tbuckley/cabot-search huggingface dataset:
Feasibility of combining spatial computing and AI for mental health support in anxiety and depression
Authors: Brennan M. R. Spiegel, Omer Liran, Allistair Clark, Jamil S. Samaan, Carine Khalil, Robert Chernoff, Kavya Reddy, Muskaan Mehra
Journal: npj Digital Medicine (2024)

Abstract The increasing need for mental health support and a shortage of therapists have led to the development of the eXtended-reality Artificial Intelligence Assistant (XAIA). This platform combines spatial computing, virtual reality (VR), and artificial intelligence (AI) to provide immersive mental health support. Utilizing GPT-4 for AI-driven therapy, XAIA engaged participants with mild-to-moderate anxiety or depression in biophilic VR environments. Speaking with an AI therapy avatar in VR was considered acceptable, helpful, and safe, with participants observed to engage genuinely with the program. However, some still favored human interaction and identified shortcomings with using a digital VR therapist. The study provides initial evidence of the acceptability and safety of AI psychotherapy via spatial computing, warranting further research on technical enhancements and clinical impact.
Prophylactic Phosphate Restriction: A Strategy to Mitigate AKI-Associated Complications
Authors: Iddo Z. Ben-Dov, Assaf Potruch, Momen Abbasi
Journal: Journal of the American Society of Nephrology (2024)

1Internal Medicine B, Laboratory of Medical Transcriptomics, Hadassah—Hebrew University Medical Center, Jerusalem, Israel 2Department of Nephrology and Hypertension, Hadassah—Hebrew University Medical Center, Jerusalem, Israel Correspondence: Prof. Iddo Z. Ben-Dov, Internal Medicine B, Hadassah—Hebrew University Center, POB 12000, Jerusalem 9112001, Israel. Email: [email protected] Published Online Ahead of Print. Publication date available at www.jasn.org See related article, "Phosphate Restriction Prevents Metabolic Acidosis and Curbs Rise in FGF23 and Mortality in Murine Folic Acid–Induced AKI," on pages 261–280.
A Printable Hydrogel Loaded with Medicinal Plant Extract for Promoting Wound Healing
Authors: Xiaoyu Wang, Yue Zhang, Anning Song, Heng Wang, Yi Wu, Wenju Chang, Bo Tian, Jialu Xu, Huaxing Dai, Qingle Ma, Chao Wang, Xiaozhong Zhou
Journal: Advanced Healthcare Materials (2024)

Abstract How to promote wound healing is still a major challenge in the healthcare while macrophages are a critical component of the healing process. Compared to various bioactive drugs, many plants have been reported to facilitate the wound healing process by regulating the immune response of wounds. In this work, a Three‐dimensional (3D) printed hydrogel scaffold loaded with natural Centella asiatica extract (CA extract) is developed for wound healing. This CA@3D scaffold uses gelatin (Gel) and sodium alginate (SA) with CA extract as bio‐ink for 3D printing. The CA extract contains a variety of bioactive compounds that make the various active ingredients in Centella asiatica work in concert. The printed CA@3D scaffold can fit the shape of wound, orchestrate the macrophages and immune responses within the wound, and promote wound healing compared to commercial wound dressings. The underlying mechanism of promoting wound healing is also illuminated by applying multi‐omic analyses. Moreover, the CA extract loaded 3D scaffold also showed great ability to promote wound healing in diabetic chronic wounds. Due to its ease of preparation, low‐cost, biosafety, and therapeutic outcomes, this work proposes an effective strategy for promoting chronic wound healing.
Protein Kinase A Is a Master Regulator of Physiological and Pathological Cardiac Hypertrophy
Authors: Yingyu Bai, Xiaoying Zhang, Ying Li, Fei Qi, Chong Liu, Xiaojie Ai, Mingxin Tang, Christopher Szeto, Erhe Gao, Xiang Hua, Mingxing Xie, Xuejun Wang, Ying Tian, Yongjie Chen, Guowei Huang, Junping Zhang, Weidong Xiao, Lili Zhang, Xueyuan Liu, Qing Yang, Steven R Houser, Xiongwen Chen
Journal: Circulation Research (2024)

