tbuckley/cabot-search huggingface dataset:
Integrative Omics Uncovers Low Tumorous Magnesium Content as A Driver Factor of Colorectal Cancer
Authors: Rou Zhang, Meng Hu, Yu Liu, Wanmeng Li, Zhiqiang Xu, Siyu He, Ying Lu, Yanqiu Gong, Xiuxuan Wang, Shan Hai, Shuangqing Li, Shiqian Qi, Yuan Li, Yang Shu, Dan Du, Huiyuan Zhang, Heng Xu, Zongguang Zhou, Peng Lei, Hai-Ning Chen, Lunzhi Dai
Journal: Genomics Proteomics & Bioinformatics (2024)

Abstract Magnesium (Mg) deficiency is associated with increased risk and malignancy in colorectal cancer (CRC), yet the underlying mechanisms remain elusive. Here, we used genomic, proteomic, and phosphoproteomic data to elucidate the impact of Mg deficiency on CRC. Genomic analysis identified 160 genes with higher mutation frequencies in Low-Mg tumors, including key driver genes such as KMT2C and ERBB3. Unexpectedly, initiation driver genes of CRC, such as TP53 and APC, displayed higher mutation frequencies in High-Mg tumors. Additionally, proteomic and phosphoproteomic data indicated that low Mg content in tumors may activate epithelial–mesenchymal transition (EMT) by modulating inflammation or remodeling the phosphoproteome of cancer cells. Notably, we observed a negative correlation between the phosphorylation of DBN1 at S142 (DBN1S142p) and Mg content. A mutation in S142 to D (DBN1S142D) mimicking DBN1S142p up-regulated MMP2 and enhanced cell migration, while treatment with MgCl2 reduced DBN1S142p, thereby reversing this phenotype. Mechanistically, Mg2+ attenuated the DBN1–ACTN4 interaction by decreasing DBN1S142p, which in turn enhanced the binding of ACTN4 to F-actin and promoted F-actin polymerization, ultimately reducing MMP2 expression. These findings shed new light on the crucial role of Mg deficiency in CRC progression and suggest that Mg supplementation may be a promising preventive and therapeutic strategy for CRC.
Variation to biology: optimizing functional analysis of cancer risk variants
Authors: Stefanie Nelson, Danielle Carrick, Danielle Daee, Ian Fingerman, Elizabeth Gillanders
Journal: JNCI Journal of the National Cancer Institute (2024)

Research conducted over the past 15+ years has identified hundreds of common germline genetic variants associated with cancer risk, but understanding the biological impact of these primarily non-protein coding variants has been challenging. The National Cancer Institute sought to better understand and address those challenges by requesting input from the scientific community via a survey and a 2-day virtual meeting, which focused on discussions among participants. Here, we discuss challenges identified through the survey as important to advancing functional analysis of common cancer risk variants: 1) When is a variant truly characterized; 2) Developing and standardizing databases and computational tools; 3) Optimization and implementation of high-throughput assays; 4) Use of model organisms for understanding variant function; 5) Diversity in data and assays; and 6) Creating and improving large multidisciplinary collaborations. We define these 6 challenges, describe how success in addressing them may look, propose potential solutions, and note issues that span all the challenges. Implementation of these ideas could help develop a framework for methodically analyzing common cancer risk variants to understand their function and make effective and efficient use of the wealth of existing genomic association data.
Research on the treatment of rifampin-susceptible tuberculosis—Time for a new approach
Authors: William Burman, Oxana Rucsineanu, C. Robert Horsburgh, James Johnston, Susan E. Dorman, Dick Menzies
Journal: PLoS Medicine (2024)

In the Perspective, William Burman and colleagues advocate improving the safety and acceptability of treatment, rather than treatment-shortening, of rifampin-susceptible tuberculosis.
Circulating tumour DNA in patients with hepatocellular carcinoma across tumour stages and treatments
Authors: Claudia Campani, Sandrine Imbeaud, Gabrielle Couchy, Marianne Ziol, Theo Z Hirsch, Sandra Rebouissou, Bénédicte Noblet, Pierre Nahon, Katia Hormigos, Sabrina Sidali, Olivier Seror, Valerie Taly, Nathalie Ganne Carrie, Pierre Laurent-Puig, Jessica Zucman-Rossi, Jean-Charles Nault
Journal: Gut (2024)

