tbuckley/cabot-search huggingface dataset:
Time-Restricted Eating and Cancer: Lessons Learned and Considerations for a Path Forward
Authors: Marissa M Shams-White, Audrey A Goldbaum, Tanya Agurs-Collins, Susan Czajkowski, Kirsten A Herrick, Linda Nebeling, Jill Reedy, Gabriela Riscuta, Sharon Ross, Edward R Sauter
Journal: JNCI Journal of the National Cancer Institute (2024)

Time-restricted eating (TRE) is a type of intermittent fasting (IF). Food can be consumed as desired during the eating period, but not during the remainder of the day. Studies suggest that many of the health benefits of fasting may not simply be the result of weight loss, but also due to the body's responses to the fasting that lead to improved metabolic functioning. While animal studies are convincing regarding the benefits of time restricted feeding, human (TRE) studies are less consistent and generally short term (< 1 year). In 2020, the National Cancer Institute (NCI) funded five IF studies, four of which focused on TRE, which addressed the question "How does intermittent fasting affect cancer incidence, treatment response, or outcome?" NCI sponsored a webinar in 2023 featuring investigators of the funded studies in which they discussed challenges as well as their thoughts regarding the most important TRE topics that should be addressed going forward. Six areas were identified, which are discussed below as well as in a recently published NOT-CA-24-073: Factors impacting how Time-Restricted Eating (TRE) influences cancer-related outcomes. Moving the science forward will allow the scientific community to better understand TRE's potential. This potential includes the development of targeted TRE interventions to optimize long-term adherence to the intervention, which is required to better understand fully explore its potential benefits in cancer risk, increased response to cancer treatment, as well as improved quality and quantity of life among cancer survivors.
Genome Assembly and Winged fruit Gene Regulation of Chinese Wingnut: Insights from Genomic and Transcriptomic Analyses
Authors: Fangdong Geng, Xuedong Zhang, Jiayu Ma, Hengzhao Liu, Hang Ye, Fan Hao, Miaoqing Liu, Meng Dang, Huijuan Zhou, Mengdi Li, Peng Zhao
Journal: Genomics Proteomics & Bioinformatics (2024)

The genomic basis and biology of winged fruit are interesting issues in ecological and evolutionary biology. Chinese wingnut (Pterocarya stenoptera) is an important garden and economic tree species in China. The genomic resources of this hardwood tree could provide advanced genomic studies of Juglandaceae and their evolutionary relationships. Here, we reported a high-quality reference genome of P. stenoptera (N50 = 35.15 Mb) and provided a comparative analysis of Juglandaceae genomes. Paralogous relationships among the 16 chromosomes of the Chinese wingnut genome revealed eight main duplications representing the subgenome. Molecular dating suggested that the most recent common ancestor of P. stenopetera and Cyclocarya paliurus diverged from Juglans around 56.7 million years ago (Mya). The expanded and contracted gene families were associated with cutin, suberine, and wax biosynthesis, cytochrome P450, and anthocyanin biosynthesis. We identified large inversion blocks between the P. stenoptera genome and its relatives, which are enriched in genes related lipid biosynthesis and metabolism, and starch and sucrose metabolism. The twenty-eight individuals were clearly clustered into three groups responding to three species, namely Pterocarya macroptera, Pterocarya hupehensis, and P. stenoptera, based on whole genome resequencing data. Morphological and gene expression analysis showed that CAD, COMT, LOX, and MADS-box play important roles during the five developmental stages of wingnuts. Our study highlights the evolutionary history of the P. stenoptera genome and supports P. stenoptera as an appropriate Juglandaceae model for studying winged fruits. These results provide a theoretical basis for the evolution, development, and diversity of woody plant winged fruits.
A predictive system comprising serum microRNAs and radiomics for residual retroperitoneal masses in metastatic nonseminomatous germ cell tumors
Authors: Xiangdong Li, Renjie Ding, Zhenhua Liu, Wilhem M S Teixeira, Jingwei Ye, Li Tian, Haojiang Li, Shengjie Guo, Kai Yao, Zikun Ma, Zhuowei Liu
Journal: Cell Reports Medicine (2024)
Risk of Nephrolithiasis Associated With SGLT2 Inhibitors Versus DPP4 Inhibitors Among Patients With Type 2 Diabetes: A Target Trial Emulation Study
Authors: Anna Shin, Ju-Young Shin, Eun Ha Kang
Journal: Diabetes Care (2024)

