiovascular (CV) or renal risk and benefitting from the treatment‘s pleiotropic effects. Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) fit best in the holistic approach because of their effects in reducing the risk of CV events and obtaining better metabolic control. Additionally, research on the SGLT-2i and GLP-1 RA modification of gut microbiota is accumulating. The microbiota plays a significant role in the relation between diet and CV disease because some intestinal bacteria lead to an increase in short-chain fatty acids (SCFA) and consequent positive effects. Thus, our review aims to describe the relation between antidiabetic non-insulin therapy (SGLT-2i and GLP-1 RA) with CV-proven benefits and the gut microbiota in patients with T2DM. We identified five randomized clinical trials including dapagliflozin, empagliflozin, liraglutide, and loxenatide, with different results. There were differences between empagliflozin and metformin regarding the effects on microbiota despite similar glucose control in both study groups. One study demonstrated that liraglutide induced gut microbiota alterations in patients with T2DM treated initially with metformin, but another failed to detect any differences when the same molecule was compared with sitagliptin. The established CV and renal protection that the SGLT-2i and GLP-1 RA exert could be partly due to their action on gut microbiota. The individual and cumulative effects of antidiabetic drugs on gut microbiota need further research.

Abstract Evidence regarding the relation between SARS-CoV-2 mortality and the underlying medical condition is scarce. We conducted an observational, retrospective study based on Romanian official data about location, age, gender and comorbidities for COVID-19 fatalities. Our findings indicate that males, hypertension, diabetes, obesity and chronic kidney disease were most frequent in the COVID-19 fatalities, that the burden of disease was low, and that the prognosis for 1-year survival probability was high in the sample. Evidence shows that age-dependent pairs of comorbidities could be a negative prognosis factor for the severity of disease for the SARS-CoV 2 infection.

Histone modifications are key contributors to the cognitive decline that occurs in aging and Alzheimer’s disease. Our lab has previously shown that elevated H3K9me3 in aged mice is correlated with synaptic loss, cognitive impairment and a reduction in brain derived neurotrophic factor (BDNF). However, the mechanism of H3K9me3 regulation remains poorly understood. In this study, we investigated the role of age-associated stressors on H3K9me3 regulation and examined if changes in H3K9me3 were age dependent. We used cultured hippocampal neurons at 6, 12, and 21 days in vitro (DIV) to examine the effect of different stressors on H3K9me3 across neuron ages. We found that the oxidative stressor hydrogen peroxide (H2O2) does not induce H3K9me3 in 12 DIV neurons. Inhibiting BDNF signaling via TrkB-Fc elevated H3K9me3 in 12 and 21 DIV neurons compared to 6 DIV neurons. Antioxidant treatment prevented H3K9me3 elevation in 12 DIV neurons treated with TrkB-Fc and H2O2. H2O2 elevated the epigenetic regulator SIRT1 in 6 DIV neurons but did not increase H3K9me3 levels. Our findings demonstrate that inhibiting BDNF signaling elevates hippocampal H3K9me3 in a manner dependent on in vitro age and oxidative stress.

Abstract Background The challenges faced by professionals when working in the field of psychiatry require the development of adequate defensive and coping mechanisms. This study aimed to explore both coping strategies and defense mechanisms and their relationship in psychiatry trainees in Romania. Methods A cross-sectional study was conducted to determine and evaluate both defensive and coping mechanisms of Romanian psychiatry trainees. Defensive Style Questionnaire-60 and COPE scale were applied to psychiatry trainees from five training centers in Romania. By applying structural equation modeling, models that presumed the existence of relationships between coping strategies and defensive mechanisms were analyzed. Results Superior defense mechanisms and task-oriented coping strategies were the commonly used approaches by psychiatry trainees. Furthermore, significantly consistent correlations (ranging from 0.2 to 0.5) between adaptive defense mechanisms and coping strategies focused on the problem or emotion were shown. Similarly, avoidant coping strategies correlated with non-adaptive defense mechanisms (correlations between 0.3 and 0.5). Our model presented good fit indices (X 2(34) = 64.324, p

