Communications medicine最新文献

{"title":"Hydroxyurea mobile directly observed therapy versus standard monitoring in patients with sickle cell anemia: a phase 2 randomized trial","authors":"Philip Sasi, Abel Makubi, Raphael Z. Sangeda, Mariam Y. Ngaeje, Bruno P. Mmbando, Joseph Soka, Caterina Rosano, Alex S. Magesa, Sharon E. Cox, Julie Makani, Enrico M. Novelli","doi":"10.1038/s43856-024-00552-5","DOIUrl":"10.1038/s43856-024-00552-5","url":null,"abstract":"Sickle cell anemia (SCA) prevalence remains high in sub-Saharan Africa. Long-term treatment with hydroxyurea (HU) increases survival, however, poor adherence to treatment could limit effectiveness. Whilst HU treatment adherence is currently high, this might decrease over time. We conducted a single-center, randomized, open-label, parallel group phase 2 controlled clinical trial to determine whether mobile Directly Observed Therapy (m-DOT) increases HU treatment adherence (NCT02844673). Eligible participants were adults with homozygous SCA. People on a chronic blood transfusion program, with hemoglobin (Hb) A levels greater than 20% of the total Hb, total Hb less than 4 g/dL, pregnant or HIV positive were excluded. After a 3-month pre-treatment period participants were randomized to either m-DOT or standard monitoring arm. All participants received smart mobile phones and were treated with HU (15 mg/kg) daily for three months. In the m-DOT arm, drug intake was video recorded on cell phone by the participant and the video sent to the study team. The primary objective was to evaluate the effect of m-DOT on adherence to HU treatment by medication possession ratio (MPR). Of the 86 participants randomized, 76 completed the trial (26.13 ± 6.97 years, 63.5 % female). Adherence was high (MPR > 95 %) in both groups, 29 (80.6 %) in m-DOT versus 37 (94.9 %) in the standard monitoring arm (P = 0.079). No HU treatment was withheld from participants due to safety concerns. m-DOT did not increase adherence to HU treatment. We recommend that further testing in larger trials with a longer follow up period be undertaken. Sickle cell anemia (SCA) is an inherited blood disorder in which there is an abnormal protein inside red blood cells. This results in red blood cells becoming sickle shaped and more easily destroyed in the body. Long-term treatment with hydroxyurea can reduce the frequency of illness and hospitalization. However, often people do not manage to take their medication regularly when treatment is long-term. We therefore investigated whether people with SCA in sub-Saharan Africa are more likely to take hydroxyurea when they are remotely monitored than when they are not. Remote monitoring did not improve adherence. However, our study is small and was undertaken over a short time period when hydroxyurea had only recently become available to people with SCA. We propose further studies, to see if remote monitoring increases medication adherence in people with SCA in other scenarios. Sasi et al. evaluate whether using a smartphone to record drug treatment improves monitoring of adherence to medication and improved treatment outcome. In a pilot study of sickle cell anemia in patients starting long-term treatment with hydroxyurea, adherence was not increased when mobile Directly Observed Therapy (m-DOT) was used.","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11315961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation and comparison of nine growth and development-based measures of pubertal timing","authors":"Ahmed Elhakeem, Monika Frysz, Ana Goncalves Soares, Joshua A. Bell, Tim J. Cole, Jon Heron, Laura D. Howe, Sylvain Sebert, Kate Tilling, Nicholas J. Timpson, Deborah A. Lawlor","doi":"10.1038/s43856-024-00580-1","DOIUrl":"10.1038/s43856-024-00580-1","url":null,"abstract":"Pubertal timing is heritable, varies between individuals, and has implications for life-course health. There are many different indicators of pubertal timing, and how they relate to each other is unclear. Our aim was to quantitatively compare nine indicators of pubertal timing. We used data from questionnaires and height, weight, and bone measurements from ages 7–17 y in a population-based cohort of 4267 females and 4251 males to compare nine growth and development-based indicators of pubertal timing. We summarise age of each indicator, their phenotypic and genetic correlations, and how they relate to established genetic risk score (GRS) for puberty timing, and phenotypic childhood body composition measures. We show that pubic hair in males (mean: 12.6 y) and breasts in females (11.5 y) are early indicators of puberty, and voice breaking (14.2 y) and menarche (12.7 y) are late indicators however, there is substantial variation between individuals in pubertal age. All indicators show evidence of positive phenotypic intercorrelations (e.g., r = 0.49: male genitalia and pubic hair ages), and positive genetic intercorrelations. An age at menarche