
Matthew Halma- PhD Student at Vrije Universiteit Amsterdam
Matthew Halma
- PhD Student at Vrije Universiteit Amsterdam
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91
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Introduction
Currently, I am studying gene regulation via programmed ribosomal frameshifting at a single-molecule level. Programmed ribosomal frameshifting (PRF) is a ubiquitous phenomenon used by organisms of all kingdoms of life, one whose impact is only recently been appreciated. PRF involves regulation of gene expression through changes in the process of translation whereby the information in RNA is used to produce proteins, much of the past research on gene regulation has focused on modifications at the
Current institution
Publications
Publications (91)
Citation: Halma, M.; Varon, J. DARE-SAFE: Denominator-Adjusted Rate Estimates of Substance Adverse Events Frequency Evaluation in Pharmaceuticals and Vaccines. Pharmacoepidemiology 2025, 4, 7. Abstract: Background/Objectives: Controversy exists over the use of passive reporting systems, especially the Vaccine Adverse Event Reporting System, in risk...
Mortality associated biomarkers are advantageous in that they are strongly associated with general health. Disease specific biomarkers, if optimized for, can often create suboptimal outcomes in another area, thereby compromising the health of the measured person. We use an existing database of mortality associated blood biomarkers to assess their a...
Background: Environmental contamination from US EPA Superfund sites has long posed a serious threat to public health and environmental sustainability. Increased environmental risk in areas near US EPA Superfund sites is evidenced by studies that have found that these areas are characterized by higher levels of toxic substances in the soil and air....
This review examines the potential of herbal medicines in treating hypothyroidism, a condition marked by a deficiency of thyroid hormones. Hypothyroidism is common in the United States, affecting approximately 4.6% of the population, with higher rates observed in females and the elderly. The review aims to provide a thorough overview of the current...
The single-molecule biophysics community has delivered significant impacts to our understanding of fundamental biological processes, yet the field is also siloed and has fragmented data structures which impede data sharing and limit the ability to conduct comprehensive meta-analyses. To advance the field of optical tweezers in single-molecule bioph...
To the Editor: N1-methyl-pseudouridylated (m1Ψ) RNA enabled the mRNA Covid-19 vaccines to save lives during the pandemic, however, many questions exist on how the modified mRNA behaves in vivo. A recent study by Monroe and coworkers, shows slight, context dependent changes in translational fidelity. The earliest study on translation of m1ΨRNA dates...
Ivermectin, originally developed for the treatment of parasitic diseases such as onchocerciasis (river blindness), has earned its title of "wonder drug" due to its broad-spectrum therapeutic activity. Ivermectin’s potential to address unmet global health challenges makes it an important focus for future medical research. This review explores iverme...
Objective: This study introduces the Denominator-Adjusted Rate Estimates of Substance Adverse Events Frequency Evaluation (DARE-SAFE) method to analyze pharmacovigilance reporting rates for vaccines and common pharmaceuticals. Methods: We calculated reporting rates for the top 250 most prescribed drugs in the US FDA Adverse Event Reporting System (...
Background: Age-related decline in musculoskeletal function is a significant concern, particularly in Western countries facing demographic shifts and increased healthcare demands. This review examines the typical trajectories of musculoskeletal deterioration with age and evaluates the effectiveness of various interventions in preventing or reversin...
Post vaccination syndrome, either acute or long term, is a significant source of disease burden, affecting up to 1% of vaccine recipients. The medical and scientific community is only beginning to define and classify the condition, and presently those affected are left with very limited support. Gaps in patient needs include disease diagnosis, trea...
BACKGROUND
Research efforts focusing on long covid have so far produced insights into the dysregulation of body processes. Development of therapeutics has been limited to a few options which have largely panned out. However, the research work has found some useful relationships between different diseases, and one important finding which lends itsel...
Biomarker-based tests are capable of predicting one’s biological age and mortality risk. To complement the suite of biomarker-based measurements, physical and cognitive performance tests can also improve the predictability of these measurement panels. Importantly, these measurements can be administered quite non-invasively and inexpensively, and tr...
