A Ludwig Cancer Research study has identified a previously unrecognized mechanism by which cancer cells of a relatively benign subtype of pancreatic tumors methodically revert—or “de-differentiate”—to a progenitor, or immature, state of cellular development to spawn highly aggressive tumors that are capable of metastasis to the liver and lymph nodes.
The study, led by Ludwig Lausanne’s Douglas Hanahan and published in Cancer Discovery, a journal of the American Association for Cancer Research, also shows that engagement of the mechanism is associated with poorer outcomes in patients diagnosed with pancreatic neuroendocrine tumors (PanNETs). Further, its findings provide concrete evidence that such cellular de-differentiation, widely observed across cancer types, is a not merely a random consequence of cancer cells’ other aberrations.
“Our study provides a clear example in a single tumor type that de-differentiation is an independently regulated and separable step in multi-step tumorigenesis,” said Hanahan, distinguished scholar at the Ludwig Lausanne Branch. “Moreover, this is not nonspecific de-differentiation, but rather, the result of a precise reversion of a developmental pathway that generated the mature cell type from which the cancer arose.”
PanNET tumors originate from the islet beta-cells of the pancreas, which produce the hormone insulin. Hanahan and his colleagues had previously reported that these tumors can be divided into two subtypes: a relatively benign, ‘well-differentiated’ subtype that maintains many features of insulin producing beta-cells, and a more aggressive and poorly-differentiated subtype that lacks those features.
Using a PanNET mouse model, they showed in the current study that the ‘poorly differentiated’ cancer cells have many characteristics of normal islet progenitor cells, and that the progression from benign to aggressive PanNET tumors requires cancer cells to retrace the pathway of beta cell differentiation and maturation to assume the progenitor state.
The researchers also uncovered a molecular circuit in cancer cells that governs this de-differentiation. They report that tumor cells poised to de-differentiate step up their production of a type of RNA molecule that regulates gene expression known as microRNA18. This ultimately causes the activation of Hmgb3, a protein that controls the expression of a suite of genes that pushes the cells into a progenitor state.
The results of this study provide new insights on de-differentiation as part of the puzzle of cancer and furnish preliminary evidence supporting its inclusion as a distinct and separable step, or perhaps sub-step, in the deadly progression toward malignancy.
This study was supported by Ludwig Cancer Research, the Swiss National Science Foundation and the Human Frontier Science Program Organization.
In addition to his Ludwig post, Douglas Hanahan is a professor emeritus at École Polytechnique Fédérale de Lausanne (EPFL).
Reference: Sadegh Saghafinia, Krisztian Homicsko, Annunziata Di Domenico, Stephan Wullschleger, Aurel Perren, Ilaria Marinoni, Giovanni Ciriello, Iacovos P Michael and Douglas Hanahan, “Cancer cells retrace a stepwise differentiation program during malignant progression”, Cancer Discovery, 2021. DOI:10.1158/2159-8290.CD-20-1637
Researchers from University of Arizona and University of Utah published a new paper in the Journal of Marketing that examines why most scholarly research is misinterpreted by the public or never escapes the ivory tower and suggests that such research gets lost in abstract, technical, and passive prose.
From developing vaccines to nudging people to eat less, scholars conduct research that could change the world, but most of their ideas either are misinterpreted by the public or never escape the ivory tower.
Why does most academic research fail to make an impact? The reason is that many ideas in scholarly research get lost in an attic of abstract, technical, and passive prose. Instead of describing “spilled coffee” and “one-star Yelp reviews,” scholars discuss “expectation-disconfirmation” and “post-purchase behavior.” Instead of writing “policies that let firms do what they want have increased the gap between the rich and the poor,” scholars write sentences like, “The rationalization of free-market capitalism has been resultant in the exacerbation of inequality.” Instead of stating, “We studied how liberal and conservative consumers respond when brands post polarizing messages on social media,” they write, “The interactive effects of ideological orientation and corporate sociopolitical activism on owned media engagement were studied.”
