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Saturday 2 April 2016: World Autism Awareness Day

Next Saturday, 2 April, is World Autism Awareness Day. This event is aimed at reminding the general public, professionals and politicians of the need to improve the quality of life of people suffering from this disorder.

Autism is a pervasive developmental disorder characterised by impaired social interactions and verbal and non-verbal communication, and by repetitive behaviours and limited areas of interest. It appears in early childhood and persists throughout life.

 

Inserm researchers are involved throughout the year in research on autism and other pervasive developmental disorders.

Recently, work done by Monica Zilbovicius’s team, Inserm Unit 1000, “Neuroimaging and Psychiatry,” has shown that stimulation of a certain area of the brain, the superior temporal sulcus, allows modification of gaze behaviour. This discovery opens new therapeutic opportunities for people with autism.

See the press release “A study demonstrates the possibility of changing the behaviour of the gaze by transcranial magnetic stimulation”.

 

Meanwhile, a team from Inserm Unit 862, “Neurocentre Magendie,” has demonstrated how impaired connections between different areas of the brain are involved in fragile X syndrome, a neurodevelopmental disorder. Their work provides an explanation for some of the symptoms of autistic spectrum disorders and fragile X syndrome.

Read the press release “Defective connections throughout the brain involved in certain autistic disorders”.

 

Researchers from Inserm Unit 930, “Imaging and Brain,” in collaboration with François-Rabelais University and Tours Regional University Hospital, have identified specific gene combinations in patients with autism that distinguish them from patients with intellectual disabilities, paving the way for new prospects for the diagnosis and understanding of the physiopathological mechanisms of autism.

Read the press release: “Autism: the value of an integrated approach to diagnosis”.

Dassault Systèmes and Inserm Announce Joint Agreement to Decipher Disease Complexity and Accelerate Clinical Research

Next Generation Scientific Innovation with the 3DEXPERIENCE Platform and Strategic Collaboration to Advance Programs in Aging, Cancer, Genomics and Microbiota

plateforme 3Dexperience

3DEXPERIENCE Plateform (c) Dassault Systèmes

Dassault Systèmes, the 3DEXPERIENCE Company, world leader in 3D design software, 3D Digital Mock Up and Product Lifecycle Management (PLM) solutions, and the French National Institute of Health and Medical Research (Inserm), the only French public research institute to focus entirely on human health and the largest in Europe, today announced the signature of a joint agreement to accelerate clinical research programs by deploying a virtual collaborative platform.  The agreement will draw from the expertise of each organization to offer new perspectives for addressing scientific and health challenges of the 21st century.

Inserm will use Dassault Systèmes’ 3DEXPERIENCE platform to conduct its strategic biomedical research programs in the areas of aging, cancer, genomics and microbiota.  The platform provides Inserm with an integrated virtual environment for open collaborative research, unified laboratory management and biological and chemical modeling and simulation from Dassault Systèmes’ flagship brand dedicated to scientific excellence, BIOVIA.

In turn, Dassault Systèmes will leverage big data from Inserm’s research programs to calibrate and validate scientific models that can be applied to future technologies for the clinical research domain. These models will enable the company to develop next-generation industry solution experiences targeting clinical trials, to accelerate decision-making and to enable earlier efficacy and safety demonstration with virtual trials.

“We seek out technologies that further our mission to observe and understand mechanisms of the living body and ultimately transfer this knowledge to therapeutic solutions for new and mutating diseases that are affecting the world’s growing population,” said Professor Yves Lévy, Chairman and CEO, Inserm.

“We lead long-term, competitive scientific programs in human health and medicine and the Dassault Systèmes’ 3DEXPERIENCE platform will help us support collaboration, project management, data, resources, traceability and other processes”

 

“At its core, Dassault Systèmes is a scientific company.  And at its core, Inserm explores the finest elements of life as we know it—fundamental science.  Clinical research has been the catalyst for life-changing discoveries during our lifetime, and introducing capabilities such as modeling and simulation coupled with big data science into translational science, opens up new horizons for investigation,” said Bernard Charlès, President & CEO, Dassault Systèmes.  “This fusion of advanced clinical research and the virtual world is a stepping stone to the future of precision medicine and brings us closer to harmonizing product, nature and life.”