Circulating tumour DNA (ctDNA) is a promising non-invasive biomarker in cancer. We aim to assess the dynamic of ctDNA in patients with hepatocellular carcinoma (HCC).
Impact of prenatal and postnatal maternal IBD status on offspring’s risk of IBD: a population-based cohort study
Authors: Linéa Bonfils, Gry Poulsen, Manasi Agrawal, Mette Julsgaard, Joana Torres, Tine Jess, Kristine Højgaard Allin
Journal: Gut (2024)

Objective In utero exposure to maternal inflammation may impact immune system development and subsequent risk of disease. We investigated whether a maternal diagnosis of IBD before childbirth is linked to a higher risk of IBD in offspring compared with a diagnosis after childbirth. Further, we analysed paternal IBD status for comparison. Design Using Danish health registers, we identified all individuals born in Denmark between 1997 and 2022 and their legal parents, as well as their IBD status. Cox proportional hazards regression analyses adjusted for calendar period and mode of delivery were used to estimate offspring IBD risk by maternal and paternal IBD status before and after childbirth. Results Of 1 290 358 children, 10 041 (0.8%) had mothers with IBD diagnosis before childbirth and 9985 (0.8%) had mothers with IBD diagnosis after childbirth. Over 18 370 420 person-years, 3537 individuals were diagnosed with IBD. Offspring of mothers with IBD before childbirth had an adjusted HR of IBD of 6.27 (95% CI 5.21, 7.54) compared with those without maternal IBD, while offspring of mothers with IBD after childbirth had an adjusted HR of 3.88 (95% CI 3.27, 4.60). Corresponding adjusted HRs were 5.26 (95% CI 4.22, 6.56) among offspring with paternal IBD before childbirth and 3.73 (95% CI 3.10, 4.50) for paternal IBD after childbirth. Conclusion Offspring had a greater risk of IBD when either parent was diagnosed before childbirth rather than later, emphasising genetic predisposition and environmental risk factors rather than maternal inflammation in utero as risk factors for IBD.
Discovery and validation of a 10-gene predictive signature for response to adjuvant chemotherapy in stage II and III colon cancer
Authors: Chaohan Xu, Peng Xia, Jie Li, Keeli.B. Lewis, Kristen K. Ciombor, Lily Wang, J. Joshua Smith, R. Daniel Beauchamp, X. Steven Chen
Journal: Cell Reports Medicine (2024)

Identifying patients with stage II and III colon cancer who will benefit from 5-fluorouracil (5-FU)-based adjuvant chemotherapy is crucial for the advancement of personalized cancer therapy. We employ a semi-supervised machine learning approach to analyze a large dataset with 933 stage II and III colon cancer samples. Our analysis leverages gene regulatory networks to discover an 18-gene prognostic signature and to explore a 10-gene signature that potentially predicts chemotherapy benefits. The 10-gene signature demonstrates strong prognostic power and shows promising potential to predict chemotherapy benefits. We establish a robust clinical assay on the NanoString nCounter platform, validated in a retrospective formalin-fixed paraffin-embedded (FFPE) cohort, which represents an important step toward clinical application. Our study lays the groundwork for improving adjuvant chemotherapy and potentially expanding into immunotherapy decision-making in colon cancer. Future prospective studies are needed to validate and establish the clinical utility of the 10-gene signature in clinical settings.
The recombinant shingles vaccine is associated with lower risk of dementia
Authors: Maxime Taquet, Quentin Dercon, John A. Todd, Paul J. Harrison
Journal: Nature Medicine (2024)

