Tuesday, June 17, 2025

 

DFG pursues closer collaboration with Brazil and Colombia




Deutsche Forschungsgemeinschaft





The Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) is strengthening its ties with Latin American research funding organisations and universities. On a trip to Brazil and Colombia, DFG President Professor Dr. Katja Becker first travelled to São Paulo, where she met with Professor Dr. Marco Antonio Zago, President of the São Paulo Research Foundation (FAPESP). In Brasília, Becker held talks with Professor Dr. Ricardo Galvão, President of the National Council of Scientific and Technological Development (CNPq), and also met Professor Antonio Gomes de Souza Filho, Vice President of the Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES). The DFG has long-standing relationships with all of these organisations and these ties are now set to be deepened further.

 

In her discussions, the DFG President emphasised the importance of Brazil as a partner to the German research community: “In view of the increasing pressure on free international research, long-term and productive partnerships built on mutual trust and shared values are more important than ever.” Becker noted that collaboration between Brazil and Germany had grown significantly over the past 20 years: “Since 2019 alone, the DFG has funded more than 390 German–Brazilian projects, almost 150 of which were co-financed,” Becker said. Some of these began with modest start-up funding and have since evolved into long-term research networks. “Offering opportunities for mutual learning, these collaborations greatly benefit both the German and Brazilian research systems.”

 

The DFG’s partner organisation in São Paulo, FAPESP, expressed strong interest in Germany’s Excellence Strategy – the decisions on the funded Clusters of Excellence, made on 22 May in Bonn, were closely followed in Brazil. More than 100 scientific advisors from FAPESP and the rectors of local universities took part in a dedicated exchange event on the Excellence Strategy in São Paulo. They discussed whether a similar initiative could be introduced in Brazil and how collaboration between Brazilian researchers and German Clusters of Excellence could be further strengthened.

 

Following her visit to Brazil, Becker travelled to Colombia’s capital, Bogotá, where she signed two Memorandums of Understanding with top research universities. The Universidad Nacional de Colombia (UNAL) and the Pontificia Universidad Javeriana (PUJ) are now set to join the DFG’s existing Colombian partner network, which already includes the Universidad de los Andes (UNIANDES) and the Universidad de Antioquia (UdeA). At the signing, Becker reiterated that in addition to academic excellence, top-level research required another essential condition in order to truly thrive: freedom of research. “Our agreements with these additional Colombian universities are also designed to foster the kind of exchange and cooperation that science and the humanities urgently need right now. Because today, more than ever, we must stand up for our shared values such as freedom of research,” she said.

 

“In recent times, science and the humanities around the world have come under increasing political pressure and faced targeted attacks on freedom of research – even in partner countries where such interference was once considered unthinkable,” Becker continued. “This is why we as a research funding organisation are building alliances with those who share our values – freedom of research, democratic principles, social responsibility and a belief in the transformative power of knowledge.”

 

New vaccine works against multiple fungal infections


Latest study shows efficacy against yeast infections in mouse model, paving the way for clinical trials in people



University of Georgia




A vaccine developed by University of Georgia researchers successfully protects against and treats vaginal yeast infections in mice, according to a newly published study.

This is the newest application of the vaccine, which was previously shown to protect against the three most common fungal pathogens in four preclinical animal models, including nonhuman primates. These three fungi are responsible for more than 80% of fatal fungal infections.

The latest finding helps clear the way for the vaccine to enter clinical trials. If successful, the vaccine will be the first to prevent pathogenic fungal infections, which the World Health Organization considers one of the top threats to public health.

"We can’t just keep … trying to make new drugs to fight fungal infections because we’re going to lose.” —Karen Norris, College of Veterinary Medicine

“The thing that’s keeping researchers like me up at night is increasing antifungal drug resistance,” said Karen Norris, lead author of the study and a professor of immunology and translational biomedicine in the UGA College of Veterinary Medicine. Norris is also the CEO and founder of NXT Biologics, the company behind the vaccine. “It’s not a prediction. We’re living it right now.

“And we can’t just keep swinging away and trying to make new drugs to fight fungal infections because we’re going to lose. These organisms are always adapting to resist new drugs.”

The vaccine, named NXT-2, aims to fill that gap, preventing fungal infections before they happen and reducing the need for antifungal medications by doing so.

First clinical trial to target yeast infections; later trials to focus on life-threatening infections

The vaccine will first be tested in women with recurrent yeast infections, also known as recurrent vulvovaginal candidiasis or RVVC.

