{"title":"Efflux pump-mediated resistance to new beta lactam antibiotics in multidrug-resistant gram-negative bacteria","authors":"Augusto Dulanto Chiang, John P. Dekker","doi":"10.1038/s43856-024-00591-y","DOIUrl":"10.1038/s43856-024-00591-y","url":null,"abstract":"The emergence and spread of bacteria resistant to commonly used antibiotics poses a critical threat to modern medical practice. Multiple classes of bacterial efflux pump systems play various roles in antibiotic resistance, and members of the resistance-nodulation-division (RND) transporter superfamily are among the most important determinants of efflux-mediated resistance in gram-negative bacteria. RND pumps demonstrate broad substrate specificities, facilitating extrusion of multiple chemical classes of antibiotics from the bacterial cell. Several newer beta-lactams and beta-lactam/beta-lactamase inhibitor combinations (BL/BLI) have been developed to treat infections caused by multidrug resistant bacteria. Here we review recent studies that suggest RND efflux pumps in clinically relevant gram-negative bacteria may play critical but underappreciated roles in the development of resistance to beta-lactams and novel BL/BLI combinations. Improved understanding of the genetic and structural basis of RND efflux pump-mediated resistance may identify new antibiotic targets as well as strategies to minimize the emergence of resistance. Dulanto Chiang and Dekker discuss recent work on efflux pump-mediated antibiotic resistance in gram-negative bacteria. They highlight evidence implicating RND-class efflux pumps in resistance to new broad spectrum beta lactam and beta lactam/beta lactamase inhibitor antibiotics, and implications for therapy and antibiotic development.","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43856-024-00591-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091196","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}
Matan Yechezkel, Gary Qian, Yosi Levi, Nadav Davidovitch, Erez Shmueli, Dan Yamin, Margaret L. Brandeau
{"title":"Comparison of physiological and clinical reactions to COVID-19 and influenza vaccination","authors":"Matan Yechezkel, Gary Qian, Yosi Levi, Nadav Davidovitch, Erez Shmueli, Dan Yamin, Margaret L. Brandeau","doi":"10.1038/s43856-024-00588-7","DOIUrl":"10.1038/s43856-024-00588-7","url":null,"abstract":"Public reluctance to receive COVID-19 vaccination is associated with safety concerns. By contrast, the seasonal influenza vaccine has been administered for decades with a solid safety record and a high level of public acceptance. We compare the safety profile of the BNT162b2 COVID-19 booster vaccine to that of the seasonal influenza vaccine. We study a prospective cohort of 5079 participants in Israel and a retrospective cohort of 250,000 members of MHS selected randomly. We examine reactions to BNT162b2 mRNA COVID-19 booster and to influenza vaccinations. All prospective cohort participants wore a smartwatch and completed a daily digital questionnaire. We compare pre-vaccination and post-vaccination smartwatch heart-rate data, and a stress measure based on heart-rate variability. We also examine adverse events from electronic health records. In the prospective cohort, 1905 participants receive the COVID-19 booster vaccine; 899 receive influenza vaccination. Focusing on those who receive both vaccines yields a total of 689 participants in the prospective cohort and 31,297 members in the retrospective cohort. Individuals reporting a more severe reaction after influenza vaccination tend to likewise report a more severe reaction after COVID-19 vaccination. In paired analysis, the increase in both heart rate and stress measure for each participant is higher for COVID-19 than for influenza in the first 2 days after vaccination. No elevated risk of hospitalization due to adverse events is found following either vaccine. Except for Bell’s palsy after influenza vaccination, no elevated risk of adverse events is found. The more pronounced side effects after COVID-19 vaccination may explain the greater concern associated with it. Nevertheless, our comprehensive analysis supports the safety profile of both vaccines. We compared the safety profiles of the COVID-19 and influenza vaccines. We analyzed data from Israel involving 5079 participants who wore smartwatches and completed daily questionnaires, as well as electronic health records from 250,000 members of Maccabi Healthcare Services. We found that side effects after the COVID-19 vaccine were more noticeable, based on self-reported symptoms and heart measures (heart-rate and stress) detected by smartwatches. The increase in heart measures was higher after COVID-19 vaccination