Microbial lysate upregulates host oxytocin

Neuropeptide hormone oxytocin has roles in social bonding, energy metabolism, and wound healing contributing to good physical, mental and social health. It was previously shown that feeding of a human commensal microbe Lactobacillus reuteri (L. reuteri) is sufficient to up-regulate endogenous oxytocin levels and improve wound healing capacity in mice. Here we show that oral L. reuteri-induced skin wound repair benefits extend to human subjects. Further, dietary supplementation with a sterile lysate of this microbe alone is sufficient to boost systemic oxytocin levels and improve wound repair capacity. Oxytocin-producing cells were found to be increased in the caudal paraventricular nucleus [PVN] of the hypothalamus after feeding of a sterile lysed preparation of L. reuteri, coincident with lowered blood levels of stress hormone corticosterone and more rapid epidermal closure, in mouse models. We conclude that microbe viability is not essential for regulating host oxytocin levels. The results suggest that a peptide or metabolite produced by bacteria may modulate host oxytocin secretion for potential public or personalized health goals.Published versio

Impact of Large Language Model Assistance on Patients Reading Clinical Notes: A Mixed-Methods Study

Patients derive numerous benefits from reading their clinical notes, including an increased sense of control over their health and improved understanding of their care plan. However, complex medical concepts and jargon within clinical notes hinder patient comprehension and may lead to anxiety. We developed a patient-facing tool to make clinical notes more readable, leveraging large language models (LLMs) to simplify, extract information from, and add context to notes. We prompt engineered GPT-4 to perform these augmentation tasks on real clinical notes donated by breast cancer survivors and synthetic notes generated by a clinician, a total of 12 notes with 3868 words. In June 2023, 200 female-identifying US-based participants were randomly assigned three clinical notes with varying levels of augmentations using our tool. Participants answered questions about each note, evaluating their understanding of follow-up actions and self-reported confidence. We found that augmentations were associated with a significant increase in action understanding score (0.63 $\pm$ 0.04 for select augmentations, compared to 0.54 $\pm$ 0.02 for the control) with p=0.002. In-depth interviews of self-identifying breast cancer patients (N=7) were also conducted via video conferencing. Augmentations, especially definitions, elicited positive responses among the seven participants, with some concerns about relying on LLMs. Augmentations were evaluated for errors by clinicians, and we found misleading errors occur, with errors more common in real donated notes than synthetic notes, illustrating the importance of carefully written clinical notes. Augmentations improve some but not all readability metrics. This work demonstrates the potential of LLMs to improve patients' experience with clinical notes at a lower burden to clinicians. However, having a human in the loop is important to correct potential model errors

Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity

Glucose ingestion after an overnight fast triggers an insulin-dependent, homeostatic program that is altered in diabetes. The full spectrum of biochemical changes associated with this transition is currently unknown. We have developed a mass spectrometry-based strategy to simultaneously measure 191 metabolites following glucose ingestion. In two groups of healthy individuals (n=22 and 25), 18 plasma metabolites changed reproducibly, including bile acids, urea cycle intermediates, and purine degradation products, none of which were previously linked to glucose homeostasis. The metabolite dynamics also revealed insulin's known actions along four key axes—proteolysis, lipolysis, ketogenesis, and glycolysis—reflecting a switch from catabolism to anabolism. In pre-diabetics (n=25), we observed a blunted response in all four axes that correlated with insulin resistance. Multivariate analysis revealed that declines in glycerol and leucine/isoleucine (markers of lipolysis and proteolysis, respectively) jointly provide the strongest predictor of insulin sensitivity. This observation indicates that some humans are selectively resistant to insulin's suppression of proteolysis, whereas others, to insulin's suppression of lipolysis. Our findings lay the groundwork for using metabolic profiling to define an individual's 'insulin response profile', which could have value in predicting diabetes, its complications, and in guiding therapy

Epidemiology and costs of cervical cancer screening and cervical dysplasia in Italy

<p>Abstract</p> <p>Background</p> <p>We estimated the number of women undergoing cervical cancer screening annually in Italy, the rates of cervical abnormalities detected, and the costs of screening and management of abnormalities.</p> <p>Methods</p> <p>The annual number of screened women was estimated from National Health Interview data. Data from the Italian Group for Cervical Cancer Screening were used to estimate the number of positive, negative and unsatisfactory Pap smears. The incidence of CIN (cervical intra-epithelial neoplasia) was estimated from the Emilia Romagna Cancer Registry. Patterns of follow-up and treatment costs were estimated using a typical disease management approach based on national guidelines and data from the Italian Group for Cervical Cancer Screening. Treatment unit costs were obtained from Italian National Health Service and Hospital Information System of the Lazio Region.</p> <p>Results</p> <p>An estimated 6.4 million women aged 25–69 years undergo screening annually in Italy (1.2 million and 5.2 million through organized and opportunistic screening programs, respectively). Approximately 2.4% of tests have positive findings. There are approximately 21,000 cases of CIN1 and 7,000–17,000 cases of CIN2/3. Estimated costs to the healthcare service amount to €158.5 million for screening and €22.9 million for the management of cervical abnormalities.</p> <p>Conclusion</p> <p>Although some cervical abnormalities might have been underestimated, the total annual cost of cervical cancer prevention in Italy is approximately €181.5 million, of which 87% is attributable to screening.</p

