tbuckley/cabot-search huggingface dataset:
PhALLCON Soars to New Heights—Faster, Stronger, but Better?
Authors: Rebecca P. Bystrom, Daniel J. DeAngelo, Jacqueline S. Garcia
Journal: JAMA (2024)

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Metastatic Hormone-Sensitive Prostate Cancer and Combination Treatment Outcomes
Authors: Maha Hussain, Karim Fizazi, Neal D. Shore, Isabel Heidegger, Matthew R. Smith, Bertrand Tombal, Fred Saad
Journal: JAMA Oncology (2024)

Metastatic hormone-sensitive prostate cancer is currently an incurable disease. Despite a high response rate to androgen-deprivation therapy, most cases progress to castration-resistant disease, the terminal phase. This review provides a summary of the most recent evidence for current and emerging management strategies, including treatment intensification with combinations of therapies. It also provides recommendations on applying the evidence in clinical practice to encourage appropriate treatment to improve survival outcomes among patients with metastatic hormone-sensitive prostate cancer.
Inhibition of protein translational machinery in triple-negative breast cancer as a promising therapeutic strategy
Authors: Arpit Dheeraj, Fernando Jose Garcia Marques, Dhanir Tailor, Abel Bermudez, Angel Resendez, Mallesh Pandrala, Benedikt Grau, Praveen Kumar, Carrsyn B. Haley, Alexander Honkala, Praveen Kujur, Stefanie S. Jeffrey, Sharon Pitteri, Sanjay V. Malhotra
Journal: Cell Reports Medicine (2024)

Y-box binding protein-1 (YB-1) is a proto-oncogenic protein associated with protein translation regulation. It plays a crucial role in the development and progression of triple-negative breast cancer (TNBC). In this study, we describe a promising approach to inhibit YB-1 using SU056, a small-molecule inhibitor. SU056 physically interacts with YB-1 and reduces its expression, which helps to restrain the progression of TNBC. Proteome profiling analysis indicates that the inhibition of YB-1 by SU056 can alter the proteins that regulate protein translation, an essential process for cancer cell growth. Preclinical studies on human cells, mice, and patient-derived xenograft tumor models show the effectiveness of SU056. Moreover, toxicological studies have shown that SU056 treatment and dosing are well tolerated without any adverse effects. Overall, our study provides a strong foundation for the further development of SU056 as a potential treatment option for patients with TNBC by targeting YB-1.
Guidance on terminology, application, and reporting of citation searching: the TARCiS statement
Authors: Julian Hirt, Thomas Nordhausen, Thomas Fuerst, Hannah Ewald, Christian Appenzeller-Herzog
Journal: BMJ (2024)

Evidence syntheses adhering to systematic literature searching techniques are a cornerstone of evidence based healthcare. Beyond term based searching in electronic databases, citation searching is a prevalent search technique to identify relevant sources of evidence. However, for decades, citation searching methodology and terminology has not been standardised. An evidence guided, four round Delphi consensus study was conducted with 27 international methodological experts in order to develop the Terminology, Application, and Reporting of Citation Searching (TARCiS) statement. TARCiS comprises 10 specific recommendations, each with a rationale and explanation on when and how to conduct and report citation searching in the context of systematic literature searches. The statement also presents four research priorities, and it is hoped that systematic review teams are encouraged to incorporate TARCiS into standardised workflows.
Incident Diabetes in Women With Patterns of Gestational Diabetes Occurrences Across 2 Pregnancies
Authors: Joseph Mussa, Elham Rahme, Mourad Dahhou, Meranda Nakhla, Kaberi Dasgupta
Journal: JAMA Network Open (2024)

