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An ultrasound-scanning in vivo light source. 一种超声扫描体内光源。
Research square Pub Date : 2025-06-19 DOI: 10.21203/rs.3.rs-6773130/v1
Shan Jiang, Marigold G Malinao, Fan Yang, Yushun Zeng, Silky S Hou, Xiang Wu, Nicholas J Rommelfanger, Lata Chaunsali, Jun Ding, Xiaoke Chen, Qifa Zhou, Harald Sontheimer, Guosong Hong
{"title":"An ultrasound-scanning <i>in vivo</i> light source.","authors":"Shan Jiang, Marigold G Malinao, Fan Yang, Yushun Zeng, Silky S Hou, Xiang Wu, Nicholas J Rommelfanger, Lata Chaunsali, Jun Ding, Xiaoke Chen, Qifa Zhou, Harald Sontheimer, Guosong Hong","doi":"10.21203/rs.3.rs-6773130/v1","DOIUrl":"10.21203/rs.3.rs-6773130/v1","url":null,"abstract":"<p><p>Biological systems operate across distributed regions with fast, localized dynamics, yet existing biointerfaces fail short in providing both high spatiotemporal precision and the ability to dynamically target any region without disturbing surrounding tissue. Here, we present an <i>in vivo</i> deep-tissue light source based on focused ultrasound (FUS) scanning of mechanoluminescent nanotransducers (MLNTs) circulating through the vasculature. We demonstrate the programmability of this approach in tissue-mimicking phantoms and the endogenous circulatory system of animals, where tunable spatial resolution and dynamic light patterning can be achieved. We validate the functionality of the ultrasound-scanning light source in opsin-expressing neurons through electrophysiological recordings and immunostaining. We showcase dynamic three-dimensional brain targeting and temporally resolved behavioral control in freely moving animals via the ultrasound-scanning <i>in vivo</i> light source. This non-invasive deep-tissue light source offers a versatile strategy for body-wide optical interfacing.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532587","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}
引用次数: 0
Dasatinib and quercetin senolytic treatment delays early onset intervertebral disc degeneration in SM/J mice. 达沙替尼和槲皮素抗衰老治疗可延缓SM/J小鼠早发性椎间盘退变。
Research square Pub Date : 2025-06-19 DOI: 10.21203/rs.3.rs-6838819/v1
Makarand Risbud, Emanuel Novais, Olivia Ottone, Esther Akande, Ruteja Barve
{"title":"Dasatinib and quercetin senolytic treatment delays early onset intervertebral disc degeneration in SM/J mice.","authors":"Makarand Risbud, Emanuel Novais, Olivia Ottone, Esther Akande, Ruteja Barve","doi":"10.21203/rs.3.rs-6838819/v1","DOIUrl":"10.21203/rs.3.rs-6838819/v1","url":null,"abstract":"<p><p>Genetic background is a major determinant of disc degeneration, a leading cause of chronic back pain and disability. Herein, we demonstrate that premature disc cell senescence contributes to early-onset degeneration in SM/J mice and test two systemic senotherapeutic strategies to mitigate it: Navitoclax (Nav.) and a cocktail of Dasatinib and Quercetin (DQ). While Nav. treatment did not improve severe degeneration in SM/J mice, DQ-treated mice showed lower grades of degeneration and decreased abundance of senescence markers p19<sup>ARF</sup> and p21. DQ improved disc cell viability and phenotype retention and retarded fibrosis of the nucleus pulposus tissue. Transcriptomic analysis showed disc compartment-specific effects of the treatment, with cell cycle regulation and JNK signaling being commonly affected across tissue types. A comparison with DQ-mediated aging-dependent amelioration of disc degeneration in C57BL/6N mice identified <i>Junb</i> and <i>Zfp36l1</i> signaling as shared DQ targets in the mouse disc. This study reinforces the efficacy of senolytic treatments in ameliorating local senescence and intervertebral disc fibrosis.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532608","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}
引用次数: 0
Disparities in multidimensional psychosocial stressors by sexual minority identity among cancer survivors from the All of Us (AoU) Research Program. 来自我们所有人(AoU)研究项目的癌症幸存者的性少数身份在多维心理社会压力因素中的差异。