than after influenza vaccination in the first 2 days post-vaccination. However, electronic health records showed no increased risk of adverse events with the COVID-19 and influenza vaccines. Our analysis supports the safety of both vaccines but may explain the greater concern about the COVID-19 vaccine. Yechezkel et al. compare the safety profiles of the BNT162b2 COVID-19 booster and the seasonal influenza vaccine using data from wearables, reported reactions, and electronic health records. Participants displayed increased heart rates and short-term stress measurements following COVID-19 boosters but overall safety of both vaccines ","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43856-024-00588-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142050570","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":"Nationwide surveys of awareness of tuberculosis in India uncover a gender gap in tuberculosis awareness","authors":"Ranganath Thimmanahalli Sobagaiah, Nitu Kumari, Divya Bharathi Gattam, Mohammed Shoyaib Khazi","doi":"10.1038/s43856-024-00592-x","DOIUrl":"10.1038/s43856-024-00592-x","url":null,"abstract":"Tuberculosis remains a major challenge in India, with an estimated 2.69 million cases each year. Although men are more affected than women, gender differences and related factors affect awareness of tuberculosis and thus impact tuberculosis diagnosis and access to treatment. Understanding the gender-specific needs and complexities when diagnosing and treating tuberculosis is essential to manage cases in India. We undertook a comparative study using data from three National Family and Health Surveys (NFHS), specifically NFHS-3, NFHS-4 and NFHS-5. We investigated the prevalence and gender disparity in awareness about tuberculosis, and associated factors, using regression analysis. Most men and women surveyed are between the ages of 15 and 19. Across the surveys, the proportion of men and women who are unaware of spreading of tuberculosis decreases from 44.9% during NFHS 3 to 29.6% during NFHS 5. However, the prevalence ratio of men to women with no knowledge about modes of transmission of Tuberculosis increases from 0.92 during NFHS 3 to 0.98 during NFHS 5. Higher odds with younger age (NFHS 5, aOR: 1.07 (1.01–1.13)) and rural residency (NFHS 5, aOR: 1.12 (1.06–1.18)), and lower odds with unmarried marital status (NFHS 5, aOR: 0.92 (0.86–0.98)) are noteworthy associations. Women and men have differences in knowledge. Gender disparity associated with awareness about tuberculosis in India is observed across all three nationwide surveys. Being aged fifteen to nineteen years and residing in rural area are risk factors. Being unmarried is a protective factor for women, but not for men. Lack of awareness of the spread of tuberculosis may be an important factor contributing to the current burden of disease. We used datasets from three rounds of the National Family Health Survey conducted in India to determine the proportion of men and women who knew how tuberculosis spreads. Using a predictive model, we showed that misconceptions are more common among both men and women. For women, younger age and living in rural areas were risk factors for lack of awareness, which was not the case for men. Such differences may represent a barrier to reducing the burden of disease. These findings can be used to develop gender-specific, comprehensive people awareness programs to raise awareness about tuberculosis. Sobagaiah et al. investigate the gender gap in awareness about how tuberculosis is transmitted 2 across three national family health surveys in India. Regression modelling shows variation in 3 awareness between men and women at a national level.","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43856-024-00592-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047562","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}
Paul Nderitu, Joan M. Nunez do Rio, Laura Webster, Samantha Mann, M. Jorge Cardoso, Marc Modat, David Hopkins, Christos Bergeles, Timothy L. Jackson