For more information on Dassault Systèmes in the life sciences industry, visit http://www.3ds.com/industries/life-sciences/

Isolated case of bovine spongiform encephalopathy (BSE) in France

This Thursday, 24 March, the Ministry of Agriculture confirmed an isolated case of bovine spongiform encephalopathy (BSE), or mad cow disease, at a farm in Ardennes. The case was detected in a 5-year-old cow sent for rendering, “a method for processing animals that die on farms, and are therefore not intended for human consumption,” states AFP. In France, the last case of bovine spongiform encephalopathy dates back to 2011.

 

BSE is a prion disease that affected UK farms in the 1980s, and spread to Europe and the rest of the world. Feeding animals meat and bone meal contaminated with crushed carcasses resulted in the spread of BSE.

The appearance of a variant of Creutzfeldt-Jakob disease in humans in the UK and France, and then in many countries around the world in the 1990s, raised deep concerns among consumers who worried about the risk of transmission of the bovine prion to humans. The link between the BSE epidemic and the new variant of Creutzfeldt-Jakob disease in humans was easily established by researchers.

The ban on meat and bone meal, livestock surveillance and BSE testing are some of the measures that have been developed since then, in order to limit the risk of contamination.

What are the routes and mechanisms for transmission of a bovine prion to humans? What are the risks of secondary transmission? What are the consequences for health? How is the disease managed?

Researchers from Inserm are available to answer your questions.

A study demonstrates the possibility of changing the behaviour of the gaze by transcranial magnetic stimulation

A study financed by the Assistance Publique-Hôpitaux de Paris[1] has been conducted under the direction of Monica Zilbovicius[2] in the Inserm Unit 1000 on a particular region of the brain, the superior temporal sulcus (STS), influencing perception and behaviour of the gaze. This work has shown that transcranial magnetic stimulation (non-invasive and painless) of the STS can selectively and transiently inhibit the subject’s gaze into the eyes of the person speaking to them. Published in the journal Cerebral Cortex, it offers new therapeutic prospects for autistic patients precisely presenting anatomical and functional differences of the superior temporal sulcus.

eye tracking

(c) Monica Zilbovicius / Inserm

It is commonly admitted that the gaze plays an essential role in social interactions. At a very young age, human beings look others in the eye, because information from the eyes allows us to guess their intentions and feelings. In the brain, many studies highlight the importance of a specific region of the brain, the superior temporal sulcus (STS), in perception and behaviour of the gaze. However, to date, no experimental data has demonstrated a possible modification of the gaze by artificial modulation of a neural network.

Work conducted by Inserm Unit 1000, financed by AP-HP, has confirmed that ad hoc intervention in the STS was able to have an impact on the behaviour of the gaze. The researchers used transcranial magnetic stimulation (TMS): this method consists of applying a non-invasive and painless magnetic impulse to the brain through the skull, in order to study changes of gaze caused by inhibition of the STS by TMS, using oculometry (‘eye-tracking’). They showed 15 subjects films of actors and recorded the way they looked at these films before and after inhibition of the STS. In this way the researchers observed a significant distancing from the gaze of control subjects relative to the eyes of the actors, compared to the base measurement (cf. pictures). Inhibition of the superior temporal sulcus therefore selectively and transiently disrupts the movement of the subject’s gaze into the eyes of another subject.

These results offer new therapeutic prospects for autistic patients. In fact, many brain imaging studies have revealed the presence of anatomical and functional differences of the STS in this type of patient not displaying a marked preference of other people’s eyes.

For Prof Monica Zilbovicius, “given that TMS can be applied so as to inhibit or stimulate a certain brain area, stimulating the STS using TMS could cause an increase in gazing into the eyes. This is an avenue we will explore during the next stage of our research”.

[1] French Hospital clinical research programme (PHRC)

[2] Inserm Unit 1000, Paediatric Radiology Department, Necker Hospital for Sick Children, AP-HP

Cycle « Santé en questions » citizen conferences: the next meetings

Since 2012, to promote dialogue between science and society, Inserm and Universcience has offered « Santé en questions », an annual cycle of citizen conferences. The aim is to provide information about advances in life sciences and healthcare research, but also to allow the public to tell their story and talk to the speakers. These conferences are chaired by a journalist and held by link up between the Cité des Sciences et de l’Industrie in Paris and a regional partner site. The filmed conferences are available on the Internet and summarised in a booklet sent to politicians and distributed with the latest edition of the French magazine La Recherche.



