tbuckley/cabot-search huggingface dataset:
Estimating Glycemia From HbA1c and CGM: Analysis of Accuracy and Sources of Discrepancy
Authors: Veronica Tozzo, Matthew Genco, Shammah O. Omololu, Christopher Mow, Hasmukh R. Patel, Chhaya H. Patel, Samantha N. Ho, Evie Lam, Batoul Abdulsater, Nikita Patel, Robert M. Cohen, David M. Nathan, Camille E. Powe, Deborah J. Wexler, John M. Higgins
Journal: Diabetes Care (2024)

OBJECTIVE To examine the accuracy of different periods of continuous glucose monitoring (CGM), hemoglobin A1c (HbA1c), and their combination for estimating mean glycemia over 90 days (AG90). RESEARCH DESIGN AND METHODS We retrospectively studied 985 CGM periods of 90 days with &amp;lt;10% missing data from 315 adults (86% of whom had type 1 diabetes) with paired HbA1c measurements. The impact of mean red blood cell age as a proxy for nonglycemic effects on HbA1c was estimated using published theoretical models and in comparison with empirical data. Given the lack of a gold standard measurement for AG90, we applied correction methods to generate a reference (eAG90) that we used to assess accuracy for HbA1c and CGM. RESULTS Using 14 days of CGM at the end of the 90-day period resulted in a mean absolute error (95th percentile) of 14 (34) mg/dL when compared with eAG90. Nonglycemic effects on HbA1c led to a mean absolute error for average glucose calculated from HbA1c of 12 (29) mg/dL. Combining 14 days of CGM with HbA1c reduced the error to 10 (26) mg/dL. Mismatches between CGM and HbA1c &amp;gt;40 mg/dL occurred more than 5% of the time. CONCLUSIONS The accuracy of estimates of eAG90 from limited periods of CGM can be improved by averaging with an HbA1c-based estimate or extending the monitoring period beyond ∼26 days. Large mismatches between eAG90 estimated from CGM and HbA1c are not unusual and may persist due to stable nonglycemic factors.
Safety and long‐term survival results of the addition of inotuzumab ozogamicin to the conditioning regimen of allogeneic stem cell transplantation: A single‐center phase 1,2 trial
Authors: Issa F. Khouri, Kamal Alzahrani, Hagop Kantarjian, Denái R. Milton, Alison M. Gulbis, Koji Sasaki, Nitin Jain, Nicholas J. Short, Tapan Kadia, May Daher, Hind Rafei, Jin S. Im, David Marin, Amanda L. Olson, Uday Popat, Muzaffar Qazilbash, Jeremy Ramdial, Gabriela Rondon, Samer Srour, Partow Kebriaei, Elizabeth Shpall, Richard Champlin, Elias J. Jabbour
Journal: American Journal of Hematology (2024)

Here we report on the first prospective study evaluating the safety and long-term survival when an escalating dose of inotuzumab ozogamicin (INO) (0.6, 1.2, or 1.8 mg/m
Surface Modification of Nerve Guide Conduits with ECM Coatings and Investigating Their Impact on Schwann Cell Response
Authors: Luis Pinzon‐Herrera, John Magness, Hector Apodaca‐Reyes, Jesus Sanchez, Jorge Almodovar
Journal: Advanced Healthcare Materials (2024)

In this study, layer-by-layer coatings composed of heparin and collagen are proposed as an extracellular mimetic environment on nerve guide conduits (NGC) to modulate the behavior of Schwann cells (hSCs). The authors evaluated the stability, degradation over time, and bioactivity of six bilayers of heparin/collagen layer-by-layer coatings, denoted as (HEP/COL)
Hierarchical Design of Tissue‐Mimetic Fibrillar Hydrogel Scaffolds
Authors: Alberto Pardo, Manuel Gomez‐Florit, Matthew D. Davidson, Meftune Özgen Öztürk‐Öncel, Rui M. A. Domingues, Jason A. Burdick, Manuela E. Gomes
Journal: Advanced Healthcare Materials (2024)