GRS positively associates with all other pubertal age indicators (e.g., difference in female age at peak height velocity per SD higher GRS: 0.24 y, 95%CI: 0.21 to 0.26), as does an age at voice breaking GRS (e.g., difference in age at male axillary hair: 0.11 y, 0.07 to 0.15). Higher childhood fat mass and lean mass associated with earlier puberty timing. Our findings provide insights into the measurements of the timing of pubertal growth and development and illustrate value of various pubertal timing indicators in life-course research. Age of puberty varies between individuals and can affect a person’s future health. We obtained information from 8500 British children as they progressed through puberty. We compared nine measures of pubertal timing. We found that the appearance of pubic hair in boys and breasts in girls are early indicators of puberty, and that voice change and onset of menstruation are late indicators. However, there was also substantial variability between individuals in age of puberty. All puberty measures were correlated with each other and related to an individual’s adult body mass index, as well as to their childhood muscle and fat mass. Our findings are useful information for health care workers and researchers who are interested in assessing and studying puberty. Elhakeem et al. evaluate and compare nine measures of pubertal timing using longitudinal assessments from a prospective British birth cohort study. The findings suggest all are consistent measures of pubertal timing and measure the same biological process.","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11306255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and preclinical testing of a selective beta-subtype agonist of thyroid hormone receptor ZTA-261","authors":"Masakazu Nambo, Taeko Nishiwaki-Ohkawa, Akihiro Ito, Zachary T. Ariki, Yuka Ito, Yuuki Kato, Muhammad Yar, Jacky C. -H. Yim, Emily Kim, Elizabeth Sharkey, Keiko Kano, Emi Mishiro-Sato, Kosuke Okimura, Michiyo Maruyama, Wataru Ota, Yuko Furukawa, Tomoya Nakayama, Misato Kobayashi, Fumihiko Horio, Ayato Sato, Cathleen M. Crudden, Takashi Yoshimura","doi":"10.1038/s43856-024-00574-z","DOIUrl":"10.1038/s43856-024-00574-z","url":null,"abstract":"Thyroid hormones (TH) regulate the basal metabolic rate through their receptors THRα and THRβ. TH activates lipid metabolism via THRβ, however, an excess amount of TH can lead to tachycardia, bone loss, and muscle wasting through THRα. In recent years, TH analogs that selectively bind to THRβ have gained attention as new agents for treating dyslipidemia and obesity, which continue to pose major challenges to public health worldwide. We developed a TH analog, ZTA-261, by modifying the existing THRβ-selective agonists GC-1 and GC-24. To determine the THRβ-selectivity of ZTA-261, an in vitro radiolabeled TH displacement assay was conducted. ZTA-261 was intraperitoneally injected into a mouse model of high-fat diet-induced obesity, and its effectiveness in reducing body weight and visceral fat, and improving lipid metabolism was assessed. In addition, its toxicity in the liver, heart, and bone was evaluated. ZTA-261 is more selective towards THRβ than GC-1. Although ZTA-261 is less effective in reducing body weight and visceral fat than GC-1, it is as effective as GC-1 in reducing the levels of serum and liver lipids. These effects are mediated by the same pathway as that of T3, a natural TH, as evidenced by similar changes in the expression of TH-induced and lipid metabolism-related genes. The bone, cardiac, and hepatotoxicity of ZTA-261 are significantly lower than those of GC-1. ZTA-261, a highly selective and less toxic THRβ agonist, has the potential to be used as a drug for treating diseases related to lipid metabolism. Nearly 10% of the world’s population suffers from obesity or is overweight. These conditions are closely related to disorders of lipid metabolism, posing significant challenges to individuals and healthcare systems. Thyroid hormone (TH) activates metabolism by binding to specific protein partners, called TH receptors (THRs). There are two types of THRs, THRα and THRβ. THRβ activates lipid metabolism; however, THRα negatively affects the heart, bone, and muscle when TH is in excess. This study developed a drug called ZTA-261 that selectively binds to THRβ. Its administration to mice with induced obesity from a high-fat diet resulted in reduced body fat without any apparent toxicity. Therefore, ZTA-261 is a promising candidate to improve lipid metabolism and address the obesity epidemic. Nambo, Nishiwaki-Ohkawa, Ito, Ariki et al. characterize a novel thyroid hormone analog, ZTA-261. The authors demonstrate a favorable toxicity profile and effects on lipid metabolism in a high fat diet-induced mouse model of obesity.","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Touchless short-wave infrared imaging for dynamic rapid pupillometry and gaze estimation in