tbuckley/cabot-search huggingface dataset:
Annular Eroded Plaque With Honey-Colored Crusting On Scrotum
Authors: Toan S. Bui, Jonathan J. Lee
Journal: JAMA Dermatology (2024)

A man in his 40s presented with a dry erythematous, annular plaque with focal erosion and a collarette of desquamative, honey-colored crusting on the scrotum. What is your diagnosis?
Ending Unequal Treatment for People With Behavioral Health Conditions
Authors: Ruth S. Shim, Margarita Alegría
Journal: JAMA Psychiatry (2024)

This Viewpoint discusses the “Ending Unequal Treatment: Strategies to Achieve Equitable Health Care and Optimal Health for All” report, which emphasizes that health inequities lead to poor mental health for all people, not only minoritized populations, and a diverse workforce is needed to achieve mental health equity.
Maui Wildfire and 988 Suicide and Crisis Lifeline Call Volume and Capacity
Authors: Alexandra C. Rivera-González, Jonathan Purtle, Joseph Keawe‘aimoku Kaholokula, Jim P. Stimpson, Alexander N. Ortega
Journal: JAMA Network Open (2024)

This cross-sectional study examines 988 Suicide Crisis Lifeline Call data after the Maui wildfire in August 2023.
Skin Inflammation, Systemic Inflammation, and Cardiovascular Disease in Psoriasis
Authors: Axel Svedbom, Lotus Mallbris, Álvaro González-Cantero, Martin Playford, Colin Wu, Nehal N. Mehta, Mona Ståhle
Journal: JAMA Dermatology (2024)

Importance Psoriasis is associated with increased cardiovascular risk, but the underlying pathogenic mechanisms remain unclear. Elucidating these mechanisms can help develop treatment strategies and enhance understanding of the link between peripheral inflammation, such as psoriatic skin lesions, and cardiovascular disease (CVD). Objective To explore whether systemic inflammation is a mediator of the association between psoriasis skin disease severity and CVD. Design, Setting, and Participants This cohort study used data from cross-sectional study (Psoriasis Atherosclerosis and Cardiometabolic Disease Initiative [PACI]), which enrolled patients from January 2013 to February 2022, and an inception cohort study (Stockholm Psoriasis Cohort [SPC]), which enrolled patients from January 2000 to December 2005. The PACI enrolled consecutive patients referred by dermatologists in Maryland, and the SPC enrolled consecutive patients referred from a wide range of practices in Sweden. Patients with prevalent psoriasis from the PACI and patients with incident psoriasis from the SPC were included. Data were analyzed from October 2023 to January 2024. Exposures Psoriasis skin disease severity was measured using the Psoriasis Area and Severity Index (PASI), and systemic inflammation was measured using glycan biomarker of N -acetyl side chains of acute-phase proteins (GlycA). Mediation analysis was performed by evaluating the associations between exposure, mediator, and outcome in patients with first-tertile and third-tertile PASI scores when GlycA level was set at the level observed in patients with first-tertile PASI. Main Outcomes and Measures Noncalcified coronary burden (NCB) measured using coronary computed tomography angiography in the PACI and hospitalization for CVD or cardiovascular death in the SPC. Results Of 260 eligible patients from the PACI, 162 (62.3%) were male, and the median (IQR) age was 51 (41-60) years; of 509 eligible patients from the SPC, 237 (46.6%) were male, and the median (IQR) age was 43 (30-57) years. In both studies, PASI was associated with GlycA level and CVD, and GlycA level was associated with CVD. The direct and indirect (through GlycA) effects of PASI on NCB were estimated at 0.94 (95% CI, 0.26-1.74) and 0.19 (95% CI, 0.02-0.47), respectively. The odds ratios for the direct and indirect effects of PASI on cardiovascular events were estimated at 1.23 (95% CI, 0.70-1.92) and 1.16 (95% CI, 1.04-1.42), respectively. Conclusions and Relevance In this study, skin disease severity measured using PASI was associated with systemic inflammation, and both PASI and systemic inflammation, measured using GlycA levels, were associated with CVD. The association between PASI and CVD may be mediated by systemic inflammation.
Active Surveillance or Watchful Waiting for Intermediate-Risk Prostate Cancer, 2010-2020
Authors: Ismail Ajjawi, Stacy Loeb, Matthew R. Cooperberg, William J. Catalona, Cary P. Gross, Xiaomei Ma, Michael S. Leapman
Journal: JAMA (2024)