Abstract Most tissues of the human body present hierarchical fibrillar extracellular matrices (ECMs) that have a strong influence over their physicochemical properties and biological behavior. Of great interest is the introduction of this fibrillar structure to hydrogels, particularly due to the water‐rich composition, cytocompatibility, and tunable properties of this class of biomaterials. Here, the main bottom‐up fabrication strategies for the design and production of hierarchical biomimetic fibrillar hydrogels and their most representative applications in the fields of tissue engineering and regenerative medicine are reviewed. For example, the controlled assembly/arrangement of peptides, polymeric micelles, cellulose nanoparticles (NPs), and magnetically responsive nanostructures, among others, into fibrillar hydrogels is discussed, as well as their potential use as fibrillar‐like hydrogels (e.g., those from cellulose NPs) with key biofunctionalities such as electrical conductivity or remote stimulation. Finally, the major remaining barriers to the clinical translation of fibrillar hydrogels and potential future directions of research in this field are discussed.
The impact of sex on platelet responses to aspirin in patients with peripheral artery disease
Authors: Sasha P. Suarez Ferreira, Ryan P. Hall, Katherine Morrow, Shiv Patel, Ivy Lee, Fanah Hagos, Nikolaos Zacharias, Kellie Machlus, Anahita Dua
Journal: American Journal of Hematology (2024)

Abstract Women with peripheral artery disease (PAD) have poorer limb salvage outcomes in spite of having lower risk factors for vascular disease than their male counterparts. Mono antiplatelet therapy with aspirin is the cornerstone of medical treatment for PAD to reduce the risk of arterial thrombosis, but platelets in women may have a variable response to this standard of care compared to men. Viscoelastic assays, such as thromboelastography with platelet mapping (TEG‐PM), have been utilized to identify prothrombotic states and may provide insight into a patient's real‐time coagulation profile and their response to specific antiplatelet medications. The aim of this prospective, observational study was to delineate the sex differences in platelet function using TEG‐PM in patients with PAD on aspirin post‐revascularization for PAD. All patients with PAD undergoing revascularization on aspirin monotherapy were prospectively enrolled between December 2020 and September 2023. The cohort was divided by sex, demographics, medications, procedure type, and outcomes were documented. Serial perioperative TEG‐PM assays (1, 3, and 6 months) were performed up to 6 months postoperatively and platelet function was evaluated in both groups. Statistical analysis between women and men was performed to identify sex‐specific differences in platelet function. Over the study period, a total of 303 patients were enrolled. Of this cohort, 149 patients met the study criteria and 266 samples were analyzed; 52 (34.89%) were women and 97 (65.11%) were men. In the platelet mapping assay, women showed significantly greater MA ActF and MA AA , than men (16.66 vs. 14.94, p &lt; .03 and 37.26 vs. 32.38, p &lt; .01, respectively) indicating stronger thrombotic propensity. Additionally, platelet inhibition was significantly lower in women compared to men (52.95% vs. 61.65%, p &lt; .05). In clinical outcomes reported as thrombotic events, women showed significantly higher occlusion in the area of intervention than men (4 vs. 1, p &lt; .05). There is a growing awareness of the variations in the natural course, underlying mechanisms, and resulting outcomes of cardiovascular conditions, including PAD, in relation to sex. In this study, women did not achieve the same levels of platelet inhibition and displayed a procoagulant tendency in comparison to men when administered aspirin. Overall, aspirin monotherapy may be potentially sufficient for men, but women may require increased doses and/or additional antiplatelet medications to achieve an equivalent therapeutic effect.
Evolutionary dynamics of the novel ST22-PT methicillin-resistant Staphylococcus aureus clone co-harbouring Panton–Valentine leucocidin and duplicated toxic shock syndrome toxin 1 genes
Authors: Tetsuo Yamaguchi, Kenji Furuno, Kohji Komori, Tomoko Abe, Takahiro Sato, Shinji Ogihara, Kotaro Aoki, Yoshikazu Ishii, Kazuhiro Tateda
Journal: Clinical Microbiology and Infection (2024)

