Charite University Medicine Berlin Research Articles

Diş Çürüklerinde Yapay Zeka Kullanımının Bibliyometrik Analizi

Background: The aim of this study is to examine the development trends and dynamics of research on the use of artificial intelligence in dental caries diagnosis, to identify the strengths and limitations of the existing literature, and to guide future research. Methods: A literature search was conducted using the Web of Science database, covering articles published before 3 June 2024. Pilot searches were conducted and 883 studies were reached. After the specified scanning and filtering processes, the study was carried out on 270 publications. In the bibliometric analysis, the Biblioshiny R package as well as the features of Web of Science and VOSviewer software were used for visualizations. Microsoft Excel was used to tabulate the data. Results: There is a general increase in the number of articles published each year. A total of 3081 citations were made to publications on the use of artificial intelligence in cariology. The average number of citations per article was found to be 11.41, and the H index was 29. The most cited country was Germany (581 citations), and the most influential author was Falk Schwendicke. On the basis of institutions, the highest contribution was made by Charite University Medicine Berlin (19 articles, 475 citations). Conclusion: Since 2008, and particularly since 2018, the utilisation of artificial intelligence (AI) in the investigation of dental caries and oral and dental diseases has garnered increasing interest. Artificial Intelligence (AI) can be said to be a groundbreaking discovery that will be increasingly applied in various branches of dentistry.

Low-dose interleukin-2 therapy in refractory systemic lupus erythematosus: an investigator-initiated, single-centre phase 1 and 2a clinical trial

Summary Background An acquired deficiency of interleukin-2 (IL-2) and related defects in regulatory T cell homeostasis are thought to play a crucial role in the pathogenesis of systemic lupus erythematosus. We hypothesised that reconstitution of regulatory T-cell homoeostasis with low doses of IL-2 would be beneficial to patients with systemic lupus erythematosus. Methods In this uncontrolled, phase 1 and 2a trial done in the Department of Rheumatology and Clinical Immunology at Charite—University Medicine Berlin (Berlin, Germany), we assessed the safety and tolerability of low-dose recombinant human IL-2 (aldesleukin) and its effects on regulatory T cells. We recruited patients aged 18–75 years with a confirmed diagnosis of systemic lupus erythematosus and moderate-to-severe disease activity despite previous treatment with at least two conventional therapies. Patients were given four cycles of low-dose aldesleukin daily for 5 days followed by a 9–16 day rest. The primary endpoints were safety and the number of patients who achieved at least a 100% increase in the proportion of CD25hi-expressing cells among circulating CD3 + CD4 + FOXP3 + CD127lo regulatory T cells at day 62 (ie, after four treatment cycles). Secondary endpoints included disease activity as measured by the Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and the British Isles Lupus Assessment Group (BILAG) score, disease flares as measured by the SLEDAI flare index, auto-antibody and complement concentrations at day 62. Exploratory endpoints included various cellular and immunological parameters. The trial is registered with WHO/ICTRP, number DRK4858. Findings Between March 31, 2014, and May 27, 2016, 13 patients were screened, of whom ten met eligibility criteria and were enrolled in the trial. Two additional patients were treated between April 1, 2013, and March 11, 2014, in a compassionate use setting. Eleven (92%) of the 12 patients achieved the primary endpoint. 159 adverse events were recorded, 75 (47%) of which were treatment related. Most treatment-related adverse events were transient and mild to moderate (grade 1–2). The most common adverse event was injection-site reaction (20%). No serious adverse events occurred during the treatment period. In ten (83%) of 12 patients, SELENA-SLEDAI scores were lower at day 62 than at baseline, and no severe disease flares were observed during the treatment period. Decreased disease activity correlated with the magnitude of increase in the proportion of activated regulatory T cells. IL-2 treatment resulted in a preferential proliferation of regulatory T cells that retained suppressive capacity. We observed decreases in cells that are involved in the regulation of germinal-centre reactions. Interpretation Low-dose IL-2 therapy is safe and well tolerated and selectively promotes the expansion of functional regulatory T cells in patients with moderate-to-severe systemic lupus erythematosus. Low-dose IL-2 treatment might also be beneficial in reducing disease activity, although larger trials are needed to address efficacy. Funding German Research Foundation.

