Press releases

After three years of intensive collaboration, leading European experts in adult acute lymphoblastic leukemia (ALL) have published therapy recommendations for those suffering from this rare and aggressive cancer. One of the world's largest ALL study groups is based at Frankfurt University Hospital. Its systematic studies have already helped significantly increase the cure rate of those affected. 

The treatment of acute lymphoblastic leukemia in adults is extremely complex, lengthy and very stressful for patients. Compared to other types of cancer in adults, ALL is relatively rare, as a result of which its treatment in Europe has been organized by multicenter study groups for decades. To achieve the greatest possible scientific impact, several medical institutions simultaneously conduct research on optimizing and systematically developing therapy algorithms. The most important instrument for improving diagnostics and therapy is prospective academic studies, i.e. studies based on a predefined question that examine the effectiveness of a treatment method, and which are planned independently of the pharmaceutical industry. 

In Germany, this task has been carried out for decades by the German Multicenter Study Group for Adult ALL (GMALL) – one of the world's largest study groups for this type of cancer, based at Frankfurt University Hospital. Under the leadership of Dr. Nicola Gökbuget, Senior Physician at the University Hospital's Medical Clinic 2, leading European experts for adult ALL have now drawn up consensus recommendations, for the first time bundling European expertise in one guideline. The European LeukemiaNet (ELN) published its findings as a two-part special report in late January and early February 2024 in the renowned US journal Blood. 

Strengthening the European perspective
"Knowledge about the disease biology and treatment options for ALL in adults is increasing exponentially," explains Dr. Gökbuget, first author of the reference recommendation and GMALL study group coordinator for more than a decade. "Given the unique constellations in the European healthcare systems, it was important for us to summarize the current state of knowledge, especially from a European perspective." The detailed ELN recommendations are intended not only to provide interested doctors with answers to the most important questions relating to patient management, but also to help standardize the reporting of clinical trials. 

Too extensive for just one publication
Due to their large scope and complexity, the treatment recommendations were published in two parts, the first of which deals with ALL diagnostics, prognostic factors and response assessments, and also defines standards for classification and evaluation in clinical trials. The second part covers the entire management, and ranges from induction and consolidation therapy to the use of new substances, stem cell transplantation, relapse therapy, the treatment of special ALL subgroups, late effects of therapy, and supportive treatment. In addition to a detailed evaluation of the available data, the recommendations also contain expert assessments of issues currently discussed. 

Based on years of systematic work, working groups from eight European countries have contributed to significantly improving the prognosis of adult patients suffering from ALL – a path the European consortium intends to continue to follow to benefit all those affected. 

Publications:
Nicola Gökbuget, Nicolas Boissel, Sabina Chiaretti, Herve Dombret, Michael Doubek, Adele K. Fielding, Robin Foà, Sebastian Giebel, Dieter Hoelzer, Mathilde Hunault, David I. Marks, Giovanni Martinelli, Oliver G. Ottmann, Anita W. Rijneveld, Philippe Rousselot, Josep-Maria Ribera, Renato Bassan: Diagnosis, Prognostic Factors and Assessment of ALL in Adults: 2023 ELN Recommendations from a European Expert Panel. Blood, January 31, 2024. https://doi.org/10.1182/blood.2023020794 (part 1) 

Nicola Gökbuget, Nicolas Boissel, Sabina Chiaretti, Herve Dombret, Michael Doubek, Adele K. Fielding, Robin Foà, Sebastian Giebel, Dieter Hoelzer, Mathilde Hunault, David I. Marks, Giovanni Martinelli, Oliver Ottmann, Anita W. Rijneveld, Philippe Rousselot, Josep-Maria Ribera, Renato Bassan: Management of ALL in Adults: 2023 ELN Recommendations from a European Expert Panel. Blood, February 2, 2024. https://doi.org/10.1182/blood.2023023568 (part 2) 

Further information
Dr. Nicola Gökbuget
Medical Clinic 2, focus on hematology / oncology
University Hospital Frankfurt
Tel.: +49 (0)69 6301 6365
goekbuget@em.uni-frankfurt.de
LinkedIn: https://www.linkedin.com/in/NGoekbuget
Twitter/X: @UK_Frankfurt @goetheuni

Editor: Dr. Markus Bernards, Science Editor, PR & Communication Office, Theodor-W.-Adorno-Platz 1, 60323 Frankfurt am Main, Tel: +49 (0) 69 798-12498, bernards@em.uni-frankfurt.de.