The sympathoadrenergic system and its major effector PKA (protein kinase A) are activated to maintain cardiac output coping with physiological or pathological stressors. If and how PKA plays a role in physiological cardiac hypertrophy (PhCH) and pathological CH (PaCH) are not clear.
Bispecific antibodies promote natural killer cell-mediated elimination of HIV-1 reservoir cells
Authors: Nathan L. Board, Zhe Yuan, Fengting Wu, Milica Moskovljevic, Meghana Ravi, Srona Sengupta, Sung Soo Mun, Francesco R. Simonetti, Jun Lai, Pablo Tebas, Kenneth Lynn, Rebecca Hoh, Steven G. Deeks, Janet D. Siliciano, Luis J. Montaner, Robert F. Siliciano
Journal: Nature Immunology (2024)

Abstract The persistence of CD4 + T cells carrying latent human immunodeficiency virus-1 (HIV-1) proviruses is the main barrier to a cure. New therapeutics to enhance HIV-1-specific immune responses and clear infected cells will probably be necessary to achieve reduction of the latent reservoir. In the present study, we report two single-chain diabodies (scDbs) that target the HIV-1 envelope protein (Env) and the human type III Fcγ receptor (CD16). We show that the scDbs promoted robust and HIV-1-specific natural killer (NK) cell activation and NK cell-mediated lysis of infected cells. Cocultures of CD4 + T cells from people with HIV-1 on antiretroviral therapy (ART) with autologous NK cells and the scDbs resulted in marked elimination of reservoir cells that was dependent on latency reversal. Treatment of human interleukin-15 transgenic NSG mice with one of the scDbs after ART initiation enhanced NK cell activity and reduced reservoir size. Thus, HIV-1-specific scDbs merit further evaluation as potential therapeutics for clearance of the latent reservoir.
Treatment-free remission after a second TKI discontinuation attempt in patients with Chronic Myeloid Leukemia re-treated with dasatinib – interim results from the DAstop2 trial
Authors: Hjalmar Flygt, Stina Söderlund, Johan Richter, Susanne Saussele, Perttu Koskenvesa, Leif Stenke, Satu Mustjoki, Andreja Dimitrijevic, Jesper Stentoft, Waleed Majeed, Lydia Roy, Dominik Wolf, Arta Dreimane, Bjørn Tore Gjertsen, Tobias Gedde-Dahl, Erik Ahlstrand, Berit Markevärn, Henrik Hjorth-Hansen, Jeroen Janssen, Ulla Olsson-Strömberg
Journal: Leukemia (2024)

Abstract Tyrosine kinase inhibitor (TKI) discontinuation in chronic myeloid leukemia (CML) has become part of routine care for patients with a sustained deep molecular response (DMR). Approximately 50% experience a molecular relapse upon TKI cessation. Most of them quickly regain DMR upon TKI resumption. Whether these patients can achieve a second treatment-free remission (TFR) remains unclear. DAstop2 (ClinicalTrials.gov ID: NCT03573596) is a prospective study including patients with a failed first TFR attempt re-treated with any TKI for ≥ one year. Upon entering the study, patients received the TKI dasatinib for additional two years. Patients with sustained DMR for ≥1 year qualified for a second TKI stop. Ninety-four patients were included between Oct 2017-Dec 2021. At the time of data analysis, 62 patients had attempted a 2 nd stop. After a median follow-up of 27 months from 2 nd stop, TFR rates were 61, 56 and 46% at 6, 12 and 24 months respectively. No progression to advanced stage disease was seen and 87% had re-achieved MR 4 within a median of 3 months from TKI re-initiation. In summary, we show that a 2 nd TFR attempt after dasatinib treatment is safe, feasible and TFR rates seem in the range of those reported in trials of a first TKI stop.
Readily releasable β cells with tight Ca2+–exocytosis coupling dictate biphasic glucose-stimulated insulin secretion
Authors: Xiaohong Peng, Huixia Ren, Lu Yang, Shiyan Tong, Renjie Zhou, Haochen Long, Yunxiang Wu, Lifen Wang, Yi Wu, Yongdeng Zhang, Jiayu Shen, Junwei Zhang, Guohua Qiu, Jianyong Wang, Chengsheng Han, Yulin Zhang, Mengxuan Zhou, Yiwen Zhao, Tao Xu, Chao Tang, Zhixing Chen, Huisheng Liu, Liangyi Chen
Journal: Nature Metabolism (2024)
Genetic architecture and biology of youth-onset type 2 diabetes
Authors: Soo Heon Kwak, Shylaja Srinivasan, Ling Chen, Jennifer Todd, Josep M. Mercader, Elizabeth T. Jensen, Jasmin Divers, Amy K. Mottl, Catherine Pihoker, Rachelle G. Gandica, Lori M. Laffel, Elvira Isganaitis, Morey W. Haymond, Lynne L. Levitsky, Toni I. Pollin, Jose C. Florez, Jason Flannick
Journal: Nature Metabolism (2024)