Early Blood-Brain Barrier Dysfunction Predicts Neurological Outcome Following Aneurysmal Subarachnoid Hemorrhage

Background: Disease progression and delayed neurological complications are common after aneurysmal subarachnoid hemorrhage (aSAH). We explored the potential of quantitative blood-brain barrier (BBB) imaging to predict disease progression and neurological outcome. Methods: Data were collected as part of the Co-Operative Studies of Brain Injury Depolarizations (COSBID). We analyzed retrospectively, blindly and semi-automatically magnetic resonance images from 124 aSAH patients scanned at 4 time points (24-48 h, 6-8 days, 12-15 days and 6-12 months) after the initial hemorrhage. Volume of brain with apparent pathology and BBB dysfunction (BBBD), subarachnoid space and lateral ventricles were measured. Neurological status on admission was assessed using the Fisher grades, World Federation of Neurosurgical Societies and Rosen-Macdonald (RMS) scores. Clinical outcome at 6 months or later was assessed using the extended Glasgow outcome scale. Findings: Based on repeated volumetric measures of pathological brain tissue and CSF, patients were categorized as having either progressive (increased pathology; 64%) or nonprogressive (36%) disease course. No differences were found between the two groups in aneurysm locations, neurological status on admission, initial brain pathology or treatment (coiling or clipping). Females were older and more likely to have a non-progressive course compared to males (p=0·01). Progressive course was associated with worse outcome at ≥6 months. A substantial brain volume with BBBD was found already 24-48 h after admission, and persisted at all time points. Brain volume with BBBD was significantly larger in patients with progressive course. BBBD increased the likelihood of a normal brain tissue to become pathological (p<0·001). A multi-linear regression model revealed a significant power for BBBD in combination with RMS at 24-48 h in predicting outcome (receiver operating characteristic area under the curve, 0·804; p<0·001). Interpretation: We suggest that early identification of BBBD may serve as a key predictive biomarker for neurological outcome in aSAH. Funding Statement: The study was designed and performed as a sub-study within the Co-Operative Study of Brain Injury Depolarizations (COSBID) study group. JPD was supported by grants from the Deutsche Forschungsgemeinschaft (DFG) (DFG DR 323/5-1), the Bundesministerium fur Bildung und Forschung (BMBF) Center for Stroke Research Berlin 01 EO 0801 and FP7 no 602150 CENTER-TBI. AF was supported by grants from the DFG (DFG DR 323/5-1), Israel Science Foundation and Canada Institute for Health Research (CIHR). JW was supported by grants from the DFG DR 323/5-1 and DFG WO 1704/1-1. Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: The protocol was approved by the ethics committees of the Charite University Medicine Berlin, the Goethe-University Frankfurt, the University Hospital Heidelberg and the University of Cologne. Research was conducted in accordance with the Declaration of Helsinki. Patients or their legal representative gave written consent for study inclusion. Results are reported in accordance with the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines.

Next Generation Biobanking - From Biorepository To Data Integration Center

Introduction/ Background Biobanks and their operators are gaining popularity. However, they face a range of growing challenges. Many of these biobanks used to be smaller and midsized collections of data and samples, but are now being developed into centralized networks within clinics and consortia. These large biobanks require the integration of as many sources of information as possible, including imaging data in addition to any relevant structured data. This is especially the case in the field of virtual microscopy. Data collection is increasingly being orchestrated by workflow based systems and must eventually be incorporated entirely into rule based IT-processes. Aims In order to achieve this goal, the Charite University Medicine Berlin, VMscope GmbH, and Kairos GmbH formed a consortium in the framework of the joint project, “Biobanking 3.0”, which is funded by the German Federal Ministry for Education and Research (BMBF). Furthermore, after this successful project, a second KMU funded project called POST (Patient-centric Open Multi Center Study Tool) will begin in the autumn of 2015 to expand the data integration to pathology information systems in a standardized manner. Methods One of the project goals is to use an IT-platform with an integrated workflow-engine to orchestrate all necessary processes and document all findings. Defined SOPs during sample extraction and information acquisition can be executed, and all result data can be made available to local research groups as well as project partners. Results Thus, the platform pursues the research approach of personalized medicine, which requires exact controlling of therapy cycles in a logical and chronological order.

