tbuckley/cabot-search huggingface dataset:
Update on Recommendations for Surveillance for Children with Predisposition to Hematopoietic Malignancy
Authors: Luke D. Maese, Marcin W. Wlodarski, Sun Young Kim, Alison A. Bertuch, Gaelle Bougeard, Vivian Y. Chang, Lucy A. Godley, Payal P. Khincha, Roland P. Kuiper, Harry Lesmana, Rose B. McGee, Lisa J. McReynolds, Julia Meade, Sharon E. Plon, Sharon A. Savage, Sarah R. Scollon, Hamish S. Scott, Michael F. Walsh, Kim E. Nichols, Christopher C. Porter
Journal: Clinical Cancer Research (2024)

Abstract Children harboring certain germline gene variants have an increased risk of developing myelodysplastic syndrome (MDS) and other hematopoietic malignancies (HM), such as leukemias and lymphomas. Recent studies have identified an expanding number of these predisposition genes, with variants most prevalent in children with MDS but also found in children with other HM. For some hematopoietic malignancy predispositions (HMP), specifically those with a high risk of MDS, early intervention through hematopoietic stem cell transplantation can favorably impact overall survival, providing a rationale for rigorous surveillance. A multidisciplinary panel of experts at the 2023 AACR Childhood Cancer Predisposition Workshop reviewed the latest advances in the field and updated prior 2017 surveillance recommendations for children with HMP. In addition to general guidance for all children with HMP, which includes annual physical examination, education about the signs and symptoms of HM, consultation with experienced providers, and early assessment by a hematopoietic stem cell transplantation specialist, the panel provided specific recommendations for individuals with a higher risk of MDS based on the affected gene. These recommendations include periodic and comprehensive surveillance for individuals with those syndromes associated with higher risk of MDS, including serial bone marrow examinations to monitor for morphologic changes and deep sequencing for somatic changes in genes associated with HM progression. This approach enables close monitoring of disease evolution based on the individual’s genetic profile. As more HMP-related genes are discovered and the disorders’ natural histories are better defined, these personalized recommendations will serve as a foundation for future guidelines in managing these conditions.
Left ventricular volume and maximal functional capacity in heart failure with preserved ejection fraction: Size matters
Authors: Rafael de la Espriella, Patricia Palau, Maurizio Losito, Giulia Crisci, Gema Miñana, Eloy Domínguez, Vicente Bertomeu‐González, Vicent Bodí, Juan Sanchis, Antoni Bayés‐Genís, Kramer J. Wahlberg, Markus Meyer, Marco Guazzi, Julio Núñez
Journal: European Journal of Heart Failure (2024)
Establishing Consensus for Mohs Micrographic Surgical Techniques in the Treatment of Melanoma in Situ for Future Clinical Trials: A Modified Delphi Study
Authors: Kristen K. Curtis, Nathan J. Fakult, Jennifer L. Strunck, Sumaira Z. Aasi, Christine S. Ahn, Murad Alam, Anna A. Bar, Ramona Behshad, Christopher K. Bichakjian, Diana Bolotin, Susan L. Boone, Jeremy S. Bordeaux, Jerry D. Brewer, David R. Carr, John A. Carucci, Jason R. Castillo, Sean R. Christensen, Melanie A. Clark, Lindsey K. Collins, Addison M. Demer, Daniel B. Eisen, Hao Feng, Bahar F. Firoz, Roy C. Grekin, Jason M. Hirshburg, Todd E. Holmes, Conway C. Huang, Thomas A. Jennings, Shang I. Brian Jiang, Sailesh Konda, Justin J. Leitenberger, Jesse M. Lewin, Ian A. Maher, Elise Ng, Ida F. Orengo, Faramarz H. Samie, Drew K. Saylor, Victoria Rose Sharon, Teo Soleymani, Susan M. Swetter, Jesalyn A. Tate, Marta J. Van Beek, Nahid Y. Vidal, Alok Vij, Ashley Wysong, Yaohui Gloria Xu, Bryan T. Carroll, Wesley Y. Yu
Journal: Journal of the National Comprehensive Cancer Network (2024)