Abstract Amplifying the impact of sustainability initiatives to foster transformations in urban and rural contexts, has received increasing attention in resilience, social innovation, and sustainability transitions research. We review the literature on amplification frameworks and propose an integrative typology of eight processes, which aim to increase the impact of such initiatives. The eight amplification processes are: stabilizing, speeding up, growing, replicating, transferring, spreading, scaling up, and scaling deep. We aggregated these processes into three categories: amplifying within, amplifying out, and amplifying beyond. This integrative typology aims to stimulate the debate on impact amplification from urban and rural sustainability initiatives across research areas to support sustainability transformations. We propose going beyond an understanding of amplification, which focuses only on the increase of numbers of sustainability initiatives, by considering how these initiatives create transformative change.

The present article was written as part of the PhD dissertation entitled “An analysis regarding the evolution of James Joyce’s writing style in ‘Dubliners’, ‘A Portrait of the Artist as a Young Man’ and ‘Ulysses’ and the strategies of translating it into Romanian”. The research starts from the hypothesis that a perfect rendition in a different language of a literary text of this type is nothing more than a utopia. However, a translator should always intend to achieve an equilibrium between the author’s intentions, the form, the content and the target culture. In “Ulysses”, James Joyce experiments with language, abandoning the definition of sense and revolutionises the art of expressing thoughts through words. The current work will concentrate on the thorough analysis of adjectival and adverbial collocations conceptualized in the ninth chapter of “Ulysses”. Our purpose is to investigate how Mircea Ivănescu’s Romanian translation deals with collocations and especially with those that typically represent Joyce’s authorial style. Mircea Ivănescu (1931-2011) is a Romanian poet and the sole translator who accomplished the difficult task of translating the entire novel, although there had been various attempts at translating only chapters of it. It is an approved work of translation, having received both praise and critical appreciation. After more than three decades from this chapter’s translation, our research aims for a further exposition of the similarities and distinctions between the source language text and the target language translation.

Necrotizing fasciitis is a rapidly destructive affliction of soft tissues, with a mortality rate that may reach 73% of the cases. It is characterized by a progressive inflammation and extended necrosis of the subcutaneous tissue and the fascia. Necrotizing fasciitis was first described in 1848, and later in 1920 Meleney identified 20 patients in China in which the infection was presumably triggered by hemolytic streptococcus, linking pathological bacteria to the condition. In 1952, Wilson coined the term necrotizing fasciitis although without successfully identifying the specific pathological bacteria involved. In most cases, both risk and aggravating factors are present, the main risk factors being diabetes mellitus, liver cirrhosis, renal failure, and immunosuppressant states. Location may vary, but most frequently the disease occurs in the limbs, the trunk, and the perineum. Treatment depends on the location and the time of diagnosis and may range from large incisions with extensive debridement to organ amputations such as those of the limbs or breasts. Treatment is complex and expensive, and besides surgery, includes the administration of broad-spectrum antibiotics, anti-inflammatory drugs, intensive therapy support, and long-term hospitalizations. The prognosis is guarded. The present case entails a 56-year old female patient who presented with many risk factors favoring the occurrence of necrotizing fasciitis, namely diabetes mellitus, liver cirrhosis (decompensated with ascites and portal encephalopathy phenomena), untreated hepatitis B infection, chronic renal failure with diabetic nephrotic syndrome, and obesity.

Even though since the beginning of the COVID-19 pandemic, the literature became more and more abundant on data and hypotheses about the various consequences on people’s lives, more clarity needs to be added to the existing information. Besides the stressful experiences related to the COVID-19 pandemic, SARS-CoV-2 infection has been proven to impact brain functioning through direct and indirect pathogenic mechanisms. In this context, we report a case of a patient presenting with a first episode of psychosis following COVID-19. In our case, a 28-year-old male patient with no personal or family psychiatric history developed psychotic symptoms (delusions, hallucinations, and disorganized behaviour) that required antipsychotic treatment and inpatient hospitalization one week after he was discharged from the hospital after COVID-19. At the six-month and one-year follow-up, the patient was in remission without any psychotic signs or symptoms. A brief review of the literature is also provided. The case presented in this article outlines the possibility that the post-COVD-19 recovery period might be a crucial time for the onset of acute psychotic disorder, and therefore, routine psychiatric assessments should be carried out during all phases of the disease. A clearer picture of the impact of the COVID-19 pandemic on mental health will most likely be revealed in the future as many consequences need long-term evaluation.