Abstract No. 303 - Volume comparison after radiofrequency ablation at two different target volumes by means of four different RF generators - MR volumetry in a 1.0 Tesla open MRI vs. macroscopic measurement

No. 303 Volume comparison after radiofrequency ablation at two different target volumes by means of four different RF generators—MR volumetry in a 1.0 Tesla open MRI vs. macroscopic measurement H. Rathke, F.V. Guettler, B. Schnackenburg, J. Rump, B. Hamm, U. Teichgraeber, M. de Bucourt; Department of Radiology, Charite University Medicine Berlin, Berlin, Germany; Department of Radiology, Jena University, Jena, Germany; Healthcare, Philips, Hamburg, Germany Purpose: In several studies radiofrequency ablation (RFA) was found to be safe and reliable for intervention of primary and secondary malignancies. The aim of this study was to evaluate MR volumetry directly after RFA in an open MRI and to validate the visualization of the produced necrosis volume. As the RF necrosis can be subdivided in three zones it was evaluated if the outer zone of the necrosis is detectable with the MR sequences used and whether or not there are differences with respect to lesion size and generator type. Materials and Methods: 64 liver specimens were ablated under constant simulated physiological conditions with four commercially available RF systems (A, B, C, D; n1⁄416 for each system; n1⁄48 for 3cm, and n1⁄48 for 5cm). Target volumes were set to 14.14cm (3cm lesion) and 65.45cm(5cm lesion). T1 and PD weighted TSE sequences were acquired in a 1.0 Tesla open MRI and MR-volumetry was performed by semi-automatic software. After manual dissection actual macroscopic ablation diameters were recorded and volumes calculated. Results: For system A with the 3cm lesion, the manual measured macroscopic volume was 28.2cm in comparison to 15.2cm/ 13.5cm (T1/PDW) using MR volumetry—with the 5cm lesion: 48.3cm vs. 19.3cm/15.6cm. System B: 3cm: 17.1cm vs. 6.5cm/ 6.0cm-5cm: 39.3cm vs. 16.7cm/15.2cm. System C: 3cm 29.7 cm vs. 12.9cm/11.5cm-5cm 71.8cm vs. 29.6cm/27.4cm. System D: 3cm 28.7cm vs. 11.3cm/12.8cm-5cm 93.9cm vs. 42.6cm/37.5cm. Conclusion: MR volumetry yielded smaller appearing volumes than manual measurement after dissection—irrespective of RF system used, target lesion size and MR sequence. Histopathological assessment showed an incomplete cellular damage in the transitional zone of the necrosis. As expected cellular apoptotic processes could not be detected immediately after RFA, probably also because of the ex vivo setting and missing blood perfusion.The exact transition from ablated to vital tissue could not be assessed directly after Intervention with the MR sequences investigated.

Vascular involvement in cardiac giant cell myocarditis: a new pathophysiological aspect