Many countries across the globe are experiencing aging populations, which brings into question the fitness and capacity of these populations. Rates of neurodegenerative diseases worldwide are increasing, even after adjusting for increasing lifespans. This worrying trend motivates taking steps in the population to prevent dementia. This review summa...
Despite extensive studies on DNA replication, the exchange mechanisms of DNA polymerase during replication remain unclear. Existing models propose that this exchange is facilitated by protein partners like helicase. Here we present data, employing a combination of mechanical DNA manipulation and single fluorescent protein observation, that reveal D...
Public health officials are currently tasked with the role of regulating medicines, both during the approval process and post-market surveillance. While several successes of pharmacovigilance systems exist, pharmacovigilance systems in place are inadequate for protecting the public, as they are slow to show causation. We argue that while pharmacovi...
Hypertension is a global public health challenge, with a high prevalence across various regions and significant implications for cardiovascular risk. This article reviews the effectiveness of herbal medicine as a potential therapeutic approach for hypertension, offering an alternative or complementary solution to conventional pharmacological treatm...
Antidepressants are among the most used medications in the US, with significant deleterious effects on people's well-being. At any given time, depression impacts approximately 1 in 10 Americans, causing wide and broad societal costs. Interest is developing for non-pharmacological treatments and preventative measures. We summarize the literature on...
Many people in the USA have lost their lives or become addicted to opioids via prescription opioids given for chronic pain. The chronic pain epidemic has emerged due to a convergence of factors, including the medicalization of pain as well as injuries happening in the workplace, in the home, or during recreation. Opioid prescriptions rose precipito...
There are significant challenges in both student and researcher engagement in both education and research, and one contributing factor is the lack of autonomy that each person experiences. This work charts a new path, whereby students and researchers are free to pursue their own interests, and the role of the teacher or university is to support and...
The aging populations observed across numerous countries worldwide necessitate a thorough exploration of interventions aimed at promoting healthy aging. As individuals age, they undergo significant physiological changes that impact their functional capacity and often necessitate increased reliance on external support systems. Enhancing the autonomy...
Optical tweezers have elucidated numerous biological processes, particularly by enabling the precise manipulation and measurement of tension. One question concerns the biological relevance of these experiments and the generalizability of these experiments to wider biological systems. Here, we categorize the applicability of the information garnered...
Exposure to vaccine lipid nanoparticles, mRNA, adenoviral DNA, and or Spike protein from one of the approved Covid-19 vaccines, or through secondary exposure, as through blood transfusion, is a potential source of harm. Blood reactions are an acknowledged side-effect of Covid-19 vaccination, not limited to hemolysis, paroxysmal nocturnal hemoglobin...
The outbreak of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has been influenced by the human response to the virus. These responses have undoubtedly impacted the evolutionary dynamics of the virus in ways distinct from a scenario lacking a widespread response. Two important pharmaceutical interventions, vaccination and the utilizat...
Graphene-based materials (GBMs) possess remarkable physiochemical properties, making them promising for diverse applications in biomedicine, agriculture, food, and industrial applications. Human and environmental exposure to GBMs is increasing at an unprecedented rate, yet there is still a knowledge gap regarding the safety of GBMs. This review sum...
Cancer is amenable to low-cost treatments, given that it has a significant metabolic component, which can be affected through diet and lifestyle change at minimal cost. The Warburg hypothesis states that cancer cells have an altered cell metabolism towards anaerobic glycolysis. Given this metabolic reprogramming in cancer cells, it is possible to t...
The question of how many deaths were averted by interventions during the COVID-19 pandemic carries important implications for policies going forward. Given that the interventions of lockdowns and mass vaccination carry acknowledged downsides, it is important to balance these against potential upsides, which were the putative reasons for health offi...
Abstract: Graphene-based nanoparticles possess remarkable physiochemical properties, making them promising for diverse applications in biomedicine, agriculture, food, and industrial applications. These nanoparticles have also been used in the fight against COVID-19. Human and environmental exposure to graphene-based nanomaterials is increasing at a...