Exercise improves cognition in the aging brain and is a key regulator of neuronal plasticity genes such as BDNF. However, the mechanism by which exercise modifies gene expression continues to be explored. The repressive histone modification H3K9me3 has been shown to impair cognition, reduce synaptic density and decrease BDNF in aged but not young mice. Treatment with ETP69, a selective inhibitor of H3K9me3’s catalyzing enzyme (SUV39H1), restores synapses, BDNF and cognitive performance. GABA receptor expression, which modulates BDNF secretion, is also modulated by exercise and H3K9me3. In this study, we examined if exercise and ETP69 regulated neuronal plasticity genes by reducing H3K9me3 at their promoter regions. We further determined the effect of age on H3K9me3 promoter binding and neuronal plasticity gene expression. Exercise and ETP69 decreased H3K9me3 at BDNF promoter VI in aged mice, corresponding with an increase in BDNF VI expression with ETP69. Exercise increased GABRA2 in aged mice while increasing BDNF 1 in young mice, and both exercise and ETP69 reduced GABRA2 in young mice. Overall, H3K9me3 repression at BDNF and GABA receptor promoters decreased with age. Our findings suggest that exercise and SUV39H1 inhibition differentially modulate BDNF and GABRA2 expression in an age dependent manner.

The following paper deals with a view on the concept of fidelity in literary translation with an analysis of the Romanian poet Mircea Ivănescu’s work on the overture of episode eleven: “Sirens” from James Joyce’s “Ulysses”. Mircea Ivănescu is a postmodernist poet who prefers to employ an ordinary language when writing. Moreover, he is a self-taught man of letters who didn’t even get a degree in the languages he translated from. When speaking of his work as a translator his attitude is often sceptical. However, “Ulise” is an acclaimed Romanian translation and critics have repeatedly praised Ivănescu’s translation skills and use of language. For that reason, the paper focuses on the concept of fidelity in translation and on the effort of the Romanian poet to efficiently render Joyce’s writing style in the target language and at the same time to preserve the original meaning of words. The paper is not intended to elicit the imperfections of the translation but rather to illustrate the intricacy of the task, the problems of non-equivalence that are difficult to avoid by any literary translator and some potential approaches.

Gut microbiota is an essential component in the pathogenesis of liver cirrhosis and its complications. There is a direct relationship between the gut and the liver called the gutliver axis through which bacteria can reach the liver through the portal venous blood. However, it remains unclear how bacteria leave the intestine and reach the fluid collection in the abdomen. A series of mechanisms have been postulated to be involved in the pathogenesis of spontaneous bacterial peritonitis (SBP) and other complications of liver cirrhosis, including bacterial translocation, bacterial overgrowth, altered intestinal permeability and dysfunctional immunity. The hepatic function may also be affected by the alteration of intestinal microbiota composition. Current treatment in SBP is antibiotic therapy, but lately, probiotics have been the useful treatment suggested to improve the intestinal barrier and prevent bacterial translocation. However, studies are contradictory regarding their usefulness. In this review, we will summarize the literature data on the pathogenesis of spontaneous bacterial peritonitis concerning the existence of a relationship with the microbiota and the useful use of probiotics.