There is emerging evidence that the live herpes zoster (shingles) vaccine might protect against dementia. However, the existing data are limited and refer only to the live vaccine, which is now discontinued in the United States and many other countries in favor of a recombinant vaccine. Whether the recombinant shingles vaccine protects against dementia remains unknown. Here we used a natural experiment opportunity created by the rapid transition from the use of live to the use of recombinant vaccines to compare the risk of dementia between vaccine types. We show that the recombinant vaccine is associated with a significantly lower risk of dementia in the 6 years post-vaccination. Specifically, receiving the recombinant vaccine is associated with a 17% increase in diagnosis-free time, translating into 164 additional days lived without a diagnosis of dementia in those subsequently affected. The recombinant shingles vaccine was also associated with lower risks of dementia than were two other vaccines commonly used in older people: influenza and tetanus-diphtheria-pertussis vaccines. The effect was robust across multiple secondary analyses, and was present in both men and women but was greater in women. These findings should stimulate studies investigating the mechanisms underpinning the protection and could facilitate the design of a large-scale randomized control trial to confirm the possible additional benefit of the recombinant shingles vaccine.
Fecal microbiota transplantation improves anti-PD-1 inhibitor efficacy in unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor
Authors: Yunjae Kim, Gihyeon Kim, Sujeong Kim, Beomki Cho, Sang-Yeob Kim, Eun-Ju Do, Dong-Jun Bae, Seungil Kim, Mi-Na Kweon, Joon Seon Song, Sang Hyoung Park, Sung Wook Hwang, Mi-Na Kim, Yeongmin Kim, Kyungchan Min, Sung-Han Kim, Mark D Adams, Charles Lee, Hansoo Park, Sook Ryun Park
Journal: Cell Host & Microbe (2024)
Errors in Introduction, Results, and Discussion
Journal: JAMA Network Open (2024)

Errors in Introduction, Results, and DiscussionIn the Original Investigation titled "Use of Oral and Emergency Contraceptives After the US Supreme Court's Dobbs Decision," 1 published June 26, 2024, there were errors in the Introduction, Results, and Discussion.In addition to typographical errors, the article stated there were 285.0 fewer oral contraceptive prescription fills per 100 000 women, and it should have stated there were 285.9 fewer prescription fills.This article has been corrected.
Longitudinal on-treatment circulating tumor DNA as a biomarker for real-time dynamic risk monitoring in cancer patients: The EP-SEASON study
Authors: Jiawei Lv, Ling-Xin Xu, Zhi-Xuan Li, Li Lin, Chen-Fei Wu, Ting-Qiu Quan, Zi-Cheng Zhen, Wen-Fei Li, Ling-Long Tang, Yan-Ping Mao, Lei Chen, Rui Guo, Lu-Lu Zhang, Xin-Lei Ai, Shi-Yue Wu, Meng-Yu Hao, Denghui Wei, Ji-Bin Li, Jun Ma, Yu-Pei Chen, Guan-Qun Zhou, Ying Sun
Journal: Cancer Cell (2024)

Recurrence risks of cancer patient can change during treatment as a result of treatment-related tumor evolution. However, biomarkers that can monitor these changes are lacking. Here, we investigated whether tracking circulating tumor DNA (ctDNA) dynamics through liquid biopsy can inform real-time recurrence risk. Nasopharyngeal carcinoma (NPC) provides an ideal model where cell-free Epstein-Barr virus (EBV) DNA (cfEBV DNA), a ctDNA, can be sensitively detected. We conducted the EP-SEASON study (NCT03855020) and prospectively recruited 1,000 NPC patients undergoing per-protocol cfEBV DNA assessments at 11 time points and receiving sequential chemo-radiotherapy. Longitudinal cfEBV DNA displayed distinct patterns during neoadjuvant chemotherapy and radiotherapy. Despite the prognostic significance of cfEBV DNA at each time point, real-time recurrence risks changed in sync with cfEBV DNA dynamics. Furthermore, we identified phenotypes of whole-course ctDNA changing dynamics associated with different survival outcomes. In conclusion, tracking longitudinal on-treatment ctDNA can forecast real-time recurrence risk, facilitating risk-adapted, individualized patient management.
Unraveling the Importance of Seizure Duration in Electroconvulsive Therapy
Authors: James Luccarelli
Journal: JAMA Network Open (2024)