Importance Gestational diabetes is a type 2 diabetes risk indicator, and recurrence further augments risk. In women with a single occurrence across 2 pregnancies, it is unclear whether first- vs second-pregnancy gestational diabetes differ in terms of risk. Objective To compare the hazards of incident diabetes among those with gestational diabetes in the first, in the second, and in both pregnancies with women without gestational diabetes in either. Design, Setting, and Participants This was a retrospective cohort study with cohort inception from April 1, 1990, to December 31, 2012. Follow-up was April 1, 1990, to April 1, 2019. Participants were mothers with 2 singleton deliveries between April 1, 1990, and December 31, 2012, without diabetes before or between pregnancies, who were listed in public health care insurance administrative databases and birth, stillbirth, and death registries in Quebec, Canada. Data were analyzed from July to December 2023. Exposure Gestational diabetes occurrence(s) across 2 pregnancies. Main outcomes and measures Incident diabetes from the second delivery until a third pregnancy, death, or the end of the follow-up period, whichever occurred first. Results The 431 980 women with 2 singleton deliveries studied had a mean (SD) age of 30.1 (4.5) years at second delivery, with a mean (SD) of 2.8 (1.5) years elapsed between deliveries; 373 415 (86.4%) were of European background, and 78 770 (18.2%) were at the highest quintile of material deprivation. Overall, 10 920 women (2.5%) had gestational diabetes in their first pregnancy, 16 145 (3.7%) in their second, and 8255 (1.9%) in both (12 205 incident diabetes events; median [IQR] follow-up 11.5 [5.3-19.4] years). First pregnancy–only gestational diabetes increased hazards 4.35-fold (95% CI, 4.06-4.67), second pregnancy–only increased hazards 7.68-fold (95% CI, 7.31-8.07), and gestational diabetes in both pregnancies increased hazards 15.8-fold (95% CI, 15.0-16.6). Compared with first pregnancy–only gestational diabetes, second pregnancy–only gestational diabetes increased hazards by 76% (95% CI, 1.63-1.91), while gestational diabetes in both pregnancies increased it 3.63-fold (95% CI, 3.36-3.93). Conclusions and relevance In this retrospective cohort study of nearly half a million women with 2 singleton pregnancies, both the number and ordinal pregnancy of any gestational diabetes occurrence increased diabetes risk. These considerations offer greater nuance than an ever or never gestational diabetes dichotomy.
Intratumoral delivery of the chitin-derived C100 adjuvant promotes robust STING, IFNAR, and CD8+ T cell-dependent anti-tumor immunity
Authors: Joanna L. Turley, Ross W. Ward, Jorge Huete-Carrasco, Natalia Muñoz-Wolf, Kate Roche, Lei Jin, Andrew Bowie, Mats Andersson, Ed C. Lavelle
Journal: Cell Reports Medicine (2024)

Stimulator of IFN genes (STING) is a promising target for adjuvants utilized in in situ cancer vaccination approaches. However, key barriers remain for clinical translation, including low cellular uptake and accessibility, STING variability necessitating personalized STING agonists, and interferon (IFN)-independent signals that can promote tumor growth. Here, we identify C100, a highly deacetylated chitin-derived polymer (HDCP), as an attractive alternative to conventional STING agonists. C100 promotes potent anti-tumor immune responses, outperforming less deacetylated HDCPs, with therapeutic efficacy dependent on STING and IFN alpha/beta receptor (IFNAR) signaling and CD8+ T cell mediators. Additionally, C100 injection synergizes with systemic checkpoint blockade targeting PD-1. Mechanistically, C100 triggers mitochondrial stress and DNA damage to exclusively activate the IFN arm of the cGAS-STING signaling pathway and elicit sustained IFNAR signaling. Altogether, these results reveal an effective STING- and IFNAR-dependent adjuvant for in situ cancer vaccines with a defined mechanism and distinct properties that overcome common limitations of existing STING therapeutics.
Epidemiology, screening, and co-management of type 2 diabetes mellitus and metabolic dysfunction–associated steatotic liver disease
Authors: Xiaolong Qi, Jie Li, Cyrielle Caussy, Gao-Jun Teng, Rohit Loomba
Journal: Hepatology (2024)

Metabolic dysfunction–associated steatotic liver disease (MASLD), previously known as NAFLD, is increasingly recognized as a prevalent global burden. Type 2 diabetes mellitus (T2DM), another important metabolic disease, is considered a major contributor to the development of MASLD. MASLD and T2DM have a strong association with each other due to shared pathogenic mechanisms. The co-existence of the 2 diseases increases the risk of liver-related adverse outcomes and imposes a heavier burden on extrahepatic outcomes, representing a substantial public health issue. Effective assessment and management of T2DM combined with MASLD necessitate a multidisciplinary approach. The emergence of numerous RCTs has shed light on the treatment of T2DM combined with MASLD. This review uncovers the epidemiology of the intertwined T2DM and MASLD, offers insights into the evaluation of hepatic fibrosis in patients with T2DM, glucose monitoring in the MASLD population, and provides comprehensive co-management strategies for addressing both diseases.
Telehealth Experience Among Patients With Limited English Proficiency
Authors: Jorge A. Rodriguez, Elaine C. Khoong, Stuart R. Lipsitz, Courtney R. Lyles, David W. Bates, Lipika Samal
Journal: JAMA Network Open (2024)