Research square Pub Date : 2025-06-18 DOI: 10.21203/rs.3.rs-6884066/v1
Angel Arizpe, Nikta Saeedi, Carol Y Ochoa-Dominguez, Theresa A Hastert, Alberto Carvajal, Sue E Kim, Albert J Farias
{"title":"Disparities in multidimensional psychosocial stressors by sexual minority identity among cancer survivors from the All of Us (AoU) Research Program.","authors":"Angel Arizpe, Nikta Saeedi, Carol Y Ochoa-Dominguez, Theresa A Hastert, Alberto Carvajal, Sue E Kim, Albert J Farias","doi":"10.21203/rs.3.rs-6884066/v1","DOIUrl":"10.21203/rs.3.rs-6884066/v1","url":null,"abstract":"<p><strong>Background: </strong>Sexual minority (SM) individuals may face discrimination and psychosocial stressors that can adversely impact their cancer care and outcomes. Therefore, we tested for disparities in psychosocial stressors by SM status among cancer survivors and explored whether observed disparities differ by governor's political affiliation.</p><p><strong>Methods: </strong>Perceived stressors and SM status data from 2018-2022 were obtained from adult cancer survivors identified in the All of Us (AoU) data repository. We evaluated associations between self-reported SM status (heterosexual vs gay, lesbian, bisexual, or other SM minorities) and binary indicators of discrimination in medical settings (any vs. none), perceived stress (high/medium vs low), and neighborhood social cohesion (high/medium vs low) using multivariable logistic regression and stratified models adjusting for sociodemographic and clinical covariates.</p><p><strong>Results: </strong>In our cohort (N=14,806), 6.3% of survivors reported being a SM. In adjusted models, odds of reporting high/medium levels of perceived stress were 46% (95% CI: 25%, 70%) higher, and odds of low neighborhood social cohesion were 47% (95% CI: 27%, 71%) higher among SM compared to non-SM survivors. In stratified analyses (p<sub>interaction</sub> 0.01), among survivors living in states with Republican governors, SM had twice the odds of experiencing discrimination in medical settings (OR: 2.31, 95% CI: 1.50, 3.71) compared to heterosexual survivors. We did not find a significant association in discrimination in the medical setting among SM living in states with Democratic governors.</p><p><strong>Conclusion: </strong>SM cancer survivors face significant disparities in reported psychosocial stressors, which may impact survivorship outcomes. Associations may differ based on broader political context.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532621","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}
引用次数: 0
Identifying and Predicting Cognitive Decline Using Multi-Modal Sensor Data and Machine Learning Approach. 使用多模态传感器数据和机器学习方法识别和预测认知衰退。
Research square Pub Date : 2025-06-18 DOI: 10.21203/rs.3.rs-6735622/v1
Aparna Joshi, Jun Ha Chang, Guillermo Basulto-Elias, Shauna Hallmark, Matthew Rizzo, Anuj Sharma
{"title":"Identifying and Predicting Cognitive Decline Using Multi-Modal Sensor Data and Machine Learning Approach.","authors":"Aparna Joshi, Jun Ha Chang, Guillermo Basulto-Elias, Shauna Hallmark, Matthew Rizzo, Anuj Sharma","doi":"10.21203/rs.3.rs-6735622/v1","DOIUrl":"10.21203/rs.3.rs-6735622/v1","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) remains a critical global health challenge, with its prevalence expected to rise dramatically by 2050, leading to substantial financial and emotional burdens. Mild Cognitive Impairment (MCI), the prodromal stage of AD, presents a crucial opportunity for early intervention, yet its diagnosis remains difficult due to the overlap with normal aging. Traditional diagnostic methods, such as neuroimaging and cerebrospinal fluid analysis, are costly and invasive, highlighting the need for alternative, scalable, and non-invasive biomarkers. This study explores the potential of naturalistic driving behavior as a digital biomarker for detecting cognitive decline in individuals at risk for AD and MCI. A total of 118 participants (8 with AD, 65 with MCI, and 45 cognitively healthy