OBJECTIVE We aim to compare the risk of nephrolithiasis among type 2 diabetes patients who initiated sodium-glucose cotransporter-2 inhibitors (SGLT2is) versus dipeptidyl-peptidase-4 inhibitors (DPP4is), individually within stone never- and ever-formers. RESEARCH DESIGN AND METHODS Using the 2010–2021 Korea National Health Insurance Service database, we conducted a population-based cohort study, comparing initiators of SGLT2is versus DPP4is. The primary outcome was incident nephrolithiasis. Osteoarthritis encounters served as a negative control outcome. After 1:1 propensity score (PS) matching in stone never- and ever-formers, pooled and individual hazard ratios (HRs), incidence rate difference (IRD), and 95% CIs were reported. Subgroup analyses by sex, age, thiazide co-use, and baseline cardiovascular risk were done. RESULTS The 17,006 PS-matched pairs of SGLT2i and DPP4i initiators were pooled from stone never- (105,378 pairs) and ever-formers (11,628 pairs). Over a mean of 654 days, the risk of nephrolithiasis was lower in SGLT2i initiators than in DPP4i: 0.65 vs. 1.12 events per 100 person-years, HR 0.54 (95% CI, 0.50–0.57), IRD −0.46 (95% CI,−0.21 to −0.52). Among never-formers, the HR was 0.43 (95% CI, 0.39–0.48) and IRD was −0.32 (95% CI,−0.27 to −0.36). Among ever-formers, the HR was 0.64 (95% CI, 0.59–0.69) and IRD was −2.26 (95% CI,−1.77 to −2.76). Near-null associations were found for osteoarthritis encounters. Results were consistent across subgroups. CONCLUSIONS We found a lower risk of nephrolithiasis associated with SGLT2is versus DPP4is in stone never- and ever-formers. Despite a greater relative risk reduction in the former, the absolute risk reduction was greater in the latter.
Cervical cesarean damage as a growing clinical problem: The association between in-labour cesarean section and recurrent preterm birth in subsequent pregnancies
Authors: Laura van der Krogt, Andrew Shennan
Journal: PLoS Medicine (2024)

Increasing evidence supports an association between in-labour cesarean section and recurrent preterm birth in subsequent pregnancies. This clinically challenging problem may be caused by cervical damage at the time of in-labour cesarean section.
Association Between Glycemia, Glycemic Variability, and Pregnancy Complications in Early GDM
Authors: Jincy Immanuel, N. Wah Cheung, Mahta Mohajeri, Daniel J. Simmons, William M. Hague, Helena Teede, Christopher J. Nolan, Michael J. Peek, Jeff R. Flack, Mark McLean, Vincent Wong, Emily J. Hibbert, Alexandra Kautzky-Willer, Jürgen Harreiter, Helena Backman, Emily Gianatti, Arianne Sweeting, Viswanathan Mohan, David Simmons, David Simmons, William Hague, Helena Teede, Wah Cheung, Christopher Nolan, Michael Peek, Jeff Flack, Mark McLean, Vincent Wong, Emily Hibbert, Alexandra Kautzky-Willer, Jürgen Harreiter, Helena Backman, Emily Gianatti, Arianne Sweeting, V. Mohan, Eric Shwarz, Glynis Ross, Uma Ram, Rohit Rajagopal, Raiyomand Dalal, Suja Padmanabhan, Victoria Rudland, Ranjit Mohan Anjana, Suzette Coat, Herbert Kiss, Georgia Soldatos, Jincy Immanuel
Journal: Diabetes Care (2024)

To investigate the association of timing of commencing glucose management with glycemia, glycemic variability, and pregnancy outcomes among women with early gestational diabetes mellitus (GDM).
Use of Additional Doses of 2024–2025 COVID-19 Vaccine for Adults Aged ≥65 Years and Persons Aged ≥6 Months with Moderate or Severe Immunocompromise: Recommendations of the Advisory Committee on Immunization Practices — United States, 2024
Authors: Lauren E. Roper, Monica Godfrey, Ruth Link-Gelles, Danielle L. Moulia, Christopher A. Taylor, Georgina Peacock, Noel Brewer, Oliver Brooks, George Kuchel, H. Keipp Talbot, Robert Schechter, Katherine E. Fleming-Dutra, Lakshmi Panagiotakopoulos
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