Why is writing like this unclear? Because it is too abstract, technical, and passive. Scholars need abstraction to describe theory. Thus, they write about “sociopolitical activism” rather than Starbucks posting a “Black Lives Matter” meme on Facebook. They are familiar with technical terms, such as “ideological orientation,” and they rely on them rather than using more colloquial terms such as “liberal or conservative.” Scholars also want to sound objective, which lulls them into the passive voice (e.g., the effects… were studied) rather than active writing (e.g., “we studied the effects…”). Scholars need to use some abstract, technical, and passive writing. The problem is that they tend to overuse these practices without realizing it.
When writing is abstract, technical, and passive, readers struggle to understand it. In one of the researchers’ experiments, they asked 255 marketing professors to read the first page of research papers published in the Journal of Marketing (JM), Journal of Marketing Research (JMR), and Journal of Consumer Research (JCR). The professors understood less of the papers that used more abstract, technical, and passive writing compared to those that relied on concrete, non-technical, and active writing.
As Warren explains, “When readers do not understand an article, they are unlikely to read it, much less absorb it and be influenced by its ideas. We saw this when we analyzed the text of 1640 articles published in JM, JMR, and JCR between 2000 and 2010. We discovered that articles that relied more on abstract, technical, and passive writing accumulated fewer citations on both Google Scholar and the Web of Science.” An otherwise average JM article that scored one standard deviation lower (clearer) on our measures of abstract, technical, and passive writing accumulated approximately 157 more Google Scholar citations as of May 2020 than a JM article with average writing.
Why do scholars write unclearly? There is an unlikely culprit: knowledge. Conducting good research requires authors to know a lot about their work. It takes years to create research that meaningfully advances scientific knowledge. Consequently, academic articles are written by authors who are intimately familiar with their topics, methods, and results. Authors, however, often forget or simply do not realize that potential readers (e.g., PhD students, scholars in other sub-disciplines, practicing professionals, etc.) are less familiar with the intricacies of the research, a phenomenon called the curse of knowledge.
The research team explores whether the curse of knowledge might be enabling unclear writing by asking PhD students to write about two research projects. The students wrote about one project on which they were the lead researcher and another project led by one of their colleagues. The students reported that they were more familiar with their own research than their colleague’s research. They also thought that they wrote more clearly about their own research, but they were mistaken. In fact, the students used more abstraction, technical language, and passive voice when they wrote about their own research than when they wrote about their colleague’s research.
“To make a greater impact, scholars need to overcome the curse of knowledge so they can package their ideas with concrete, technical, and active writing. Clear writing gives ideas the wings needed to escape the attics, towers, and increasingly narrow halls of their academic niches so that they can reduce infection, curb obesity, or otherwise make the world a better place,” says Farmer.
The Journal of Marketing develops and disseminates knowledge about real-world marketing questions useful to scholars, educators, managers, policy makers, consumers, and other societal stakeholders around the world. Published by the American Marketing Association since its founding in 1936, JM has played a significant role in shaping the content and boundaries of the marketing discipline. Christine Moorman (T. Austin Finch, Sr. Professor of Business Administration at the Fuqua School of Business, Duke University) serves as the current Editor in Chief. https://www.ama.org/jm
About the American Marketing Association (AMA)
As the largest chapter-based marketing association in the world, the AMA is trusted by marketing and sales professionals to help them discover what is coming next in the industry. The AMA has a community of local chapters in more than 70 cities and 350 college campuses throughout North America. The AMA is home to award-winning content, PCM® professional certification, premiere academic journals, and industry-leading training events and conferences. https://www.ama.org
Researchers from Niigata University , the University of Tokyo, Osaka University and Tokyo Medical University, Japan have developed a new approach that could revolutionize the treatment, prevention, and possibly reversal of the damages caused by liver diseases. This novel strategy exploits small extracellular vesicles (sEVs) derived from interferon-γ (IFN-γ) pre-conditioned MSCs (γ-sEVs).