individuals) were included in this study. At baseline year, we measured their demographics, cognitive status administrated by dementia experts, 3 consecutive months of naturalistic driving performance and driving life-space from participants' own vehicle and sleep data via wrist-worn actigraphy, integrated into multi-modal data to feed to XGBoost-based framework. After 1-year follow, their cognitive status was assessed. We implemented a two-phase validation framework: first, classification model using Leave-One-Subject-Out Cross-Validation (LOSO-CV) to classify baseline cognitive status, and then, conducting a prediction model with to assess the model's ability to predict 1-year follow-up cognitive status. Our results demonstrate that the multi-modal classifier achieved strong classification performance (accuracy = 68.64%; precision = 73.97%; F1-score=74.48%), with the highest recall (76.39%) from a model incorporating demographics and driving features, and prediction performance (accuracy = 70.48%; precision = 71.88%; F1-score = 74.80%, recall = 77.97%). Key predictive features included sex, mean awakening duration, age, average acceleration, and sleep efficiency, underscoring the relevance of driving behavior and sleep characteristics in cognitive assessment. By leveraging everyday activities such as driving, this framework provides a novel, non-invasive approach for identifying individuals at risk for cognitive decline. Furthermore, its ability to predict future disease progression establishes a forward-looking paradigm for early detection and monitoring. Beyond cognitive impairment, this methodology offers a scalable and generalizable framework for disease prediction, with potential applications in detecting and monitoring other neurodegenerative and chronic conditions.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532538","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}
引用次数: 0
Facilitators and Barriers to COVID-19 Vaccination in Vietnamese Americans in Texas: A Survey. 德克萨斯州越南裔美国人COVID-19疫苗接种的促进者和障碍:一项调查。
Research square Pub Date : 2025-06-18 DOI: 10.21203/rs.3.rs-6762383/v1
Diana Omenge, Zeeshan Ali, Paul G Yeh, Angelica Nguyen, Jannette Diep, Shielene Vargas, Saba Siddiqi, Celine Nguyen, Carlos Fuentes, Bich-May Nguyen
{"title":"Facilitators and Barriers to COVID-19 Vaccination in Vietnamese Americans in Texas: A Survey.","authors":"Diana Omenge, Zeeshan Ali, Paul G Yeh, Angelica Nguyen, Jannette Diep, Shielene Vargas, Saba Siddiqi, Celine Nguyen, Carlos Fuentes, Bich-May Nguyen","doi":"10.21203/rs.3.rs-6762383/v1","DOIUrl":"10.21203/rs.3.rs-6762383/v1","url":null,"abstract":"<p><strong>Background: </strong>The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected Asian American communities, highlighting the need to understand the factors that influence vaccination rates, especially within subpopulations. Many trust studies have found that healthcare institutions, peers, and nonmedical health drivers play key roles in shaping vaccination decisions within specific subgroups, underscoring the need to examine these factors among subpopulations like Vietnamese Americans to develop targeted interventions. Unfortunately, Vietnamese Americans, a significant population in Texas, have limited disaggregated data available, a knowledge gap this study seeks to fill.</p><p><strong>Methods: </strong>The National Institutes of Health (NIH) Community Engagement Alliance (CEAL) Common Survey 2 instrument was used online and via paper in English and Vietnamese. Trained volunteers, outreach events, and local Texas clinics recruited adults of Vietnamese heritage from December 2022 to April 2023. The data were analyzed through multivariable logistic regression.