Globally, the isolation of community-associated methicillin-resistant Staphylococcus aureus (MRSA) harbouring both the Panton-Valentine leucocidin (PVL) and toxic shock syndrome toxin 1 (TSST-1) genes is rare. However, we encountered an outbreak of the ST22-PT clone exhibiting this phenotype in Japan. Notably, the TSST-1 gene was duplicated in most of the strains. This study aimed to elucidate the mechanisms underlying this gene duplication.
Walk, talk, think, see and feel: harnessing the power of digital biomarkers in healthcare
Authors: Dylan Powell
Journal: npj Digital Medicine (2024)

Check for updatesThe critical role of biomarkersA key pillar of healthcare's journey towards precision medicine has been the proliferation and development of biomarkers to detect, monitor and manage disease.Over the last fifty years, healthcare has seen a rapid acceleration in the discovery of traditional biomarkers for a variety of conditions, including cancer, namely Carcinoembryonic antigen (CEA), and in the 1980s, CA15-3 for breast cancer 1 (Fig. 1).Biomarkers remain a crucial source of data and insight for early detection and diagnosis, assessing the response of treatment and prognosis 1,2 .However, with both the complexity and increasing demands for healthcare, research is increasingly exporting novel opportunities that augment and build upon traditional biomarker approaches 2,3 .
<scp><i>NPM1</i></scp>‐mutated myeloid neoplasm with low percentage of blasts
Authors: Brunangelo Falini, Patrizia Chiusolo, Luana Fianchi, Livio Pagano
Journal: American Journal of Hematology (2024)

B.F. holds a patent on NPM1 mutants (number 102004901256449). The remaining authors declare no competing financial interests. All data and information concerning this study will be made available from the corresponding authors upon reasonable request.
Epigenetic modifications in obesity‐associated diseases
Authors: Yiqian Long, Chao Mao, Shuang Liu, Yongguang Tao, Desheng Xiao
Journal: MedComm (2024)

The global prevalence of obesity has reached epidemic levels, significantly elevating the susceptibility to various cardiometabolic conditions and certain types of cancer. In addition to causing metabolic abnormalities such as insulin resistance (IR), elevated blood glucose and lipids, and ectopic fat deposition, obesity can also damage pancreatic islet cells, endothelial cells, and cardiomyocytes through chronic inflammation, and even promote the development of a microenvironment conducive to cancer initiation. Improper dietary habits and lack of physical exercise are important behavioral factors that increase the risk of obesity, which can affect gene expression through epigenetic modifications. Epigenetic alterations can occur in early stage of obesity, some of which are reversible, while others persist over time and lead to obesity-related complications. Therefore, the dynamic adjustability of epigenetic modifications can be leveraged to reverse the development of obesity-associated diseases through behavioral interventions, drugs, and bariatric surgery. This review provides a comprehensive summary of the impact of epigenetic regulation on the initiation and development of obesity-associated cancers, type 2 diabetes, and cardiovascular diseases, establishing a theoretical basis for prevention, diagnosis, and treatment of these conditions.
Rapid and Repeated Climate Adaptation Involving Chromosome Inversions following Invasion of an Insect
Authors: Li-Jun Ma, Li-Jun Cao, Jin-Cui Chen, Meng-Qing Tang, Wei Song, Fang-Yuan Yang, Xiu-Jing Shen, Ya-Jing Ren, Qiong Yang, Hu Li, Ary Anthony Hoffmann, Shu-Jun Wei
Journal: Molecular Biology and Evolution (2024)