Cirrhosis and other chronic liver diseases remain a global health concern, with close to 2 million deaths reported annually, these account for approximately 3.5% of annual worldwide deaths. All these statistics are largely driven by the fact that 75 million of the 2 billion people who consume alcohol worldwide are diagnosed with alcohol-use disorders and are at risk of developing alcohol- induced liver disease. In addition, the high prevalence of viral hepatitis-induced liver damage continues to be on the rise.
These sobering numbers inspired a team of scientists led by Prof. Shuji Terai of the Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, to build upon previous knowledge that the ability to control fibrosis—which is the development of fibrous connective tissue as a reparative response to injury or damage—in livers under advanced cirrhosis, is often lost. In an interview Prof. Terai said, “Our results showed that modified extracellular vesicles can become a new therapeutic strategy for liver cirrhosis”
Since clinically advanced cirrhosis is an end-stage disease that can effectively be treated only by liver transplantation at present, there is a race in the field with many scientists developing targeted therapies for modulating fibrosis and aiding tissue regeneration.
One of the most popular approaches is cell therapy, where mesenchymal stromal cells (MSCs) and macrophages have shown potential towards inducing liver fibrosis regression. The popularity of this approach is centered on its cost-effectiveness; because MSCs are not only obtainable from the bone marrow, but also from medical waste that include umbilical cord tissue, adipose tissue, and dental pulp. Apart from the ease of availability, MSCs can also be grown relatively easily in the lab. Furthermore, rather than acting directly by replacing the damaged tissues, MSCs have previously been shown to be medical signaling cells that indirectly produce cytokines, chemokines, growth factors, and exosomes that are crucial for repairing and regenerating damaged tissue. Over the years, considerable progress has been made towards capacity building for research and clinical trials for novel treatment strategies against liver diseases. This is exemplified by previous demonstrations that MSCs have anti-inflammatory, anti-fibrotic, and anti-oxidative effects through these humoral factors. Despite tissue rejection being one of the barriers to cell/tissue transplantation interventions; MSCs are attractive for possessing low immunogenicity, and this can facilitate their use for both autologous (same individual) and allogeneic (different individuals of the same species) transplantation, as evidenced by applications in nearly 1000 clinical trials involving other fields, including the treatment of liver diseases.
In a series of experimental mice studies, this team of researchers, from Niigata University , the University of Tokyo, Osaka University and Tokyo Medical University, Japan may have discovered that IFN-γ pre-conditioned human AD-MSC-derived sEVs (AD-MSC-γ-sEVs) can induce anti-inflammatory macrophage counts, which are the key players in tissue repair, including the regression of fibrosis and promotion of tissue regeneration in vitro.
They report that both human adipose tissue-derived MSCs (AD-MSC-sEVs) and AD-MSC-γ-sEVs can promote macrophage motility and phagocytic activity. In addition, they also show that AD-MSC-γ- sEVs contain anti-inflammatory macrophage inducible proteins and can effectively control inflammation and fibrosis in a mouse model of cirrhosis. Following single-cell RNA-seq application, they confirmed AD-MSC-γ-sEVs therapy can induce multidimensional transcriptional changes. Taken together, these results suggest that AD-MSC-derived sEVs can affect the shape and function of macrophages and effectively recruit them into damaged areas, thereby promoting damaged liver tissue repair.
In an interview, Dr. Atsunori Tsuchiya of the Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, who was part of the research team said, “Both mesenchymal stromal cells and macrophages are reported to have therapeutic effects for liver cirrhosis, however relationship of both cells and mechanisms of action was not clear. We challenged this problem”. He went on to add, “We found the important fact that extracellular vesicles from interferon-γ can induce the tissue repair macrophages, which can regress fibrosis and promote liver regeneration effectively”. These words were also echoed by Dr. Suguru Takeuchi of the Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, who was also part of the research team, “In our previous study, we reported that intravenous administration of mesenchymal stromal cells migrated to the lung, can work as “conducting cells” and affect to macrophages “ working cells” in the liver.” “In this study we first elucidated that extracellular vesicles from mesenchymal stromal cells are key molecules to affect the macrophages”, added Dr. Takeuchi.