{"title":"Predicting 1, 2 and 3 year emergent referable diabetic retinopathy and maculopathy using deep learning","authors":"Paul Nderitu, Joan M. Nunez do Rio, Laura Webster, Samantha Mann, M. Jorge Cardoso, Marc Modat, David Hopkins, Christos Bergeles, Timothy L. Jackson","doi":"10.1038/s43856-024-00590-z","DOIUrl":"10.1038/s43856-024-00590-z","url":null,"abstract":"Predicting diabetic retinopathy (DR) progression could enable individualised screening with prompt referral for high-risk individuals for sight-saving treatment, whilst reducing screening burden for low-risk individuals. We developed and validated deep learning systems (DLS) that predict 1, 2 and 3 year emergent referable DR and maculopathy using risk factor characteristics (tabular DLS), colour fundal photographs (image DLS) or both (multimodal DLS). From 162,339 development-set eyes from south-east London (UK) diabetic eye screening programme (DESP), 110,837 had eligible longitudinal data, with the remaining 51,502 used for pretraining. Internal and external (Birmingham DESP, UK) test datasets included 27,996, and 6928 eyes respectively. Internal multimodal DLS emergent referable DR, maculopathy or either area-under-the receiver operating characteristic (AUROC) were 0.95 (95% CI: 0.92–0.98), 0.84 (0.82–0.86), 0.85 (0.83–0.87) for 1 year, 0.92 (0.87–0.96), 0.84 (0.82–0.87), 0.85 (0.82–0.87) for 2 years, and 0.85 (0.80–0.90), 0.79 (0.76–0.82), 0.79 (0.76–0.82) for 3 years. External multimodal DLS emergent referable DR, maculopathy or either AUROC were 0.93 (0.88–0.97), 0.85 (0.80–0.89), 0.85 (0.76–0.85) for 1 year, 0.93 (0.89–0.97), 0.79 (0.74–0.84), 0.80 (0.76–0.85) for 2 years, and 0.91 (0.84–0.98), 0.79 (0.74–0.83), 0.79 (0.74–0.84) for 3 years. Multimodal and image DLS performance is significantly better than tabular DLS at all intervals. DLS accurately predict 1, 2 and 3 year emergent referable DR and referable maculopathy using colour fundal photographs, with additional risk factor characteristics conferring improvements in prognostic performance. Proposed DLS are a step towards individualised risk-based screening, whereby AI-assistance allows high-risk individuals to be closely monitored while reducing screening burden for low-risk individuals. Diabetic retinopathy (DR) is a disease where the light-sensing layer at the back of the eye (retina) becomes damaged by raised blood sugar levels. It affects around one in three of the 463 million people with diabetes worldwide and is a leading cause of acquired vision loss in working-age adults. In this study, we developed computer-based models to predict when DR would reach a stage where vision could be threatened up to 3-years in the future. Our study shows that this system can accurately predict sight-threatening DR in patients with diabetes. This could mean fewer unnecessary visits for individuals at low-risk of DR progression, but closer monitoring and potentially earlier treatment for individuals at high-risk of DR progression, which could reduce the risk of vision loss. Nderitu et al. present deep learning systems developed to predict emergent referable diabetic retinopathy and maculopathy over 1, 2 and 3 years. Using validated tabular, image and multimodal systems they aim to individualise risk-based screening.","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43856-024-00590-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019721","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":"The effect of aging and asymmetrical hearing on speech discrimination","authors":"Koichiro Wasano, Takashi Nakagawa, Kimitaka Kaga, Kaoru Ogawa","doi":"10.1038/s43856-024-00587-8","DOIUrl":"10.1038/s43856-024-00587-8","url":null,"abstract":"Speech discrimination (SpD) is exacerbated by hearing loss, but the relationship between pure-tone audiometry (PTA) and SpD is poorly described and understood in the aging process. It is also unclear whether severity of left-right (L-R) differences in PTA threshold disproportionately affects SpD. We conducted a retrospective cross-sectional study of a broad age range (10–99 years) of patients in Japan. Demographic data, SpD, and PTA threshold data were collected for each patient and side (L-R). We evaluated the association between chronological age and overall SpD, and SpD according to severity of PTA-threshold difference for ear pairs. Asymmetries in L-R PTA thresholds were stratified into four equally spaced categories: <10dB L-R difference to ≥40 dB L-R difference. Among the 2760 eligible participants, data from 5508 ears are analyzed. Overall SpD gradually decreases with age, with SpD scores in the oldest groups being significantly worse (Kruskal-Wallis followed by Dunn’s test; p < 0.0001) than those of the youngest group. Comparison of worse-hearing ears to better-hearing ears within the same severity of hearing impairment reveals significant differences on SpD in ears that have moderate or severe hearing impairment (p < 0.0001). Post-hoc analysis identifies significant differences in SpD between the worse-hearing ears and the better-hearing ears that have hearing differences of 20 dB or more. SpD is dramatically affected by age and asymmetrical hearing. Therefore, appropriate audiological interventions should be proactively considered according to an individual’s hearing level, age, and difference in L-R