Abstract Following invasion, insects can become adapted to conditions experienced in their invasive range, but there are few studies on the speed of adaptation and its genomic basis. Here, we examine a small insect pest, Thrips palmi, following its contemporary range expansion across a sharp climate gradient from the subtropics to temperate areas. We first found a geographically associated population genetic structure and inferred a stepping-stone dispersal pattern in this pest from the open fields of southern China to greenhouse environments of northern regions, with limited gene flow after colonization. In common garden experiments, both the field and greenhouse groups exhibited clinal patterns in thermal tolerance as measured by critical thermal maximum (CTmax) closely linked with latitude and temperature variables. A selection experiment reinforced the evolutionary potential of CTmax with an estimated h2 of 6.8% for the trait. We identified 3 inversions in the genome that were closely associated with CTmax, accounting for 49.9%, 19.6%, and 8.6% of the variance in CTmax among populations. Other genomic variations in CTmax outside the inversion region were specific to certain populations but functionally conserved. These findings highlight rapid adaptation to CTmax in both open field and greenhouse populations and reiterate the importance of inversions behaving as large-effect alleles in climate adaptation.
Association between diet quality and ovarian cancer risk and survival
Authors: Anlan Cao, Denise A Esserman, Brenda Cartmel, Melinda L Irwin, Leah M Ferrucci
Journal: JNCI Journal of the National Cancer Institute (2024)

Research on diet quality and ovarian cancer is limited. We examined the association between diet quality and ovarian cancer risk and survival in a large prospective cohort.
COVID-19 vaccination, infection, and symptoms among cancer survivors in the United States
Authors: Nuo Nova Yang, Jingxuan Zhao, Zhiyuan Zheng, K Robin Yabroff, Xuesong Han
Journal: JNCI Journal of the National Cancer Institute (2024)

The experiences of cancer survivors with the COVID-19 pandemic in the United States during 2021 and 2022, when vaccinations became widely available, are largely undocumented. Using nationally representative survey data in 2021 and 2022, we found that compared with adults without a cancer history, cancer survivors were more likely to have at least 2 COVID-19 vaccines (2021: 66.6% vs 62.3%, P = .003; 2022: 77.0% vs 72.4%, P < .001) and as likely to have a COVID-19 infection history (2021: 14.1% vs 14.2%, P = .93; 2022: 39.9% vs 39.3%, P = .55) but, once infected, were more likely to develop moderate to severe symptoms (2021: 62.5% vs 54.2%, P = .02; 54.5% vs 61.3%; P = .13). Among cancer survivors, younger age, lower educational attainment, lack of health insurance, and more comorbidities were statistically significantly associated with lower vaccination rates (P < .001). Among infected cancer survivors, being female and younger were associated with higher likelihood of developing moderate to severe symptoms (P < .001). Our findings suggest tailored efforts to prevent and control COVID-19 infections for cancer survivors.
Correlates of feeding difficulties among children of Chinese transgender parents
Authors: Haibing Yang, Xiaona Na, Yuefeng Tan, Menglu Xi, Yucheng Yang, Ai Zhao
Journal: International Journal of Transgender Health (2024)

Ensuring proper early feeding for young children is crucial, as encountering feeding difficulties (FD) during this stage can give rise to a cascade of health problems, the repercussions of which may endure into late childhood and adolescence. Children raised by transgender parents may be at risk of encountering FD, however, there is no research conducted on Chinese transgender families.
Patterns of metastasis from a multicenter cohort of metastatic basal cell carcinoma
Authors: Morgan Groover, Neha Gupta, Emily Granger, Vernon J. Forrester, Emily J. Anstadt, William Su, Lauren Heusinkveld, John N. Lukens, Ann W. Silk, Jonathan D. Schoenfeld, Shlomo A. Koyfman, Allison T. Vidimos, Emily S. Ruiz
Journal: Journal of the American Academy of Dermatology (2024)
Defective exercise-related expiratory muscle recruitment in patients with PHOX2B mutations: A clue to neural determinants of the congenital central hypoventilation syndrome
Authors: P. Laveneziana, Q. Fossé, M. Bret, M. Patout, B. Dudoignon, C. Llontop, C. Morélot-Panzini, F. Cayetanot, L. Bodineau, C. Straus, T. Similowski
Journal: Pulmonology (2024)