This proof-of-concept pilot study that complements macrophage therapy, holds potential as a strategy for treating liver diseases using IFN-γ pre-conditioned sEVs. However, further development and determination of the mechanisms underlying Treg cell count induction by IFN-γ pre-conditioned MSCs and sEVs still form part of their future research plans before these findings can be translated to humans in phased and controlled clinical trials.
During a floristic exploration of Medog in Tibet in June and November 2016 and June 2017, researchers from the Kunming Institute of Botany (KIB) and the Xishuangbanna Tropical Botanical Garden (XTBG) collected an interesting plant from three locations in the understory of a primeval tropical forest.
After morphological studies and literature review, the researchers confirmed that the plant belong to Amblyanthus, a small genus in the family Primulaceae of flowering plants and not previously recorded in China.
They named the new species as Amblyanthus chenii in honor of Prof. CHEN Jie (Chieh Chen, 1928–2011) from KIB, who devoted his life to the study of Chinese plants and Yunnan flora. And got it published in Systematic Botany.
Amblyanthus chenii is a small shrub. It is most morphologically similar to A. multiflorus, particularly in its axillary inflorescence and connate filaments, but it differs from A. multiflorus in its inflorescence pattern and the connation extent of its sepals and petals. It has condensed and short panicles branched only at the top of the rachis and sepals and petals connate up to the middle.
Moreover, a phylogenetic analysis based on nuclear ribosomal internal transcribed spacer (ITS) and six plastid markers indicated that A. chenii and Amblyanthopsis burmanica form a clade that is nested within the large pantropical genus Ardisia and is sister to Ardisia subgenus Crispardisia.
“Actually, fruiting specimens of this species had been collected in 1993 by the Expedition Team to Medog (ETM) from KIB. Prof. CHEN Jie first identified these specimens as a new species, but not validly published due to the lack of a new or cited description or diagnosis,” said an author of the study.
A. chenii is known only from Medog County, Xizang Province, China. It grows in the understory of primary forests and montane tropical forests at an altitude of 850 m. Its conservation status is judged as Data Deficient (DD), based on International Union for Conservation of Nature (IUCN 2012) version 3.1 criteria.
Featured image: Fruits of Amblyanthus chenii (Image by TAN Yunhong)
Reference: Zhou, Zhuo, Guo, Yong-jie et al., “Amblyanthus chenii (Primulaceae), a New Species and Generic Record from Xizang, China”, Systematic Botany, Volume 46, Number 1, March 2021, pp. 152-161(10). DOI:https://doi.org/10.1600/036364421X16128061711250
If a base station in a local area network tries to use a directional beam to transmit a signal to a user trying to connect to the network — instead of using a wide area network broadcast, as base stations commonly do — how does it know which direction to send the beam?
Researchers from Rice University and Brown University developed a link discovery method in 2020 using terahertz radiation, with high-frequency waves above 100 gigahertz. For this work, they deferred the question of what would happen if a wall or other reflector nearby creates a non-line-of-sight (NLOS) path from the base station to the receiver and focused on the simpler situation where the only existing path was along the line-of-sight (LOS).
In APL Photonics, from AIP Publishing, those same researchers address this question by considering two different generic types of transmitters and exploring how their characteristics can be used to determine whether an NLOS path contributes to the signal received by the receiver.
“One type of transmitter sends all frequencies more or less in the same direction,” said Daniel Mittleman, co-author and an engineering professor at Brown, “while the other type sends different frequencies in different directions, exhibiting strong angular dispersion. The situation is quite different in these two different cases.”