Most patients with giant cell myocarditis (GCM) present with acute fulminant heart failure due to rapidly progressive myocyte necrosis [1, 2]. Immunosuppressive therapies, including high-dose steroids and cyclosporine, have only modestly improved the prognosis in GCM [3, 4]. Morbidity and mortality remain high and many patients still require heart transplantation. GCM has been reported in association with autoimmune disorders. This supports an autoimmune etiologic role. Nevertheless, autoantigens in GCM remain poorly defined [5]. To gain insight into the pathogenesis of this mercurial disease, we studied patients with GCM with regard to histopathological appearances and gene expression pattern of inflammation in endomyocardial biopsies (EMB). Between January 2009 and November 2011 we verified eight patients with GCM in EMB (mean age 42 ± 8.6 years, 5 male/3 female) admitted to our hospital for evaluation of suspected myocarditis. EMBs were obtained from the right ventricular septum. Coronary artery disease and other possible causes of myocardial dysfunction (i.e. valvular heart disease) had been excluded by angiography prior to EMB in all patients. Other comorbidities such as uncontrolled hypertension and diabetes, increased alcohol or drug uptake as well as systemic or autoimmune diseases were also excluded. Histology was developed by hematoxylin eosin (HE) and Elastica-van-Gieson (EvG) staining in light microscopy. For immunohistological evaluation, antibodies were used as follows: CD3 lymphocytes (Dako, Glostrup, Denmark, dilution 1:25), CD11a/LFA-1 lymphocytes (Immuno Tools, Friesoythe, Germany, dilution 1:250), CD11b/Mac-1 macrophages (ImmunoTools, Friesoythe, Germany, dilution 1:500), HLA-1 (Dako, Glostrup, Denmark, dilution 1:2,000), ICAM-1/CD54 (ImmunoTools, Friesoythe, Germany, dilution 1:500), VCAM-1/CD106 (ImmunoTools, Friesoythe, Germany, dilution 1:1,000), and CD31 (Dako, Glostrup, Denmark, dilution 1:100). Nested PCR for cardiotropic viral genomes was performed and was negative for erythrovirus, entero and adenovirus, human herpes virus type 6 and Epstein–Barr virus. Differential gene expression for TLR5, TLR7, TLR8, CCL20 and CCR6 was determined by real-time PCR. 20 genderand age-matched patients (mean age 45.2 ± 9.2 years, 11 male/9 female) without evidence of inflammation in EMB served as controls. They were referred for evaluation of repeated chest discomfort but had no symptoms of heart failure. The diagnostic workup finally revealed that their complaints were non-cardiac in origin. The study was performed within the CRC Transregio 19 and was approved by the local ethics committees as well as by the committees of respective federal states. An informed written consent is obtained from each patient. Regarding the baseline characteristics of GCM patients, mean LVEF was significantly reduced, paralleled by an increase in LVEDD in contrast to controls (LVEF 37.5 ± 10.7 %, LVEDD 59.7 ± 3.1 mm vs. LVEF 67.6 ± 4.4 %, LVEDD 51.2 ± 2.1 mm, P \ 0.0001). All S. Elezkurtaj Institute of Pathology, Charite-University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany

Clinical Decisions in Acute Patients: ACS-POCT-Hypertension and Biomarkers

1 Division of Emergency Medicine/CPU, Charite-University Medicine Berlin, Campus Virchow-Klinikum and Campus Charite Mitte, 13353 Berlin, Germany 2 Kerckhoff Heart and Thorax Center, Bad Nauheim and Medical Clinic I, University of Giessen, 61231 Bad Nauheim, Germany 3Department of Internal Medicine III, Cardiology, University Hospital Heidelberg, 69120 Heidelberg, Germany 4 European Society for Emergency Medicine, EuSEM and Emergency Medicine Department, Faculty of Medicine, Rennes University Hospital, 35033 Rennes, France

Role of magnetic resonance spectroscopy in differentiating parkinsonian syndromes of various etiologies

Role of magnetic resonance spectroscopy in differentiating parkinsonian syndromes of various etiologies

N-Methyl-D-Aspartate Receptor Antibodies in Herpes Simplex Encephalitis

Researchers at Charite University Medicine Berlin, and other centers in Germany, Spain and the US performed a retrospective analysis of 44 patients with polymerase chain reaction-proven herpes simplex encephalitis (HSE) for the presence of onconeuronal and synaptic receptor antibodies.

Fatigue and sleep disorders in multiple sclerosis: is obstructive sleep apnea a link?