The human congenital central hypoventilation syndrome (CCHS) is caused by mutations in the PHOX2B (paired-like homeobox 2B) gene. Genetically engineered PHOX2B rodents exhibit defective development of the brainstem retrotrapezoid nucleus (RTN), a carbon dioxide sensitive structure that critically controls expiratory muscle recruitment. This has been linked to a blunted exercise ventilatory response. Whether this can be extrapolated to human CCHS is unknown and represents the objective of this study.
Outcomes of rheumatic fever in Uganda: a prospective cohort study
Authors: Scott H Wirth, Jafesi Pulle, JangDong Seo, Nicholas J Ollberding, Doreen Nakagaayi, Craig Sable, Asha C Bowen, Tom Parks, Jonathan Carapetis, Emmy Okello, Andrea Beaton, Emma Ndagire
Journal: The Lancet Global Health (2024)
An update on the global disparities in kidney disease burden and care across world countries and regions
Authors: Aminu K Bello, Ikechi G Okpechi, Adeera Levin, Feng Ye, Sandrine Damster, Silvia Arruebo, Jo-Ann Donner, Fergus J Caskey, Yeoungjee Cho, M Razeen Davids, Sara N Davison, Htay Htay, Vivekanand Jha, Rowena Lalji, Charu Malik, Masaomi Nangaku, Emily See, Stephen M Sozio, Marcello Tonelli, Marina Wainstein, Emily K Yeung, David W Johnson
Journal: The Lancet Global Health (2024)
FFAR2 expressing myeloid-derived suppressor cells drive cancer immunoevasion
Authors: Zeda Zhao, Juliang Qin, Ying Qian, Chenshen Huang, Xiaohong Liu, Ning Wang, Liqin Li, Yuqing Chao, Binghe Tan, Na Zhang, Min Qian, Dali Li, Mingyao Liu, Bing Du
Journal: Journal of Hematology & Oncology (2024)

Abstract Background Emerging evidences suggest that aberrant metabolites contributes to the immunosuppressive microenvironment that leads to cancer immune evasion. Among tumor immunosuppressive cells, myeloid-derived suppressor cells (MDSCs) are pathologically activated and extremely immunosuppressive, which are closely associated with poor clinical outcomes of cancer patients. However, the correlation between MDSCs mediated immunosuppression and particular cancer metabolism remained elusive. Methods Spontaneous lung adenocarcinoma and subcutaneous mouse tumor models, gas chromatography–mass spectrometry (GC–MS) and immunofluorescence assay of patient-derived lung adenocarcinoma tissues, and flow cytometry, RNA sequencing and Western blotting of immune cells, were utilized. Results Metabolite profiling revealed a significant accumulation of acetic acids in tumor tissues from both patients and mouse model, which contribute to immune suppression and cancer progression significantly through free fatty acid receptor 2 (FFAR2). Furthermore, FFAR2 is highly expressed in the myeloid-derived suppressor cells (MDSCs) from the tumor of lung adenocarcinoma (LUAD) patients which is greatly associated with poor prognosis. Surprisingly, whole or myeloid Ffar2 gene deletion markedly inhibited urethane-induced lung carcinogenesis and syngeneic tumor growth with reduced MDSCs and increased CD8 + T cell infiltration. Mechanistically, FFAR2 deficiency in MDSCs significantly reduced the expression of Arg1 through Gαq/Calcium/PPAR-γ axis, which eliminated T cell dysfunction through relieving L-Arginine consumption in tumor microenvironment. Therefore, replenishment of L-Arginine or inhibition to PPAR-γ restored acetic acids/FFAR2 mediated suppression to T cells significantly. Finally, FFAR2 inhibition overcame resistance to immune checkpoint blockade through enhancing the recruitment and cytotoxicity of tumor-infiltrating T cells. Conclusion Altogether, our results demonstrate that the acetic acids/FFAR2 axis enhances MDSCs mediated immunosuppression through Gαq/calcium/PPAR-γ/Arg1 signaling pathway, thus contributing to cancer progression. Therefore, FFAR2 may serve as a potential new target to eliminate pathologically activated MDSCs and reverse immunosuppressive tumor microenvironment, which has great potential in improving clinical outcomes of cancer immunotherapy.
Real-time and non-invasive acute lung rejection diagnosis using confocal LASER Endomicroscopy in lung transplant recipients: Results from the CELTICS study
Authors: T. Villeneuve, C. Hermant, A. Le Borgne, M. Murris, G. Plat, V. Héluain, M. Colombat, M. Courtade-Saïdi, S. Evrard, S. Collot, M. Salaün, N. Guibert
Journal: Pulmonology (2024)