This cross-sectional study evaluates trends and factors associated with selecting active surveillance or watchful waiting among individuals with intermediate-risk prostate cancer.
A combined deep learning framework for mammalian m6A site prediction
Authors: Rui Fan, Chunmei Cui, Boming Kang, Zecheng Chang, Guoqing Wang, Qinghua Cui
Journal: Cell Genomics (2024)

N6-methyladenosine (m6A) is the most prevalent chemical modification in eukaryotic mRNAs and plays key roles in diverse cellular processes. Precise localization of m6A sites is thus critical for characterizing the functional roles of m6A in various conditions and dissecting the mechanisms governing its deposition. Here, we design a combined framework of Transformer architecture and recurrent neural network, deepSRAMP, to identify m6A sites using sequence-based and genome-derived features. As a result, deepSRAMP achieves a notably enhanced performance compared to its predecessor, SRAMP, the most-used predictor in this field. Moreover, based on multiple benchmark datasets, deepSRAMP greatly outperforms other state-of-the-art m6A predictors, including WHISTLE and DeepPromise, with an average 16.1% and 18.3% increase in AUROC and a 43.9% and 46.4% increase in AUPRC. Finally, deepSRAMP can be successfully exploited on mammalian m6A epitranscriptome mapping under diverse cellular conditions and can potentially reveal differential m6A sites among transcript isoforms of individual genes.
Acute suppression of mitochondrial ATP production prevents apoptosis and provides an essential signal for NLRP3 inflammasome activation
Authors: Benedikt S Saller, Svenja Wöhrle, Larissa Fischer, Clara Dufossez, Isabella L Ingerl, Susanne Kessler, Maria Mateo-Tortola, Oliver Gorka, Felix Lange, Yurong Cheng, Emilia Neuwirt, Adinarayana Marada, Christoph Koentges, Chiara Urban, Philipp Aktories, Peter Reuther, Sebastian Giese, Susanne Kirschnek, Carolin Mayer, Johannes Pilic, Hugo Falquez-Medina, Aline Oelgeklaus, Veerasikku Gopal Deepagan, Farzaneh Shojaee, Julia A Zimmermann, Damian Weber, Yi-Heng Tai, Anna Crois, Kevin Ciminski, Remi Peyronnet, Katharina S Brandenburg, Gang Wu, Ralf Baumeister, Thomas Heimbucher, Marta Rizzi, Dietmar Riedel, Martin Helmstädter, Joerg Buescher, Konstantin Neumann, Thomas Misgeld, Martin Kerschensteiner, Peter Walentek, Clemens Kreutz, Ulrich Maurer, Angelika S Rambold, James E Vince, Frank Edlich, Roland Malli, Georg Häcker, Katrin Kierdorf, Chris Meisinger, Anna Köttgen, Stefan Jakobs, Alexander N R Weber, Martin Schwemmle, Christina J Groß, Olaf Groß
Journal: Immunity (2024)

How mitochondria reconcile roles in functionally divergent cell death pathways of apoptosis and NLRP3 inflammasome-mediated pyroptosis remains elusive, as is their precise role in NLRP3 activation and the evolutionarily conserved physiological function of NLRP3. Here, we have shown that when cells were challenged simultaneously, apoptosis was inhibited and NLRP3 activation prevailed. Apoptosis inhibition by structurally diverse NLRP3 activators, including nigericin, imiquimod, extracellular ATP, particles, and viruses, was not a consequence of inflammasome activation but rather of their effects on mitochondria. NLRP3 activators turned out as oxidative phosphorylation (OXPHOS) inhibitors, which we found to disrupt mitochondrial cristae architecture, leading to trapping of cytochrome c. Although this effect was alone not sufficient for NLRP3 activation, OXPHOS inhibitors became triggers of NLRP3 when combined with resiquimod or Yoda-1, suggesting that NLRP3 activation requires two simultaneous cellular signals, one of mitochondrial origin. Therefore, OXPHOS and apoptosis inhibition by NLRP3 activators provide stringency in cell death decisions.
Opportunities to Improve Health Equity for Employees in Low-Wage Industries in the United States
Authors: Peggy A. Hannon, Jeffrey R. Harris, David R. Doody
Journal: Annual Review of Public Health (2024)