Researchers from Goethe University Frankfurt and the Senckenberg Biodiversity and Climate Research Centre have modeled the spatial distributional patterns of black flies in Hesse, North Rhine-Westphalia, Rhineland-Palatinate and Saxony for the first time. In the study published in the renowned journal "Science of the Total Environment", the research team shows that black flies in Germany can be categorized into three groups with different distribution patterns and ecological requirements. The researchers point out that medically relevant species in particular could become more prevalent as a result of ongoing climate and land-use change. 

FRANKFURT. Only six millimeters in length, black flies (Simuliidae) may look harmless like house flies, but their bites can be very unpleasant. Similar to mosquitoes, the females of these insects that are able to fly need a blood meal to produce eggs. Known as “pool feeders", they use their sharp “teeth" to scratch the skin of the host and then ingest the resulting drop of blood. “The anticoagulant and anesthetic substances introduced into the wound by mosquitoes can trigger serious allergic reactions or lead to secondary bacterial infections," states Prof. Dr. Sven Klimpel from the Senckenberg Biodiversity and Climate Research Centre, Goethe University Frankfurt, the LOEWE Centre for Translational Biodiversity Genomics (TBG), and the Fraunhofer IME Giessen. Klimpel continues: "Black flies are also vector-competent, meaning they are able to transmit pathogens that cause infectious diseases through their bites." One of the most well-known diseases transmitted by black flies is onchocerciasis, also known as “river blindness", caused by the nematode Onchocerca volvulus, which is native to Africa. According to the World Health Organization, more than 1.15 million people worldwide have already lost their sight as a result of the disease. 

Black flies can be found on all continents except Antarctica. Over 2,000 black fly species are known worldwide, in Germany 57 of them. According to Sarah Cunze, from Goethe University Frankfurt and the first author of the study, almost all black fly species (98%) require a blood meal before laying their eggs. “In our study, we were able to categorize the 12 most common species into three biogeographical groups," explains Cunze, adding that “these groups are a) montane species living upper reaches of watercourses, b) species with broad niches and thus widely distributed across different landscapes, and c) lowland species." These results are based on a valid data set comprising 1,526 records of black fly larvae in the four federal states of Hesse, North Rhine-Westphalia, Rhineland-Palatinate and Saxony and provide valuable insights of the distributional patters of these species. 

In their study, the researchers deduce different trends in population development for the three groups under the ongoing climate and land-use change: While the montane group is considered to be at risk due to increasing temperatures and growing chemical pollution of water bodies, the other species are characterized by a broad niche or higher tolerance to anthropogenic changes. Consequently, the black fly species of veterinary and human medical relevance, which predominantly belong to the third group, could be promoted by the ongoing anthropogenic change and be subject to positive population trends. “Medically relevant species are characterized by particularly aggressive biting behavior against mammals and humans and often occur in very high numbers. These observed mass occurrences are the result of synchronized hatching of the aquatic larvae," explains Cunze. Neighboring countries like Poland have responded to this mass occurrence by keeping livestock only indoors or letting them out to graze only at night during these outbreaks. "The expected future rise in temperature could reduce development times and thus lead to more generations per year – resulting in a more frequent occurrence of black flies overall," adds Cunze. 

In further studies, the team would like to support its findings with empirical research and use laboratory tests to clarify the extent to which the simuliid species are vector-competent, – i.e. capable of transmitting certain pathogens – under the conditions currently prevailing in Europe. "The trends for medically relevant black fly species derived from the findings of our study are an example of how global changes can promote vector-borne infectious diseases. Our modelling approaches and results will help us to structure monitoring and prevention programs for vector-competent species more efficiently and to provide predictions about future developments," concludes Klimpel. 

