Yale Journal of Biology and Medicine最新文献

{"title":"Public Health Policies and the Role of the State in Latin America: Workers' Housing Projects in Chile and Peru (1880-1940).","authors":"Patricia Palma, Lucas Maubert","doi":"10.59249/AUEJ3614","DOIUrl":"10.59249/AUEJ3614","url":null,"abstract":"<p><p>The debates regarding the impact and costs of public and private health, and the responsibility of the State to offer access to healthcare are ongoing discussions in Latin American countries. This paper discusses the relationship between State formation and public health in Latin America, using case studies from Chile and Peru from the late 19th- to mid-20th centuries. In this period, public health was a determining factor in State consolidation. Multiple sectors debated and pushed the State to embrace public health as a national issue and provide healthcare as a citizens' right. We focus on the efforts of an elite group led by doctors, hygienists, and politicians to place the relationships between healthcare, urban living conditions, and demographic crises on the political and media agenda. Following these efforts, in the early 20th century governments in both countries established public health as a major concern, understanding the issue as synonymous with modernity and progress. In the context of urban and industrial growth, the inadequate sanitary conditions of lower-class housing were considered the main factor in the spread of contagious infections. Legislation transformed the nascent issue of worker housing into a State obligation, while access to sanitary housing became a cornerstone of healthcare and, in turn, one of the earliest public health policies. Given this context, we trace the evolution of housing policies in the two countries through primary sources such as presidential speeches and legislative debates, newspapers, and medical essays and reports.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"98 3","pages":"357-367"},"PeriodicalIF":3.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145201683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Weaving MAPS: Historiographical Perspectives on Writing Postcolonial Histories of the Modern Hospital.","authors":"Joseph Aaron S Joe","doi":"10.59249/ZQQN4213","DOIUrl":"10.59249/ZQQN4213","url":null,"abstract":"<p><p>This paper explores how we can write about the postcolonial histories of the modern hospital. With the Philippine General Hospital (PGH), Manila, Philippines as a starting point, I locate the <i>colonial hospital</i> in the broader and often separate historiographies of the modern hospital and the postcolonial histories of science, technology, and medicine in Southeast Asia. Broadly, hospital histories focus more on organizational management and less on the socio-material entanglements that emerge within the hospital space. Historical studies explicitly centered on the <i>modern hospital</i> are almost exclusively written from the perspective of architectural histories. While the current literature presents valuable discourse on the interface of medical and architectural ideas on hospital design, these histories may present Eurocentric and Whiggish narratives, largely excluding histories of modern hospitals in colonies. However, emerging intersections between emotional and architectural histories of imperial infrastructures highlight the potential of material-affective approaches for advancing postcolonial studies (MAPS) of the modern hospital. The second historiographical stream traces the formation of increasingly critical and agential postcolonial histories of science, technology, and medicine in Southeast Asia. Critical science studies have generated compelling analyses of modern hospitals as biopolitical sites in the colonial period. Moreover, the colonial hospital persists as fertile ground for revealing autonomous histories and new relations and subjectivities in Southeast Asia's postcolonial reconfigurations. Critical historians of medicine and science in the region also urge more engagement between historical and ethnographic approaches. By weaving these historiographies, I argue that material-affective methods are vital to writing the postcolonial history of modern hospitals and propose a combined MAPS approach to potentially answer the question: how do we write the postcolonial history of colonial hospitals?</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"98 3","pages":"315-328"},"PeriodicalIF":3.