</p><p><strong>Results: </strong>Of the 425 participants who responded to a survey, the responses of 278 who completed all pertinent questions were included in the analysis. Respondents demonstrated high trust in healthcare providers (AOR [adjusted odds ratio] 2.97, 95% CI: 1.28-6.86; p = 0.011) and in the federal government (AOR 3.02, 95% CI: 1.32-6.88; p = 0.009) for COVID-19 information were associated with increased odds of COVID-19 vaccination. In contrast, high trust in peers at work or school for COVID-19 information (AOR 0.51, 95% CI: 0.22-0.89; p = 0.041) and a pandemic-related challenge of having clean water to drink in the past month (AOR 0.30, 95% CI: 0.13-0.71; p = 0.006) were associated with decreased odds of COVID-19 vaccination.</p><p><strong>Conclusions: </strong>Trust in healthcare providers and the federal government was associated with increased COVID-19 vaccine receipt among Vietnamese Americans, whereas trust in peers and endorsing COVID-19 challenges decreased COVID-19 vaccine receipt. Understanding the facilitators and barriers to vaccination among Vietnamese Americans can improve COVID-19 health equity and outcomes.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532629","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}
引用次数: 0
Negative Hits Hit Different. 负面冲击带来不同的冲击。
Research square Pub Date : 2025-06-18 DOI: 10.21203/rs.3.rs-6857483/v1
Arkadiy L Maksimovskiy, Abigail Moline, Daniel G Dillon
{"title":"Negative Hits Hit Different.","authors":"Arkadiy L Maksimovskiy, Abigail Moline, Daniel G Dillon","doi":"10.21203/rs.3.rs-6857483/v1","DOIUrl":"10.21203/rs.3.rs-6857483/v1","url":null,"abstract":"<p><p>Neuroimaging of recognition memory reveals that the striatum responds more strongly to Hits (encoded stimuli recognized as old) vs. Correct Rejections (CRs: lures recognized as new), possibly because remembering old items is rewarding. If this is so, then Hits should elicit higher valence ratings than CRs for emotional and neutral stimuli. Alternatively, memory may interact with emotion such that while positive and neutral Hits drive valence up, negative Hits drive valence down (relative to CRs of the same type). We investigated this by analyzing data from 47 healthy participants who encoded negative, neutral, and positive pictures, completed a recognition memory test, and rated the emotions elicited by each picture. Valence ratings were higher for neutral and positive Hits vs. CRs but only positive FAs (FAs; falsely recognized lures) elicited higher valence ratings than CRs. Strikingly, negative Hits elicited lower valence ratings than negative CRs. The impact of memory on subjective experience thus varied: for neutral pictures, accurate memory enhanced valence; for positive pictures, perceived oldness (accurate or not) boosted valence; and for negative pictures, accurate memory reduced valence. The impact of memory retrieval on subjective experience thus depends on the emotional nature of the memoranda.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532602","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}
引用次数: 0
Emotion Regulation as a Transdiagnostic Link Between ADHD and Depression Symptoms: Evidence from a Network Analysis of Youth in the ABCD Study. 情绪调节作为ADHD和抑郁症状之间的跨诊断联系:来自ABCD研究中青年网络分析的证据
Research square Pub Date : 2025-06-18 DOI: 10.21203/rs.3.rs-6823726/v1
Jessica B Tharaud, Molly A Nikolas
{"title":"Emotion Regulation as a Transdiagnostic Link Between ADHD and Depression Symptoms: Evidence from a Network Analysis of Youth in the ABCD Study.","authors":"Jessica B Tharaud, Molly A Nikolas","doi":"10.21203/rs.3.rs-6823726/v1","DOIUrl":"10.21203/rs.3.rs-6823726/v1","url":null,"abstract":"<p><strong>Background: </strong>Childhood ADHD is associated with greater risk of depression in adolescence and adulthood, with emotion regulation (ER) identified as a potential mediator. However, it remains unclear how distinct domains of ER differentially relate to ADHD and depression symptoms in early adolescence.</p><p><strong>Methods: </strong>The current analysis estimated a network model using longitudinal, parent-reported data from the Adolescence Brain and Cognitive Development (ABCD) Study 5.1 Data Release in 2023 (<i>n</i> = 4,460 complete cases). Nodes were item-level ADHD symptoms averaged across ages 9-12, ER domains (Catastrophize, Distracted, Attuned, and Negative Secondary Emotions) at ages 12-13, and item-level depression symptoms at ages 13-14. We also examined differences in network structure and connectivity by sex, history of ADHD diagnosis, and ADHD polygenic risk score (PRS).