Cecilia Gillving, MB; Carl Johan Ekman, MD, PhD; Åsa Hammar, PhD; Mikael Landén, MD, PhD; Johan Lundberg, MD, PhD; Pouya Movahed Rad, MD, PhD; Pia Nordanskog, MD, PhD; Lars von Knorring, MD, PhD; Axel Nordenskjöld, MD, PhD
Seizure Duration and Electroconvulsive Therapy in Major Depressive Disorder
Authors: Cecilia Gillving, Carl Johan Ekman, Åsa Hammar, Mikael Landén, Johan Lundberg, Pouya Movahed Rad, Pia Nordanskog, Lars von Knorring, Axel Nordenskjöld
Journal: JAMA Network Open (2024)

Electroconvulsive therapy (ECT), wherein a generalized epileptic seizure is induced, is a treatment for major depressive disorder (MDD). Currently, it is unclear whether there is an association between seizure length and treatment outcome.
Longitudinal integrative cell-free DNA analysis in gestational diabetes mellitus
Authors: Zhuangyuan Tang, Shuo Wang, Xi Li, Chengbin Hu, Qiangrong Zhai, Jing Wang, Qingshi Ye, Jinnan Liu, Guohong Zhang, Yuanyuan Guo, Fengxia Su, Huikun Liu, Lingyao Guan, Chang Jiang, Jiayu Chen, Min Li, Fangyi Ren, Yu Zhang, Minjuan Huang, Lingguo Li, Haiqiang Zhang, Guixue Hou, Xin Jin, Fang Chen, Huanhuan Zhu, Linxuan Li, Jingyu Zeng, Han Xiao, Aifen Zhou, Lingyan Feng, Ya Gao, Gongshu Liu
Journal: Cell Reports Medicine (2024)
Health Care Resource Use for Modern First-Line Treatments in Metastatic Renal Cell Carcinoma
Authors: Neil J. Shah, Reshma Shinde, Kristin J. Moore, Amy Sainski-Nguyen, Lisa B. Le, Feng Cao, Rui Song, Puneet Singhal, Robert J. Motzer
Journal: JAMA Network Open (2024)

Importance Immuno-oncology agents have changed the treatment paradigm for metastatic renal cell carcinoma (mRCC). Such therapies improve survival but can impose considerable health care resource use (HCRU) and associated costs, necessitating their examination. Objective To compare HCRU, costs, and clinical outcomes among patients receiving first-line pembrolizumab plus axitinib (P+A) or ipilimumab plus nivolumab (I+N). Design, Setting, and Participants This retrospective cohort study used data from an administrative claims database on patients with mRCC receiving first-line P+A or I+N that was initiated between January 2018 and May 2020. Data were analyzed from February 2021 to July 2022. Exposure First-line P+A or I+N. Main Outcome and Measures HCRU and costs during the first 90 days, full first-line treatment, and full follow-up periods were assessed. Using Kaplan-Meier analysis, time on treatment, overall survival, time to first emergency department (ED) visit, and time to first inpatient stay were compared. Results Among 507 patients, there were 126 patients receiving P+A (91 male [72.2%]; mean [SD] age, 67.93 [9.66] y) and 381 patients receiving I+N (271 male [71.1%]; mean [SD] age, 66.52 [9.94] years). The median time on treatment was longer for the P+A compared with I+N group (12.4 months [95% CI, 8.40 months to not estimable] vs 4.1 months [95% CI, 3.07 to 5.30 months]; P &amp;amp;lt; .001). The median time to first ED visit was longer for the P+A than I+N group (7.2 months [95% CI 3.9 to 11.1 months ] vs 3.3 months [95% CI, 2.6 to 3.9 months]; P = .005), as was time to first inpatient stay (9.0 months [95% CI 6.5 months to not estimable] vs 5.6 months [95% CI, 3.9 to 7.9 months]; P = .02). During the first 90 days, a lower proportion of the P+A than N+I group had ED visits (43 patients [34.1%] vs 182 patients [47.8%] and inpatient stays (24 patients [19.1%) vs144 patients [37.8%]; P &amp;amp;lt; .001). During full follow-up, mean total adjusted costs were similar for P+A and I+N groups, but adjusted 12-month estimated total costs were higher for P+A than I+N groups ($325 574 vs $ 263 803; P = .03). Conclusions and Relevance In this study, treatment with P+A was associated with longer time on treatment, time to first ED visit, and inpatient stay, while 12-month estimated costs were higher for the P+A group. This is among the first clinical studies to evaluate economic burden associated with modern treatments for mRCC.
Provision of Stroke Care Services by Community Disadvantage Status in the US, 2009-2022
Authors: Renee Y. Hsia, Nandita Sarkar, Yu-Chu Shen
Journal: JAMA Network Open (2024)