This review describes employees working in low-wage industries in the United States, their health risks, and their access to health promotion and other health-related resources through their employers. We use publicly available datasets to illustrate how low-wage jobs affect employees’ social determinants of health, health risk behaviors, and chronic conditions. We also discuss how the COVID-19 pandemic has shifted these employees’ and employers’ health-related priorities and work settings. We describe employees’ access to health supports through federal programs and their employers and the potential ways in which low-wage employers could support employee health and well-being. We close with a brief research and practice agenda to improve health equity for employees in low-wage industries. The goal of this review is to help practitioners and researchers in workplace health promotion, occupational health, and public health reach employees and employers in low-wage industries with interventions that address employees’ health risks and employees’ and employers’ health priorities.
Lipid Nanoparticle Delivery of TALEN mRNA Targeting LPA Causes Gene Disruption and Plasma Lipoprotein(a) Reduction in Transgenic Mice.
Authors: Daniel A Garcia, Abigail F Pierre, Linda Quirino, Grishma Acharya, Aishwarya Vasudevan, Yihua Pei, Emily Chung, Jason Y H Chang, Samuel Lee, Michael Endow, Kristen Kuakini, Michael Bresnahan, Maria Chumpitaz, Kumar Rajappan, Suezanne Parker, Padmanabh Chivukula, Stefen A Boehme, Ramon Diaz-Trelles
Journal: Molecular Therapy (2024)

Lipoprotein(a), or Lp(a), is encoded by the LPA gene and is a causal genetic risk factor for cardiovascular disease. Individuals with high Lp(a) are at risk for cardiovascular morbidity and are refractory to standard lipid-lowering agents. Lp(a)-lowering therapies currently in clinical development require repetitive dosing, while a gene editing approach presents an opportunity for a single-dose treatment. In this study, mRNAs encoding Transcription Activator-Like Effector Nucleases (TALENs) were designed to target human LPA for gene disruption and permanent Lp(a) reduction. TALEN mRNAs were screened in vitro and found to cause on-target gene editing and target protein reduction with minimal off-target editing. TALEN mRNAs were then encapsulated with LUNAR®, a proprietary lipid nanoparticle (LNP), and administered to transgenic mice that expressed a human LPA transgene. A single dose of TALEN mRNA-LNPs reduced plasma Lp(a) levels in mice by over 80%, which was sustained for at least 5 weeks. Moreover, both standard and long-read next generation sequencing confirmed the presence of gene-inactivating deletions at LPA transgene loci. Overall, this study serves as a proof-of-concept for using TALEN-mediated gene editing to disrupt LPA in vivo, paving the way for the development of a feasible gene editing therapy for patients with high Lp(a).
A trinity STING-activating nanoparticle harnesses cancer cell STING machinery for enhanced immunotherapy
Authors: Yanming Xia, Bo Shi, Keke Wang, Lixin Hu, Qiran Wang, Shuxian Xu, Xiaohu Wang, Pengcheng Xu, Yuanbin She, Haitang Xie, Suxin Li, Lifang Yin
Journal: Journal of Controlled Release (2024)
Backpack-carrying macrophage immunotherapy for periodontitis
Authors: Mayuka Nakajima, Neha Kapate, John R Clegg, Mayumi Ikeda-Imafuku, Kyung Soo Park, Ninad Kumbhojkar, Vinny Chandran Suja, Supriya Prakash, Lily Li-Wen Wang, Koichi Tabeta, Samir Mitragotri
Journal: Journal of Controlled Release (2024)
G-quadruplex stabilizer CX-5461 effectively combines with radiotherapy to target ATRX-deficient malignant glioma
Authors: Sharvari Dharmaiah, Prit Benny Malgulwar, William E Johnson, Brandon A Chen, Vladislav Sharin, Benjamin T Whitfield, Christian Alvarez, Vasudev Tadimeti, Ahsan S Farooqi, Jason T Huse
Journal: Neuro-Oncology (2024)