Abstract The prevalence of youth-onset type 2 diabetes (T2D) and childhood obesity has been rising steadily 1 , producing a growing public health concern 1 that disproportionately affects minority groups 2 . The genetic basis of youth-onset T2D and its relationship to other forms of diabetes are unclear 3 . Here we report a detailed genetic characterization of youth-onset T2D by analysing exome sequences and common variant associations for 3,005 individuals with youth-onset T2D and 9,777 adult control participants matched for ancestry, including both males and females. We identify monogenic diabetes variants in 2.4% of individuals and three exome-wide significant ( P &lt; 2.6 × 10 −6 ) gene-level associations ( HNF1A , MC4R , ATXN2L ). Furthermore, we report rare variant association enrichments within 25 gene sets related to obesity, monogenic diabetes and β-cell function. Many youth-onset T2D associations are shared with adult-onset T2D, but genetic risk factors of all frequencies—and rare variants in particular—are enriched within youth-onset T2D cases (5.0-fold increase in the rare variant and 3.4-fold increase in common variant genetic liability relative to adult-onset cases). The clinical presentation of participants with youth-onset T2D is influenced in part by the frequency of genetic risk factors within each individual. These findings portray youth-onset T2D as a heterogeneous disease situated on a spectrum between monogenic diabetes and adult-onset T2D.
Immune checkpoints in cardiac physiology and pathology: therapeutic targets for heart failure
Authors: Tamás G. Gergely, Zsófia D. Drobni, Marinos Kallikourdis, Han Zhu, Wouter C. Meijers, Tomas G. Neilan, Tienush Rassaf, Péter Ferdinandy, Zoltán V. Varga
Journal: Nature Reviews Cardiology (2024)
Cotargeting CDK4/6 and BRD4 Promotes Senescence and Ferroptosis Sensitivity in Cancer
Authors: Xianbing Zhu, Zheng Fu, Kendall Dutchak, Azadeh Arabzadeh, Simon Milette, Jutta Steinberger, Geneviève Morin, Anie Monast, Virginie Pilon, Tim Kong, Bianca N. Adams, Erika Prando Munhoz, Hannah J.B. Hosein, Tianxu Fang, Jing Su, Yibo Xue, Roni Rayes, Veena Sangwan, Logan A. Walsh, Guojun Chen, Daniela F. Quail, Jonathan D. Spicer, Morag Park, David Dankort, Sidong Huang
Journal: Cancer Research (2024)

Abstract Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are approved for breast cancer treatment and show activity against other malignancies, including KRAS-mutant non–small cell lung cancer (NSCLC). However, the clinical efficacy of CDK4/6 inhibitors is limited due to frequent drug resistance and their largely cytostatic effects. Through a genome-wide cDNA screen, we identified that bromodomain-containing protein 4 (BRD4) overexpression conferred resistance to the CDK4/6 inhibitor palbociclib in KRAS-mutant NSCLC cells. Inhibition of BRD4, either by RNA interference or small-molecule inhibitors, synergized with palbociclib to induce senescence in NSCLC cells and tumors, and the combination prolonged survival in a KRAS-mutant NSCLC mouse model. Mechanistically, BRD4-inhibition enhanced cell-cycle arrest and reactive oxygen species (ROS) accumulation, both of which are necessary for senescence induction; this in turn elevated GPX4, a peroxidase that suppresses ROS-triggered ferroptosis. Consequently, GPX4 inhibitor treatment selectively induced ferroptotic cell death in the senescent cancer cells, resulting in tumor regression. Cotargeting CDK4/6 and BRD4 also promoted senescence and ferroptosis vulnerability in pancreatic and breast cancer cells. Together, these findings reveal therapeutic vulnerabilities and effective combinations to enhance the clinical utility of CDK4/6 inhibitors. Significance: The combination of cytostatic CDK4/6 and BRD4 inhibitors induces senescent cancer cells that are primed for activation of ferroptotic cell death by targeting GPX4, providing an effective strategy for treating cancer.
Trends in Encounters for Emergency Contraception in US Emergency Departments, 2006-2020
Authors: Emily L. Vogt, Shani Chibber, Charley Jiang, Rieham Owda, Martina T. Caldwell, Lisa H. Harris, Erica E. Marsh
Journal: JAMA Network Open (2024)