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145201804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bodies that Pay the Price: Institutional Ahistoricity and Persistent Gendered Marginality in Indian Medical Education.","authors":"Rimi Nandy","doi":"10.59249/OFBW2804","DOIUrl":"10.59249/OFBW2804","url":null,"abstract":"<p><p>Despite obstetric violence inflicted upon marginal female bodies by the Indian medical system being well-documented through the decades, the exploration of the historical production of this attitude has received limited attention. However, the present modes of violences are deeply rooted in a history of culturally-transmitted medicolegal anxiety about unwanted bodies on a shared planet, and their unwanted medicosocial behavior - in particular their reproductive choices. This history of anxiety, unwritten but encoded in multiple implicit and explicit ways, has shaped contemporary medical institutions' perception of reproductive-aged cisgendered Indian women as a source of multifaceted risk-a medicolegal risk to the medical institution, an economic risk to the nation's development, a biosecurity risk to the global stability-that can only be mitigated by clinically intervening in their bodies.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"98 3","pages":"397-411"},"PeriodicalIF":3.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12509455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145259745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic Regulation of Bone Healing: Implications for Fracture Repair and Clinical Treatment Strategies.","authors":"Sathya Subramoniam Iyer","doi":"10.59249/HSYL8000","DOIUrl":"10.59249/HSYL8000","url":null,"abstract":"<p><p>Bone healing and fracture repair are complex processes involving multiple phases that rely on coordination and differentiation of multiple cell types, such as mesenchymal stem cells (MSCs), osteoblasts, osteoclasts, chondrocytes, and endothelial cells. The functions of growth factor and mechanical force in bone regeneration are well established, but recent research has revealed epigenetic mechanisms to play a major role in regulating cellular differentiation and tissue repair. Various studies have indicated epigenetic mechanisms like DNA methylation, histone modifications, and regulation by non-coding RNAs (ncRNA) are responsible for major gene expression regulation during bone regeneration. Moreover, systemic factors such as inflammation, aging, and metabolic disturbances regulate epigenetic regulation of bone cells to result in defective fracture healing. Emerging concepts in epigenetic therapy reveal new approaches to optimize bone regeneration and improve clinical results. This review focuses on the role of epigenetic regulation in the process of bone healing, highlighting its clinical implications.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"98 2","pages":"159-170"},"PeriodicalIF":2.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Gene and Isoform-Level Transcriptomic Analysis of Adverse Childhood Experiences in the Human Prefrontal Cortex.","authors":"Diana L Núñez-Ríos, Sheila T Nagamatsu, José Jaime Martínez-Magaña, Janitza L Montalvo-Ortiz","doi":"10.59249/VLMZ6974","DOIUrl":"10.59249/VLMZ6974","url":null,"abstract":"<p><p>Adverse childhood experiences (ACE) can lead to diverse outcomes, ranging from resilience to an increased risk of psychiatric disorders such as anxiety, depression, and posttraumatic stress disorder (PTSD). In mammals, most multiexon genes encode an average of 3.9 protein-coding isoforms, which amplify transcriptomic diversity and potentially exhibit distinct functional characteristics. Recent research has shown long-lasting transcriptomic changes associated with ACE, particularly in immune-related genes. However, differential isoform usage may not be captured when analyses are confined to gene-level expression. To date, no studies have explored isoform-level dysregulation in postmortem brains of individuals exposed to ACEs. Our study investigated transcriptomic dynamics across four prefrontal regions-the dorsolateral (dlPFC), dorsal Anterior Cingulate (dACC), orbitofrontal (OFC), and subgenual prefrontal (sgPFC) cortices-in a cohort of 22 donors with PTSD, comprising 11 with and 11 without ACE history. The OFC exhibited the highest number of differentially expressed genes (DEGs), followed by the sgPFC. Correspondingly, these regions also showed the most pronounced differential isoform usage, or \"isoform switching\". Notably, our integrated transcriptomic analysis revealed that while <i>PAQR6</i> was downregulated in the sgPFC among ACE-exposed individuals, its principal isoform (PAQR6-201) showed increased usage. Several genes exhibiting significant isoform switching did not display substantial differential gene expression. Functional pathway analysis revealed that genes with altered expression or isoform usage converged on neurogenesis regulation, with isoform-switching genes specifically enriched in gliogenesis. This study demonstrates that examining differential isoform usage unveils previously unrecognized genes potentially implicated in ACE. Future research should focus on characterizing the functional consequences of isoform-specific up- or downregulation to comprehensively understand transcriptomic dysregulation in complex psychiatric disorders.