Publication: Sarah Cunze, Jonas Jourdan, Sven Klimpel (2024): Ecologically and medically important black flies of the genus Simulium: Identification of biogeographical groups according to similar larval niches, Science of The Total Environment, Volume 917, 2024, 170454, https://doi.org/10.1016/j.scitotenv.2024.170454 

Images for download: https://www.uni-frankfurt.de/149310328 

Captions:
(Image 1) Simulium ornatum is a black fly species of veterinary and human medical relevance. Photo: Dorian Dörge
(Image 2) Black flies are semi-aquatic species and depend on flowing waters in their egg, larval and – as seen here – pupal stages. Photo: Dorian Dörge 

Further information
Prof. Dr. Sven Klimpel
Senckenberg Biodiversity and Climate Research Centre
Goethe University Frankfurt
Tel. +49 (0)69 798 42237
sven.klimpel@senckenberg.de

Editor: Pia Barth, Science Editor, PR & Communication Office, Theodor-W.-Adorno-Platz 1, 60323 Frankfurt, Tel. +49 (0)69 798-12481, Fax +49 (0)69 798-763-12531, p.barth@em.uni-frankfurt.de

Bats live in a world of sounds. They use vocalizations both to communicate with their conspecifics and for navigation. For the latter, they emit sounds in the ultrasonic range, which echo and enable them to create an “image" of their surroundings. Neuroscientists at Goethe University Frankfurt have now discovered how Seba's short-tailed bat, a species native to South America, manages to filter out important signals from ambient sound and especially to distinguish between echolocation and communication calls. 

FRANKFURT. Seba's short-tailed bat (Carollia perspicillata) lives in the subtropical and tropical forests of Central and South America, where it mostly feeds on pepper fruit. The animals spend their days in groups of 10 to 100 individuals in hollow trunks and rocky caverns, and at night they go foraging together. They communicate using sounds that create distinct ambient noise in the colony – like the babble of voices at a lively party. At the same time, the bats also use vocalizations to navigate their surroundings: a phenomenon known as echolocation, for which they emit ultrasonic sounds that reflect off solid surfaces. The animals then assemble these echoes into an “image" of their surroundings. 

But how does Seba's short-tailed bat manage to filter out important sounds from constant ambient noise? A common explanation is that the brain constantly predicts the next signal and reacts more strongly to an unexpected signal than to an expected one. This is referred to as deviance detection, and neuroscientists led by Johannes Wetekam and Professor Manfred Kössl from the Neurobiology and Biosensors Working Group at the Institute of Cell Biology and Neuroscience at Goethe University Frankfurt are exploring its mechanisms. Together with colleagues, they were already able to show in 2021 that signal processing does not begin in high-level regions of the brain but already in the brainstem, which is responsible for controlling vital functions such as breathing and heart rate. However, these studies only used artificial stimuli that are not meaningful to the animals. 

In a study recently published, the team led by Wetekam and Kössl repeated the experiments with natural communication and echolocation calls. “With our study, we wanted to find out what happens in deviation detection when, instead of meaningless stimuli, ones are presented to Seba's short-tailed bat that actually occur in its auditory world," says Wetekam, summing up. 

To do this, two electrodes the thickness of a human hair were inserted under the bats' scalps to record their brain waves. Although this was painless for the animals, the measurements were carried out under general anesthetic, as any movement could distort the results. 

The bat's brain reacts to sounds even when the animal is anesthetized and fast asleep. Either echolocation or communication calls were then played to the animals, each interspersed with the other sound, with a 10% probability of it occurring. 

It was then possible to read from the brain waves measured that the brainstem processes echolocation and communication calls differently. While infrequent echolocation sounds indeed induced stronger signals than frequent ones – i.e. showed deviation detection – in the case of communication sounds, the probability of them occurring did not influence the strength of the response. “Bats probably need to react faster during echolocation than when communicating with conspecifics," presumes Manfred Kössl. “The brainstem is the first station in the brain to receive the acoustic signals, which is why calculating the probability of echolocation calls might be necessary first of all there, and especially their echoes, so that the animal can dodge obstacles in good time." The stronger response to less frequent calls is presumably due to better neural synchronization. 

The study also showed that the brainstem can utilize other features of bat calls for deviance detection, such as rapid changes in frequency or volume, in addition to differences in pitch. “This is astonishing, as the brainstem is a rather primitive part of the brain that scientists did not previously think capable of any substantial involvement in signal processing," says Wetekam. “They saw its role more in receiving signals from the auditory nerve and transmitting them to high-level regions of the brain." 