This cross-sectional study of female emergency contraception users examines emergency contraception–related emergency department use disparities and associations with policy changes.
Incidence of Fit Test Failure During N95 Respirator Reuse and Extended Use
Authors: Ralph C. Wang, Nida F. Degesys, Jahan Fahimi, Chengshi Jin, Efrat Rosenthal, Ann A. Lazar, Anna Q. Yaffee, Susan Peterson, Richard E. Rothmann, Courtney M. C. Jones, Vaishal Tolia, Manish N. Shah, Maria C. Raven, Anna R. Harris, Robin Kemball, Alexis Mitchner, Angela Wong, Alex Hall, Rabbiya Iqbal, Michael Kramer, Kendall Maliszewski, Breana McBryde, John DeAngelis, Emily Corbett-Valade, Edward Castillo, Apoorva Maru, Angela Gifford
Journal: JAMA Network Open (2024)

Importance The COVID-19 pandemic resulted in a widespread acute shortage of N95 respirators, prompting the Centers for Disease Control and Prevention to develop guidelines for extended use and limited reuse of N95s for health care workers (HCWs). While HCWs followed these guidelines to conserve N95s, evidence from clinical settings regarding the safety of reuse and extended use is limited. Objective To measure the incidence of fit test failure during N95 reuse and compare the incidence between N95 types. Design, Setting, and Participants This prospective cohort study, conducted from April 2, 2021, to July 15, 2022, at 6 US emergency departments (EDs), included HCWs who practiced N95 reuse for more than half of their clinical shift. Those who were unwilling to wear an N95 for most of their shift, repeatedly failed baseline fit testing, were pregnant, or had facial hair or jewelry that interfered with the N95 face seal were excluded. Exposures Wearing the same N95 for more than half of each clinical shift and for up to 5 consecutive shifts. Participants chose an N95 model available at their institution; models were categorized into 3 types: dome (3M 1860R, 1860S, and 8210), trifold (3M 1870+ and 9205+), and duckbill (Halyard 46727, 46767, and 46827). Participants underwent 2 rounds of testing using a different mask of the same type for each round. Main Outcomes and Measures The primary outcome was Occupational Safety and Health Administration–approved qualitative fit test failure. Trained coordinators conducted fit tests after clinical shifts and recorded pass or fail based on participants tasting a bitter solution. Results A total of 412 HCWs and 824 N95s were fit tested at baseline; 21 N95s (2.5%) were withdrawn. Participants’ median age was 34.5 years (IQR, 29.5-41.8 years); 252 (61.2%) were female, and 205 (49.8%) were physicians. The overall cumulative incidence of fit failure after 1 shift was 38.7% (95% CI, 35.4%-42.1%), which differed by N95 type: dome, 25.8% (95% CI, 21.2%-30.6%); duckbill, 28.3% (95% CI, 22.2%-34.7%); and trifold, 61.3% (95% CI, 55.3%-67.3%). The risk of fit failure was significantly higher for trifold than dome N95s (adjusted hazard ratio, 1.75; 95% CI, 1.46-2.10). Conclusions and Relevance In this cohort study of ED HCWs practicing N95 reuse, fit failure occurred in 38.7% of masks after 1 shift. Trifold N95s had higher incidence of fit failure compared with dome N95s. These results may inform pandemic preparedness, specifically policies related to N95 selection and reuse practices.
Cost-Effectiveness of Whole-Genome vs Whole-Exome Sequencing Among Children With Suspected Genetic Disorders
Authors: Mario Cesare Nurchis, Francesca Clementina Radio, Luca Salmasi, Aurora Heidar Alizadeh, Gian Marco Raspolini, Gerardo Altamura, Marco Tartaglia, Bruno Dallapiccola, Elena Pizzo, Maria Michela Gianino, Gianfranco Damiani
Journal: JAMA Network Open (2024)