closed eyes","authors":"Omer Ben Barak-Dror, Barak Hadad, Hani Barhum, David Haggiag, Michal Tepper, Israel Gannot, Yuval Nir","doi":"10.1038/s43856-024-00572-1","DOIUrl":"10.1038/s43856-024-00572-1","url":null,"abstract":"Assessments of gaze direction (eye movements), pupil size, and the pupillary light reflex (PLR) are critical for neurological examination and neuroscience research and constitute a powerful tool in diverse clinical settings ranging from critical care through endocrinology and drug addiction to cardiology and psychiatry. However, current bedside pupillometry is typically intermittent, qualitative, manual, and limited to open-eye cases, restricting its use in sleep medicine, anesthesia, and intensive care. We combined short-wave infrared (SWIR, ~0.9-1.7μm) imaging with image processing algorithms to perform rapid (~30 ms) pupillometry and eye tracking behind closed eyelids. Forty-three healthy volunteers participated in two experiments with PLR evoked by visible light stimuli or directing eye movements towards screen targets. Imaging was performed simultaneously on one eye closed, and the other open eye serving as ground truth. Data analysis was performed with a custom approach quantifying changes in brightness around the pupil area or with a deep learning U-NET-based procedure. Here we show that analysis of SWIR imaging data can successfully measure stimulus-evoked PLR in closed-eye conditions, revealing PLR events in single trials and significant PLRs in nearly all individual subjects, as well as estimating gaze direction. The neural net-based analysis could successfully use closed-eye SWIR data to recreate estimates of open-eye images and assess pupil size. Continuous touchless monitoring of rapid dynamics in pupil size and gaze direction through closed eyes paves the way for developing devices with wide-ranging applications, fulfilling long-standing goals in clinical and research fields. Monitoring eye movements and pupil size is important for both clinical assessments and in biomedical research. However, measurements are usually made on open eyes. We developed a method that continuously monitors pupil size when eyes are closed and compared it to results obtained when eyes are open. Our approach is contactless and can measure pupil size and gaze direction for hours. This approach has many potential clinical and research uses. For example, it could be used to monitor the extent of arousal during and following anesthesia, sleep, and in unconscious patients. Ben Barak-Dror et al. present a short-wave infrared imaging method for touchless monitoring of pupillary light reflex (PLR) and gaze direction in closed eyes. Data obtained is comparable to that obtained from open eyes.","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent and projected changes in global climate may increase nicotine absorption and the risk of green tobacco sickness","authors":"Lewis H. Ziska, Robbie M. Parks","doi":"10.1038/s43856-024-00584-x","DOIUrl":"10.1038/s43856-024-00584-x","url":null,"abstract":"Dermal transfer of nicotine during tobacco harvest can cause green tobacco sickness (GTS), characterized by nausea, vomiting, headache and dizziness. Rainfall and high temperatures are etiological factors known to increase the prevalence of GTS. We analyzed recent and projected trends in these factors for major tobacco-growing regions to assess potential exacerbation in GTS occurrence. We analyzed climate parameters, including recent trends (since the 1970s) in temperature and precipitation metrics during the tobacco harvest period for Southern Brazil; Yunnan Province, China; Andhra State, India; and North Carolina, USA. We applied Shared Socio-economic Pathways (SSPs) based scenarios for Tier 1 Scenario Model Intercomparison Project (ScenarioMIP) within the Coupled Model Intercomparison Project phase 6 (CMIP6), (SSPs of 1–2.6, 3–7.0 and 5–8.5 from 2020 to 2100). Established protocol for nicotine dermal patches and temperature were used as a proxy to estimate potential nicotine absorption. For three locations, cumulative maximum temperatures during harvest and temperature extremes rose significantly since the 1970s as did cumulative rainfall during harvest. Projected maximum temperatures at SSP 3–7.0 and 5–8.5 projections through 2100 did increase for all locations. Estimates of nicotine skin absorption with rising temperature show significant increases for both recent changes in three locations, and for all locations for SSP projections of 3–7.0 and 5–8.5 from 2020 to 2100. This study across multiple continents, highlights a potential link between recent and projected anthropogenic change and potential increases in GTS risk. Under SSP 5–8.5, nicotine absorption could increase by ~50% by the end of the century, which may have widespread impacts on the incidence of GTS, especially among younger tobacco workers. Transfer of nicotine from tobacco leaves to the skin can result