Background. The relationship between chronic pancreatitis and diabetes is well established. This form of diabetes is secondary to exocrine pancreatic disorder and is known as diabetes mellitus type 3c (T3cDM). Materials and Methods. In this retrospective study we included 261 patients, 59 patients being diagnosed with chronic pancreatitis and secondary diabetes mellitus, and admitted in the Fundeni Clinical Institute, 2nd Department of Gastroenterology or N.C. Paulescu Institute/ Carol Davila University of Medicine and Pharmacy. Results and Discussions. Patients were 22.2% women and 77.8% men, with an average age of 56.8 years and 53.4 years respectively. 63% came from urban areas. The mean duration of chronic pancreatitis was six years. Non-diabetic patients were compared with patients who were previously diagnosed with T3cDM and who had been analyzed for body mass index (BMI). Imaging investigations were also performed to confirm pseudotumors or pancreatic tumours. Patients already considered non-diabetic had basal blood glucose values and were mostly overweight and obese. In this context, insulin resistance cannot be excluded for this group of patients. Conclusions. T3cDM is a new pathological entity that needs to be explored more deeply, and that should benefit from both a diagnostic stratification and treatment.

One of the most frequent kidney pathologies encountered in daily practice is represented by the presence of renal cysts. Most of them are asymptomatic and are found accidentally during periodical check-ups because they don’t have clinical signs until they grow and compress the surrounding organs. We have reviewed the current data regarding this pathology, in order to underline the risk of malignant transformation and its impact on the patient’s life. It is estimated that the prevalence rate of renal cysts in the general population is approximately 10% and it increases with age.Imaging investigations, such as contrast tomography or magnetic resonance imaging, are essential for establishing the cysts characteristics, especially when ultrasonography raises the suspicion of a modified renal cyst, as well as in guiding the therapeutical protocol. The Bosniak classification is based on contrast tomography scans and has allowed the standardization of the kidney cysts, considering their characteristics. More attention should be given to Bosniak IIF and III cystic renal masses, which contain thickened walls and more septa, but no enhanced nodules/soft tissue components, because more than half of these cysts can have a malignant component.

The 2019 novel coronavirus, known as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), is causing a global pandemic. The virus primarily affects the upper and lower respiratory tracts and raises the risk of a variety of non-pulmonary consequences, the most severe and possibly fatal of which are cardiovascular problems. Data show that almost one-third of the patients with a moderate or severe form of COVID-19 had preexisting cardiovascular comorbidities such as diabetes mellitus, obesity, hypertension, heart failure, or coronary artery disease. SARS-CoV2 causes hyper inflammation, hypoxia, apoptosis, and a renin–angiotensin system imbalance in a variety of cell types, primarily endothelial cells. Profound endothelial dysfunction associated with COVID-19 can be the cause of impaired organ perfusion that may generate acute myocardial injury, renal failure, and a procoagulant state resulting in thromboembolic events. We discuss the most recent results on the involvement of endothelial dysfunction in the pathogenesis of COVID-19 in patients with cardiometabolic diseases in this review. We also provide insights on treatments that may reduce the severity of this viral infection.

With Rasmussen’s abstraction hierarchy as starting point, the present article focuses on understanding some of the aspects guiding the development of a simulation exercise (SimEx) from a multi-faceted perspective, based on interviews and post-exercise evaluations conducted with both exercise designers and participants. The results show that, in order to achieve its overarching objective, an exercise must fulfill a wide range of “functions”, which in turn can take various kinds of “forms” or actual representations in the physical world. The paper discusses a number of identified required functions of a SimEx, sometimes labeled as design elements, and furthermore elaborates on differences and specific requirements at form level, e.g., virtual vs. physical exercises.