This cross-sectional study assesses the implication of patients’ English language skills for telehealth use and visit experience.
Dose-Adjusted EPOCH Plus Inotuzumab Ozogamicin in Adults With Relapsed or Refractory B-Cell ALL
Authors: Noam E. Kopmar, Kim Quach, Ted A. Gooley, Christen H. Martino, Sindhu Cherian, Mary-Elizabeth M. Percival, Anna B. Halpern, Cristina M. Ghiuzeli, Vivian G. Oehler, Janis L. Abkowitz, Roland B. Walter, Ryan D. Cassaday
Journal: JAMA Oncology (2024)

Options for adults with relapsed or refractory B-cell acute lymphoblastic leukemia or lymphoma (B-ALL) are limited, and new approaches are needed. Inotuzumab ozogamicin (InO) has been combined with low-intensity chemotherapy, with modest improvements over historical controls, and dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) treatment is safe and active for newly diagnosed ALL.
Risk Factors for Hydroxychloroquine Retinopathy and Its Subtypes
Authors: April M. Jorge, Ronald B. Melles, Michael F. Marmor, Baijun Zhou, Yuqing Zhang, Hyon K. Choi
Journal: JAMA Network Open (2024)

Importance The major toxic effect of hydroxychloroquine is retinopathy. Thus, current guidelines recommend limiting the dose and screening annually for retinopathy among all long-term users, but individual patient factors may be associated with retinopathy risk. Objective To identify risk factors beyond hydroxychloroquine dose and duration of use for hydroxychloroquine retinopathy. Design, Setting, and Participants This cohort study of 4677 patients in the Kaiser Permanente Northern California integrated health network who initiated hydroxychloroquine, continued treatment, and underwent retinopathy screening after 5 years of use was conducted from July 1, 1997, to December 31, 2020, with up to 15 years of follow-up. Statistical analysis was performed in August 2023. Exposure Candidate risk factors included age at hydroxychloroquine initiation, sex, race and ethnicity, indications, chronic kidney disease (CKD), liver disease, diabetes, tamoxifen use, and medications that interact with hydroxychloroquine metabolism. Hydroxychloroquine dose was assessed from pharmacy dispensing records. Main Outcome and Measures Incident hydroxychloroquine retinopathy was adjudicated from masked review of guideline-recommended screening studies and classified as parafoveal or pericentral pattern. Multivariable Cox proportional hazards regression was used to assess potential risk factors for hydroxychloroquine retinopathy within 15 years of initiation. Results Of 4677 long-term hydroxychloroquine users (mean [SD] age at initiation, 52.4 [14.1] years; 3877 women [82.9%]), 125 patients developed hydroxychloroquine retinopathy within 15 years (102 parafoveal, 23 pericentral). Older age at time of hydroxychloroquine initiation was associated with retinopathy risk, with adjusted hazard ratios (HRs) of 2.48 (95% CI, 1.28-4.78) for those aged 45 to 54 years, 3.82 (95% CI, 2.05-7.14) for those aged 55 to 64 years, and 5.68 (95% CI, 2.99-10.79) for those aged 65 years or older compared with those younger than 45 years. The risk of retinopathy was higher among females than males (HR, 3.83 [95% CI, 1.86-7.89]), among patients with CKD stage 3 or greater (HR, 1.95 [95% CI, 1.25-3.04]), and among individuals with tamoxifen use (HR, 3.43 [95% CI, 1.08-10.89]). The likelihood of pericentral retinopathy was higher among Asian patients (HR, 15.02 [95% CI, 4.82-46.87]) and Black patients (HR, 5.51 [95% CI, 1.22-24.97]) compared with non-Hispanic White patients. Conclusions and Relevance This study suggests that increasing age, female sex, CKD stage 3 or greater, and tamoxifen use were associated with a higher risk of hydroxychloroquine retinopathy, whereas being younger than 45 years at hydroxychloroquine initiation and male sex were associated with a lower risk. Race and ethnicity were also associated with the pattern of retinopathy. These factors should be incorporated into hydroxychloroquine dosing decisions.
Lhx2 promotes axon regeneration of adult retinal ganglion cells and rescues neurodegeneration in mouse models of glaucoma
Authors: Chang-Ping Li, Shen Wu, Yong-Quan Sun, Xue-Qi Peng, Maolei Gong, Hong-Zhen Du, Jingxue Zhang, Zhao-Qian Teng, Ningli Wang, Chang-Mei Liu
Journal: Cell Reports Medicine (2024)