Caused by a type of candida fungus, the condition affects hundreds of millions of women globally. It also costs billions of dollars in health care visits, medication and lost productivity each year in the U.S. alone.

“RVVC is not life-threatening, but it is miserable,” Norris said. As many as one in 10 women develop the condition during their lifetime, suffering three or more yeast infections per year. “This is a huge need.”

The current treatment protocol relies on one class of drug, increasing the likelihood that the medication will develop resistance and be harder to treat going forward. They also can’t be used during pregnancy and don’t prevent future infections.

"I believe this vaccine will do the most good in people who are at high risk for highly dangerous, life-threatening infections.” —Karen Norris

Most of the women suffering from recurrent yeast infections are young and otherwise healthy, which makes them an ideal population for a Phase 1 clinical trial.

The results will inform future trials in more vulnerable patient populations, such as transplant recipients and cancer patients, two groups that are particularly vulnerable to life-threatening fungal infections, also covered by the vaccine.

“I’ve had a physician say to me, ‘I have patients that I get through stem cell transplants for their cancer treatment, and then they get aspergillosis. I often don’t have adequate treatment for that,’” Norris said. Pulmonary aspergillosis is a serious complication of this treatment and up to half those patients will die from the infection.

“That’s where I believe this vaccine will do the most good: in people who are at high risk for highly dangerous, life-threatening infections.”

Fungal infections: A growing public health threat

Fungal infections are most commonly seen in people with immune disorders, including those with uncontrolled HIV or impaired immunity from therapies like chemotherapy or anti-inflammatories.

But previous research from Norris, postdoctoral fellow Emily Rayens and the College of Public Health’s José Cordero showed that the at-risk population has expanded in recent years.

That study showed people with diabetes; chronic obstructive pulmonary disease (or COPD); or co-infections such as COVID-19, tuberculosis or flu are likewise at higher risk of developing fungal infections.

As drug resistance grows and infections become more difficult to treat, prevention becomes more critical, Norris said.

This is the first fungal vaccine that has shown broad, cross-protective antifungal immunity in multiple animal models, which bodes well for future clinical trials.

Published in Nature’s NPJ Vaccinesthe study was co-authored by the UGA Center for Vaccines and Immunology’s Daniel Wychrij, Taylor Chapman, Whitney Rabacal, Hubertine Willems and Kwadwo Oworae. Additional co-authors include Emily Rayens, a doctoral graduate from UGA’s Department of Infectious Diseases, and Brian Peters of the University of Tennessee.

 

Safeguarding Mendelian randomization: editorial urges rethink in methodological rigor




First Hospital of Jilin University
The comparison of publications/citations in Mendelian randomisation from 2015 to 2024. On the top, it reflects the trend of total publications and citations each year. 

image: 

The comparison of publications/citations in Mendelian randomisation from 2015 to 2024. On the top, it reflects the trend of total publications and citations each year. The keywords in this field are displayed at the bottom.

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Credit: By Lanlan Chen, Adrien Guillot, Carolin Victoria Schneider





In recent years, Mendelian randomisation (MR) has revolutionised observational epidemiology by offering a tool to infer causal relationships using genetic variants as instrumental variables (IVs). However, its popularity has come at a cost. The editorial by Chen, Guillot, and Schneider in eGastroenterology (2025) titled "Attention to the misuse of Mendelian randomisation in medical research" delivers a timely critique of the field's current trajectory. As MR studies surge, so too do concerns about their quality and interpretive validity. The authors call for stricter methodological scrutiny and offer practical recommendations to preserve MR’s scientific integrity.

The Rise and Risk of MR

The exponential increase in MR publications—from 3,545 in 2023 to over 6,600 in 2024—is a double-edged sword. While the proliferation indicates growing interest and recognition, it also reflects a decline in study quality. A significant portion of recent literature relies heavily on simplified two-sample MR designs and summary-level data, often without the robust framework needed to draw meaningful conclusions. Many of these studies lack careful evaluation of MR assumptions, making them susceptible to misleading or overstated findings. The editorial warns that this trend could erode the field’s credibility, overwhelm journal editors and reviewers, and ultimately diminish MR’s role in evidence-based medicine.

Understanding MR and Its Assumptions

MR infers causality by leveraging the random assortment of genes to mimic the randomisation in clinical trials. To be valid, MR must satisfy three critical assumptions: (1) Relevance: The genetic instruments must strongly correlate with the exposure of interest. (2Independence: There should be no confounding factors that influence both the instrument and the outcome. (3) Exclusion Restriction: The instrument affects the outcome only through the exposure, not through alternative pathways (i.e., no horizontal pleiotropy). However, assumptions (2) and (3) are rarely testable and often violated in practice, particularly when using summary data or unvetted genetic instruments.