On Twitter: follow LT via #ConfSanT and ask your questions at @InsermLive @indesciences @ConfCitePalais

On Facebook, find all the details on the pages for Conf Palais de la découverte and Cité des sciences

Programme
« Allergies: Spring is here again! »
Thursday 14 April 2016, from 7pm to 8.30pm
A link-up between the Cité des Sciences et de l’Industrie in Paris
And the Bachut Mediacentre in Lyon

Respiratory allergies affected more than 20% of the French population in 2015 and are ranked in fourth place among world diseases. Exposure to allergens has been intensifying over the last ten years, particularly with the effects of climate change. How do allergenic substances act? How to protect yourself against them? What can you do in your house?

Speakers

At the Paris site:
Jocelyne Just, head of the paediatric allergies department at Trousseau Hospital, AP-HP, whose research work particularly covers events in early life and the development of allergic and respiratory diseases. Her team is also interested in the impact of atmospheric pollution on allergic and respiratory diseases.

Jean-François Nicolas, dermatologist, director of the Inserm team ‘Immunology of skin allergy and vaccination’ at the Lyon International Infectiology Research Centre. Its research has demonstrated that inflammatory skin diseases are the consequence of the failure of immune tolerance towards allergens.
Contact: rf.mresni.noyl-ivrec@salocin /+33 (0)4 37 28 23 48

Sophie Rigard, policy officer to Bernard Jomier, Deputy Mayor of Paris responsible for healthcare, disability and relations with the Paris public hospitals (AP-HP).

At the Lyon site:
Guillaume Faburel, lecturer in urban studies at Lyon 2 University / UMR Triangle, LabEx ‘Intelligence of urban worlds’, whose work relates to sustainable towns, participative projects, environmental injustices and new urban social support structures.

The next three conferences

« Sport: what limits for the body? » – Thursday 22 September 2016, from 7pm to 8.30pm
A link-up between the Cité des Sciences et de l’Industrie in Paris and the Lyon Musée des Confluences
Sport is good for health. But top-level sportsmen and women often perform to the limits of their bodies. How can research help them? Definition of rules for progression, studies on motor function and balance, understanding brain processes in sports performance: nothing is ignored, for them and for all of us.

« Vaccines: why do they cause fear? » – Thursday 13 October 2016, from 7pm to 8.30pm
A link-up between the Cité des Sciences et de l’Industrie in Paris and the Montbéliard Pavillon des Sciences
More and more French people opposed to vaccines, undoubtedly due to a lack of information and misunderstanding of side effects. What actually are they? What is the mode of action of these unusual medicines? What is the collective challenge of vaccination? What is the future for vaccines?

« Predicting brain diseases: what precautions? » – Thursday 3 November, from 7pm to 8.30pm
A link-up between the Cité des Sciences et de l’Industrie in Paris and the Marseille Bibliothèque de l’Alcazar
The goal of predictive medicine is to treat illnesses before they appear. Thus, strokes, anorexia and neurodegenerative diseases are the focus of research into a genetic diagnosis. But how do you live with the knowledge of this potential risk of illness? What risk of discrimination are we running based on our genetic heritage?

The conference is open to all and admission is free, however we recommended registering to attend at: rf.ecneicsrevinu@secnerefnoc

Conferences in the « Santé en questions » cycle are organised in partnership with:

Bibliothèque de l’Alcazar, Bibliothèques Municipales de Marseille, Casden, Cerveau & Psycho, Indésciences, La Recherche, Paris City Hall, Bachut Mediacentre, Musée des Confluences, Pavillon des Sciences de Montbéliard, Pour la science, Pourquoi docteur, Sciences et Avenir, City of Lyon

Discovery of a gene associated with radiosensitivity and post-radiotherapy complications

Scientists at the CEA’s Institute of Cellular and Molecular Radiation Biology, in collaboration with INSERM, Université Paris-Sud, and international partners, have demonstrated a connection between the expression of the TRAIL gene, which plays a role in cell death, and the radiosensitivity of certain human T lymphocytes. This research also showed a relationship between three genetic forms of TRAIL and the radiosensitivity of these T lymphocytes. Finally, two of these genetic forms of TRAIL were linked with serious skin complications in breast cancer patients treated with radiotherapy. These results, published on the Oncotarget website on 16th March 2016, indicate how determining the radiosensitivity of lymphocytes and studying the gene polymorphisms associated with this radiosensitivity could lead to personalised radiotherapy. 