The axons of retinal ganglion cells (RGCs) form the optic nerve, transmitting visual information from the eye to the brain. Damage or loss of RGCs and their axons is the leading cause of visual functional defects in traumatic injury and degenerative diseases such as glaucoma. However, there are no effective clinical treatments for nerve damage in these neurodegenerative diseases. Here, we report that LIM homeodomain transcription factor Lhx2 promotes RGC survival and axon regeneration in multiple animal models mimicking glaucoma disease. Furthermore, following N-methyl-D-aspartate (NMDA)-induced excitotoxicity damage of RGCs, Lhx2 mitigates the loss of visual signal transduction. Mechanistic analysis revealed that overexpression of Lhx2 supports axon regeneration by systematically regulating the transcription of regeneration-related genes and inhibiting transcription of Semaphorin 3C (Sema3C). Collectively, our studies identify a critical role of Lhx2 in promoting RGC survival and axon regeneration, providing a promising neural repair strategy for glaucomatous neurodegeneration.
Declination of Treatment, Racial and Ethnic Disparity, and Overall Survival in US Patients With Breast Cancer
Authors: Jincong Q. Freeman, James L. Li, Susan G. Fisher, Katharine A. Yao, Sean P. David, Dezheng Huo
Journal: JAMA Network Open (2024)

Declining treatment negatively affects health outcomes among patients with cancer. Limited research has investigated national trends of and factors associated with treatment declination or its association with overall survival (OS) among patients with breast cancer.
Precision Colorectal Cancer Fecal Immunological Test Screening With Fecal-Hemoglobin-Concentration–Guided Interscreening Intervals
Authors: Amy Ming-Fang Yen, Chen-Yang Hsu, Ting-Yu Lin, Chiu-Wen Su, Han-Mo Chiu, Tony Hsiu-Hsi Chen, Sam Li-Sheng Chen
Journal: JAMA Oncology (2024)

Given a gradient relationship between fecal hemoglobin (f-Hb) concentration and colorectal neoplasia demonstrated previously, using f-Hb-guided interscreening interval has increasingly gained attention in population-based fecal immunological test (FIT), but it is very rare to address how to implement such a precision strategy and whether it can economize the use of FIT and colonoscopy.
A human omentum-specific mesothelial-like stromal population inhibits adipogenesis through IGFBP2 secretion
Authors: Radiana Ferrero, Pernille Yde Rainer, Marie Rumpler, Julie Russeil, Magda Zachara, Joern Pezoldt, Guido van Mierlo, Vincent Gardeux, Wouter Saelens, Daniel Alpern, Lucie Favre, Nathalie Vionnet, Styliani Mantziari, Tobias Zingg, Nelly Pitteloud, Michel Suter, Maurice Matter, Kai-Uwe Schlaudraff, Carles Canto, Bart Deplancke
Journal: Cell Metabolism (2024)

Adipose tissue plasticity is orchestrated by molecularly and functionally diverse cells within the stromal vascular fraction (SVF). Although several mouse and human adipose SVF cellular subpopulations have by now been identified, we still lack an understanding of the cellular and functional variability of adipose stem and progenitor cell (ASPC) populations across human fat depots. To address this, we performed single-cell and bulk RNA sequencing (RNA-seq) analyses of >30 SVF/Lin- samples across four human adipose depots, revealing two ubiquitous human ASPC (hASPC) subpopulations with distinct proliferative and adipogenic properties but also depot- and BMI-dependent proportions. Furthermore, we identified an omental-specific, high IGFBP2-expressing stromal population that transitions between mesothelial and mesenchymal cell states and inhibits hASPC adipogenesis through IGFBP2 secretion. Our analyses highlight the molecular and cellular uniqueness of different adipose niches, while our discovery of an anti-adipogenic IGFBP2+ omental-specific population provides a new rationale for the biomedically relevant, limited adipogenic capacity of omental hASPCs.
A latent pool of neurons silenced by sensory-evoked inhibition can be recruited to enhance perception
Authors: Oliver M. Gauld, Adam M. Packer, Lloyd E. Russell, Henry W.P. Dalgleish, Maya Iuga, Francisco Sacadura, Arnd Roth, Beverley A. Clark, Michael Häusser
Journal: Neuron (2024)