hearing levels. The ability to understand speech is impacted by hearing loss. Pure-tone hearing tests are commonly used to test hearing. The relationship between pure-tone hearing tests and speech perception tests during aging is poorly understood. It is also unclear whether severity of differences in hearing between the ears affect speech perception. We evaluated the association between chronological age and speech perception score, as well as speech perception score according to severity of hearing difference between ears, in a large dataset from Japan. We found speech perception is dramatically affected by age and the presence of asymmetrical hearing. Our results suggest that appropriate audiological interventions should be proactively considered according to an individual’s hearing level, age, and whether they have asymmetrical hearing. Wasano et al. evaluate the impact of age and asymmetrical hearing on pure-tone hearing thresholds and speech discrimination in a large number of participants aged between 10 and 99 years. Age and asymmetrical hearing are shown to affect the relationship between pure-tone hearing thresholds and speech discrimination.","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43856-024-00587-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019722","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}
Sophie J. Miller, Lucy Carpenter, Steven L. Taylor, Steve L. Wesselingh, Jocelyn M. Choo, Andrew P. Shoubridge, Lito E. Papanicolas, Geraint B. Rogers, GRACE Investigator Group
{"title":"Intestinal microbiology and urinary tract infection associated risk in long-term aged care residents","authors":"Sophie J. Miller, Lucy Carpenter, Steven L. Taylor, Steve L. Wesselingh, Jocelyn M. Choo, Andrew P. Shoubridge, Lito E. Papanicolas, Geraint B. Rogers, GRACE Investigator Group","doi":"10.1038/s43856-024-00583-y","DOIUrl":"10.1038/s43856-024-00583-y","url":null,"abstract":"Urinary tract infections (UTI) are the most frequently diagnosed infection in residents of long-term care and are a major risk factor for urosepsis, hospitalisation, and death. Translocation of gut pathobionts into the urinary tract is the presumed cause of most UTIs. While specific gut microbiota characteristics have been linked to UTI risk in younger adults, their relevance in aged care residents remains uncertain. The faecal microbiome was assessed in 54 long-term aged care residents with a history of UTIs and 69 residents without a UTI history. Further comparisons were made to microbiome characteristics in 20 younger adults without UTIs. Microbiome characteristics were examined in relation to prior and subsequent UTIs, as well as antibiotic therapy. In long-term aged care residents, prior UTI history and exposure to UTI-exclusive antibiotics do not significantly affect microbiome composition or functional capacity. However, exposure to antibiotics unrelated to UTI treatment is associated with distinct microbiota compositional traits. Adjustment for dementia, incontinence, diabetes, and prior antibiotic use finds no microbiota characteristic linked to UTI development. However, prior UTI is identified as a predictor of future UTIs. Comparison with younger adults identifies greater within-participant dispersion in aged care residents, as well as lower microbiota diversity and altered microbiome functional potential. No association between the gut microbiome and UTI incidence, as has been reported in younger individuals, is evident in long-term aged care residents. Considerable variability in gut microbiome characteristics, relating to high antibiotic exposure and age-related physiological and immunological factors, could mask such a relationship. However, it cannot be discounted that increased UTI risk in the elderly is independent of microbiome-mediated mechanisms. Urinary tract infections (UTIs) are common in residents of long-term aged care facilities, posing serious health risks. Harmful bacteria moving from the gut to the urinary tract is thought to cause most UTIs. It is still unclear, however, how differences in gut bacteria contribute to UTI risk in older adults. Here, we investigate the gut bacteria of aged care residents, both with and without a history of UTIs, and compare them to younger adults. While prior UTIs did not alter gut bacteria, antibiotic use did. We observed greater variability in gut bacteria among aged care residents compared to younger adults. These observations suggest that both high antibiotic exposure and age-related factors may mask any potential relationship between gut bacteria and UTI risk in this population. Understanding these factors could lead to improved UTI prevention and treatment strategies for elderly individuals. Miller et al. investigate the gut microbiome in long-term aged care residents with and without UTI history, as well as younger adults. Findings reveal considerable variability in gut microbio","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43856-024-00583-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141991751","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}