Global change presents risks and opportunities for social-ecological systems worldwide. Key challenges for sustainability science are to identify plausible future changes in social-ecological systems and find ways to reach socially and environmentally desirable conditions. In this context, regional-scale studies are important, but to date, many such studies have focused on a narrow set of issues or applied a narrow set of tools. Here, we present a holistic approach to work through the complexity posed by cross-scale interactions, spatial heterogeneity, and multiple uncertainties facing regional social-ecological systems. Our approach is spatially explicit and involves assessments of social conditions and natural capital bundles, social-ecological system dynamics, and current development trends. The resulting understanding is used in combination with scenario planning to map how current development trends might be amplified or dampened in the future. We illustrate this approach via a detailed case study in southern Transylvania, Romania, one of Europe's most significant biocultural refugia. Our goal was to understand current social-ecological dynamics and assess risks and opportunities for sustainable development. Our findings show that historical events have strongly shaped current conditions and current development trends in southern Transylvania. Moreover, although external drivers (including EU policies) set the general direction of regional development trajectories, local factors, including education, leadership, and the presence of bridging organizations, can enhance or counteract their effects. Our holistic approach was useful for generating an in-depth understanding of a regional social-ecological system and could be transferred to other parts of the world.

Many traditional cultural landscapes evolved as coupled social-ecological systems. It is important to understand how such systems navigate novel challenges posed by globalization. To address this issue, we bring together two components of a pilot study carried out in a cultural landscape from Central Romania. The region was affected by major social and economic perturbations in the past century, affecting ethnic composition, community cohesion, land property regimes, and the management of common resources. The first component of our study investigated how rural inhabitants appreciated ecosystem services through questionnaires with 98 people in 30 villages. The second component aimed to assess the perception of people about ongoing changes in their communities through semistructured interviews with 50 people in 5 villages. Rural inhabitants particularly valued provisioning ecosystem services such as firewood, water, and crops, but also healthy soils. Rural communities were characterized by a number of social and economic issues, especially individualism, lack of trust, corruption, and poverty. People from communities with many initiatives, e.g., NGOs, associations, and active individuals, were more optimistic regarding the future of their communities than people from villages with few or no initiatives. A major challenge for cultural landscapes such as those in Central Romania is to find new, meaningful ways to keep the social and ecological systems connected. Otherwise there is a risk that (short-term) socioeconomic interests may impair the provisioning of important ecosystem services.

Cultural ecosystem services constitute a growing field of research that is characterized by an increasing number of publications from various academic disciplines. We conducted a semiquantitative review of publications explicitly dealing with cultural ecosystem services. Our aims were: (1) to provide an overview of the current state of research, (2) to classify the diversity of research approaches by identifying clusters of publications that address cultural ecosystem services in similar ways, and (3) to highlight some important challenges for the future of cultural ecosystem services research. We reviewed 107 publications and extracted 20 attributes describing their type and content, including methods, scales, drivers of change, and trade-offs between services. Using a cluster analysis on a subset of attributes we identified five groups of publications: Group 1, conceptual focus, deals with theoretical issues; Group 2, descriptive reviews, consists mostly of desktop studies; Group 3, localized outcomes, deals with case studies coming from different disciplines; Group 4, social and participatory, deals mainly with assessing preferences and perceptions; and Group 5, economic assessments, provides economic valuations. Emerging themes in cultural ecosystem services research relate to improving methods for cultural ecosystem services valuation, studying cultural ecosystem services in the context of ecosystem service bundles, and more clearly articulating policy implications. Based on our findings, we conclude that: (1) cultural ecosystem services are well placed as a tool to bridge gaps between different academic disciplines and research communities, (2) capitalizing on the societal relevance of cultural ecosystem services could help address real-world problems, and (3) cultural ecosystem services have the potential to foster new conceptual links between alternative logics relating to a variety of social and ecological issues.

Clonal hematopoiesis of indeterminate potential (CHIP) describes the age-related acquisition of somatic mutations in hematopoietic stem/progenitor cells (HSPC) leading to clonal blood cell expansion. Although CHIP mutations drive myeloid malignancies like myelodysplastic syndromes (MDS) it is unknown if clonal expansion is attributable to changes in cell type kinetics, or involves reorganization of the hematopoietic hierarchy. Using computational modeling we analyzed differentiation and proliferation kinetics of cultured hematopoietic stem cells (HSC) from 8 healthy individuals, 7 CHIP, and 10 MDS patients. While the standard hematopoietic hierarchy explained HSPC kinetics in healthy samples, 57% of CHIP and 70% of MDS samples were best described with alternative hierarchies. Deregulated kinetics were found at various HSPC compartments with high inter-individual heterogeneity in CHIP and MDS, while altered HSC rates were most relevant in MDS. Quantifying kinetic heterogeneity in detail, we show that reorganization of the HSPC compartment is already detectable in the premalignant CHIP state., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