This report describes CDC's recommendation that all people aged ≥65 years and people ages 6 months–64 years with moderate or severe immunocompromise receive a second 2024–2025 COVID-19 vaccine dose 6 months after their last dose.
Real-world efficacy and safety of azvudine in hospitalized older patients with COVID-19 during the omicron wave in China: A retrospective cohort study
Authors: Yuanchao Zhu, Fei Zhao, Yubing Zhu, Xingang Li, Deshi Dong, Bolin Zhu, Jianchun Li, Xin Hu, Zinan Zhao, Wenfeng Xu, Yang Jv, Dandan Wang, Yingming Zheng, Yiwen Dong, Lu Li, Shilei Yang, Zhiyuan Teng, Ling Lu, Jingwei Zhu, Linzhe Du, Yunxin Liu, Lechuan Jia, Qiujv Zhang, Hui Ma, Ana Zhao, Hongliu Jiang, Xin Xu, Jinli Wang, Xuping Qian, Wei Zhang, Tingting Zheng, Chunxia Yang, Xuguang Chen, Kun Liu, Huanhuan Jiang, Dongxiang Qu, Jia Song, Hua Cheng, Wenfang Sun, Hanqiu Zhan, Xiao Li, Yafeng Wang, Aixia Wang, Li Liu, Lihua Yang, Nan Zhang, Shumin Chen, Jingjing Ma, Wei Liu, Xiaoxiang Du, Meiqin Zheng, Liyan Wan, Guangqing Du, Hangmei Liu, Pengfei Jin
Journal: Acta Pharmaceutica Sinica B (2024)

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T NANC), time to symptom improvement (T SI), and time of hospital stay (T HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.
Impact of metabolism-disrupting chemicals and folic acid supplementation on liver injury and steatosis in mother-child pairs
Authors: Sandra India-Aldana, Vishal Midya, Larissa Betanzos-Robledo, Meizhen Yao, Cecilia Alcalá, Syam S Andra, Manish Arora, Antonia M Calafat, Jaime Chu, Andrea Deierlein, Guadalupe Estrada-Gutierrez, Ravikumar Jagani, Allan C Just, Itai Kloog, Julio Landero, Youssef Oulhote, Ryan W Walker, Shirisha Yelamanchili, Andrea A Baccarelli, Robert O Wright, Martha María Téllez Rojo, Elena Colicino, Alejandra Cantoral, Damaskini Valvi
Journal: Journal of Hepatology (2024)
Author Correction: Itaconate drives mtRNA-mediated type I interferon production through inhibition of succinate dehydrogenase
Authors: Shane M O'Carroll, Christian G Peace, Juliana E Toller-Kawahisa, Yukun Min, Alexander Hooftman, Sara Charki, Louise Kehoe, Maureen J O'Sullivan, Aline Zoller, Anne F Mcgettrick, Alessia Zotta, Emily A Day, Maria Simarro, Neali Armstrong, Justin P Annes, Luke A J O'Neill
Journal: Nature Metabolism (2024)
Novel approaches in myelofibrosis
Authors: Steffen Koschmieder
Journal: HemaSphere (2024)

Myelofibrosis (MF) is a clonal myeloid neoplasm characterized by bone marrow fibrosis, splenomegaly, and disease-associated symptoms, as well as increased mortality, due to thrombosis, severe bleeding, infections, or progression to acute leukemia. Currently, the management of MF patients is tailored according to risk scores, with higher-risk (intermediate-2 and high-risk) patients being assessed for allogeneic stem cell transplantation, which remains the only potentially curative treatment option. On the other hand, lower risk (low- and intermediate-1 risk) patients who are symptomatic may be treated with JAK inhibitors or other drugs. However, none of these drug treatments have induced relevant rates of durable complete remissions, and, therefore, novel treatments are needed to improve the long-term outcomes of MF patients. This review summarizes current preclinical and clinical approaches to MF therapy, including novel drug combinations involving JAK inhibitors and innovative monotherapies. These drugs target transcription, nuclear export, survival pathways, or various intracellular pathways, ranging from JAK-STAT signaling to PI3-Kinase, TP53, PIM1, or S100A8/A9/toll-like receptor pathways. Also, extracellular targeting using interferon, calreticulin mutant-specific antibodies, and other immunotherapeutic approaches are discussed, as well as various antifibrotic strategies. In addition, preclinical approaches that target individual mutated clones, for example, by mutation-specific JAK2V617F inhibitors or DNA repair pathway inhibitors, are presented. Finally, current efforts of generating novel endpoints for clinical trials aim more at disease modification and overall survival than at improvements of splenomegaly or symptoms. Together, the new generations of clinical trials promise to offer substantial improvements in the management of MF patients and long-term disease control.
Clinical tolerance but no protective efficacy in a placebo-controlled trial of repeated controlled schistosome infection
Authors: Jan Pieter R. Koopman, Emma L. Houlder, Jacqueline J. Janse, Olivia A.C. Lamers, Geert V.T. Roozen, Jeroen C. Sijtsma, Miriam Casacuberta-Partal, Stan T. Hilt, M.Y. Eileen C. van der Stoep, Inge M. van Amerongen-Westra, Eric A.T. Brienen, Linda J. Wammes, Lisette van Lieshout, Govert J. van Dam, Paul L.A.M. Corstjens, Angela van Diepen, Maria Yazdanbakhsh, Cornelis H. Hokke, Meta Roestenberg
Journal: Journal of Clinical Investigation (2024)