Jiehu Yuan, Lan Li, Meihong Dong, Hau Chi So, Benjamin J. Cowing, Dennis Kai Ming Ip, Qiuyan Liao
{"title":"Parental vaccine hesitancy and influenza vaccine type preferences during and after the COVID-19 Pandemic","authors":"Jiehu Yuan, Lan Li, Meihong Dong, Hau Chi So, Benjamin J. Cowing, Dennis Kai Ming Ip, Qiuyan Liao","doi":"10.1038/s43856-024-00585-w","DOIUrl":"10.1038/s43856-024-00585-w","url":null,"abstract":"Seasonal influenza vaccine (SIV) greatly reduces disease burden among school-aged children, yet parental vaccine hesitancy remains a persistent challenge. Two types of SIV are available for children in Hong Kong and other locations: inactivated influenza vaccine (IIV), administered through intramuscular injection, and live attenuated influenza vaccine (LAIV), administered via nasal spray. We aimed to understand how vaccine hesitancy shaped parental preference for LAIV versus IIV, particularly amidst important public health events, such as the COVID-19 pandemic and the massive rollout of COVID-19 vaccination campaigns. We employed a concurrent mixed-methods design. The quantitative part involves longitudinal surveys spanning three years, from pre-pandemic to post-pandemic periods, tracking parental vaccine hesitancy and preference for SIV types. The qualitative part involves 48 in-depth interviews, providing insights into parental preference for SIV types, underlying reasons, and related values. Our quantitative analyses show an overall increase in parental vaccine hesitancy and preference for LAIV over IIV after the onset of the COVID-19 pandemic and especially after the rollout of the COVID-19 vaccination campaign. Further logistic regression modelling based on the cohort data shows that higher vaccine hesitancy, coupled with the COVID-19 vaccination campaign rollout, predicts a greater preference for LAIV over IIV. The qualitative analysis complements these results, highlighting that LAIV’s non-invasive nature aligns with parental values of prioritizing natural immunity and concerns about overmedication, leading to a more acceptable attitude towards LAIV. Leveraging the higher acceptability of LAIV compared to IIV among parents with high vaccine hesitancy could promote childhood vaccination uptake. We examined how parents’ concerns about vaccines and major public health events affected their preference for different types of seasonal influenza vaccines for children. Currently, children can receive either an injected vaccine or a nasal-spray vaccine. We tracked parental vaccine hesitancy and their preferences for different types of vaccines over three years covering a period before the COVID-19 pandemic and a period during the pandemic. Parents became more hesitant about seasonal influenza vaccines for children after the start of the COVID-19 pandemic and the rollout of COVID-19 vaccines. Higher vaccine hesitancy and the rollout of COVID-19 vaccines predicted a greater preference for nasal-spray vaccines for children among parents. Parents preferred the non-invasive nature of the nasal-spray vaccines and were concerned about overmedication, particularly vaccines that were administered via injection. We suggest that the nasal-spray vaccines could be one option offered to address high parental vaccine hesitancy. Yuan et. al examine how parental vaccine hesitancy and the rollout of COVID-19 vaccination programs affected preferences f","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43856-024-00585-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141991742","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}
Nic G. Reitsam, Bianca Grosser, David F. Steiner, Veselin Grozdanov, Ellery Wulczyn, Vincenzo L’Imperio, Markus Plass, Heimo Müller, Kurt Zatloukal, Hannah S. Muti, Jakob N. Kather, Bruno Märkl