The researchers’ work shows that the transmitter sending different frequencies in different directions has distinct advantages in its ability to detect the NLOS path and distinguish them from the LOS path.
“A well-designed receiver would be able to detect both frequencies and use their properties to recognize the two paths and tell them apart,” Mittleman said.
Many recent reports within academic literature have focused on various challenges involved in using terahertz signals for wireless communications. Indeed, the term 6G has become a buzzword to encompass future generations of wireless systems that use these ultrahigh-frequency signals.
“For terahertz signals to be used for wireless communications, many challenges must be overcome, and one of the biggest is how to detect and exploit NLOS paths,” said Mittleman.
This work is among the first to provide a quantitative consideration of how to detect and exploit NLOS paths, as well as a comparison of the behavior of different transmitters within this context.
“For most realistic indoor scenarios we can envision for an above-100 gigahertz wireless network, the issue of NLOS path is definitely going to require careful consideration,” said Mittleman. “We need to know how to exploit these link opportunities to maintain connectivity.”
If, for example, the LOS path is blocked by something, an NLOS path can be used to maintain the link between the base station and receiver.
“Interestingly, with a transmitter creating strong angular dispersion, sometimes an NLOS link can provide even faster connectivity than the LOS link,” said Yasaman Ghasempour, co-author formerly at Rice University and currently an assistant professor at Princeton University. “But you can’t take advantage of such opportunities if you don’t know the NLOS path exists or how to find it.”
Featured image: Representation of a transmitter (left) broadcasting a signal with strong angular dispersion. Each frequency is represented by a different color and comes out in a different direction, which produces a rainbowlike structure. Two of the frequencies make it to the receiver (right), one represented by yellow (LOS path) and another by blue (NLOS path incorporating a reflection off a surface). CREDIT: Mittleman Lab, Brown University
Traffic accidents, tumor resections, and congenital diseases can cause significant trauma, which can lead to large bone deformations and/or bone loss. Although bone has some capacity to regenerate, large bone defects cannot be healed without major medical procedures.
In these situations, metallic implants are widely used, but the bioinertness of such implants poses a major challenge in bone tissue engineering. Bioinert metal implants lack bone integration, loosen over time, and may lead to adverse reactions around the area in which they are implanted.
In Biointerphases, by AIP Publishing, researchers from Middle East Technical University in Turkey showcase a variety of approaches that are alternatives to metallic implants and use natural polymer coatings to improve bone-implant integration, also known as osseointegration.
“We utilized a soft structure, which is very similar to human tissues, and placed this structure between human or animal bone and a metal surface,” said author Zafer Evis. “This serves as an interphase increasing bone tendency to attach on implants and prevent loosening or bacterial invasion.”
Establishing a strong and robust chemical interaction between a metal and a completely organic and natural polymer is a significant advancement in the field of bone tissue engineering. It opens a new era of applications with a broader range of modalities that can be applied in almost all hard tissue defects and traumas.
The research showcases several important findings. First, natural polymer coatings significantly improved metal electrochemical corrosion properties, and metals tend to resist corrosion after polymer coating. Second, polysaccharides and proteins can be successfully grafted onto metal surfaces without losing their biological nature.
“One of the surprises is that the coatings can be modified in unlimited ways,” said Evis. “They can be composited, reconfigured, and tailored to allow or disallow certain biological activities, such as allowing cell attachment while disallowing bacterial attachment.”
Coatings may also be designed to possess multifunctionality, which is the goal in tissue engineering applications.
The researchers plan to improve biological functionality of natural polymer coatings on titanium implants. Even though natural polymers can be successfully coated on metal implants, the robustness, yield, and mechanical stability of polymers on metal are still very problematic.
They will try to surpass the need for complex devices and method to improve the stability of polymer-metal interactions and eventually achieve long-term interphase durability. The methods discussed could be used in tandem with other implant surface modification methods to further enhance bioactivity of the metallic implants.