Importance The diagnosis of rare diseases and other genetic conditions can be daunting due to vague or poorly defined clinical features that are not recognized even by experienced clinicians. Next-generation sequencing technologies, such as whole-genome sequencing (WGS) and whole-exome sequencing (WES), have greatly enhanced the diagnosis of genetic diseases by expanding the ability to sequence a large part of the genome, rendering a cost-effectiveness comparison between them necessary. Objective To assess the cost-effectiveness of WGS compared with WES and conventional testing in children with suspected genetic disorders. Design, Setting, and Participants In this economic evaluation, a bayesian Markov model was implemented from January 1 to June 30, 2023. The model was developed using data from a cohort of 870 pediatric patients with suspected genetic disorders who were enrolled and underwent testing in the Ospedale Pediatrico Bambino Gesù, Rome, Italy, from January 1, 2015, to December 31, 2022. The robustness of the model was assessed through probabilistic sensitivity analysis and value of information analysis. Main Outcomes and Measures Overall costs, number of definitive diagnoses, and incremental cost-effectiveness ratios per diagnosis were measured. The cost-effectiveness analyses involved 4 comparisons: first-tier WGS with standard of care; first-tier WGS with first-tier WES; first-tier WGS with second-tier WES; and first-tier WGS with second-tier WGS. Results The ages of the 870 participants ranged from 0 to 18 years (539 [62%] girls). The results of the analysis suggested that adopting WGS as a first-tier strategy would be cost-effective compared with all other explored options. For all threshold levels above €29 800 (US $32 408) per diagnosis that were tested up to €50 000 (US $54 375) per diagnosis, first-line WGS vs second-line WES strategy (ie, 54.6%) had the highest probability of being cost-effective, followed by first-line vs second-line WGS (ie, 54.3%), first-line WGS vs the standard of care alternative (ie, 53.2%), and first-line WGS vs first-line WES (ie, 51.1%). Based on sensitivity analyses, these estimates remained robust to assumptions and parameter uncertainty. Conclusions and Relevance The findings of this economic evaluation encourage the development of policy changes at various levels (ie, macro, meso, and micro) of international health systems to ensure an efficient adoption of WGS in clinical practice and its equitable access.
<i>Bacteroides thetaiotaomicron</i> ameliorates mouse hepatic steatosis through regulating gut microbial composition, gut-liver folate and unsaturated fatty acids metabolism
Authors: Hu Li, Xue-Kai Wang, Mei Tang, Lei Lei, Jian-Rui Li, Han Sun, Jing Jiang, Biao Dong, Hong-Ying Li, Jian-Dong Jiang, Zong-Gen Peng
Journal: Gut Microbes (2024)

Gut microbiota plays an essential role in the progression of nonalcoholic fatty liver disease (NAFLD), making the gut-liver axis a potential therapeutic strategy. Bacteroides genus, the enriched gut symbionts, has shown promise in treating fatty liver. However, further investigation is needed to identify specific beneficial Bacteroides strains for metabolic disorders in NAFLD and elucidate their underlying mechanisms. In this study, we observed a positive correlation between the abundance of Bacteroides thetaiotaomicron (B. theta) and the alleviation of metabolic syndrome in the early and end stages of NAFLD. Administration of B. theta to HFD-fed mice for 12 weeks reduced body weight and fat accumulation, decreased hyperlipidemia and insulin resistance, and prevented hepatic steatohepatitis and liver injury. Notably, B. theta did not affect these indicators in low-fat diet (LFD)-fed mice and exhibited good safety. Mechanistically, B. theta regulated gut microbial composition, characterized by a decreased Firmicutes/Bacteroidetes ratio in HFD-Fed mice. It also increased gut-liver folate levels and hepatic metabolites, alleviating metabolic dysfunction. Additionally, treatment with B. theta increased the proportion of polyunsaturated fatty acid in the mouse liver, offering a widely reported benefit for NAFLD improvement. In conclusion, this study provides evidence that B. theta ameliorates NAFLD by regulating gut microbial composition, enhancing gut-liver folate and unsaturated fatty acid metabolism, highlighting the therapeutic role of B. theta as a potential probiotic for NAFLD.
Microbial stars: shedding light on gut microbes’ role in insulin resistance and innovative diabetes therapies
Authors: Jinwei Zhang
Journal: Gut Microbes (2024)