{"title":"Converging deep learning and human-observed tumor-adipocyte interaction as a biomarker in colorectal cancer","authors":"Nic G. Reitsam, Bianca Grosser, David F. Steiner, Veselin Grozdanov, Ellery Wulczyn, Vincenzo L’Imperio, Markus Plass, Heimo Müller, Kurt Zatloukal, Hannah S. Muti, Jakob N. Kather, Bruno Märkl","doi":"10.1038/s43856-024-00589-6","DOIUrl":"10.1038/s43856-024-00589-6","url":null,"abstract":"Tumor-Adipose-Feature (TAF) as well as SARIFA (Stroma AReactive Invasion Front Areas) are two histologic features/biomarkers linking tumor-associated adipocytes to poor outcomes in colorectal cancer (CRC) patients. Whereas TAF was identified by deep learning (DL) algorithms, SARIFA was established as a human-observed histopathologic biomarker. To study the overlap between TAF and SARIFA, we performed a systematic pathological review of TAF based on all published image tiles. Additionally, we analyzed the presence/absence of TAF in SARIFA-negative CRC cases to elucidate the biologic and prognostic role of a direct tumor-adipocyte contact. TCGA-CRC gene expression data is investigated to assess the association of FABP4 (fatty-acid binding protein 4) and CD36 (fatty-acid translocase) with both TAF and CRC prognosis. By investigating the TAF/SARIFA overlap, we show that many TAF patches correspond to the recently described SARIFA-phenomenon. Even though there is a pronounced morphological and biological overlap, there are differences in the concepts. The presence of TAF in SARIFA-negative CRCs is not associated with poor outcomes in this cohort, potentially highlighting the importance of a direct tumor-adipocyte interaction. Upregulation of FABP4 and CD36 gene expression seem both linked to a poor prognosis in CRC. By proving the substantial overlap between human-observed SARIFA and DL-based TAF as morphologic biomarkers, we demonstrate that linking DL-based image features to independently developed histopathologic biomarkers is a promising tool in the identification of clinically and biologically meaningful biomarkers. Adipocyte-tumor-cell interactions seem to be crucial in CRC, which should be considered as biomarkers for further investigations. Different methods exist in assessing samples removed from cancer patients during surgery. We linked two independently established tissue-based methods for determining the outcome of colorectal cancer patients together: tumor adipose feature (TAF) and Stroma AReactive Invasion Front Areas (SARIFA). SARIFA as biological feature was observed solely by humans and TAF was identified by the help of a computer algorithm. We examined TAF in many cancer slides and looked at whether they showed similarities to SARIFA. TAF often matched SARIFA, but not always. Interestingly, these methods could be used to predict outcomes for patients and are associated with specific gene expression involved in tumor and fat cell interaction. Our study shows that combining computer algorithms with human expertize in evaluating tissue samples can identify meaningful features in patient samples, which may help to predict the best treatment options. Reitsam et al. assess the overlap between deep learning- and human observer-based identification of tumor-adipocyte interaction as a promising biomarker in colorectal cancer. They demonstrate that combining artificial intelligence and human pathological expertize is beneficial in id","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43856-024-00589-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986142","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}
Sabine Kling, Matteo Frigelli, M. Enes Aydemir, Vahoora Tahsini, Emilio A. Torres-Netto, Leonard Kollros, Farhad Hafezi
{"title":"Optical coherence tomography quantifies gradient refractive index and mechanical stiffness gradient across the human lens","authors":"Sabine Kling, Matteo Frigelli, M. Enes Aydemir, Vahoora Tahsini, Emilio A. Torres-Netto, Leonard Kollros, Farhad Hafezi","doi":"10.1038/s43856-024-00578-9","DOIUrl":"10.1038/s43856-024-00578-9","url":null,"abstract":"As a key element of ocular accommodation, the inherent mechanical stiffness gradient and the gradient refractive index (GRIN) of the crystalline lens determine its deformability and optical functionality. Quantifying the GRIN profile and deformation characteristics in the lens has the potential to improve the diagnosis and follow-up of lenticular disorders and guide refractive interventions in the future. Here, we present a type of optical coherence elastography able to examine the mechanical characteristics of the human crystalline lens and the GRIN distribution in vivo. The concept is demonstrated in a case series of 12 persons through lens displacement and strain measurements in an age-mixed group of human subjects in response to an external (ambient pressure modulation) and an intrinsic (micro-fluctuations of accommodation) mechanical deformation stimulus. Here we show an excellent agreement between the high-resolution strain map retrieved during steady-state micro-fluctuations and earlier reports on lens stiffness in the cortex and nucleus suggesting a 2.0 to 2.3 times stiffer cortex than the nucleus in young