These findings might also be important in relation to medical applications in humans. For example, the low-level regions of the brain ought to be included when studying diseases such as ADHD or schizophrenia, which are associated with impaired processing of extraneous stimuli. The fact that the bat brainstem processes various complex acoustic signals differently can also help scientists to understand how the brain deciphers and processes complex human speech. 

Publication: Johannes Wetekam, Julio Hechavarria, Luciana López-Jury, Eugenia Gonzáles-Palomares, Manfred Kössl: Deviance detection to natural stimuli in population responses of the brainstem of bats. Journal of Neuroscience (2024) https://doi.org/10.1523/JNEUROSCI.1588-23.2023

Background: How the brain filters out sounds (2022)
https://aktuelles.uni-frankfurt.de/english/how-the-brain-filters-out-sounds 

Picture download: https://www.uni-frankfurt.de/150019112 

Caption: Seba's short-tailed bat (Carollia perspicillata) filters out important signals from ambient sound and distinguishes between echolocation and communication calls. Photo: Julio Hechavarría, Goethe University Frankfurt 

Further Information
Johannes Wetekam
Neurobiology and Biosensors Working Group
Tel.: +49 69 798-42066 '
wetekam@bio.uni-frankfurt.de 

Professor Manfred Kössl
Institute of Cell Biology and Neuroscience
Head of the Neurobiology and Biosensors Working Group
Goethe University Frankfurt
Tel.: +49 (0)69 798 42052
Koessl@bio.uni-frankfurt.de
https://www.bio.uni-frankfurt.de/36526663/Abt__K%C3%B6ssl___Biowissenschaften 

Twitter/X: @JohannesWetekam @goetheuni

Editor: Dr. Markus Bernards, Science Editor, PR & Communication Office, Theodor-W.-Adorno-Platz 1, 60323 Frankfurt am Main, Tel: +49 (0) 69 798-12498, bernards@em.uni-frankfurt.de.

Incidences of eating disorders such as bulimia and anorexia are becoming more common, especially among young people. In addition to the urgent need for medical and psychological therapy, the dental health of those afflicted also bears consideration. A new offer from Goethe University's Center for Dentistry, Oral and Maxillofacial Medicine (Carolinum) offers advice, prevention and therapy. 

FRANKFURT. Eating disorders such as anorexia and bulimia can lead to severe dental damage. The cause: due to frequent vomiting, the pH value in the oral cavity is acidic over a longer period of time and the teeth gradually lose their minerals. This can result in discoloration and indentations on the teeth, which can also become more sensitive. If the tooth structure is subject to frequent acid attacks, the shape of the tooth may change, potentially resulting in pain and tooth decay. 

Early dental intervention can prevent damage to the tooth's structure and treat existing erosions. To this end, Prof. Jan-Frederik Güth, Head of the Polyclinic for Dental Prosthetics, and Prof. Stefan Rüttermann, Head of the Polyclinic for Tooth Preservation, have set up an interdisciplinary consultation specialized in dental therapy for eating disorders. An early focus on the connection between eating disorders and dental health can help avoid extensive dental treatment at a later stage, and therefore save on high costs. 

As part of the consultations, dentists Miriam Ruhstorfer and Charlène Bamberg offer patients two-phased advice. The initial focus is on diagnostics and prophylaxis, including an intraoral scan that enables a three-dimensional analysis. Also part of this stage is oral hygiene training aimed at optimizing the cleaning of the teeth. Offering additional protection to the teeth while simultaneously also strengthening them is fluoride, administered with the help of custom-made transparent splints. The second stage encompasses the treatment of existing damage to the tooth structure and, if necessary, to the jaw joints, as well as dental check-ups for the early detection of new damage. 

Images for download: https://www.uni-frankfurt.de/149521941 

Caption: Severely damaged teeth of a bulimia patient before and after treatment. (Photo: Carolinum) 

Further information
Miriam Ruhstorfer/Charlène Bamberg
Polyclinic for Dental Conservation
Center for Dentistry, Oral and Maxillofacial Medicine
Faculty of Medicine
Goethe University Frankfurt
Tel. +49 (0)69 6301-4247
E-Mail es-zahnmedizin@med.uni-frankfurt.de
www.carolinum.uni-frankfurt.de

Editor: Dr. Anke Sauter, Science Editor, PR & Communication Office, Tel: +49 (0)69 798-13066, Fax: +49 (0) 69 798-763 12531, sauter@pvw.uni-frankfurt.de

If gravitational condensate stars (or gravastars) actually existed, they would look similar to black holes to a distant observer. Two theoretical physicists at Goethe University Frankfurt have now found a new solution to Albert Einstein's theory of general relativity, according to which gravitational stars could be structured like a Russian matryoshka doll, with one gravastar located inside another. 