</p><p><strong>Results: </strong>Catastrophize and Distracted were the most important ER bridges between earlier ADHD and later depression symptoms. Two distinct pathways emerged: inattentive ADHD symptoms were linked to depression symptoms (poor eating, feeling worthless) via the Distracted ER dimension, while hyperactive-impulsive ADHD symptoms were linked to depressed mood and anhedonia via the Catastrophize ER dimension. Exploratory network comparisons found similar networks by sex, structural differences by history of ADHD diagnosis, and differences in structure and connectivity by ADHD PRS.</p><p><strong>Conclusions: </strong>Multiple pathways from ADHD in childhood to depression in early adolescence appear to involve ER difficulty through catastrophizing and distraction when upset. A denser, more interconnected network of symptoms was found among youth with higher genetic risk for ADHD.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532624","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}
引用次数: 0
A hypothalamic circuit for circadian regulation of corticosterone secretion. 皮质酮分泌的昼夜节律调节下丘脑回路
Research square Pub Date : 2025-06-18 DOI: 10.21203/rs.3.rs-4718850/v1
Oscar D Ramirez-Plascencia, Roberto De Luca, Natalia L S Machado, Dominique Eghlidi, Mudasir A Khanday, Sathyajit S Bandaru, Francesca Raffin, Nina Vujovic, Elda Arrigoni, Clifford B Saper
{"title":"A hypothalamic circuit for circadian regulation of corticosterone secretion.","authors":"Oscar D Ramirez-Plascencia, Roberto De Luca, Natalia L S Machado, Dominique Eghlidi, Mudasir A Khanday, Sathyajit S Bandaru, Francesca Raffin, Nina Vujovic, Elda Arrigoni, Clifford B Saper","doi":"10.21203/rs.3.rs-4718850/v1","DOIUrl":"10.21203/rs.3.rs-4718850/v1","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The secretion of cortisol in humans and corticosterone (Cort) in rodents follows a daily rhythm which is important in readying the individual for daily activity. This rhythm is orchestrated by the suprachiasmatic nucleus (SCN), but how it ultimately regulates the circadian rhythm of activity of neurons in the paraventricular nucleus of the hypothalamus that produce corticotropin-releasing hormone (PVH&lt;sup&gt;CRH&lt;/sup&gt; neurons) is not known. We hypothesized that the SCN may exert this influence by projections to the subparaventricular zone (SPZ), which in turn innervates neurons in the dorsomedial nucleus of the hypothalamus (DMH) that regulate PVH&lt;sup&gt;CRH&lt;/sup&gt; neurons. First, we found that ablating SPZ&lt;sup&gt;Vgat&lt;/sup&gt; neurons eliminates the circadian rhythm of Cort secretion, but that deleting &lt;i&gt;Vgat&lt;/i&gt; from them does not, suggesting that they predominantly use some other transmitter. Next, we found that either ablating or acutely inhibiting the DMH glutamatergic (DMH&lt;sup&gt;Vglut2&lt;/sup&gt;) neurons resulted in a 40-70% reduction in the daily peak of Cort. Deletion of the &lt;i&gt;Vglut2&lt;/i&gt; gene within the DMH produced a similar effect, highlighting the indispensable role of glutamatergic signaling. Chemogenetic stimulation of DMH&lt;sup&gt;Vglut2&lt;/sup&gt; neurons led to an increase of Cort levels, and optogenetic activation of their terminals in the PVH in hypothalamic slices directly activated PVH&lt;sup&gt;CRH&lt;/sup&gt; neurons through glutamate action on AMPA receptors (the DMH&lt;sup&gt;Vglut2&lt;/sup&gt; → PVH&lt;sup&gt;CRH&lt;/sup&gt; pathway). Similar to the disruption of DMH&lt;sup&gt;Vglut2&lt;/sup&gt; neurons, ablating, inhibiting, or disrupting GABA transmission by DMH GABAergic (DMH&lt;sup&gt;Vgat&lt;/sup&gt;) neurons diminished the circadian peak of Cort, particularly under constant darkness conditions. Chemogenetic stimulation