In this small pilot study, published in the current issue of Sleep and Breathing, Dias and colleagues [1] try to identify multiple sclerosis (MS) patients who are at risk for obstructive sleep apnea (OSA) by applying the STOP-BANG questionnaire which has been validated as a screening tool for OSA in various populations, but not yet in MS patients [2]. Interestingly, almost half of the cohort exhibited STOPBANG scores indicative of a high OSA risk, which was approximately threefold higher in men than in women. In men, a significant correlation between STOP-BANG scores and measures of daytime sleepiness (Epworth Sleepiness Scale) and fatigue (Fatigue Severity Scale) was reported. Although the study has some obvious methodological limitations discussed by the authors, such as a lack of a subsequent polysomnography (PSG) to confirm the presence of OSA in patients at high risk according to the STOP-BANG questionnaire, the attempt to shed light on the elusive influence of nocturnal sleep abnormalities on daytime sleepiness and fatigue in MS is laudable. Fatigue is defined as “a subjective lack of physical and/or mental energy that is perceived by the individual or caregiver to interfere with usual and desired activities” [3]. Fatigue is the most frequent MS symptom, reported by up to 97% of patients [4–6], two thirds of whom consider it as their most disabling symptom [7]. Fatigue does not only exert a substantial negative impact on quality of life, but is also a major cause of unemployment in MS [8]. Fatigue has been related to neuroimaging findings [9], neuroendocrine dysregulation [10], XMRV virus infections [11], depression and cognitive dysfunction [12, 13]. However, despite its high prevalence, our knowledge on pathophysiology and treatment of MS-related fatigue is insufficient. Unfortunately, many neurologists exhibit a therapeutic nihilism towards this debilitating symptom in regarding fatigue as some immanent and intractable feature of the condition with which the patient “has to learn to live”. Only in recent years, a possible association of daytime fatigue with sleep disorders has become into focus; however, only very few studies have attempted to investigate the relationship between sleep disorders in general and MS-related fatigue by PSG or accelerometry and not only by questionnaires on sleep quality [14–17]. In sum, it is undoubtful that sleep disorders can contribute to daytime fatigue in MS. In a recently published study [18], the authors proposed a screening instrument for sleep disorders because owing to limited resources not every MS patient complaining of fatigue can be admitted to a sleep laboratory. Beyond that, it makes sense to develop a screening instrument especially for OSA in the context of MS-related fatigue to identify patients at high risk. Further polysomnographic investigations have to validate this specific STOP-BANG questionnaire in the context ofMS-related fatigue. Secondly, prospective studies have to evaluate whether a consequent treatment of the respective sleep disorder will beneficially influence fatigue in MS. If this can be demonstrated, a new therapeutic horizon F. Paul (*) NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Charite University Medicine Berlin, Chariteplatz 1, 10117 Berlin, Germany e-mail: friedemann.paul@charite.de

Predicting BCI performance to study BCI illiteracy

a Berlin Institute of Technology, Machine Learning Laboratory, Berlin, Germany b Fraunhofer FIRST IDA, Berlin, Germany c Dept. of Neurology, Campus Benjamin Franklin, Charite University Medicine Berlin, Germany d Institute of Medical Psychology and Behavioral Neurobiology, Universitat Tubingen, Germany e Department of Biological Psychology, Clinical Psychology and Psychotherapy, University of Wurzburg, Germany

P.1.24 Serotonin transporter gene and adverse life events in adult ADHD

Serotonin Transporter Gene and Adverse Life Events in Adult ADHD Daniel J. Muller, Laura Mandelli, Alessandro Serretti,* Colin G. DeYoung, Vincenzo De Luca, Tricia Sicard, Subi Tharmalingam, Jurgen Gallinat, Pierandrea Muglia, Diana De Ronchi, Umesh Jain, and James L. Kennedy** Department of Psychiatry, Charite University Medicine Berlin, Campus Mitte, Berlin, Germany Neurogenetics Section, Centre for Addiction and Mental Health (CAMH), University of Toronto, Ontario, Canada Institute of Psychiatry, University of Bologna, Bologna, Italy Department of Psychology, Yale University, New Haven, Connecticut