in a type of poisoning called green tobacco sickness (GTS) for field workers who harvest tobacco. Transfer is linked to temperature and rainfall, which are both impacted by global climate change. We examined recent (from 1970-present) and projected future (present to 2100) changes in these measures for four global locations where tobacco is grown. North Carolina, Brazil, China and India all show an increase in average maximum temperatures or rainfall since the 1970s. We find that recent or future changes in the climate are associated with an increased likelihood of skin absorption of nicotine. This study, across multiple continents, highlights a potential link between climate change that could increase the risk of GTS for tobacco workers. Ziska and Parks explore the potential impact of anthropogenic climate change on nicotine absorption in major tobacco-growing regions. Analysis of recent and projected environmental changes suggests the likelihood of increased dermal transfer of nicotine, leading to increased green tobacco sickness incidence amongst tobacco workers.","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Robotic scrub nurse to anticipate surgical instruments based on real-time laparoscopic video analysis","authors":"Lars Wagner, Sara Jourdan, Leon Mayer, Carolin Müller, Lukas Bernhard, Sven Kolb, Farid Harb, Alissa Jell, Maximilian Berlet, Hubertus Feussner, Peter Buxmann, Alois Knoll, Dirk Wilhelm","doi":"10.1038/s43856-024-00581-0","DOIUrl":"10.1038/s43856-024-00581-0","url":null,"abstract":"Machine learning and robotics technologies are increasingly being used in the healthcare domain to improve the quality and efficiency of surgeries and to address challenges such as staff shortages. Robotic scrub nurses in particular offer great potential to address staff shortages by assuming nursing tasks such as the handover of surgical instruments. We introduce a robotic scrub nurse system designed to enhance the quality of surgeries and efficiency of surgical workflows by predicting and delivering the required surgical instruments based on real-time laparoscopic video analysis. We propose a three-stage deep learning architecture consisting of a single frame-, temporal multi frame-, and informed model to anticipate surgical instruments. The anticipation model was trained on a total of 62 laparoscopic cholecystectomies. Here, we show that our prediction system can accurately anticipate 71.54% of the surgical instruments required during laparoscopic cholecystectomies in advance, facilitating a smoother surgical workflow and reducing the need for verbal communication. As the instruments in the left working trocar are changed less frequently and according to a standardized procedure, the prediction system works particularly well for this trocar. The robotic scrub nurse thus acts as a mind reader and helps to mitigate staff shortages by taking over a great share of the workload during surgeries while additionally enabling an enhanced process standardization. Staff shortages in healthcare are an emerging problem leading to undersupply of medical experts such as scrub nurses in the operating room. The absence of these scrub nurses, who are responsible for providing surgical instruments, means that surgeries must be postponed or canceled. Robotic technologies and artificial intelligence offer great potential to address staff shortages in the operating room. We developed a robotic scrub nurse system that is able to take over the tasks of a human scrub nurse by delivering the required surgical tools. To maintain the pace of the surgery, our robotic scrub nurse system is also capable of predicting these required surgical tools in advance using artificial intelligence. The system is tested on laparoscopic cholecystectomies, a surgery, where the gallbladder is removed in a minimally invasive technique. We show that our prediction system can predict the majority of surgical instruments for this specific surgery facilitating a smoother surgical workflow and reducing the need for verbal communication. With further development, our system may help to cover the need for surgery while streamlining the surgical process through predictive support, potentially improving patient outcomes. Wagner et al. present a robotic scrub nurse (RSN) system that predicts and delivers required instruments based on real-time laparoscopic video analysis. The machine learning based system accurately anticipates the necessary tools required for laparoscopic cholecystectomies, streaml","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to multiple ambient air pollutants changes white matter microstructure during early adolescence with sex-specific differences","authors":"Devyn L. Cotter, Hedyeh Ahmadi, Carlos Cardenas-Iniguez, Katherine L. Bottenhorn, W. James Gauderman, Rob McConnell, Kiros Berhane, Joel Schwartz, Daniel A. Hackman, Jiu-Chiuan Chen, Megan