T4EM[1] lymphocytes are lymphocytes that constitute a part of the “memory” of a person’s immune system. Using a simple radiosensitivity test[2] on these cells in 373 individuals, scientists at the Institute of Cellular and Molecular Radiation Biology showed that, without irradiation, the TRAIL[3] gene, which regulates cell death, was strongly expressed in radiosensitive T4EM lymphocytes and weakly expressed in radioresistant T4EM lymphocytes.

Using functional studies, these scientists showed that the TRAIL protein receptor was activated after irradiation and that the interaction between TRAIL and its receptor killed T4EM lymphocytes. These results explain the correlation between the level of expression of TRAIL in T4EM lymphocytes and their radiosensitivity.

PhotoCP web © P.Stroppa / CEA

© P.Stroppa / CEA

schéma

A study of the genetic link between TRAIL and the radiosensitivity of T4EM lymphocytes has identified three single nucleotide polymorphisms (SNP) of this gene related to the radiosensitivity of these lymphocytes. This indicates that this radiosensitivity is genetically determined. Finally, the study of a cohort of 113 breast cancer patients who developed complications after radiotherapy showed a correlation between two of the SNPs of the TRAIL gene and the onset of acute or subacute radiation-induced dermatitis after radiotherapy.

This pioneering study shows how genetics, associated with functional cellular radiosensitivity tests, can open up the possibility of personalising the dose delivered when treating cancer by radiotherapy.

[1] Lymphocyte T4 effector-memory

[2] This test uses flow cytometry to quantify the death of T4EM lymphocytes according to the irradiation dose to which they have been subjected.

[3] TNF-Related Apoptosis Inducing Ligand

Reuters Ranking: CEA, CNRS and Inserm in the Top 10 worldwide research institutions for innovation

The ranking compiled by Thomson Reuters covers the “25 public institutions that contribute most to scientific and technological advancement worldwide” according to Reuters. The CEA is topping the list of worldwide organisations, with CNRS in 5th place and Inserm in 10th place.

 

This ranking is based on the integration of data regarding intellectual property; the number of patents and publications stored in the Thomson Reuters database platforms over the last 8 years.

The first 25 listed public organisations are ranked according to 10 criteria, including: the total number of identified publications, the percentage of publications containing at least one co-author affiliated with a private entity, the volume of WIPO-registered patents, the patent success rate (rate of application), the patent registration percentage covering the US, Europe and Japan, or the patent citation rate (Patent Citation Index).

Note: the Fraunhofer (Germany) is ranked 2nd, the Japan Science and Technology Agency is 3rd, and Health & Human Services (HHS), a subsidiary of the American NIH and CDC in charge of industrial property matters, is in 4th place.

A similar ranking of universities was published by Reuters last year.

According to CEA Chairman Daniel Verwaerde, “this result acknowledges CEA’s efforts to validate the outcome of its research and the international recognition it has today. The impact of our patents is clearly evident in the industrial and commercial field, as well as the professionalism of the teams in charge of managing intellectual property. ”

This unique, international and professional ranking shows how innovation and transmission are at the heart of French research, with performances that contradict the preconceived notions communicated throughout France”, states Alain Fuchs, Chairman of CNRS.

According to Yves Lévy, Chairman and CEO of Inserm “this ranking perfectly illustrates the ongoing dynamic of innovation within national organisations. Inserm’s ranking, along with its subsidiary Inserm-Transfert, once again confirms its position as a global leader in the sector of health innovation”.

For further information: click here

Brain Awareness Week 2016: 14–20 March

The 17th edition of Brain Awareness Week will take place from 14 to 20 March 2016, in 62 countries as well as France. During this week, the general public is invited to come and meet researchers in order to better understand the workings of the brain and to find out about advances in research.

Researchers from large research bodies, including Inserm, neuroscience institutes and the hospital/university sector, will be offering 400 free events: bistrot sciences, exhibitions, films, scientific workshops and lectures, in over 30 towns and cities in France.