Featured image: Natural polymer coatings on a metallic implant surface may provide a multipurpose interphase layer to support bone-implant integration through tailored properties. CREDIT: Ahmet Engin Pazarçeviren
In a study published in Science Advances, the researchers from the Institute of Zoology of the Chinese Academy of Sciences unraveled the dynamic of Dicing bodies (D-bodies), an important membraneless organelle that processes microRNA precursors into microRNAs, under normal conditions and in response to virus infection.
Organelles, the basic components of cells, are formed by the separation of membrane (membrane-bound organelles) or via liquid-liquid phase separation (membraneless organelles). The membraneless feature allows membraneless organelles to easily communicate with cell matrix or other organelles, and even form or collapse in the response of organisms to stresses, modulating the cell resistance. However, little is known about the dynamic mechanism of membraneless organelles response to stress.
The massive replications of viruses cause severe cellular stresses to host cells. The viral RNAs and proteins are thus targeted by host membraneless organelles. In the process of long-term adaptation, viruses change the accumulation of resistance-related membranous organelles in different ways to inhibit the host resistance system and facilitate the infections and proliferations of viruses. Therefore, virus infection provides a convenient system for studying the dynamic balance mechanism of membraneless organelles.
The researchers found three RNA helicase proteins, RNA helicase 6 (RH6), RH8, and RH12, associated with the core components of D-bodies. The knockdown of these three genes resulted in a significant decrease, even disappearance, of D-bodies. These helicases interact with and facilitate the phase separation of SE, a core component of D-body, which subsequently promote the formation of D-bodies. Therefore, as novel components of D-body, RH6, RH8, and RH12 modulate D-bodies homeostasis through liquid-liquid phase separation (LLPS).
Besides, the researchers studied the dynamic mechanism of membraneless organelles upon the infection of viruses. They found that the number of D-body in cells significantly decreases after viral infection. Meanwhile, after virus infection, the accumulations of RH6, RH8, and RH12 in the nucleus are significantly reduced, while the total amounts of these helicases remain unchanged, indicating viral infection alters the localizations of these RNA helicases and reduces their accumulation in the nucleus, resulting in the depolymerization of D-body.
In addition, the researchers found that these proteins are enriched at the viral replication sites. These helicases interact with viral protein VPg at viral replication sites and promote the phase separation of VPg to form a novel membraneless organelle, viral protein-containing bodies, and subsequently facilitate viral proliferation.
This study used D-body as a model to explore the mechanism of the formation of membraneless organelles and the dynamic of membraneless organelles in response to virus stress. It provides a theoretical basis for the development of new antiviral targets and the reduction of virus damage to crops.
Reference: Qi Li, Ningkun Liu et al., “DEAD-box helicases modulate dicing body formation in Arabidopsis”, Science Advances 28 Apr 2021: Vol. 7, no. 18, eabc6266 DOI: 10.1126/sciadv.abc6266
Chinese tallow, due to its vibrant of the autumn colors, is one of the essential commercial trees widely planted in China. However, the coloration effect of the Chinese tallow leaves is not as good as expected with changes of the environment.
A research team led by Prof. WU Lifang from the Institute of Intelligent Machines, Hefei Institutes of Physical Science (HFIPS) investigated the genetic regulation of red pigment formation in Chinese tallow leaves and identified an R2R3-MYB transcription factor SsMYB1 that positively regulates anthocyanin biosynthesis and determines leaf color in Chinese tallow.
The researchers found that the anthocyanin content of Chinese tallow leaves was dependent on the expression of SsMYB1. Overexpression of the SsMYB1 in Arabidopsis showed higher anthocyanin contents, whereas silence of SsMYB1 significantly reduced its accumulation.
“The basic helix-loop-helix protein SsbHLH1 worked as a putative SsMYB1 co-regulator here. It directly interacted with SsMYB1 to regulate the anthocyanin biosynthetic pathway,” said CHEN Xue, a researcher in the team.