P184 NUTRITIONAL ASPECTS OF PERIOPERATIVE THERAPY FOR RECTAL RESECTIONS IN AUSTRIA AND GERMANY

P184 NUTRITIONAL ASPECTS OF PERIOPERATIVE THERAPY FOR RECTAL RESECTIONS IN AUSTRIA AND GERMANY T. Hasenberg1, F. Langle2, P. Rittler3, S. Post1, K.W. Jauch3, C. Spies4, M. Senkal5, W. Schwenk6, E. Shang1. 1Department of Surgery, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany; 2Department of Surgery, Vienna Medical University, Vienna, Austria; 3Department of Surgery, University Hospital Munich-Grosshadern, Ludwig-Maximilian University, Munich, 4Department of Anesthesiology and Intensive Care Medicine, Campus Charite Mitte, Charite-University Medicine Berlin, Berlin, 5Department of Surgery, Marienhospital Witten, Witten, 6Department of General, Visceral, Vascular, and Thoracic Surgery, Campus Charite Mitte, Charite-University Medicine Berlin, Berlin, Germany

Use of very old and very new antibiotics in intensive care units in Germany

Institute of Environmental Medicine and Hospital Epidemiology, University Medical Centre Freiburg, Breisacher Str. 115B, 79106 Freiburg, Germany; Institute of Hygiene and Environmental Medicine, Charite—University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm 27, 12203 Berlin, Germany; National Reference Centre for Surveillance of Nosocomial Infections, Heubnerweg 6, 14059 Berlin, Germany; Institute of Medical Microbiology and Hospital Epidemiology, Medical School Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany

Can Aerobic Exercise Reduce Chances of Panic Attack?

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessCan Aerobic Exercise Reduce Chances of Panic Attack?Joan Arehart-TreichelJoan Arehart-TreichelSearch for more papers by this authorPublished Online:20 Jan 2006https://doi.org/10.1176/pn.41.2.0017aA young career woman in Chicago, “Liz,” was under a lot of stress. The stress led to anxiety, which led to chest pains, which led to a panic attack. She rushed to the hospital emergency room, convinced that she was seriously ill.If Liz had engaged in strenuous physical activity shortly before her panic attack set in, could she have prevented it? Perhaps, a new study out of Germany suggests.Previous researchers found that physical exercise can reduce anxiety in both healthy individuals and those with panic disorder. Andreas Stroehle, M.D., an assistant professor of psychiatry at Charite-University Medicine Berlin, and coworkers decided to build on that work by conducting a small pilot crossover-design study to see whether an acute round of exercise can prevent panic attacks.A compound called cholecystokinin tetrapeptide (CCK-4) is known to induce panic attacks reliably in healthy subjects. So Stroehle and his colleagues wanted to see whether exercise or rest would alter CCK-4–induced panic attacks.They first had 15 healthy subjects, average age 26 years, engage in 30 minutes of aerobic exercise (treadmill walking) before receiving CCK-4. After that, the subjects' psychological responses to CCK-4 were measured with the Acute Panic Inventory.The subjects then remained in a quiet, restful state before getting CCK-4 the second time. Once again, their psychological responses to CCK-4 were measured with the Acute Panic Inventory.Finally, Stroehle and his group measured the subjects' psychological responses to CCK-4 under the two conditions.Panic attacks occurred in 12 subjects after rest, but in only six subjects after exercise, the researchers found. In both conditions, CCK-4 administration was followed by a significant increase in Acute Panic Inventory scores. However, prior exercise resulted in significantly lower scores than quiet rest.“Our results for the first time suggest that exercise has an acute antipanic activity,” they wrote in the December 2005 American Journal of Psychiatry.The challenge now, Stroehle and his colleagues continued, is to determine whether acute exercise can also prevent panic attacks in individuals with panic disorder, and if so, what the optimum dosage (intensity and duration) of acute exercise is for preventing an attack. “We are doing further studies in patients,” Stroehle told Psychiatric News.Also to be answered, Stroehle said, is whether acute exercise might counter a panic attack after it has begun. “Because most panic attacks resolve within about 30 minutes, the beneficial effects [of exercise after an attack has started] are questionable. In addition, in most of the situations where panic attacks occur, cognitive strategies may be more appropriate and applicable than exercise.”The study was funded by Charite-University Medicine Berlin.“The Acute Antipanic Activity of Aerobic Exercise” is posted at<http://ajp.psychiatryonline.org/cgi/content/full/162/12/2376>.▪ Am J Psychiatry 2005 162 2376 ISSUES NewArchived