Stroke center certification is granted to facilities that demonstrate distinct capabilities for treating patients with stroke. A thorough understanding of structural discrimination in the provision of stroke centers is critical for identifying and implementing effective interventions to improve health inequities for socioeconomically disadvantaged populations.
Suicide Rates Among Asian American and Pacific Islander Youths—A Cause for Alarm
Authors: Anthony L. Bui, Anna S. Lau
Journal: JAMA Network Open (2024)

Suicide is the leading cause of death for Asian American and Pacific Islander youths. 1 Asian American individuals are the fastest growing racial group in the United States, and Native Hawaiian and Pacific Islander individuals are the third fastest.Despite the critical importance of preventing suicide among this growing population, the study of mental health among Asian American and Pacific Islander populations has been historically understudied and underfunded nationally. 2 Elsewhere in JAMA Network Open, Keum et al 3 present a cross-sectional analysis examining trends in suicide rates among Asian American and Pacific Islander youths aged 10 to 19 years.Utilizing national mortality data from the National Center for Health Statistics, the authors calculate crude suicide rates across male and female groups and conduct a trend analysis to assess annual percent changes.The authors found that Asian American and Pacific Islander youth suicide rates have been increasing.In 2021, the Asian American and Pacific Islander male and female youth suicide rates were 6.49 and 3.72 per 100 000 individuals, respectively.The authors found large increases in suicide rates from 1999 to 2021, with a 72% increase in youth suicide rates for males and 125% increase for females during the 22-year period.They detected that Asian American and Pacific Islander male and female youths experienced growth in suicide rates, starting in 2009 and 2004 and peaking in 2019 and 2020, respectively.The findings of this study bring up several important points for discussion.
A correctable immune niche for epithelial stem-cell reprogramming and post-viral lung diseases
Authors: Kangyun Wu, Yong Zhang, Huiqing Yin-DeClue, Kelly Sun, Dailing Mao, Kuangying Yang, Stephen R. Austin, Erika C. Crouch, Steven L. Brody, Derek E. Byers, Christy M. Hoffmann, Michael E. Hughes, Michael J. Holtzman
Journal: Journal of Clinical Investigation (2024)

Epithelial barriers are programmed for defense and repair but are also the site of long-term structural remodeling and disease. In general, this paradigm features epithelial stem cells (ESCs) that are called on to regenerate damaged tissues but can also be reprogrammed for detrimental remodeling. Here we identified a Wfdc21-dependent monocyte-derived dendritic cell (moDC) population that functioned as an early sentinel niche for basal ESC reprogramming in mouse models of epithelial injury after respiratory viral infection. Niche function depended on moDC delivery of ligand GPNMB to the basal ESC receptor CD44 so that properly timed antibody blockade of ligand or receptor provided long-lasting correction of reprogramming and broad disease phenotypes. These same control points worked directly in mouse and human basal ESC organoids. Together, the findings identify a mechanism to explain and modify what is otherwise a stereotyped but sometimes detrimental response to epithelial injury.
Online Search Interest in Gynecologists After the Release of the Film <i>Barbie</i>
Authors: Eva Senechal, Charles F. Bray, Christopher M. Worsham, Anupam B. Jena
Journal: JAMA Network Open (2024)

This cross-sectional study evaluates whether the film Barbie was associated with increased public interest in gynecologic care in the US after its release.
Microglia rescue neurons from aggregate-induced neuronal dysfunction and death through tunneling nanotubes
Authors: Hannah Scheiblich, Frederik Eikens, Lena Wischhof, Sabine Opitz, Kay Jüngling, Csaba Cserép, Susanne V. Schmidt, Jessica Lambertz, Tracy Bellande, Balázs Pósfai, Charlotte Geck, Jasper Spitzer, Alexandru Odainic, Sergio Castro-Gomez, Stephanie Schwartz, Ibrahim Boussaad, Rejko Krüger, Enrico Glaab, Donato A. Di Monte, Daniele Bano, Ádám Dénes, Eike Latz, Ronald Melki, Hans-Christian Pape, Michael T. Heneka
Journal: Neuron (2024)