In a fast-moving world, speed from conceptualization to execution, and in the case of science, publishing, is getting faster, where scientists optimize their flows and bring their A-game to their work. Similarly, science, while often regarded as an almost purely cognitive exercise, cannot be detached from the health and well-being of those that pra...
The seminal book, the E-myth posited that most entrepreneurs end up getting themselves into a job, and the same can be said for scientists. The fundamental issue identified as technicians with entrepreneurial envy ending up in a technician role can translate to science. Here, the role of a principal investigator evolves from working in the lab, to...
While science seeks to find stable, general principles, it assumes that over the temporal scale, the phenomena are unchanging, or at least changing gradually. What about the situations in which the change in the phenomenon studied is comparable or faster than the cycle time that science can update? Typically, these look like anomalies in data, but...
The Lean startup is a market centric framework for product development which requires dialogue and information gathering from potential customers without biasing them towards any one conclusion (one's product or product idea). The approach can be applied to science, where the 'customer' is the scientific commons themselves, and the dialogue serves...
This paper explores the application of the Theory of Constraints (ToC) to optimize knowledge production in research settings. While ToC is traditionally used in manufacturing and project management, its principles can be adapted to improve the efficiency and effectiveness of scientific research. By identifying and addressing bottlenecks and ineffic...
Delineating the epidemic of vaccine injury from the coterminous condition long covid is a challenging prospect, but one with many implications not just for treatment, but also has important legal considerations for settlements of vaccine injury. The shared etiological factor of the spike protein in both vaccine injury and long covid make differenti...
Fasting, a practice with historical roots in various cultures, has recently garnered significant interest in the field of medicine. In this article, we delve into the mechanisms underlying fasting-induced autophagy and its therapeutic applications for spike protein associated pathology. We explore the therapeutic potential of fasting on spike prote...
Fasting, a practice with historical roots in various cultures, has recently garnered significant interest in the field of medicine. In this article, we delve into the mechanisms underlying fasting induced autophagy and its therapeutic applications for spike protein associated pathology. We explore the therapeutic potential of fasting on spike prote...
Bacteriophage T7 single-stranded DNA-binding protein (gp2.5) binds to and protects transiently exposed regions of single-stranded DNA (ssDNA) while dynamically interacting with other proteins of the repli-cation complex. We directly visualize fluorescently labelled T7 gp2.5 binding to ssDNA at the single-molecule level. Upon binding, T7 gp2.5 reduc...
The COVID crisis of the past three years has greatly impacted stakeholder relationships between scientists, health providers, policy makers, pharmaceutical industry employees, and the public. Lockdowns and restrictions of civil liberties strained an already fraught relationship between the public and policy makers, with scientists also seen as comp...
Background
The relationship between the quality of the learning environment and student outcomes is receiving more serious attention from educational psychologists, neurologists, ophthalmologists, orthopedists, surgeons, oncologists, architects, ergonomists, nutritionists, and Michelin star chefs. There is a role for ergonomic office and school des...
In the wake of the COVID-19 crisis, a need has arisen to prevent and treat two related conditions, COVID-19 vaccine injury and long COVID-19, both of which can trace at least part of their aetiology to the spike protein, which can cause harm through several mechanisms. One significant mechanism of harm is vascular, and it is mediated by the spike p...
Pharmacovigilance databases are showing evidence of injury in the context of the modified COVID-19 mRNA products. According to recent publications, adverse event reports linked to the mRNA COVID-19 injections largely point to the spike protein as an aetiological agent of adverse events, but we propose that the platform itself may be culpable. To as...
In the wake of the Covid-19 crisis, a need has arisen to prevent and treat two related conditions, Covid vaccine injury and long Covid, both of which have a significant vascular component. Therefore, the management of these conditions require the development of strategies to prevent or dissolve blood clots and restore circulatory health. This revie...
In the wake of the Covid-19 crisis, a need has arisen to prevent and treat two related conditions, Covid vaccine injury and long Covid, both of which have a significant vascular component. Therefore, the management of these conditions require the development of strategies to prevent or dissolve blood clots and restore circulatory health. This revie...