The inaugural lecture, “Les Multiples Facettes de la Dopamine: du Contrôle du Mouvement aux Addictions”, will be given by Jean-Antoine Girault, President of the French Neuroscience Society, on Monday 14 March, 6:30–8:30 pm, at the auditorium of the Brain and Spine Institute (ICM), Paris.

Registration required: gro.etutitsni-mci@uaevrecudeniames

 

Brain Awareness Week will be preceded by a conference, “Cerveau: du Soin à l’Homme Augmenté”, on Thursday 10 March, 7:00–8:30 pm, hosted simultaneously by Cité des Sciences et de l’Industrie (Paris) and the Bibliothèque de la Part-Dieu (Lyon), as part of the “Santé en Questions” series organised by Inserm, Universcience and regional players involved in scientific culture.

It will also be attended by:

Hervé Chneiweiss, President of the Inserm Ethics Committee (Paris)

Pierre Cassous Noguès, philosopher and professor at Université Paris 8 (Paris)

François Berger, neuro-oncologist, Inserm team leader and Director of Clinatec (Lyon)

Jérémie Mattout, researcher on brain/machine interfaces at the Lyon Neuroscience Research Center (Lyon)

Follow the live tweet via #ConfSanT and ask your questions @InsermLive

The complete programme for Brain Awareness Week is at www.semaineducerveau.fr

Towards better understanding of the side effects of radiotherapy

Two studies, one theoretical and the other biological and clinical, conducted by Nicolas Foray, radiobiologist at the Combined Research Unit 1052 ‘Cancer Research Centre of Lyon’ (Inserm/CNRS/Centre Léon-Bérard/Lyon I University), have just been published in the International Journal of Radiation Biology and the International Journal of Radiation Oncology. These two studies allow a better understanding of the adverse side effects of radiotherapy. They propose a new theory about the cellular response to ionising radiation. This theory is based on having revealed a protein called ATM passing from the cytoplasm to the nucleus of irradiated cells. Once inside the nucleus, the ATM protein initiates repair of breaks in the DNA: the longer this transit is delayed, the greater the radio-sensitivity of the cells and the more marked the adverse side effects of the radiotherapy.

PhotoCP web radiothérapie (c) Inserm, Institut Curie - Guénet, François

(c) Inserm/Institut Curie/ Guénet, François

 

These two studies were possible by virtue of the COPERNIC collection (started in 2003) of more than a hundred cell lines from radiosensitive patients.

  • The theoretical study resolves an enigma in radiotherapy dating back 50 years, by giving a biological interpretation to an empirical formula. This formula links the survival of cells to the radiation dose.
  • The biological and clinical study validates the theoretical study. It combines 67 co-authors, including 50 French radiotherapists, representing thirty cancer research centres or hospitals. It now enables us to develop predictive tests of radiosensitivity for the adverse side effects of radiotherapy.

 

What innovation have these two studies provided?

The ATM protein was discovered in 1995. This protein is known because its mutations cause the syndrome associated with the strongest form of human radiosensitivity, ataxia telangiectasia. Up until now, the ATM protein has always been considered as cell nucleus protein and no study had probed its presence in the cytoplasm. The radiobiology group of Inserm Unit 1052 analysed more than a hundred cell lines from patients suffering from adverse tissue reactions following radiotherapy (dermatitis, proctitis, etc.). These analyses showed that the ATM protein is instead found in the cytoplasm of cells and transits into the nucleus after irradiation.

 

How was the theoretical study conducted? What was its scope?

Larry Bodgi and Nicolas Foray mathematically modelled all the steps leading the ATM protein from the cytoplasm to the nucleus. Firstly, the oxidation produced by irradiation leads to a change in the shape of the ATM protein. This change facilitates its passage into the nucleus. An ATM then activates recognition of double-stranded breaks (DSB) in the DNA, triggering their repair. The result of this modelling was that the final mathematical formula linking cell survival to the radiation dose proved to be identical to that from the empirical model (called linear-quadratic), proposed in the 1970s. As a result of this theoretical study, we can now better understand at cellular level why a cell is radiosensitive and the consequences arising from a recognition or repair defect for DSB after irradiation. It remained to confirm it in the patient by means of a biological and clinical study, to predict the adverse side effects of radiotherapy.

 

How was the biological and clinical study conducted? What was its scope?