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"98 2","pages":"89-103"},"PeriodicalIF":2.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"For All the Primate FANS: Optimized Isolation of Nuclei from Frozen Postmortem Primate Brain for Fluorescence-Assisted Nuclei Sorting (FANS).","authors":"Elaine E Guevara, Begün Erbaba, Gregory M Cresswell, Melissa K Edler, Chet C Sherwood","doi":"10.59249/LLUJ2834","DOIUrl":"10.59249/LLUJ2834","url":null,"abstract":"<p><p>Epigenetic alterations are cell type-specific and require methods like single cell sequencing and cell type sorting by flow cytometry. These methods often rely on the availability of fresh tissue, yet postmortem frozen tissue is typically the only material available from non-experimental subjects, including humans and other nonhuman primates (NHP). Many insights can be gained from analysis of these precious samples. To this end, we developed a protocol for isolating intact nuclei from small starting amounts of postmortem frozen chimpanzee (<i>Pan troglodytes</i>) cerebral cortex tissue. Isolated nuclei can be input directly into single cell epigenomics protocols like ATAC-seq or can be immunostained for enrichment of neuronal nuclei via fluorescent-activated nuclei sorting (FANS) followed by bulk epigenetic methods like methylome sequencing. We adapted and optimized this protocol based on existing human brain tissue protocols. Our protocol specifically addresses challenges presented by postmortem frozen NHP brain tissue, including high levels of myelin debris and reduced RNA integrity. We include key steps and troubleshooting guidance to improve nuclei quality and sorting outcomes, and we also discuss limitations and considerations for researchers interested in using these methods.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"98 2","pages":"135-145"},"PeriodicalIF":2.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Bioinformatic Analysis Based on Functional Studies of MEF-2 Family in NSCLC.","authors":"Yanping Wang, Gaoyang Lin, Wenwen Li, Xue Zhu, Zhentong Zhao, Quanxin Wang","doi":"10.59249/PMMF2985","DOIUrl":"10.59249/PMMF2985","url":null,"abstract":"<p><p>Lung cancer remains the malignancy with the highest morbidity and mortality worldwide. There are no effective guiding therapies and prognosis biomarkers, and the overall prognosis of lung cancer remains poor. The cardiomyocyte enhancer factor 2 (MEF-2) family is a highly evolutionarily conserved transcription factor that plays important roles in a variety of diseases, including tumors. Still, the overall bioinformatics function of the MEF-2 gene family in non-small cell lung cancer (NSCLC) has not been systematically reported yet. MEF-2 family members have low expression in NSCLC tissues and are associated with clinicopathological stages. MEF-2B/2D is highly expressed in lung metastatic tissues. MEF-2A, MEF-2B, and MEF-2D have obvious advantages in the diagnosis of NSCLC. Survival analysis of lung adenocarcinoma (LUAD) patients in the Cancer Genome Atlas (TCGA) database shows that MEF-2C is strongly associated with poor overall survival (OS) and disease-specific survival (DSS). Univariate and multivariate Cox analyses demonstrated that MEF-2A independently predicts the progression-free interval (PFI) in NSCLC patients. Gene set enrichment analysis (GSEA) showed that MEF-2 family members are associated with immune cell receptor function and regulation of immunoglobulin complexes. The differentially expressed genes (DEGs) associated with MEF-2 family members were significantly enriched in the cAMP signaling pathway and gastric acid secretion. Gene ontology (GO) analysis revealed DEGs that play critical roles in the cytochrome-c oxidase activity, electron transfer activity, oxidoreduction-driven active transmembrane transporter activity; the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis shows that they are mainly enriched in oxidative phosphorylation, thermogenesis, and diabetic cardiomyopathy. MEF-2A is a potential diagnostic, prognostic biomarker, and promising therapeutic target for NSCLC. Further studies are needed to verify and clarify the underlying mechanisms.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"98 2","pages":"117-134"},"PeriodicalIF":2.