Public trust in science was tested and relied on during the SARS-CoV-2 pandemic, which has shaped global events since the WHO declaration in March 11, 2020. Public trust has been impacted through the government recommendations and mandates informed by public health guidance, including non-pharmaceutical and pharmaceutical interventions. The free-fl...
Single-stranded DNA-binding proteins (SSBs) play vital roles in DNA metabolism. Proteins of the SSB family exclusively and transiently bind to ssDNA, preventing the DNA double helix from re-annealing and maintaining genome integrity. In the meantime, they interact and coordinate with various proteins vital for DNA replication, recombination, and re...
Pharmacovigilance databases are showing evidence of injury in the context of the COVID-19 modified mRNA shots. According to recent publications, adverse event reports linked to the mRNA COVID-19 products largely point to the spike protein as an aetiological agent of adverse events, but we propose that the platform itself may be culpable. To assess...
Pharmacovigilance databases are showing evidence of injury in the context of the COVID-19 modified mRNA shots. According to recent publications, adverse event reports linked to the mRNA COVID-19 products largely point to the spike protein as an aetiological agent of adverse events, but we propose that the platform itself may be culpable. To assess...
The economical and societal impact of COVID-19 has made the development of vaccines and drugs to combat SARS-CoV-2 infection a priority. While the SARS-CoV-2 spike protein has been widely explored as a drug target, the SARS-CoV-2 helicase (nsp13) does not have any approved medication. The helicase shares 99.8% similarity with its SARS-CoV-1 homolog...
The time taken and the cost of producing novel therapeutic drugs presents a significant burden – a typical target-based drug discovery process involves computational screening of drug libraries, compound assays and expensive clinical trials. This review summarises the value of dynamic conformational information obtained by optical tweezers and how...
UNSTRUCTURED
The formation of amyloids is of significant concern in several disease processes. Yet, there has not been an effective treatment developed for reversing the process of amyloidogenesis. Recently, it is proposed that the spike protein of SARS-CoV-2, as well as the SARS-CoV-2 vaccines has the possibility to produce amyloids. We evaluate t...
Recurrent outbreaks of novel zoonotic coronavirus (CoV) diseases in recent years have highlighted the importance of developing therapeutics with broad-spectrum activity against CoVs. Because all CoVs use −1 programmed ribosomal frameshifting (−1 PRF) to control expression of key viral proteins, the frameshift signal in viral mRNA that stimulates −1...
Recurrent outbreaks of novel zoonotic coronavirus (CoV) diseases since 2000 have high-lighted the importance of developing therapeutics with broad-spectrum activity against CoVs. Because all CoVs use −1 programmed ribosomal frameshifting (−1 PRF) to control expression of key viral proteins, the frameshift signal in viral mRNA that stimulates −1 PRF...
1 programmed ribosomal frameshifting (−1 PRF) is stimulated by structures in messenger RNA (mRNA), but the factors determining −1 PRF efficiency are unclear. We show that −1 PRF efficiency varies directly with the conformational heterogeneity of the stimulatory structure, quantified as the Shannon entropy of the state occupancy, for a panel of stim...
1 Programmed ribosomal frameshifting (−1 PRF) is stimulated by structures in mRNA, but the factors determining −1 PRF efficiency are unclear. We show that −1 PRF efficiency varies directly with the conformational heterogeneity of the stimulatory structure, quantified as the Shannon entropy of the state occupancy, for a panel of stimulatory structur...
An outline for a book on consciousness
The advent of massive-scale genotyping has paved the way for examination of the role of genetic variability in high-level observables such as lifespan. Genome-wide association studies are able to determine whether a particular allele is associated with a certain high-level outcome, but such studies may only grasp at a mechanistic explanation.
One...
A proposal for looking at genetic variation in lifespan owing to coding SNPs in the serotonin 5HT2A receptor
Differences in responses to compounds can vary by individual. This can be due to a multitude of factors, but this study will focus on genetic polymorphisms resulting in non-synonymous differences in receptor protein amino acid sequence. Certain genetic polymorphisms are known to influence an individual's response to cannabis 1. A review 1 on the to...