Traditionally, the diagnosis of acute rejection (AR) relies on invasive transbronchial biopsies (TBBs) to obtain histopathological samples. We aimed to evaluate the diagnostic yield of probe-based confocal laser endomicroscopy (pCLE) as a complementary and non-invasive tool for ACR screening, comparing its results with those obtained from TBBs. Between January 2015 and April 2022, we conducted a retrospective study of all lung transplant recipients aged over 18 years at Toulouse University Hospital (France). All patients who underwent bronchoscopies with both TBBs and pCLE imaging were included. Two experienced interpreters (TV and MS) reviewed the pCLE images independently, blinded to all clinical information and pathology results. From 120 procedures in 85 patients, 34 abnormal histological samples were identified. Probe-based confocal laser endomicroscopy revealed significant associations between both alveolar (ALC) and perivascular (PVC) cellularities and abnormal histological samples (p<0.0001 and 0.003 respectively). Alveolar cellularity demonstrated a sensitivity (Se) of 85.3 %, specificity (Spe) of 43 %, positive predictive value (PPV) of 37.2 % and negative predictive value (NPV) of 88.1 %. For PVC, Se was 70.6 %, Spe 80.2 %, PPV 58.5 % and NPV 87.3 %. Intra-interpreter correlation (TV) was 88.3 % for the number of vessels (+/-1), 98.3 % for ALC and 90 % for PVC. Inter-interpreter correlation (TV and MS) was 80 % for vessels (+/-1), 97.5 % for ALC and 83.3 % for PVC. Our study demonstrates the feasibility of incorporating pCLE into clinical practice, demonstrating good diagnostic yield and reproducible outcomes in the screening of AR in lung transplant recipients.
Multi-tissue transcriptome-wide association studies identified 235 genes for intrinsic subtypes of breast cancer
Authors: James L Li, Julian C McClellan, Haoyu Zhang, Guimin Gao, Dezheng Huo
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background Although genome-wide association studies (GWAS) of breast cancer (BC) identified common variants which differ between intrinsic subtypes, genes through which these variants act to impact BC risk have not been fully established. Transcriptome-wide association studies (TWAS) have identified genes associated with overall BC risk, but subtype-specific differences are largely unknown. Methods We performed two multi-tissue TWAS for each BC intrinsic subtype, including an expression-based approach that collated TWAS signals from expression quantitative trait loci (eQTLs) across multiple tissues and a novel splicing-based approach that collated signals from splicing QTLs (sQTLs) across intron clusters and subsequently across tissues. We used summary statistics for five intrinsic subtypes including Luminal A-like, Luminal B-like, Luminal B/HER2-negative-like, HER2-enriched-like, and triple-negative BC, generated from 106 278 BC cases and 91 477 controls in the Breast Cancer Association Consortium. Results Overall, we identified 235 genes in 88 loci that were associated with at least one of the five intrinsic subtypes. Most genes were subtype-specific, and many have not been reported in previous TWAS. We discovered common variants that modulate expression of CHEK2 confer increased risk to Luminal A-like BC, in contrast to the viewpoint that CHEK2 primarily harbors rare, penetrant mutations. Additionally, our splicing-based TWAS provided population-level support for MDM4 splice variants that increased the risk of triple-negative BC. Conclusion Our comprehensive, multi-tissue TWAS corroborated previous GWAS loci for overall BC risk and intrinsic subtypes, while underscoring how common variation that impacts expression and splicing of genes in multiple tissue types can be used to further elucidate the etiology of BC.