Mohs micrographic surgery (MMS) is a promising treatment modality for melanoma in situ (MIS). However, variations in surgical technique limit the generalizability of existing data and may impede future study of MMS in clinical trials.
Current insights on gut microbiome and chronic urticaria: progress in the pathogenesis and opportunities for novel therapeutic approaches
Authors: Rui Cai, Changhan Zhou, Ruisi Tang, Yuanling Meng, Jumei Zeng, Yuqing Li, Xiang Wen
Journal: Gut Microbes (2024)

Chronic urticaria (CU) is a prevalent skin disorder greatly impacting the patients' life quality, in which immune dysregulation mediated by gut microbiome plays a significant role. Several studies have found the gut dysbiosis exists in patients with CU. In addition, infection may also be one of the causes of CU. The primary treatment currently used for CU is the second-generation non-sedating H1-antihistamines (nsAH). However, there are some limitations in current therapies. Based on the latest evidence, this review provides an updated overview of how the gut dysbiosis influences CU development, explores potential therapeutic approaches based on the gut microbiota and summarizes the interaction between gut microbiota and current treatment.
Pneumothorax Secondary to Cavitating Pulmonary Kaposi Sarcoma in an Immunocompetent Adult
Authors: Robert Chapman, Nafisa Hussain, Guy Tinson, Ian Moonsie
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Pneumothorax Secondary to Cavitating Pulmonary Kaposi Sarcoma in an Immunocompetent Adult." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Transcranial static magnetic stimulation for amyotrophic lateral sclerosis: a bicentric, randomised, double-blind placebo-controlled phase 2 trial
Authors: Vincenzo Di Lazzaro, Federico Ranieri, Alberto Doretti, Marilisa Boscarino, Luca Maderna, Eleonora Colombo, Davide Soranna, Antonella Zambon, Nicola Ticozzi, Gabriella Musumeci, Fioravante Capone, Vincenzo Silani
Journal: The Lancet Regional Health - Europe (2024)

Enhanced glutamatergic transmission leading to motor neuron death is considered the major pathophysiological mechanism of amyotrophic lateral sclerosis (ALS). Motor cortex excitability can be suppressed by transcranial static magnetic stimulation (tSMS), thus tSMS can be evaluated as a potential treatment for ALS. The aim of present study was to investigate the efficacy and safety of tSMS in ALS.
Genomic and transcriptomic analyses of chemical hepatocarcinogenesis aggravated by oncoprotein loss
Authors: Xinyi Wang, Yingluo Liu, Shuo Zhang, Jiemeng Zhang, Xiaoxue Lin, Yan Liang, Min Zong, Kaisa L. Hanley, Jin Lee, Michael Karin, Gen-Sheng Feng
Journal: Hepatology (2024)

The chemical carcinogen diethylnitrosamine (DEN) is often used to induce HCC in mice. Curiously, several labs have reported that the removal of oncoproteins from hepatocytes exacerbated DEN-induced HCC, with mechanisms unknown. This study aimed at deciphering molecular mechanisms underlying the tumor suppressive effect of oncoproteins.
Regional gray matter changes in steatotic liver disease provide a neurobiological link to depression: A cross-sectional UK biobank cohort study
Authors: Dominic Arold, Stefan R. Bornstein, Nikolaos Perakakis, Stefan Ehrlich, Fabio Bernardoni
Journal: Metabolism (2024)