BACKGROUND. Partial protective immunity to schistosomiasis develops over time, following repeated praziquantel treatment. Moreover, animals develop protective immunity after repeated immunisation with irradiated cercariae. Here, we evaluated development of natural immunity through consecutive exposure-treatment cycles with Schistosoma mansoni (Sm) in healthy, Schistosoma-naïve participants using single-sex controlled human Sm infection.
Red Blood Cells Capture and Deliver Bacterial DNA to Drive Host Responses During Polymicrobial Sepsis
Authors: LK Metthew Lam, Nathan J. Klingensmith, Layal Sayegh, Emily Oatman, Joshua S. Jose, Christopher V. Cosgriff, Kaitlyn A. Eckart, John McGinnis, Piyush Ranjan, Matthew Lanza, Nadir Yehya, Nuala J. Meyer, Robert P. Dickson, Nilam S. Mangalmurti
Journal: Journal of Clinical Investigation (2024)

Red blood cells (RBCs), traditionally recognized for their role in transporting oxygen, play a pivotal role in the body's immune response by expressing TLR9 and scavenging excess host cell-free DNA. DNA capture by RBCs leads to accelerated RBC clearance and triggers inflammation. Whether RBCs can also acquire microbial DNA during infections is unknown. Murine RBCs acquire microbial DNA in vitro and bacterial-DNA-induced macrophage activation was augmented by WT but not Tlr9-deleted RBCs. In a mouse model of polymicrobial sepsis, RBC-bound bacterial DNA was elevated in WT but not in erythroid Tlr9-deleted mice. Plasma cytokine analysis in these mice revealed distinct sepsis clusters characterized by persistent hypothermia and hyperinflammation in the most severely affected subjects. RBC-Tlr9 deletion attenuated plasma and tissue IL-6 production in the most severe group. Parallel findings in human subjects confirmed that RBCs from septic patients harbored more bacterial DNA compared to healthy individuals. Further analysis through 16S sequencing of RBC-bound DNA illustrated distinct microbial communities, with RBC-bound DNA composition correlating with plasma IL-6 in patients with sepsis. Collectively, these findings unveil RBCs as overlooked reservoirs and couriers of microbial DNA, capable of influencing host inflammatory responses in sepsis.
Intermittent fasting and neurodegenerative diseases: Molecular mechanisms and therapeutic potential
Authors: Renjun Lv, Bin Liu, Ziying Jiang, Runfa Zhou, Xiaoxing Liu, Tangsheng Lu, Yanping Bao, Chunxia Huang, Guichang Zou, Zongyong Zhang, Lin Lu, Qingqing Yin
Journal: Metabolism (2024)
Senescence of endothelial cells increases susceptibility to Kaposi's sarcoma-associated herpesvirus infection via CD109-mediated viral entry
Authors: Myung-Ju Lee, Jun-Hee Yeon, Jisu Lee, Yun Hee Kang, Beom Seok Park, Joo Hee Park, Sung-Ho Yun, Dagmar Wirth, Seung-Min Yoo, Changhoon Park, Shou-Jiang Gao, Myung-Shin Lee
Journal: Journal of Clinical Investigation (2024)