of rostral DMH&lt;sup&gt;Vgat&lt;/sup&gt; neurons increased Cort, although with a lower magnitude compared to DMH&lt;sup&gt;Vglut2&lt;/sup&gt; neuron stimulation, suggesting a role in disinhibiting PVH&lt;sup&gt;CRH&lt;/sup&gt; neurons. Supporting this hypothesis, we found that rostral DMH&lt;sup&gt;Vgat&lt;/sup&gt; neurons project directly to GABAergic neurons in the caudal ventral part of the PVH and adjacent peri-PVH area (cvPVH), which directly inhibit PVH&lt;sup&gt;CRH&lt;/sup&gt; neurons, and that activating the rostral DMH&lt;sup&gt;Vgat&lt;/sup&gt; terminals in the cvPVH in brain slices reduced GABAergic afferent input onto the PVH&lt;sup&gt;CRH&lt;/sup&gt; neurons. Finally, ablation of cvPVH&lt;sup&gt;Vgat&lt;/sup&gt; neurons resulted in increased Cort release at the onset of the active phase, affirming the pivotal role of the DMH&lt;sup&gt;Vgat&lt;/sup&gt; → cvPVH&lt;sup&gt;Vgat&lt;/sup&gt; → PVH&lt;sup&gt;CRH&lt;/sup&gt; pathway in Cort secretion. In summary, our study delineates two parallel pathways transmitting temporal information to PVH&lt;sup&gt;CRH&lt;/sup&gt; neurons, collectively orchestrating the daily surge in Cort in anticipation of the active phase. These findings are crucial to understand the neural circuits regulating Cort secretion, shedding light on the mechanisms governing this physiological p","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11261983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750172","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}
引用次数: 0
Single-cell tumor microenvironment profiling informs a circulating proteome test for the interception of malignant transformation in NF1 nerve sheath tumors. 单细胞肿瘤微环境分析为NF1神经鞘肿瘤恶性转化的阻断提供了循环蛋白质组测试。
Research square Pub Date : 2025-06-18 DOI: 10.21203/rs.3.rs-6865989/v1
Jack Shern
{"title":"Single-cell tumor microenvironment profiling informs a circulating proteome test for the interception of malignant transformation in NF1 nerve sheath tumors.","authors":"Jack Shern","doi":"10.21203/rs.3.rs-6865989/v1","DOIUrl":"10.21203/rs.3.rs-6865989/v1","url":null,"abstract":"<p><p>The most common cause of death in neurofibromatosis type 1 (NF1) is the development of malignant peripheral nerve sheath tumor (MPNST), a deadly sarcoma that can transform from benign plexiform neurofibromas (PN) or premalignant atypical neurofibromas (AN). We built a single-cell dataset of 55 NF1-associated PN, AN, and MPNST to define cellular changes in neurofibroma at-risk of malignant transformation. Integrative analysis of changes in the tumor microenvironment revealed the emergence of malignant tumor cells, regulatory T cells, and loss of activated macrophages in MPNST. Using this reference dataset, we validated findings using anchor-based label transfer in an additional 19 NF1 nerve sheath tumors profiled with single cell sequencing, and public datasets. We then defined protein biomarkers of malignant transformation from high-throughput proteomic analysis of plasma samples collected from 45 NF1 patients that correlated to mRNAs specific to MPNST cell populations. Fifty plasma proteins accurately and non-invasively distinguished patients with MPNST from those with premalignant tumors. These markers should improve the ability to identify high-risk neurofibromas for improved cancer surveillance and enable early detection of malignant transformation in NF1.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532560","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}
引用次数: 0
Patient-Led Peer Support Groups Improve Anti-Hypertensive Drugs Access For Adults Living With HIV And Hypertension In Rural Uganda - A Cross-Sectional Study. 患者主导的同伴支持小组改善了乌干达农村艾滋病毒和高血压成年人抗高血压药物的获取-一项横断面研究。
Research square Pub Date : 2025-06-18 DOI: 10.21203/rs.3.rs-6445280/v1
Mucunguzi Atukunda, Brian Twinamatsiko, Michael Ayebare, Elizabeth Arinitwe, Aida N Kawuma, Ronald Kiguba, Joan Nangendo, Gerald Mutungi, Fred C Semitala, Moses R Kamya, Jane Kabami
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