Steatotic liver disease (SLD) is characterized by excessive accumulation of lipids in the liver. It is associated with elevated risk of hepatic and cardiometabolic diseases, as well as mental disorders such as depression. Previous studies revealed global gray matter reduction in SLD. To investigate a possible shared neurobiology with depression, we examined liver fat-related regional gray matter alterations in SLD and its most significant clinical subgroup metabolic dysfunction-associated steatotic liver disease (MASLD).
Adrenomedullin as a marker of hypoxia, not hypoperfusion. Letter regarding the article ‘Biologically active adrenomedullin as a marker for residual congestion and early rehospitalization in patients hospitalized for acute heart failure: Data from <scp>STRONG</scp>‐<scp>HF</scp>’
Authors: Yorito Hattori, Masafumi Ihara
Journal: European Journal of Heart Failure (2024)
Development of a functional beige fat cell line uncovers independent subclasses of cells expressing UCP1 and the futile creatine cycle
Authors: Ariana Vargas-Castillo, Yizhi Sun, Amanda L. Smythers, Louisa Grauvogel, Phillip A. Dumesic, Margo P. Emont, Linus T. Tsai, Evan D. Rosen, Nathan W. Zammit, Sydney M. Shaffer, Martha Ordonez, Edward T. Chouchani, Steven P. Gygi, Tongtong Wang, Anand K. Sharma, Miroslav Balaz, Christian Wolfrum, Bruce M. Spiegelman
Journal: Cell Metabolism (2024)
Epigenomic identification of vernalization cis-regulatory elements in winter wheat
Authors: Yanhong Liu, Pan Liu, Lifeng Gao, Yushan Li, Xueni Ren, Jizeng Jia, Lei Wang, Xu Zheng, Yiping Tong, Hongcui Pei, Zefu Lu
Journal: Genome biology (2024)

Abstract Background Winter wheat undergoes vernalization, a process activated by prolonged exposure to low temperatures. During this phase, flowering signals are generated and transported to the apical meristems, stimulating the transition to the inflorescence meristem while inhibiting tiller bud elongation. Although some vernalization genes have been identified, the key cis -regulatory elements and precise mechanisms governing this process in wheat remain largely unknown. Results In this study, we construct extensive epigenomic and transcriptomic profiling across multiple tissues—leaf, axillary bud, and shoot apex—during the vernalization of winter wheat. Epigenetic modifications play a crucial role in eliciting tissue-specific responses and sub-genome-divergent expressions during vernalization. Notably, we observe that H3K27me3 primarily regulates vernalization-induced genes and has limited influence on vernalization-repressed genes. The integration of these datasets enables the identification of 10,600 putative vernalization-related regulatory elements including distal accessible chromatin regions (ACRs) situated 30Kb upstream of VRN3 , contributing to the construction of a comprehensive regulatory network. Furthermore, we discover that TaSPL7/15, integral components of the aging-related flowering pathway, interact with the VRN1 promoter and VRN3 distal regulatory elements. These interactions finely regulate their expressions, consequently impacting the vernalization process and flowering. Conclusions Our study offers critical insights into wheat vernalization’s epigenomic dynamics and identifies the putative regulatory elements crucial for developing wheat germplasm with varied vernalization characteristics. It also establishes a vernalization-related transcriptional network, and uncovers that TaSPL7/15 from the aging pathway participates in vernalization by directly binding to the VRN1 promoter and VRN3 distal regulatory elements.
The centromere landscapes of four karyotypically diverse Papaver species provide insights into chromosome evolution and speciation
Authors: Shenghan Gao, Yanyan Jia, Hongtao Guo, Tun Xu, Bo Wang, Stephen J. Bush, Shijie Wan, Yimeng Zhang, Xiaofei Yang, Kai Ye
Journal: Cell Genomics (2024)

Understanding the roles played by centromeres in chromosome evolution and speciation is complicated by the fact that centromeres comprise large arrays of tandemly repeated satellite DNA, which hinders high-quality assembly. Here, we used long-read sequencing to generate nearly complete genome assemblies for four karyotypically diverse Papaver species, P. setigerum (2n = 44), P. somniferum (2n = 22), P. rhoeas (2n = 14), and P. bracteatum (2n = 14), collectively representing 45 gapless centromeres. We identified four centromere satellite (cenSat) families and experimentally validated two representatives. For the two allopolyploid genomes (P. somniferum and P. setigerum), we characterized the subgenomic distribution of each satellite and identified a "homogenizing" phase of centromere evolution in the aftermath of hybridization. An interspecies comparison of the peri-centromeric regions further revealed extensive centromere-mediated chromosome rearrangements. Taking these results together, we propose a model for studying cenSat competition after hybridization and shed further light on the complex role of the centromere in speciation.
Strep Throat and the Backstory for PANS and PANDAS
Authors: J. Patrick Whelan
Journal: JAMA Network Open (2024)