The aging process is characterized by cellular functional decline and increased susceptibility to infections. Understanding the association between virus infection and aging is crucial for developing effective strategies against viral infections in older individuals. However, the relationship between Kaposi's sarcoma-associated herpesvirus (KSHV) infection, a cause of Kaposi's sarcoma prevalent among the elderly without HIV infection, and cellular senescence remains enigmatic. This study uncovers a fascinating link between cellular senescence and enhanced KSHV infectivity in human endothelial cells. Through a comprehensive proteomic analysis, we identified caveolin-1 and CD109 as novel host factors significantly upregulated in senescent cells that promote KSHV infection. Remarkably, CRISPR-Cas9-mediated knockout of these factors reduced KSHV binding and entry, leading to decreased viral infectivity. Furthermore, surface plasmon resonance analysis and confocal microscopy revealed a direct interaction between KSHV virions and CD109 on the cell surface during entry, with recombinant CD109 protein exhibiting an intriguing ability to inhibit infection by blocking virion binding. These findings uncover a previously unrecognized role of cellular senescence in enhancing KSHV infection through upregulation of specific host factors and provide novel insights into the complex interplay between aging and viral pathogenesis.
Exosome-membrane and polymer-based hybrid-complex for systemic delivery of plasmid DNA into brains for the treatment of glioblastoma
Authors: Youngki Lee, Subin Kang, Le Thi Thuy, Mincheol Son, Jae Young Park, Sung Bin Ahn, Minji Kang, Jihun Oh, Joon Sig Choi, Minhyung Lee
Journal: Asian Journal of Pharmaceutical Sciences (2024)

Herpes simplex virus thymidine kinase (HSVtk) gene therapy is a promising strategy for glioblastoma therapy. However, delivery of plasmid DNA (pDNA) encoding HSVtk into the brain by systemic administration is a challenge since pDNA can hardly penetrate the blood-brain barrier. In this study, an exosome-membrane (EM) and polymer-based hybrid complex was developed for systemic delivery of pDNA into the brain. Histidine/arginine-linked polyamidoamine (PHR) was used as a carrier. PHR binds to pDNA by electrostatic interaction. The pDNA/PHR complex was mixed with EM and subjected to extrusion to produce pDNA/PHR-EM hybrid complex. For glioblastoma targeting, T7 peptide was attached to the pDNA/PHR-EM complex. Both pDNA/PHR-EM and T7-decorated pDNA/PHR-EM (pDNA/PHR-EM-T7) had a surface charge of -5 mV and a size of 280 nm. Transfection assays indicated that pDNA/PHR-EM-T7 enhanced the transfection to C6 cells compared with pDNA/PHR-EM. Intravenous administration of pHSVtk/PHR-EM-T7 showed that pHSVtk/PHR-EM and pHSVtk/PHR-EM-T7 delivered pHSVtk more efficiently than pHSVtk/lipofectamine and pHSVtk/PHR into glioblastoma in vivo. pHSVtk/PHR-EM-T7 had higher delivery efficiency than pHSVtk/PHR-EM. As a result, the HSVtk expression and apoptosis levels in the tumors of the pHSVtk/PHR-EM-T7 group were higher than those of the other control groups. Therefore, the pDNA/PHR-EM-T7 hybrid complex is a useful carrier for systemic delivery of pHSVtk to glioblastoma.
A deep intronic mutation causes RAD50 deficiency through an unusual mechanism of distant exon activation
Authors: Kristine Bousset, Stefano Donega, Najim Ameziane, Tabea Fleischhammer, Dhanya Ramachandran, Miriam Poley-Gil, Detlev Schindler, Ingrid M. van de Laar, Franco Pagani, Thilo Dörk
Journal: Journal of Clinical Investigation (2024)

This study identifies and characterizes a novel type of splicing mutation in RAD50 deficiency, a rare genetic disorder.
Flavell JR, Baumforth KRN, Wood VHJ, et al. Down-regulation of the TGF-beta target gene, <i>PTPRK</i>, by the Epstein-Barr virus–encoded EBNA1 contributes to the growth and survival of Hodgkin lymphoma cells. <i>Blood.</i> 2008;111(1):292-301.
Journal: Blood (2024)
Sudan has spiralled into a humanitarian catastrophe, but the International Rescue Committee is helping to restore hope in communities
Authors: Eatizaz Yousif
Journal: BMJ (2024)

Sudan has spiralled into a humanitarian catastrophe, but the International Rescue Committee is helping to restore hope in communities Women and girls have experienced some of the most brutal consequences of Sudan's conflict.Eatizaz Yousif explains the role of the IRC in delivering essential services and psychosocial support Eatizaz Yousif,