M. Herting","doi":"10.1038/s43856-024-00576-x","DOIUrl":"10.1038/s43856-024-00576-x","url":null,"abstract":"Air pollution is ubiquitous, yet questions remain regarding its impact on the developing brain. Large changes occur in white matter microstructure across adolescence, with notable differences by sex. We investigate sex-stratified effects of annual exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) at ages 9–10 years on longitudinal patterns of white matter microstructure over a 2-year period. Diffusion-weighted imaging was collected on 3T MRI scanners for 8182 participants (1–2 scans per subject; 45% with two scans) from the Adolescent Brain Cognitive Development (ABCD) Study®. Restriction spectrum imaging was performed to quantify intracellular isotropic (RNI) and directional (RND) diffusion. Ensemble-based air pollution concentrations were assigned to each child’s primary residential address. Multi-pollutant, sex-stratified linear mixed-effect models assessed associations between pollutants and RNI/RND with age over time, adjusting for sociodemographic factors. Here we show higher PM2.5 exposure is associated with higher RND at age 9 in both sexes, with no significant effects of PM2.5 on RNI/RND change over time. Higher NO2 exposure is associated with higher RNI at age 9 in both sexes, as well as attenuating RNI over time in females. Higher O3 exposure is associated with differences in RND and RNI at age 9, as well as changes in RND and RNI over time in both sexes. Criteria air pollutants influence patterns of white matter maturation between 9–13 years old, with some sex-specific differences in the magnitude and anatomical locations of affected tracts. This occurs at concentrations that are below current U.S. standards, suggesting exposure to low-level pollution during adolescence may have long-term consequences. Air pollution is known to affect health, but it is unclear whether it affects the growing human brain. We investigated whether there were differences in the development of white matter connections, which allow for faster communication between different brain regions, in children aged 9-13 years living in areas with relatively low or high air pollution in the USA. In a large group of U.S. teens, we find that polluted air is linked to differences in white matter at ages 9-10 years old and over the next two years. In some cases, males and females showed differences in the part of the brain showing changes and the amount of white matter change. Our study suggests that air pollution levels that are deemed acceptable under current regulations in the USA could have long-term effects on how a child’s brain grows. Further studies are needed to better understand the impact of these changes. Cotter et al. investigate associations between low levels of ambient pollutant exposure and white matter microstructural development during the transition from childhood to adolescence. There are sex-stratified associations, with NO2 primarily affecting females and O3 affecting both sexes over time.","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11294340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A network-based trans-omics approach for predicting synergistic drug combinations","authors":"Midori Iida, Yurika Kuniki, Kenta Yagi, Mitsuhiro Goda, Satoko Namba, Jun-ichi Takeshita, Ryusuke Sawada, Michio Iwata, Yoshito Zamami, Keisuke Ishizawa, Yoshihiro Yamanishi","doi":"10.1038/s43856-024-00571-2","DOIUrl":"10.1038/s43856-024-00571-2","url":null,"abstract":"Combination therapy can offer greater efficacy on medical treatments. However, the discovery of synergistic drug combinations is challenging. We propose a novel computational method, SyndrumNET, to predict synergistic drug combinations by network propagation with trans-omics analyses. The prediction is based on the topological relationship, network-based proximity, and transcriptional correlation between diseases and drugs. SyndrumNET was applied to analyzing six diseases including asthma, diabetes, hypertension, colorectal cancer, acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). Here we show that SyndrumNET outperforms the previous methods in terms of high accuracy. We perform in vitro cell survival assays to validate our prediction for CML. Of the top 17 predicted drug pairs, 14 drug pairs successfully exhibits synergistic anticancer effects. Our mode-of-action analysis also reveals that the drug synergy of the top predicted combination of capsaicin and mitoxantrone is due to the complementary regulation of 12 pathways, including the Rap1 signaling pathway. The proposed method is expected to be useful for discovering synergistic drug combinations for various complex diseases. Adding drug treatments together can sometimes produce better results for patients. We introduced a new computer-based method called SyndrumNET, designed to identify effective drug combinations for treating diseases. The method uses data about how diseases