Meiqian Ma, MD; Erin E. Masterson, PhD; Jaynelle Gao, MS; Hannah Karpel, MS; Avis Chan, MD; Rajdeep Pooni, MD; Jesse Sandberg, MD; Erika Rubesova, MD; Bahare Farhadian, FNP-c; Theresa Willet, MD; Yuhuan Xie, MD; Paula Tran, MD; Melissa Silverman, MD; Margo Thienemann, MD; Elizabeth Mellins, MD; Jennifer Frankovich, MD
Pharmacologic inhibition of eIF4A blocks NRF2 synthesis to prevent osteosarcoma metastasis
Authors: Michael M. Lizardo, Christopher Hughes, Yue Z. Huang, Taras Shyp, Alberto Delaidelli, Hai-Feng Zhang, Sol Snir. Shaool, Annalena F. Renner, Fares Burwag, Leanne C. Sayles, Alex G. Lee, E. Alejandro Sweet-Cordero, Poul H. Sorensen
Journal: Clinical Cancer Research (2024)

Effective therapies for metastatic osteosarcoma (OS) remain a critical unmet need. Targeting mRNA translation in metastatic OS offers a promising option, as selective translation drives the synthesis of cytoprotective proteins under harsh microenvironmental conditions to facilitate metastatic competence.
Care Patterns and Barriers to Outpatient Care for Adults With AML Following Intensive Chemotherapy at NCCN Member Institutions
Authors: Anna B. Halpern, Jessica M. Sugalski, Lindsey Bandini, Megan Othus, F. Marc Stewart, Roland B. Walter
Journal: Journal of the National Comprehensive Cancer Network (2024)