Low loss coatings for the VIRGO large mirrors

présentée par L. PinardThe goal of the VIRGO program is to build a giant Michelson type interferometer (3 kilometer long arms) to detect gravitational waves. Large optical components (350 mm in diameter), having extremely low loss at 1064 nm, are needed. Today, the Ion beam Sputtering is the only deposition technique able to produce optical components with such performances. Consequently, a large ion beam sputtering deposition system was built to coat large optics up to 700 mm in diameter. The performances of this coater are described in term of layer uniformity on large scale and optical losses (absorption and scattering characterization). The VIRGO interferometer needs six main mirrors. The first set was ready in June 2002 and its installation is in progress on the VIRGO site (Italy). The optical performances of this first set are discussed. The requirements at 1064 nm are all satisfied. Indeed, the absorption level is close to 1 ppm (part per million), the scattering is lower than 5 ppm and the R.M.S. wavefront of these optics is lower than 8 nm on 150 mm in diameter. Finally, some solutions are proposed to further improve these performances, especially the absorption level (lower than 0.1 ppm) and the mechanical quality factor Q of the mirrors (thermal noise reduction)

Genomic epidemiology reveals multiple introductions of Zika virus into the United States

Zika virus (ZIKV) is causing an unprecedented epidemic linked to severe congenital abnormalities. In July 2016, mosquito-borne ZIKV transmission was reported in the continental United States; since then, hundreds of locally acquired infections have been reported in Florida. To gain insights into the timing, source, and likely route(s) of ZIKV introduction, we tracked the virus from its first detection in Florida by sequencing ZIKV genomes from infected patients and Aedes aegypti mosquitoes. We show that at least 4 introductions, but potentially as many as 40, contributed to the outbreak in Florida and that local transmission is likely to have started in the spring of 2016-several months before its initial detection. By analysing surveillance and genetic data, we show that ZIKV moved among transmission zones in Miami. Our analyses show that most introductions were linked to the Caribbean, a finding corroborated by the high incidence rates and traffic volumes from the region into the Miami area. Our study provides an understanding of how ZIKV initiates transmission in new regions

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Relating Noninvasive Cardiac Output and Total Peripheral Resistance Estimates to Physical Activity in an Ambulatory Setting

The prevalence and cost of heart disease indicate the need for better methods of detecting, diagnosing and treating this pervasive problem. Appropriate monitoring outside of the hospital can potentially lead to earlier diagnosis and reduced costs. We use electrocardiogram (ECG) and continuous arterial blood pressure (ABP) data collected in an ambulatory setting to examine two important cardiovascular quantities, namely cardiac output (CO) and total peripheral resistance (TPR), over a range of physical activities. CO and TPR can be estimated from heart rate, pulse pressure and mean arterial blood pressure, which in turn are directly obtained from the ECG and ABP signals. More specifically, we employ a wearable cardiac and motion monitor designed by colleagues at MIT to simultaneously record ECG and 3-axis acceleration to onboard memory. The acceleration data is used to generate an estimate of physical activity at each time point. Additionally, we use a Portapres continuous blood pressure monitor to concurrently record the ABP waveform. We present representative results from data collected in a controlled ambulatory setting. Heart rate, mean ABP, CO and TPR responses to physical activity are generally consistent with what might be expected from cardiovascular physiology. The longer-term challenge is to correlate the dynamic behavior of these quantities with the state of cardiac health.Texas Instruments IncorporatedUnited States. Dept. of Defense National Defense Science & Engineering Graduate Fellowship (NDSEG) Program

Horizon scan of conservation issues for inland waters in Canada

Horizon scanning is a systematic approach increasingly used in conservation to explore emerging trends, issues, opportunities, and threats. We present the results from one such exercise aimed at identifying emerging issues that could have important scientific, social, technological, and managerial implications for the conservation of inland waters in Canada. We recognized six opportunities and nine challenges, and provide research implications and the policy options, such that scientists, policy makers, and the Canadian society as a whole could prepare for a potential growth in each of the topic areas we identified. The issues spanned a broad range of topics from recognizing the opportunities and challenges of community-enabled science and the need to consider the legal rights of nature, to the likely increase of pharmaceuticals in waste water due to an aging population. These issues represent an important baseline that could help decision makers identify and prioritize efforts, while simultaneously stimulate new research avenues. We hope our horizon scan will pave the way for similar exercises related to the conservation of natural resources and biodiversity in Canada.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author