Abstract Background Inactivation of α-thalassemia/mental retardation X-linked (ATRX) represents a defining molecular feature in large subsets of malignant glioma. ATRX deficiency gives rise to abnormal G-quadruplex (G4) DNA secondary structures, enhancing replication stress and genomic instability. Building on earlier work, we evaluated the extent to which pharmacological G4 stabilization selectively enhances DNA damage and cell death in ATRX-deficient preclinical glioma models. Methods Using the G4 stabilizer CX-5461, we treated patient-derived glioma stem cells (GSCs) in vitro and GSC flank and intracranial murine xenografts in vivo to evaluate efficacy as both a single agent and in combination with ionizing radiation (IR), the latter a central element of current treatment standards. Results CX-5461 promoted dose-sensitive lethality in ATRX-deficient GSCs relative to ATRX-intact controls. Mechanistic studies revealed that CX-5461 disrupted histone variant H3.3 deposition, enhanced replication stress and DNA damage, activated p53-independent apoptosis, and induced G2/M arrest to a greater extent in ATRX-deficient GSCs than in ATRX-intact counterparts. These data were corroborated in vivo, where CX-5461/IR treatment profoundly delayed tumor growth and prolonged survival in mice bearing ATRX-deficient flank xenografts. Histopathological analyses revealed decreased proliferation, increased apoptosis, and significant G4 induction, replication stress, and DNA damage in CX-5461-treated tumors, both alone and in combination with IR. Finally, despite suboptimal blood-brain-barrier penetration, systemic CX-5461 treatment induced tangible pharmacodynamic effects in ATRX-deficient intracranial GSC models. Conclusions In totality, our work substantively demonstrates efficacy and defines mechanisms of action for G4 stabilization as a novel therapeutic strategy targeting ATRX-deficient malignant glioma, laying the groundwork for clinical translation.
The boom in fruit flavour cigarettes is driving youth smoking in Latin America—despite the tobacco industry’s promises
Authors: María Pérez, Jason McLure, Francisca Skoknic
Journal: BMJ (2024)

Fruit flavour "click" or "capsule" cigarettes are an expanding market for big tobacco companies despite their promises to cut smoking and protect young people. <b><i>The Examination</i></b>, <b>Salud Con Lupa</b>, and <b>LaBot</b> investigate
Injectable and Adhesive MgO2-Potentiated Hydrogel with Sequential Tumor Synergistic Therapy and Osteogenesis for Challenging Postsurgical Osteosarcoma Treatment
Authors: Wenjing Zhang, Long Li, Zishuo Wang, Yangyi Nie, Yipei Yang, Cairong Li, Yuyang Zhang, Yuxi Jiang, Yuhui Kou, Wei Zhang, Yuxiao Lai
Journal: Biomaterials (2024)
Clonal hematopoiesis in large granular lymphocytic leukemia
Authors: Naomi Kawashima, Carmelo Gurnari, Carlos Bravo-Perez, Yasuo Kubota, Simona Pagliuca, Luca Guarnera, Nakisha D. Williams, Arda Durmaz, Arooj Ahmed, Danai Dima, Fauzia Ullah, Hetty E. Carraway, Abhay Singh, Valeria Visconte, Jaroslaw P. Maciejewski
Journal: Leukemia (2024)
Circulating Tumor DNA: A Pan-Cancer Biomarker in Solid Tumors with Prognostic and Predictive Value
Authors: Nadia Hitchen, Adel Shahnam, Jeanne Tie
Journal: Annual Review of Medicine (2024)

Circulating tumor DNA (ctDNA), often referred to as a liquid biopsy, represents a promising biomarker in the management of both localized and advanced solid tumors. It has garnered significant attention due to its potential to inform prognosis and guide therapeutic decisions. The clinical utility of ctDNA spans early cancer detection, minimal residual disease identification, recurrence surveillance, treatment monitoring, and precision oncology treatment decision-making in the advanced setting. Unlike conventional radiological assessments, the short half-life of ctDNA allows for more timely insights into disease dynamics. Several technological approaches are available to measure ctDNA, including next-generation sequencing and droplet digital polymerase chain reaction, although their clinical accuracy depends on multiple biological and technical factors. This review evaluates current evidence surrounding ctDNA's utility in early and advanced solid tumors.
FDG PET/CT Scan Still Can Help in Evaluation of Prostate Cancer
Authors: Abtin Doroudinia, Taylor Wolfe
Journal: Clinical Nuclear Medicine (2024)