They also discovered that, compared with SsMYB1 alone, tobacco leaves transient overexpressing SsMYB1 and SsbHLH1 showed deeper red pigmentation. It proved that SsbHLH1 physically interacted with SsMYB1 to enhance anthocyanin biosynthesis.
“After binding to the promoters of SsDFR1 and SsANS, SsMYB1 activated anthocyanin biosynthesis and promoted their transcription activity, which can be further enhanced by SsbHLH1,” said CHEN Xue.
The identification and characterization of novel regulatory genes for leaf coloration in Chinese tallow paved an avenue for the cultivation of new varieties.
While most children diagnosed with ASD at early ages retain their diagnosis, a significant number of children have more dynamic presentations of clinical features associated with autism and may show changes as they develop, particularly around the time they are between two and three years old. These changes may lead a minority of children to actually lose or gain their ASD diagnosis over time. Recent studies have introduced the notion that this change in diagnosis is the result of intermediate cases of ASD, where children are neither clearly affected nor clearly unaffected.
Although researchers have been aware of these intermediate cases and possible diagnostic shifts, no prior studies have quantitatively evaluated the transition region between these ASD and non-ASD cases. Using a data-driven approach, the study team wanted to explore the links between early diagnostic shifts in ASD and the “fuzzy nature” of the diagnostic boundary.
“This study is the first to really develop a quantitative understanding of how each person is unique and how some of their core attributes change in small ways over the third year of their life,” said Robert T. Schultz, PhD, director of CAR and senior author of the study. “Past studies called attention to diagnostic instability at early ages without understanding why this was happening for each child and that these changes are gradual. Children grow in a continuous manner, and we now have a principled way to measure this steady growth and how it may push these children into and out of the diagnostic category of autism.”
Study participants and findings
The researchers used a cohort of children with high risk of developing ASD, since all participants had an older sibling diagnosed with autism. The cohort included 222 participants assessed at 24 months of age and then at 36 months of age. Using machine learning, the team was able to empirically characterize the classification boundary between ASD and non-ASD participants by quantifying developmental and adaptive skills.
The study found that most children who switched diagnostic labels (dynamic group) – either from ASD to non-ASD or vice versa – had intermediate clinical feature profiles. They were, on average, closer to the classification boundary compared with children who had stable diagnoses, both at 24 and 36 months of age. The magnitude of the shift was similar for both the dynamic and stable diagnostic groups, suggesting that diagnostic shifts were not associated with a large change in clinical profiles.
However, when children were examined at an individual level, a few children in the dynamic group showed substantial change. There were also substantial improvements in some children with severe impairments, suggesting that not all diagnostic shifts are due to having an intermediate clinical profile. Diagnostic shifts could be due to a variety of factors, including different causes of ASD, varying timing of the onset of ASD, and different treatment histories.
“Our study clearly shows the inherently dynamic nature of early diagnoses of autism,” said Birkan Tunç, PhD, a computational scientist with CAR and lead author of the study. “If we can identify predictive behavioral or neurobiological patterns of children who might have a change in their diagnosis, we may advance current clinical practices and better tailor individualized intervention strategies. Our findings call for more vigilant surveillance and faster initiation of intervention rather than waiting for a categorical diagnosis to begin treatment.”
This work was supported by grants from the National Institutes of Health (R01-HD055741, U54-HD086984, U54-HD087011, R01-HD088125, R01-MH073084, R01-MH118362, R01-MH121462, R01-MH116961, R01-ES026961) and the Pennsylvania Department of Health (SAP 4100047863, SAP 4100042728).
Reference: Tunç et al, “Diagnostic shifts in autism spectrum disorder can be linked to the fuzzy nature of the diagnostic boundary: a data-driven approach.” J Child Psychol Psychiatry, online April 7, 2021. DOI: 10.1111/jcpp.13406.