lenses and a 1.0 to 7.0 times stiffer nucleus than the cortex in the old lenses. Optical coherence tomography is suitable to quantify the internal stiffness and refractive index distribution of the crystalline lens in vivo and thus might contribute to reveal its inner working mechanism. Our methodology provides new routes for ophthalmic pre-surgical examinations and basic research. The lens of the eye changes in shape to enable objects at different distances from the eye to be seen clearly. Loss of ability to change the eyes’ focus occurs during aging. We have developed a new way to image the eye that assesses how different lens regions change their shape. We evaluated our approach on twelve people of different ages and showed that those who were older had a stiffer lens, particularly in the central part of the lens. Further development and testing of our method could enable it to be used to both improve routine eye assessments as well as enable more research into how the eye works. Kling et al. use optical coherence tomography to quantify the gradient refractive index and the strain distribution within the human crystalline lens in vivo. A substantial decrease of the strain in the lens nucleus is seen above the age of 50 years, i.e. with the onset of presbyopia.","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43856-024-00578-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972346","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 micro-disc-based multiplex method for monitoring emerging SARS-CoV-2 variants using the molecular diagnostic tool Intelli-OVI","authors":"Md Belal Hossain, Yoshikazu Uchiyama, Samiul Alam Rajib, Akhinur Rahman, Mitsuyoshi Takatori, Benjy Jek Yang Tan, Kenji Sugata, Mami Nagashima, Mamiyo Kawakami, Hitoshi Ito, Ryota Kumagai, Kenji Sadamasu, Yasuhiro Ogi, Tatsuya Kawaguchi, Tomokazu Tamura, Takasuke Fukuhara, Masahiro Ono, Kazuhisa Yoshimura, Yorifumi Satou","doi":"10.1038/s43856-024-00582-z","DOIUrl":"10.1038/s43856-024-00582-z","url":null,"abstract":"Highly transmissible viruses including SARS-CoV-2 frequently accumulate novel mutations that are detected via high-throughput sequencing. However, there is a need to develop an alternative rapid and non-expensive approach. Here we developed a novel multiplex DNA detection method Intelli-OVI for analysing existing and novel mutations of SARS-CoV-2. We have developed Intelli-OVI that includes the micro-disc-based method IntelliPlex and computational algorithms of objective variant identification (OVI). More than 250 SARS-CoV-2 positive samples including wastewater ones were analysed to verify the efficiency of the method. IntelliPlex uses micro-discs printed with a unique pictorial pattern as a labelling conjugate for DNA probes, and OVI allows simultaneous identification of several variants using multidimensional data obtained by the IntelliPlex method. Importantly, de novo mutations can be identified by decreased signals, which indicates that there is an emergence of de novo variant virus as well as prompts the need to design additional primers and probes. We have upgraded probe panel according to the emergence of new variants and demonstrated that Intelli-OVI efficiently identified more than 20 different SARS-CoV-2 variants by using 35 different probes simultaneously. Intelli-OVI can be upgraded to keep up with rapidly evolving viruses as we showed in this study using SARS-CoV-2 as an example and may be suitable for other viruses but would need to be validated. As the COVID-19 pandemic progresses, it is increasingly becoming important to be able to detect emerging new variants of concerns of SARS-CoV-2, the virus that causes COVID-19, for accurate surveillance and timely interventions. We developed a rapid diagnostic method for detecting multiple SARS-CoV-2 variants and tested it using various starting materials such as sputum, nasopharyngeal swabs and wastewater. The method could accurately detect multiple subvariants of Omicron and showed potential for rapid adaptability to detect the virus as it evolves. This technology could enable continuous monitoring of emerging SARS-CoV-2 variants and the opportunity to intercept transmission with timely interventions to prevent viral spread. Hossain et al. establish a molecular diagnostic tool that can rapidly distinguish various SARS-CoV-2 variants by combining multiplex DNA detection and bioinformatics approaches. This approach can be useful in timely detection of newly emerging SARS-CoV-2 variants of concern.","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/PMC11316138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914703","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}