Although 18F-FDG PET/CT scan is not the preferred modality to evaluate prostate cancer patients due to generally low uptake of FDG in prostate cancer cells, it can still be helpful in some selected cases with diagnostic dilemma. Here we are presenting an unusual prostate cancer case, status post radical prostatectomy, with heterogenous uptake in osseous lesions on 68Ga-PSMA PET/CT scan and low PSA values. He was referred for further evaluation with 18F-FDG PET/CT scan, revealing widely metastatic lesions in bone and liver, in addition to mildly avid recurrence in prostatectomy surgical bed and also metastasis in the spleen.
Immunometabolic Targets in CD8+ T Cells within the Tumor Microenvironment of Hepatocellular Carcinoma
Authors: Yanze Lin, Rexiati Ruze, Ruiqing Zhang, Talaiti Tuergan, Maolin Wang, Alimu Tulahong, Dalong Zhu, ZhongDian Yuan, Tiemin Jiang, Tuerganaili Aji, Yingmei Shao
Journal: Liver Cancer (2024)

Background: CD8+ T cells are critical for the oncogenesis and progression of the hepatocellular carcinoma (HCC) tumor microenvironment, receiving antigen signals from antigen-presenting cells and directly contributing to antitumor responses. Summary: CD8+ T cells mediate immunogenic cell death, facilitate immune signal transmission, and play a significant role in various treatments, including surgery, transarterial chemoembolization, and immunotherapy. Extensive research on the role of CD8+ T cells within the HCC microenvironment has shown considerable progress. Immunometabolic targets on CD8+ T cells have demonstrated potential in combination with immunotherapies for HCC; however, they have not yet reached the clinical trial stage. Key messages: This review provides a comprehensive overview of recent research on immune and immunometabolic targets of CD8+ T cells within the HCC microenvironment. By highlighting advances and potential mechanisms, this review aims to support the development of effective clinical strategies in this field.
Ferroptosis of select skin epithelial cells initiates and maintains chronic systemic immune-mediated psoriatic disease
Authors: Kavita Vats, Hua Tian, Kunal Singh, Yulia Y. Tyurina, Louis J. Sparvero, Vladimir A. Tyurin, Oleg Kruglov, Alexander Chang, Jiefei Wang, Felicia Green, Svetlana N. Samovich, Jiying Zhang, Ansuman Chattopadhyay, Natalie Murray, Vrusha K. Shah, Alicia R. Mathers, Uma R. Chandran, Joseph M. Pilewski, John A. Kellum, Sally E. Wenzel, Hülya Bayir, Valerian E. Kagan, Yuri L. Bunimovich
Journal: Journal of Clinical Investigation (2024)