Out of 380,000 cancer case per year [in France], half of patients are treated using radiotherapy. From 5 to 20% of these patients can suffer adverse tissue reactions that extend from simple redness to even radio-induced burn, and in exceptional cases death.  From the COPERNIC collection, the cells of each patient were amplified in the laboratory then irradiated under the exact conditions of a radiotherapy session (a dose of 2 Gy[1]). Researchers in the radiobiology group of Inserm Unit 1052 examined the DSB repair rate by using 3 immunofluorescence biomarkers (a technique used to visualise certain proteins on the actual site of DNA breaks) applied under many irradiation conditions. In parallel, 50 radiotherapists, co-authors of the study, supplied patient-specific clinical information, particularly the severity score[2] of tissue reactions (grade 0, no reaction; grade 5, death of patient), reflecting their tissue radiosensitivity. A significant correlation was obtained between the transit speed of ATM protein and the severity score of radio-induced tissue reactions. Such a correlation remains valid irrespective of the type of cancer treated or how early or late the adverse tissue reaction occurs after radiotherapy. From this correlation, human radiosensitivity is classified into 3 groups:

  • Group I: Rapid ATM transit: radioresistance
  • Group II: Delayed ATM transit: moderate radiosensitivity.
  • Group III: Massive defect in recognition or repair of DSB: hyper radiosensitivity

This classification now makes it possible to anticipate care strategies for radiotherapy treatments, because this approach is also valid for tumours. Given the impact and applications of this work, patents applications have been submitted jointly with the Neolys Diagnostics start-up created in 2014, with the support of Inserm Transfer and Lyon SATT. The aim of Neolys Diagnostics is to industrialise radiosensitivity tests arising from these 2 studies, to give radiotherapy a new tool to improve personalisation of anti-cancer radiotherapy treatment.

Financial support

These two studies are part of the Investissements d’Avenir [Future Investments] (INDIRA project, Radioprotection and Nuclear Safety) directed by the Commissariat Général à l’Investissement [French General Investment Commission]. Other [French] financial support was received from: Association for research on Ataxia Telangiectasia (APRAT), AVIESAN- Cancer Plan calls to tender (Physicancer and Health and Environment programmes), the EDF Radioprotection Committee, National Centre for Space Studies (CNES), Rhône-Alpes Auvergne CLARA cancer centre (Oncostarter and Proof of Concept programmes). All experiments were performed at the Léon-Bérard Cancer Centre in Lyon.

[1] The radiation dosage unit is the Gray (Gy).

[2] Agreed international scales now allow tissue reactions to be classified irrespective of the location and organs affected (e.g. CTCAE and RTOG scales).

1st case of acute myelitis in a patient infected with Zika virus

A first case of acute myelitis following infection with Zika virus has been reported for the first time by a research team from Inserm Unit 1127 Brain and Spinal Cord Institute (Inserm/CNRS/Sorbonne University) and neurologists at Pointe-à-Pitre University Hospital and the University of the Antilles. A young patient in the acute phase of an infection by Zika virus presented motor deficiency in the 4 limbs, associated with very intense pain and acute urinary retention. The presence of the virus was confirmed in the cerebrospinal fluid, blood and urine.
This case was the subject of a Case report published in The Lancet on 3 March 2016.

PhotoCP Zika

(c) Fotolia

In January 2016, a 15-year old girl was admitted to the Pointe-à-Pitre University Hospital in Guadeloupe, with left-side hemiplegia. The girl showed urinary retention on her second day in hospital. The left-side hemiplegia and pain became worse and the doctors recorded a loss of sensation in the legs.

The researchers detected high concentrations of Zika virus in the serum and cerebrospinal fluid on the second day after admission (9 days after the symptoms began). Tests for shingles, chickenpox, herpes virus, legionellosis and mycoplasma pneumonia were negative.

The patient was treated with methylprednisolone (1 g), an anti-inflammatory drug, from the first day and daily for 5 days. Seven days after admission, her neurological condition had improved. At present, the patient is still in hospital but she is out of danger. She has signs of moderate weakness in both legs but is walking unaided again.

For the researchers, “this case strengths the hypothesis regarding the neurotropic nature of the Zika virus. It highlights the existence of neurological complications in the acute phase of the infection, while Guillain Barré syndromes are post-infectious complications. Furthermore, this is a single case. Future studies will be needed.”

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