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating Aging and DNA Methylation: A Path to Improving Health Span?","authors":"Mark T Mc Auley, Amy E Morgan","doi":"10.59249/BYOI5042","DOIUrl":"10.59249/BYOI5042","url":null,"abstract":"<p><p>Investigating aging has become a subject of intense biomedical focus. This has coincided with an unprecedented rise in epigenetic research. DNA methylation (DNAm) is the most comprehensively investigated epigenetic process. Epigenetic clocks are capable of statistically correlating DNAm changes with chronological age. DNAm changes are also proving to be a worthwhile biomarker of age-related disease, while emerging evidence suggests this epigenetic mechanism could be an effective diagnostic tool for disease detection. Such investigative progress has significant implications for health care. In this brief review we examine some recent findings in this area. The overarching aim and scope of the work is to address the relationship between aging, DNAm, and health. We commence by briefly introducing aging. Next, DNAm and age-related disease are discussed. Thirdly, we critically examine epigenetic clocks. We conclude by exploring recent advances in the use of biosensors for measuring DNAm and disease detection.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"98 2","pages":"237-244"},"PeriodicalIF":2.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-Derived Epigenomic Markers of Chronic Stress Distinguish Breast Cancer Phenotypes.","authors":"Amrita Acharya, Anthony S Zannas","doi":"10.59249/YYQN6894","DOIUrl":"10.59249/YYQN6894","url":null,"abstract":"<p><p>Breast cancer (BC) is a highly prevalent malignancy in women and is often resistant to available therapies, calling for urgent investigation of the molecular mechanisms underlying its pathogenesis and progression. BC is thought to result from a complex interplay between genetic and environmental factors. Among key factors, chronic stress has been associated with worse cancer outcomes and can profoundly impact the epigenome. However, both stress and BC phenotypes are complex and heterogeneous, making studies that examine their molecular links challenging. Despite their heterogeneity, stressors trigger a neuroendocrine response that in humans culminates in the release of cortisol, a highly lipophilic hormone that traverses essentially every cell and induces widespread genomic effects. Modeling such effects at the epigenetic level, here we examine whether cellular DNA methylation (DNAm) markers of chronic stress - derived from human fibroblasts undergoing prolonged exposure to physiological stress cortisol levels - distinguish BC phenotypes in two independent human cohorts. Our results show that methylomic signatures of stress are consistently higher in tumor samples as compared to normal samples and in more advanced tumor stages and grades. Follow-up analyses further identify specific DNAm sites driving these associations, which are significantly enriched for cell adhesion pathways in both cohorts. These findings provide insights into the molecular mechanisms linking stress with BC and a proof-of-concept for utilizing cell model-derived disease biomarkers in environmental epigenetics.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"98 2","pages":"147-157"},"PeriodicalIF":2.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overweight/Obesity and Ancestral Environmental Smoking Exposures: A Summary of Results from the ALSPAC Cohort.","authors":"Sarah Watkins, Matthew Suderman, Yasmin Iles-Caven, Kate Northstone, Marcus Pembrey, Jean Golding","doi":"10.59249/PKHX6518","DOIUrl":"10.59249/PKHX6518","url":null,"abstract":"<p><p>There is considerable discussion concerning the recent increase in the prevalence of overweight/obesity in children and adults. Although it is assumed that current diet and sedentary behavior are key contributors, these factors do not seem to be the only characteristics responsible. In this paper we summarize the findings we have obtained when assessing whether exposures in previous generations may have played a part in this change over time. In particular, we show that ancestral smoking may be an important contributor. We used data collected from parents and grandparents by the Avon Longitudinal Study of Parents and Children (ALSPAC), which has followed children born in 1991-1992 to women resident in south-west England. We have shown that ancestral smoking characteristics were associated with fetal growth and with increased measures of adiposity in their children and grandchildren. Here we describe the detailed findings of the ancestral exposure to cigarette smoking of ancestors at various time points using ALSPAC data and indicate the support for the findings in other cohorts. Since body mass index (BMI) can be a measure of lean (muscle) mass as well as fat mass, we concentrate on associations with body composition from dual-energy x-ray absorptiometry (DXA). Few birth cohorts have collected data on smoking of individuals in the male line and few have used details of fat, bone, and lean mass. Findings concerning grandmaternal smoking in pregnancy and pre-pubertal smoking of male ancestors were nevertheless replicated. We consider the likelihood of epigenetic explanations for these findings.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"98 2","pages":"79-87"},"PeriodicalIF":2.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}