Dysregulations of epithelial-immune interactions frequently culminate in chronic inflammatory diseases of the skin, lungs, kidneys, and gastrointestinal tract. Yet, the intraepithelial processes which initiate and perpetuate inflammation in these organs are poorly understood. Here, by utilizing redox lipidomics we identified ferroptosis-associated peroxidation of polyunsaturated phosphatidylethanolamines in the epithelia of patients with asthma, cystic fibrosis, psoriasis and renal failure. Focusing on psoriasis as a disease model, we used high-resolution mass spectrometry imaging and identified keratin 14 (K14)-expressing keratinocytes executing a ferroptotic death program in human psoriatic skin. Psoriatic phenotype with characteristic Th1/Th17 skin and extracutaneous immune responses was initiated and maintained in a murine model designed to actuate ferroptosis in a fraction of K14+ glutathione peroxidase 4 (Gpx4)-deficient epidermal keratinocytes. Importantly, an anti-ferroptotic agent, Liproxstatin-1, was as effective as clinically relevant biologic IL-12/IL-23/TNFα-targeting therapies or the depletion of T cells in completely abrogating molecular, biochemical and morphologic features of psoriasis. As ferroptosis in select epidermal keratinocytes triggers and sustains a pathologic psoriatic multi-organ inflammatory circuit, we suggest that strategies targeting ferroptosis, or its causes, may be effective in preventing or ameliorating a variety of chronic inflammatory diseases.
Temporal genomic analysis of homogeneous tumor models reveals key regulators of immune evasion in melanoma
Authors: Sapir Cohen Shvefel, Joy A. Pai, Yingying Cao, Lipika R. Pal, Osnat Bartok, Ronen Levy, Marie J. Zemanek, Chen Weller, Ella Herzog, Winnie Yao, Kamir J. Hiam-Galvez, Kuoyuan Cheng, Yajie Yin, Peter P. Du, Colin J. Raposo, Nofar Gumpert, Michele Welti, Julia M. Martínez Gómez, Federica Sella, Elizabeta Yakubovich, Irit Orr, Shifra Ben-Dor, Roni Oren, Liat Fellus-Alyagor, Ofra Golani, Ori Jacob. Brenner, Tomer M. Salame, Mirie Zerbib, Inna Goliand, Dean Ranmar, Ilya Savchenko, Nadav Ketrarou, Alejandro A. Schaffer, Rony Dahan, Mitchell P. Levesque, Eytan Ruppin, Ansuman T. Satpathy, Yardena Samuels
Journal: Cancer Discovery (2024)

In this study, we find that Mif expression is associated with tumor growth and aggressiveness, specifically in tumors with low heterogeneity. These findings could facilitate the development of new strategies to treat patients with homogeneous, high MIF-expressing tumors that are unresponsive to immune checkpoint therapy.
Disseminated Extranodal Natural Killer/T-Cell Lymphoma Mimicking a Paraneoplastic Polymyositis
Authors: Mudassir Mumtaz, Sampanna Rayamajhi
Journal: Clinical Nuclear Medicine (2024)

Abstract Extranodal natural killer/T-cell lymphoma (ENKTCL) is an aggressive EBV-associated non-Hodgkin lymphoma, most commonly arising from within the mucosa of the upper aerodigestive tract, typically with nasal presentation. Here, we present an interesting case of a 36-year-old man with ENKTCL with an atypical pattern of disease progression despite 3 cycles of SMILE chemotherapy. Restaging 18 F-FDG PET/CT demonstrated widespread uptake within the skeletal musculature in a distribution concerning for a paraneoplastic polymyositis. However, muscle biopsy confirmed ENKTCL dissemination.
Mutations in unfolded protein response regulator ATF6 cause hearing and vision loss syndrome
Authors: Eun-Jin Lee, Kyle Kim, Monica Sophia Diaz-Aguilar, Hyejung Min, Eduardo Chavez, Korina J. Steinbergs, Lance A. Safarta, Guirong Zhang, Allen F. Ryan, Jonathan H. Lin
Journal: Journal of Clinical Investigation (2024)

Activating transcription factor 6 (ATF6) is a key regulator of the unfolded protein response (UPR) and is important for ER function and protein homeostasis in metazoan cells. Patients carrying loss-of-function ATF6 disease alleles develop the cone dysfunction disorder achromatopsia. The effect of loss of ATF6 function on other cell types, organs, and diseases in people remains unclear. Here, we report that progressive sensorineural hearing loss was a notable complaint in some patients carrying ATF6 disease alleles and that Atf6-/- mice also showed progressive auditory deficits affecting both sexes. In mice with hearing deficits, we found disorganized stereocilia on hair cells and focal loss of outer hair cells. Transcriptomics analysis of Atf6-/- cochleae revealed a marked induction of the UPR, especially through the protein kinase RNA-like endoplasmic reticulum kinase (PERK) arm. These findings identify ATF6 as an essential regulator of cochlear health and function. Furthermore, they support the idea that ATF6 inactivation in people causes progressive sensorineural hearing loss as part of a blindness-deafness genetic syndrome targeting hair cells and cone photoreceptors. Last, our genetic findings indicate that ER stress is an important pathomechanism underlying cochlear damage and hearing loss, with clinical implications for patient lifestyle modifications that minimize environmental and physiological sources of ER stress to the ear.