Background: Prolonged hospitalization following intensive (re)induction chemotherapy for acute myeloid leukemia (AML), while standard, is costly and resource intense, limits inpatient bed capacity, and negatively impacts quality of life. Early hospital discharge (EHD) following completion of chemotherapy has proven safe as an alternative at select institutions, but is not widely implemented. Patients and Methods: From February 2023 through May 2023, the NCCN Best Practices Committee conducted a survey evaluating AML hospitalization patterns, care models, and barriers to EHD at its 33 member institutions. Results: A total of 30 (91%) institutions completed the survey; two-thirds treat &gt;100 patients with AML annually and 45% treat more than half of these with intensive chemotherapy. In the (re)induction setting, 80% of institutions keep patients hospitalized until blood count recovery, whereas 20% aim to discharge patients after completion of chemotherapy if medically stable and logistically feasible. The predominant reasons for the perceived need for ongoing hospitalization were high risk of infection, treatment toxicities, and lack of nearby/accessible housing. There was no significant association between ability to practice EHD and annual AML volume or treatment intensity patterns ( P =.60 and P =.11, respectively). In contrast, in the postremission setting, 87% of centers support patients following chemotherapy in the outpatient setting unless toxicities arise requiring readmission. Survey responses showed that 80% of centers were interested in exploring EHD after (re)induction but noted significant barriers, including accessible housing (71%), transportation (50%), high toxicity/infection rate (50%), high transfusion burden (50%), and limited bed availability for rehospitalization (50%). Conclusions: Hospitalization and care patterns following intensive AML therapy vary widely across major US cancer institutions. Although only 20% of surveyed centers practice EHD following intensive (re)induction chemotherapy, 87% do so following postremission therapy. Given the interest in exploring the EHD approach given potential advantages of EHD for both patients and health care systems, strategies to address identified medical and logistical barriers should be explored.
Pharmacogenomic Score Effectively Personalizes Treatment of Acute Myeloid Leukemia
Authors: Richard J. Marrero, Huiyun Wu, Xueyuan Cao, Phani Krishna Parcha, Abdelrahman H. Elsayed, Hiroto Inaba, Dennis John Kuo, Barbara A. Degar, Kenneth Heym, Jeffrey W. Taub, Norman Lacayo, Ching-Hon Pui, Raul C. Ribeiro, Jeffrey E. Rubnitz, Stanley B. Pounds, Jatinder K. Lamba
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Cytarabine (also known as ara-C) has been the backbone of acute myeloid leukemia (AML) chemotherapy for more than five decades. Recent pharmacogenomics-based 10-SNP ara-C (ACS10) scores showed low ACS10 (≤0) to be associated with poor outcomes in patients with AML treated with standard chemotherapy. Here, we evaluated the ACS10 score in the context of three different induction I regimens in patients with pediatric AML. Experimental Design: ACS10 score groups (low, ≤0, or high, &amp;gt;0) were evaluated for association with event-free survival (EFS) and overall survival (OS) by three randomized treatment arms in patients treated on the AML02 (NCT00136084) and AML08 (NCT00703820) clinical trials: AML02 low-dose ara-C (LDAC arm, n = 91), AML02 + AML08 high-dose ara-C (HDAC arm, n = 194), and AML08 clofarabine + ara-C (Clo/ara-C arm, n = 105) induction I regimens. Results: Within the low-ACS10 score (≤0) group, significantly improved EFS and OS were observed among patients treated with Clo/ara-C as compared with LDAC (EFS, HR = 0.45; 95% CI, 0.23–0.88; P = 0.020; OS, HR = 0.44; 95% CI, 0.19–0.99; P = 0.048). In contrast, within the high-ACS10 score group (score &amp;gt;0), augmentation with Clo/ara-C was not favorable as compared with LDAC (Clo/ara-C vs. LDAC, EFS, HR = 1.95; 95% CI, 1.05–3.63; P = 0.035; OS, HR = 2.10; 95% CI, 0.96–4.59; P = 0.063). Personalization models predicted 9% improvement in the outcome in ACS10 score–based tailored induction (Clo/ara-C for low and LDAC for high-ACS10 score groups) as compared with nonpersonalized approaches (P &amp;lt; 0.002). Conclusions: Our findings suggest that tailoring induction regimens using ACS10 scores can significantly improve outcomes in patients with AML. Given the SNPs are germline, preemptive genotyping can accelerate matching the most effective remission induction regimen.
Concordance and Prognostic Relevance of Different Definitions of Systemic Sclerosis Interstitial Lung Disease Progression
Authors: Enrico De Lorenzis, Francesco Del Galdo, Gerlando Natalello, Francesco Varone, Stefano Di Donato, Lucrezia Verardi, Lucio Calandriello, Vishal Kakkar, Pier Giacomo Cerasuolo, Anna Rita Larici, Maria Antonietta D'Agostino, Silvia Laura Bosello, Luca Richeldi
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Interstitial lung disease (ILD) in systemic sclerosis (SSc) is a common complication that has varied progression rate and prognosis. Different progression definitions are available: include minimal clinically important worsening of forced vital capacity (FVC MCIW), EUSTAR (EUropean Scleroderma Trials and Research group) progression, OMERACT (Outcome Measures in Rheumatology Clinical Trials) progression, and Erice ILD working group progression. Pulmonary function and symptoms changes may act as specific confounding factors applying these definitions in SSc.
Inhaled Corticosteroids Attenuate the Association of Fine Particulate Matter and Acute Asthma Events
Authors: Kristen A. Staggers, Paula Sierra, Drew A. Helmer, Charles Minard, Meredith C. McCormack, Tianshi David Wu
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Inhaled Corticosteroids Attenuate the Association of Fine Particulate Matter and Acute Asthma Events." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Associations Between Glucose Metabolism Measures and Amyloid-β and Tau Load on PET 14 Years Later: Findings From the Framingham Heart Study
Authors: Veerle van Gils, Qiushan Tao, Ting F.A. Ang, Christina B. Young, Elizabeth C. Mormino, Wei Qiao Qiu, Pieter Jelle Visser, Rhoda Au, Willemijn J. Jansen, Stephanie J.B. Vos
Journal: Diabetes Care (2024)