Common Pitfalls in MR Studies

(1Weak or Non-Genetic Exposures: Some studies have attempted to evaluate exposures that lack clear genetic underpinnings—like air pollution or dietary habits (e.g., noodle consumption). Such exposures are primarily environmental and not suitable for MR unless a gene–environment interaction is biologically justified.

(2) Inadequate Instrument Selection: Instrument choice is central to MR validity. Many studies rely solely on statistical significance from genome-wide association studies (GWAS) without confirming biological plausibility. This can lead to horizontal pleiotropy, where genetic variants influence outcomes via multiple pathways. The authors argue for a balanced strategy that combines statistical strength with biological insight, supported by SNP pruning strategies to reduce linkage disequilibrium bias.

(3) Misuse of Two-Sample MR: The accessibility of large-scale GWAS has led to a surge in two-sample MR studies. While efficient, these studies often neglect confounding, pleiotropy, and sensitivity analyses. The authors caution that replication without rigour creates an illusion of robustness and contributes to publication bloat.

Best Practices for Conducting Robust MR Analyses

The editorial outlines essential criteria for valid MR research: (1) Ensure Genetic Relevance: Exposures must be influenced by well-characterised genetic variants. For instance, HDL-C is genetically regulated by HMGCR variants, making it a valid MR exposure. In contrast, exposures like air pollution require alternative strategies, such as studying metabolite interactions under genetic control. (2) Careful Instrument Selection: Researchers should combine biological plausibility with statistical thresholds. Preferably, instruments should be close to the causal gene and pruned using stringent thresholds (e.g., clump r² ≤ 0.01). Using mechanistic knowledge can reduce pleiotropic bias but may limit the number of usable instruments. (3) Use Multiple Statistical Models: No single model suffices for all MR analyses. Standard models like inverse variance-weighted (IVW) assume all instruments are valid, while more robust alternatives (e.g., MR-Egger, MR-CAUSE, MR-APSS) accommodate violations and reduce type I errors. Employing diverse models strengthens the credibility of findings. (4) Integrate Complementary Evidence: MR findings should be validated using external datasets, colocalisation analyses, or real-world observational studies. When functional experiments are unavailable, in silico methods can provide corroborative evidence. This multi-method approach ensures that MR results are not interpreted in isolation. (5) Cautious Interpretation: Researchers should describe their results as “genetically predicted associations” rather than definitive causal relationships. Comparisons with randomised trials and exploration of mediating pathways can contextualise findings and highlight translational relevance. Furthermore, the effect sizes of genetic associations should be contrasted with those of modifiable risk factors such as medications or behaviours.

Recommendations for the Scientific Community

For Readers:

  1. Look for adherence to STROBE-MR guidelines. 
  2. Scrutinise genetic plausibility and IV assumptions.
  3. Be wary of exaggerated causal claims lacking sensitivity analyses.
  4. Cross-reference MR findings with other epidemiological data or RCTs.

For Editors and Reviewers:

  1. Reject submissions that analyse weakly genetic or environmental exposures without justification.
  2. Demand detailed instrument selection processes and bias assessments.
  3. Discourage redundant publications and require robust methodological justification for novel approaches.
  4. Encourage interdisciplinary collaborations to bridge genetics, clinical practice, and biological mechanism.

Reclaiming MR's Potential

Despite the current challenges, MR remains a transformative method in modern medicine. Its ability to draw causal inferences from observational data is unparalleled when correctly applied. The editorial underscores that methodological rigour, biological reasoning, and cross-validation with complementary evidence can restore confidence in MR research. As the field matures, its future will hinge not on volume, but on quality. To preserve its promise, MR must evolve from a tool of convenience to one of precision.

 

See the article:

Chen L, Guillot A, Schneider CV. Attention to the misuse of Mendelian randomisation in medical research. eGastroenterology 2025;3:e100187. doi:10.1136/egastro-2025-100187

 

About eGastroenterology

eGastroenterology is a new, open-access, and open peer-reviewed BMJ Journal, which focuses on basic, clinical, translational, and evidence-based medicine research in all areas of gastroenterology (including hepatology, pancreatology, esophagology, and gastrointestinal surgery). eGastroenterology is now indexed by PubMed, Scopus, CAS, DOAJ, Dimensions, OpenAlex, ROAD, and COPE, with more to come!

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