and drugs interact at a molecular level to predict which drugs work well together. Tested on six different diseases, such as asthma and different types of cancer, SyndrumNET proved to be more accurate than previous approaches. For example, most of the drug combinations predicted by SyndrumNET to rank highly have shown better combination effects on leukemia cells. This method also helped understand why certain drug combinations work better by analyzing their effects on cellular pathways. The findings suggest that SyndrumNET could be a valuable tool in developing more effective treatment for various complex diseases. Iida et al. predict synergistic drug combinations using a computational method termed SyndrumNET. Validation of predictions in chronic myeloid leukemia using in vitro cell survival assays reveal synergistic anticancer effects in 14 of 17 top predicted drug pairings.","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Publisher Correction: Unified metagenomic method for rapid detection of microorganisms in clinical samples","authors":"Adela Alcolea-Medina, Christopher Alder, Luke B. Snell, Themoula Charalampous, Alp Aydin, Gaia Nebbia, Tom Williams, Simon Goldenberg, Sam Douthwaite, Rahul Batra, Penelope R. Cliff, Hannah Mischo, Stuart Neil, Mark Wilks, Jonathan D. Edgeworth","doi":"10.1038/s43856-024-00579-8","DOIUrl":"10.1038/s43856-024-00579-8","url":null,"abstract":"","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141768267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and tolerability of the protein C activator AB002 in end-stage renal disease patients on hemodialysis: a randomized phase 2 trial","authors":"Norah G. Verbout, Christina U. Lorentz, Brandon D. Markway, Michael Wallisch, Thomas C. Marbury, Enrico Di Cera, Joseph J. Shatzel, András Gruber, Erik I. Tucker","doi":"10.1038/s43856-024-00575-y","DOIUrl":"10.1038/s43856-024-00575-y","url":null,"abstract":"The protein C system regulates blood coagulation, inflammation, and vascular integrity. AB002 is an injectable protein C activating enzyme under investigation to safely prevent and treat thrombosis. In preclinical models, AB002 is antithrombotic, cytoprotective, and anti-inflammatory. Since prophylactic use of heparin is contraindicated during hemodialysis in some end-stage renal disease (ESRD) patients, we propose using AB002 as a short-acting alternative to safely limit blood loss due to clotting in the dialysis circuit. This phase 2, randomized, double-blind, placebo-controlled, single-dose study evaluates the safety and tolerability of AB002 administered into the hemodialysis line of ESRD patients during hemodialysis at one study center in the United States (ClinicalTrials.gov: NCT03963895). In this study, 36 patients were sequentially enrolled into two cohorts and randomized to AB002 or placebo in a 2:1 ratio. In cohort 1, patients received 1.5 µg/kg AB002 (n = 12) or placebo (n = 6); in cohort 2, patients received 3 µg/kg AB002 (n = 12) or placebo (n = 6). Patients underwent five heparin-free hemodialysis sessions over 10 days and were dosed with AB002 or placebo during session four. Here we show that AB002 is safe and well-tolerated in ESRD patients, with no treatment-related adverse events. Clinically relevant bleeding did not occur in any patient, and the time to hemostasis at the vascular access sites is not affected by AB002. As far as we are aware, this proof-of-concept study is the first clinical trial assessing the therapeutic potential of protein C activation. The results herein support additional investigation of AB002 to safely prevent and treat thrombosis in at-risk populations. Some people with kidney disease require hemodialysis, a process in which a machine filters the blood to remove waste products. The process of hemodialysis can trigger blood clotting in the hemodialysis circuit. Therefore, the blood-thinner heparin is commonly used to prevent blood from clotting. However, some patients cannot tolerate heparin. Here we describe a clinical trial in which we tested whether a drug called AB002 is safe and can reduce hemodialysis circuit clotting in people with permanent kidney disease (end-stage renal disease) undergoing hemodialysis. AB002 appears to be safe and well-tolerated, and we observed reduced clotting without any signs of increased bleeding. Further studies are required in more patients to determine whether AB002 can be used routinely during hemodialysis to safely prevent or treat blood clots. Verbout et al. report findings from a phase 2 proof-of-concept study of the protein C activator AB002 in patients with end stage renal disease undergoing heparin-free hemodialysis. AB002 appears safe and well-tolerated, while demonstrating reduced dialyzer clot severity and no increased bleeding at the vascular access site compared to placebo.","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141768268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}