OBJECTIVE Type 2 diabetes and glucose metabolism have previously been linked to Alzheimer disease (AD). Yet, findings on the relation of glucose metabolism with amyloid-β and tau pathology later in life remain unclear. RESEARCH DESIGN AND METHODS We included 288 participants (mean age 43.1 years, SD 10.7, range 20–70 years) without dementia, from the Framingham Heart Study, who had available measures of glucose metabolism (i.e., one-time fasting plasma glucose and insulin) and positron emission tomography (PET) measures of amyloid-β and/or tau 14 years later. We performed linear regression analyses to test associations of plasma glucose (continuously and categorically; elevated defined as &amp;gt;100 mg/dL), plasma insulin, homeostatic model assessment for insulin resistance (HOMA-IR) with amyloid-β or tau load on PET. When significant, we explored whether age, sex, and APOE ε4 allele carriership (AD genetic risk) modified these associations. RESULTS Our findings indicated that elevated plasma glucose was associated with greater tau load 14 years later (B [95% CI] = 0.03 [0.01–0.05], P = 0.024 after false discovery rate [FDR] correction) but not amyloid-β. APOE ε4 carriership modified this association (B [95% CI] = −0.08 [−0.12 to −0.03], P = 0.001), indicating that the association was only present in APOE ε4 noncarriers (n = 225). Plasma insulin and HOMA-IR were not associated with amyloid-β or tau load 14 years later after FDR correction. CONCLUSIONS Our findings suggest that glucose metabolism is associated with increased future tau but not amyloid-β load. This provides relevant knowledge for prevention strategies and prognostics to improve health care.
Where hematology meets rheumatology—<scp>VEXAS</scp> syndrome
Authors: Hajer Oun, William Gordon, Mike Leach, Barbara J. Bain
Journal: American Journal of Hematology (2024)

The bone marrow aspirate was cellular with no abnormal infiltration. The myeloid series was prominent and a proportion of promyelocytes and myelocytes showed prominent cytoplasmic (and some apparently intranuclear) vacuolation (all images ×100 objective). There was maturation to neutrophils, with some showing abnormal nuclear segmentation. The erythroid series showed cytoplasmic vacuolation in the earlier stages (top center, top right), with some cells having giant vacuoles (bottom right). These morphological findings in the context of the clinical presentation raised the suspicion of the VEXAS syndrome. Next-generation molecular sequencing confirmed a p.Met41Thr missense mutation in UBA1 (c.122T>C) confirming VEXAS syndrome. A DNMT3A gene splice variant mutation c1429+1G>A was also present. The patient continues on oral prednisolone, and the JAK1/JAK2 inhibitor, barcitinib, and has been referred for consideration for an allogeneic bone marrow transplant. VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory Somatic) syndrome is a recently described auto-inflammatory condition driven by a somatic mutation in UBA1 in a hematopoietic progenitor cell.1 Hematological manifestations include cytopenias with clonal evolution, sometimes leading to the development of a myelodysplastic syndrome. There may be macrocytosis and the incidence of venous thromboembolism is increased. The vacuoles are present in both early myeloid and early erythroid precursors in most (but not all) patients with a UBA1 mutation, and may also be present in plasma cells and lymphocytes. A threshold of vacuolization of more than 10% of promyelocytes and myelocytes has been proposed as a sensitive and fairly specific indicator of the condition.2 Vacuolization of bone marrow progenitors is not, however, exclusive to the VEXAS syndrome, and can be seen in other inflammatory disorders, alcoholism, copper deficiency, and malnutrition. Having been only recently defined, the prevalence of the disease is likely underestimated, but the morphological and molecular features should be sought in male patients presenting with both cytopenias and systemic inflammatory disease. The authors declare no conflicts of interest.