T cell ignorance is a specific form of immunological tolerance. It describes the maintenance of naivety in antigen-specific T cells in vivo despite the presence of their target antigen. It is thought to mainly play a role during the steady state, when self-antigens are presented in absence of costimulatory signals and at low density or to T cells of low affinity. In how far antigen-specific T cells can also remain clonally ignorant to foreign antigens, presented in the inflammatory context of systemic infection, remains unclear. Using single-cell in vivo fate mapping and high throughput flow cytometric enrichment, we find that high-affinity antigen-specific CD8 + T cells are efficiently recruited upon systemic infection. In contrast, most low-affinity antigen-specific T cells ignore the priming antigen and persist in the naïve state while remaining fully responsive to subsequent immunization with a high-affinity ligand. These data establish the widespread clonal ignorance of low-affinity T cells as a major factor shaping the composition of antigen-specific CD8 + T cell responses to systemic infection., (© 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)

The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer-reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state-of-the-art handbook for basic and clinical researchers., (© 2021 Wiley-VCH GmbH.)

Adoptive transfer of T cells expressing a transgenic T cell receptor (TCR) has the potential to revolutionize immunotherapy of infectious diseases and cancer. However, the generation of defined TCR-transgenic T cell medicinal products with predictable in vivo function still poses a major challenge and limits broader and more successful application of this "living drug." Here, by studying 51 different TCRs, we show that conventional genetic engineering by viral transduction leads to variable TCR expression and functionality as a result of variable transgene copy numbers and untargeted transgene integration. In contrast, CRISPR/Cas9-mediated TCR replacement enables defined, targeted TCR transgene insertion into the TCR gene locus. Thereby, T cell products display more homogeneous TCR expression similar to physiological T cells. Importantly, increased T cell product homogeneity after targeted TCR gene editing correlates with predictable in vivo T cell responses, which represents a crucial aspect for clinical application in adoptive T cell immunotherapy., Competing Interests: D.H.B. is co-founder of STAGE Cell Therapeutics GmbH (now Juno Therapeutics, a Bristol-Myers Squibb Company) and T Cell Factory B.V. (now Kite, a Gilead Company). D.H.B. has a consulting contract with and receives sponsored research support from Juno Therapeutics., (© 2021 The Authors.)

Aggressive brain tumors like glioblastoma depend on support by their local environment and subsets of tumor parenchymal cells may promote specific phases of disease progression. We investigated the glioblastoma microenvironment with transgenic lineage-tracing models, intravital imaging, single-cell transcriptomics, immunofluorescence analysis as well as histopathology and characterized a previously unacknowledged population of tumor-associated cells with a myeloid-like expression profile (TAMEP) that transiently appeared during glioblastoma growth. TAMEP of mice and humans were identified with specific markers. Notably, TAMEP did not derive from microglia or peripheral monocytes but were generated by a fraction of CNS-resident, SOX2-positive progenitors. Abrogation of this progenitor cell population, by conditional Sox2-knockout, drastically reduced glioblastoma vascularization and size. Hence, TAMEP emerge as a tumor parenchymal component with a strong impact on glioblastoma progression., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Cell alterations during isolation and preparation for flow cytometry cell sorting by antibodies, temperature, homogenization, buffer composition and mitogens are well known. In contrast, little is known about cell alteration caused by the instrument or the sorting process itself. We systematically evaluated cellular responses to different sorter-induced physical forces. In summary, flow cytometry cell-sorting induced forces can affect cellular signaling cascades, especially the MAPK p38. Functional assays, related to the p38 MAPK pathway, of human primary T cells after flow cytometry sorting did lead to minor physiological modulation but no functional impairments. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry., (© 2020 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.)