Microglia are crucial for maintaining brain health and neuron function. Here, we report that microglia establish connections with neurons using tunneling nanotubes (TNTs) in both physiological and pathological conditions. These TNTs facilitate the rapid exchange of organelles, vesicles, and proteins. In neurodegenerative diseases like Parkinson's and Alzheimer's disease, toxic aggregates of alpha-synuclein (α-syn) and tau accumulate within neurons. Our research demonstrates that microglia use TNTs to extract neurons from these aggregates, restoring neuronal health. Additionally, microglia share their healthy mitochondria with burdened neurons, reducing oxidative stress and normalizing gene expression. Disrupting mitochondrial function with antimycin A before TNT formation eliminates this neuroprotection. Moreover, co-culturing neurons with microglia and promoting TNT formation rescues suppressed neuronal activity caused by α-syn or tau aggregates. Notably, TNT-mediated aggregate transfer is compromised in microglia carrying Lrrk22(Gly2019Ser) or Trem2(T66M) and (R47H) mutations, suggesting a role in the pathology of these gene variants in neurodegenerative diseases.
International consensus on fasting terminology
Authors: Daniela A. Koppold, Carolin Breinlinger, Etienne Hanslian, Christian Kessler, Holger Cramer, Anika Rajput Khokhar, Courtney M. Peterson, Grant Tinsley, Claudio Vernieri, Richard J. Bloomer, Michael Boschmann, Nicola L. Bragazzi, Sebastian Brandhorst, Kelsey Gabel, Alan C. Goldhamer, Martin M. Grajower, Michelle Harvie, Leonie Heilbronn, Benjamin D. Horne, Spyridon N. Karras, Jost Langhorst, Eva Lischka, Frank Madeo, Sarah J. Mitchell, Ioannis-Eleemon Papagiannopoulos-Vatopaidinos, Maria Papagiannopoulou, Hanno Pijl, Eric Ravussin, Martha Ritzmann-Widderich, Krista Varady, Lilian Adamidou, Melika Chihaoui, Rafael de Cabo, Mohamed Hassanein, Nader Lessan, Valter Longo, Emily N.C. Manoogian, Mark P. Mattson, J. Brent Muhlestein, Satchidananda Panda, Sousana K. Papadopoulou, Nikolaos E. Rodopaios, Rainer Stange, Andreas Michalsen
Journal: Cell Metabolism (2024)

Although fasting is increasingly applied for disease prevention and treatment, consensus on terminology is lacking. Using Delphi methodology, an international, multidisciplinary panel of researchers and clinicians standardized definitions of various fasting approaches in humans. Five online surveys and a live online conference were conducted with 38 experts, 25 of whom completed all 5 surveys. Consensus was achieved for the following terms: "fasting" (voluntary abstinence from some or all foods or foods and beverages), "modified fasting" (restriction of energy intake to max. 25% of energy needs), "fluid-only fasting," "alternate-day fasting," "short-term fasting" (lasting 2-3 days), "prolonged fasting" (≥4 consecutive days), and "religious fasting." "Intermittent fasting" (repetitive fasting periods lasting ≤48 h), "time-restricted eating," and "fasting-mimicking diet" were discussed most. This study provides expert recommendations on fasting terminology for future research and clinical applications, facilitating communication and cross-referencing in the field.
Low-Dose Aspirin and Progression of Age-Related Hearing Loss
Authors: David P. Q. Clark, Zhen Zhou, Sultana M. Hussain, Cammie Tran, Carlene Britt, Elsdon Storey, Judy A. Lowthian, Raj C. Shah, Harvey Dillon, Rory Wolfe, Robyn L. Woods, Gary Rance, John J. McNeil
Journal: JAMA Network Open (2024)

Age-related hearing loss is common in an aging population, affecting communication and contributing to a worsened quality of life. It occurs as a result of cochlear degeneration and may be further exacerbated by inflammation and microvascular changes, as observed in animal models.