FRANKFURT. The interior of black holes remains a conundrum for science. In 1916, German physicist Karl Schwarzschild outlined a solution to Albert Einstein's equations of general relativity, according to which the center of a black hole consists of a so-called singularity, a point at which space and time no longer exist. Here, the theory goes, all physical laws, including Einstein's general theory of relativity, no longer apply; the principle of causality is suspended. This constitutes a great nuisance for science: after all, it means that no information can escape from a black hole beyond the so-called event horizon. This could be a reason why Schwarzschild's solution did not attract much attention outside the theoretical realm for a long time – that is, until the first candidate for a black hole was discovered in 1971, followed by the discovery of the black hole in the center of our Milky Way in the 2000s, and finally the first image of a black hole, captured by the Event Horizon Telescope Collaboration in 2019. 

In 2001, Pawel Mazur and Emil Mottola proposed a different solution to Einstein's field equations that led to objects which they called gravitational condensate stars, or gravastars. Contrary to black holes, gravastars have several advantages from a theoretical astrophysics perspective. On the one hand, they are almost as compact as black holes and also exhibit a gravity at their surface that is essentially as strong as that of a black hole, hence resembling a black hole for all practical purposes. On the other hand, gravastars do not have an event horizon, that is, a boundary from within which no information can be sent out, and their core does not contain a singularity. Instead, the center of gravastars is made up of an exotic – dark – energy that exerts a negative pressure to the enormous gravitational force compressing the star. The surface of gravastars is represented by a wafer-thin skin of ordinary matter, the thickness of which approaches zero. 

Theoretical physicists Daniel Jampolski and Prof. Luciano Rezzolla of Goethe University Frankfurt have now presented a solution to the field equations of general relativity that describes the existence of a gravastar inside another gravastar. They have given this hypothetical celestial object the name "nestar" (from the English “nested"). 

Daniel Jampolski, who discovered the solution as part of his Bachelor's thesis supervised by Luciano Rezzolla, says: “The nestar is like a matryoshka doll", adding that, “our solution to the field equations allows for a whole series of nested gravastars." Whereas Mazur and Mottola posit that the gravastar has a near infinite thin skin consisting of normal matter, the nestar's matter-composed shell is somewhat thicker: “It's a little easier to imagine that something like this could exist." 

Luciano Rezzolla, Professor of Theoretical Astrophysics at Goethe University, explains: “It's great that even 100 years after Schwarzschild presented his first solution to Einstein's field equations from the general theory of relativity, it's still possible to find new solutions. It's a bit like finding a gold coin along a path that has been explored by many others before. Unfortunately, we still have no idea how such a gravastar could be created. But even if nestars don't exist, exploring the mathematical properties of these solutions ultimately helps us to better understand black holes". 

Publication: Daniel Jampolski, Luciano Rezzolla: Nested solutions of gravitational condensate stars. Classical Quantum Gravity (2024) https://doi.org/10.1088/1361-6382/ad2317 

Images for download: https://www.uni-frankfurt.de/149345988 

Caption: According to findings by physicists at Goethe University Frankfurt, a gravastar could look like a matryoshka doll. Image: Daniel Jampolski and Luciano Rezzolla, Goethe University Frankfurt 

Further information
Professor Luciano Rezzolla
Institute for Theoretical Physics
Goethe University Frankfurt
Phone: +49 (69) 798-47871
rezzolla@itp.uni-frankfurt.de
https://astro.uni-frankfurt.de/rezzolla/

Editor: Dr. Markus Bernards, Science Editor, PR & Communication Office, Theodor-W.-Adorno-Platz 1, 60323 Frankfurt, Tel: +49 (0) 69 798-12498, bernards@em.uni-frankfurt.de