Programmed ribosomal frameshifting (PRF) presents a mechanism of gene regulation which may regulate ~10% of human genes. Until recently, it has been thought as largely exclusive to viruses, however, recent high throughput assays have been able to find multiple PRF events within the human genome, corroborating previous bioinformatic predictions.
Th...
Associating different 5-HT2A receptor polymorphisms with different outcomes in individuals through docking simulations with serotonin.
Significance
Programmed ribosomal frameshifting (PRF) is important to many viruses, but how structures in mRNA stimulate PRF remains uncertain. By studying a frameshift signal stimulating very high PRF in West Nile virus (WNV), we identify features that differ from other structures stimulating more modest PRF levels. Using single-molecule force spe...
Phylogenetic analysis reveals recruitment of slippery sequence to stem-loop structure inhibits frameshifting Matthew TJ Halma We analyze a fork in the phylogenetic tree of Flaviviridae separating programmed ribosomal frameshift competent (PRFc) sequences from non-competent (PRFnc) sequences. We find that a set of 6 mutations results in the energeti...
Programmed ribosomal frameshifting (PRF) represents an important mechanism for translational genetic recoding, especially in viruses. The components of a PRF stimulator have been well characterized, though accounting for the variation in the frameshift stimulating efficiency has thus far been elusive. Frameshift efficiencies at known PRF sites vary...
A brief introduction to lncRNAs centered around a journal club literature presentation
A literature presentation based on (Y. S. Dagdas, J. S. Chen, S. H. Sternberg, J. A. Doudna, and A. Yildiz, “A conformational checkpoint between DNA binding and cleavage by CRISPR-Cas9,” Sci. Adv., vol. 3, no. 8, Aug. 2017.) providing a brief introduction to CRISPR and explanation of the results.
This is a review of the article "First Results from the LUX Dark Matter Experiment at the Sanford Underground Research Facility" in concordance with the course requirements for Introductory Particle Physics (PHYS 485) taken during the Winter 2016 semester of studies at the University of Alberta. The paper in question presents results that suggest d...
The properties of an acrylic wave-guide are determined through several tests. It is found that for a microwave wavelength of λ = 3.22 ± 0.02 cm, the corresponding index of refraction is 1.60 ± 0.03. Additionally, several output distributions are studied and compared with ray simulations, we find a connection between the distribution shape of the si...
The effect of additive corn syrup in pure honey was investigated through Pulsed Nuclear Magnetic Resonance (PNMR) at intermediate levels between 0% adulteration (pure honey) and 100% adulteration (pure corn syrup). Additionally, other samples were taken, including mineral oil, and other supermarket honeys. A semi-linear correlation was found betwee...
The abstract should provide a brief summary of the main findings of the paper.
Inverse problems frequently arise in areas of seis-
mic tomography, medical imaging, underwater acoustics
and non-destructive testing, as well as a multitude of
other areas. Compressive Sensing methods, a sub�eld
of numerical and harmonic analysis, initially proposed
in 2005, provide excellent reconstructions while keep-
ing computational and memor...
Within the field of image processing, it has long been understood that in order to recreate an analog
signal sampled at discrete times, the minimal sampling rate must be at least twice the highest frequency
present in the signal. This is known as the Shannon Sampling Theorem and it has been the dominant
paradigm in signal and image processing for a...
Questions
Questions (10)
Dear all,
I hope this doesn't come across as a naïve question, but in the laboratory, we use DMSO to dissolve flavonoids and other compounds which don't dissolve well in water.
I am aware for a few of these supplements, such as resveratrol, bioavailability is a challenge. Given that solubility is related to bioavailability (at least for the case of drugs absorbed in GI fluids), is dissolving formulations in DMSO a potential way to increase their bioavailability? It is my understanding that there are some risks to DMSO use, but it has a history of use in humans for interstitial cystitis.
Thank you,
Matthew
Dear readers,
Thanks for your attention. I am wondering about the health economic problem of quantifying the value of interventions which a) prevent, b) improve symptom profile and c) ultimately reverse (i.e. cure) diseases.
As a rough number if a preventative measure reduces incidence of a disease by 10%, I can calculate savings by multiplying this by the total direct and indirect costs of the disease.