The role of gut microbiota in insulin resistance (IR), Metabolic Syndrome (MetS), and Type 2 Diabetes Mellitus (T2DM) is rapidly gaining recognition. However, the mechanisms and implications of gut bacteria in these conditions remain enigmatic. This commentary not only highlights the findings of a recent multi-omics study by Takeuchi et al. but also offers a unique perspective by integrating personal opinions and insights. The discussion revolves around the intricate connection between gut microbes and IR, suggesting novel therapeutic potential in targeting gut microbial carbohydrate metabolism for improved IR management and metabolic health.
Breast Cancer Incidence Among US Women Aged 20 to 49 Years by Race, Stage, and Hormone Receptor Status
Authors: Shuai Xu, Sara Murtagh, Yunan Han, Fei Wan, Adetunji T. Toriola
Journal: JAMA Network Open (2024)

Importance Breast cancer in young women has a less favorable prognosis compared with older women. Yet, comprehensive data on recent trends and how period and cohort effects may affect these trends among young women are not well-known. Objective To evaluate breast cancer incidence among young women in the US over a 20-year period by race and ethnicity, hormone receptor status (estrogen receptor [ER] and progesterone receptor [PR]), tumor stage, and age at diagnosis, as well as how period and cohort effects may affect these trends. Design, Setting, and Participants This cross-sectional study used data from Surveillance, Epidemiology, and End Results 17 registries (2000-2019). Women aged 20 to 49 years with a primary invasive breast cancer were included. Data were analyzed between February and June 2023. Main Outcomes and Measures Age-standardized incidence rates (ASIR), incidence rate ratios (IRR), and average annual percent changes (AAPC) stratified by race and ethnicity, hormone receptor status, tumor stage, and age at diagnosis. Results Out of 217 815 eligible women (1485 American Indian or Alaska Native [0.7%], 25 210 Asian or Pacific Islander [11.6%], 27 112 non-Hispanic Black [12.4%], 37 048 Hispanic [17.0%], 126 960 non-Hispanic White [58.3%]), the majority were diagnosed with an ER+/PR+ tumor (134 024 [61.5%]) and were diagnosed with a stage I tumor (81 793 [37.6%]). Overall, invasive breast cancer incidence increased (AAPC, 0.79; 95% CI, 0.42 to 1.15), with increasing trends across almost all racial and ethnic groups. ASIR increased for ER+/PR+ (AAPC, 2.72; 95% CI, 2.34 to 3.12) and ER+/PR− tumors (AAPC, 1.43; 95% CI, 1.00 to 1.87), and decreased for ER−/PR+ (AAPC, −3.25; 95% CI, −4.41 to −2.07) and ER−/PR− tumors (AAPC, −0.55; 95% CI, −1.68 to 0.60). For women aged 20 to 29 and 30 to 39 years, ASIRs were highest among non-Hispanic Black women (age 20-29 years: IRR, 1.53; 95% CI, 1.43 to 1.65; age 30-39 years: IRR, 1.15; 95% CI, 1.12 to 1.18). For women aged 40 to 49 years, ASIR was lower for non-Hispanic Black women (IRR, 0.96; 95% CI, 0.94 to 0.97) compared with non-Hispanic White women. Incidence rates increased for stages I and IV tumors but decreased for stage II and III tumors. Age-period-cohort analysis demonstrated both cohort and period effects on breast cancer incidence ( P &amp;amp;lt; .001). Conclusions and Relevance In this population-based cross-sectional analysis, an increase in breast cancer incidence rates among young US women and age-related crossover between non-Hispanic White and Black women were observed. Prevention efforts in young women need to adopt a targeted approach to address racial disparities in incidence rates observed at different age phases.