To investigate which activity patterns in sensory cortex are relevant for perceptual decision-making, we combined two-photon calcium imaging and targeted two-photon optogenetics to interrogate barrel cortex activity during perceptual discrimination. We trained mice to discriminate bilateral whisker deflections and report decisions by licking left or right. Two-photon calcium imaging revealed sparse coding of contralateral and ipsilateral whisker input in layer 2/3, with most neurons remaining silent during the task. Activating pyramidal neurons using two-photon holographic photostimulation evoked a perceptual bias that scaled with the number of neurons photostimulated. This effect was dominated by optogenetic activation of non-coding neurons, which did not show sensory or motor-related activity during task performance. Photostimulation also revealed potent recruitment of cortical inhibition during sensory processing, which strongly and preferentially suppressed non-coding neurons. Our results suggest that a pool of non-coding neurons, selectively suppressed by network inhibition during sensory processing, can be recruited to enhance perception.
NRP1 is a receptor for mammalian orthoreovirus engaged by distinct capsid subunits
Authors: Pengcheng Shang, Rita dos Santos Natividade, Gwen M. Taylor, Ankita Ray, Olivia L. Welsh, Kay L. Fiske, Danica M. Sutherland, David Alsteens, Terence S. Dermody
Journal: Cell Host & Microbe (2024)
Standardized Ketogenic Dietary Preparation for Metabolic PET Imaging in Suspected and Known Cardiac Sarcoidosis
Authors: Erika Hutt, Ghazaleh Goldar, Wael A Jaber, Paul C Cremer
Journal:  (2024)

Abstract Aims A major limitation of cardiac positron emission tomography (PET) with F18-fluorodeoxyglucose (F18-FDG) for the evaluation of cardiac sarcoidosis (CS) is associated with physiologic myocardial glucose uptake. The optimal dietary protocol to suppress physiologic myocardial F18-FDG uptake is not well-established. We aimed to evaluate the diagnostic performance of a novel dietary preparation using a ketone-based infant formula. Methods and results Between 2018 and 2021, consecutive studies using a ketogenic dietary preparation were identified (n = 198). The rate of non-diagnostic studies due to failure to suppress myocardial glucose was 7.1% (n = 14) with a similar incidence in diabetics (n = 6, 8.1%). Among studies reported to have no inflammation (n = 137), 130 studies (66%) had mean myocardial standardized uptake value (SUV) less than or equal to mean blood pool SUV. Conclusion Patient preparation with a ketone-based infant formula resulted in low rate of inappropriate myocardial glucose suppression in patients undergoing F18-FDG cardiac PET to evaluate CS.
<i>Notes from the Field:</i> Increases in Imported Malaria Cases — Three Southern U.S. Border Jurisdictions, 2023
Authors: Cedar L. Mitchell, Audrey Kennar, Yvonne Vasquez, Kaitlyn Noris, Thomas Williamson, Andrea Mannell, Anissa Taylor, Irene Ruberto, Theresa A. Cullen, Mariana Singletary, Seema Shah, Hector Ocaranza, Alfonso Rodriguez Lainz, Kimberly E. Mace
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Malaria is a severe and potentially fatal mosquitoborne disease caused by infection with Plasmodium spp. parasites. Although malaria is no longer endemic in the United States, imported infections are reported annually; the primary risk group has been U.S. residents traveling to areas where malaria is endemic (1). In 2023, sporadic locally acquired mosquito-transmitted malaria cases were reported in several U.S. states (2,3). This report describes increases in imported malaria cases in 2023 compared with 2022 in three public health jurisdictions along the U.S. southern border.