However, for conditions where the intervention exerts a partial improvement in symptom profile (not total reversal), the calculation of savings can be more difficult. What I was thinking is using absolute changes in an accepted scale. Such as the HAMD scale for depression, which defines cutoffs as:
no depression (0-7); mild depression (8-16); moderate depression (17-23); and severe depression (≥24).
Max value: 52
From other information, I have found that depression for a single patient brings costs of $11446 per patient (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798200/). Assuming spending per patient scales linearly with severity, and goes to zero at clinical remission.
Of course the figure is an average, so one would in principle find the distribution of HAMD scores for diagnosed patients to find where the 'average' patient lies in terms of severity. Even more preferable, you would have expenditure-severity data for multiple individuals, but we have to extrapolate otherwise. Roughly, I'll put the $11446 as the cost per patient with a severity of someone in the middle of the scale, which is roughly 14 on the scale .
If that is the case, one point is roughly (and this is very rough) would be $11446/14 or $820. It's probably less as the value 14 is probably too low, but somewhere in this range.
I am wondering if there is a better methodology to estimate the value of interventions which improve symptoms? Or if this approach is acceptable.
Dear all,
I am seeking to build a resource linking diseases with bioactive compounds, and include source (plant species) and range information as well. To make sure that I am not reinventing the wheel, do you know of something that exists like this already?
Currently, the missing step would be a database of drug-disease associations, ideally ones that have a high degree of validation. I'm aware that there are DBs based on literature co-occurence but I don't know how strong these associations are and I believe it will be a lot of false positives.
I would prefer a smaller database of clinically validated associations only.
Many thanks and much appreciation,
Matt
I am wondering about publishing a protocol for an interventional, prospective trial, but I am unsure about funding the trial. On one hand, I believe publishing a study protocol generates interest, on the other hand, I am not sure if there will be funding or participation from the relevant clinics.
I have been doing feasibility studies on the use of microbial biostimulants in agriculture. Compared to conventional fertilizers, they have many advantages, they require a much smaller application and if they can help with increasing yield, a small application can provide a large value proposition.
My question is, if biostimulants are used in a real world agricultural setting, what increases in yield could one see with optimistic assumptions (assuming the choice of crop and associated biostimulant are matched, etc) while being reasonable.
Thank you !
Dear all,
I am having difficulty finding useful numbers on transport infrastructure, I wish to investigate quality changes over time, so such statistics on the percentage of trains/busses/trams that arrive on time or some measure on the quality of the road.
I am aware of some sources, such as the 'Infrastructure Report Card' in the USA, reports by consultancies or the congressional budget office. However, these are not scholarly sources and I would prefer to avoid them.
So the question is: are you aware of longitudinal studies of transport infrastructure and service quality?
Thank you!
Hello, first I shall share that I do not have a lot of familiarity with this topic so excuse my ignorance if there is any.
We know that anti-drug antibodies exist, with some against small molecule drugs, usually these are haptens bound to some proteins.
At some level of structural complexity, it becomes difficult to produce an antibody that is selective enough to target the specific antigen without off target effects.
My question is this.
1) What is the simplest structure which antibodies can be formed against? i.e. what is found experimentally?
2) Is there some sort of theoretically imposed lower bound on the informational complexity of an antigen against which antibodies can form.
I should mention that I am aware of riboswitches and their ability to recognize individual ions and discriminate them from other ions, even with identical charge.
Especially one with a negative connotation
Dear all,
I am wondering what the state of the art is for detecting m1Ψ in RNA sequences and how it can be differentiated from U. I am thinking of just using RNA-seq and then a separate assay to determine m1Ψ concentration, but ideally I would like to know if an individual base is m1Ψ or U.
Thank you!
Dear all,
I am wondering if there is an easy data format to share the composition of a biochemical solution, for example a buffer consisting of certain concentrations of different substances, as well as some biologically active molecules (peptides, oligonucleotides, proteins, etc). Preferably the latter would have links to their accession numbers in different databases, or if that is not available, a FASTA sequence. I am seeking to improve the re-usability of data within the single molecule field.
Thank you!