tbuckley/cabot-search huggingface dataset:
Mapping of Segmental and Partial Segmental Infantile Hemangiomas of the Face and Scalp
Authors: Alyson A. Endicott, Sarah L. Chamlin, Beth A. Drolet, Anthony J. Mancini, Dawn H. Siegel, Sterling Vitcov, Erin F. Mathes, Ilona J. Frieden, Anita N. Haggstrom
Journal: JAMA Dermatology (2021)

<h3>Importance</h3> Recognizing segmental infantile hemangioma (IH) patterns is important for risk stratification and provides clues to pathogenesis. Previously, segmental hemangiomas were mapped to 4 facial regions, 3 corresponding to known facial metameres. <h3>Objectives</h3> To refine existing maps of facial segmental IHs, examine so-called indeterminate hemangiomas as they relate to known segmental patterns, and define a novel pattern of segmental scalp hemangiomas. <h3>Design, Setting, and Participants</h3> This retrospective cohort study was conducted at 4 pediatric dermatology centers (University of California, San Francisco; Indiana University; Medical College of Wisconsin; and Northwestern University/Ann &amp; Robert H. Lurie Children's Hospital of Chicago) using photographic archives of patients younger than 12 years with segmental and indeterminate hemangiomas on the face and scalp. Clinical images were used to map hemangioma distribution onto standardized facial templates. Heat map densiometry identified recurrent patterns that were compared with previously published patterns of facial segmental hemangiomas. Patterns of indeterminate hemangiomas were compared with those of segmental hemangiomas. Data collection took place in 2017, and analysis took place from 2017 to 2019. <h3>Main Outcomes and Measures</h3> Distribution and patterning of segmental and indeterminate IHs of the face and scalp. <h3>Results</h3> A total of 549 IHs were mapped. The borders of the frontotemporal (S1) and frontonasal (S4) segments agreed with previous segmental maps; however, the maxillary (S2) and mandibular (S3) segment borders differed with respect to the preauricular skin. In contrast with previous reports, preauricular skin segregated with the mandibular (S3) rather than the maxillary (S2) segment. Indeterminate hemangiomas occurred within and respected the same borders as segmental hemangiomas. Hemangiomas on the lateral scalp commonly occurred in a C shape extending from the posterior auricular region. <h3>Conclusions and Relevance</h3> This cohort study provides an updated map of facial segmental IHs with redefined maxillary (S2) and mandibular (S3) segment borders. It provides evidence that indeterminate hemangiomas are partial segmental hemangiomas respecting anatomic boundaries of their larger segmental counterparts. A newly recognized C-shaped pattern of segmental scalp hemangioma is reported.
Glioblastoma genetic drivers dictate the function of tumor-associated macrophages/microglia and responses to CSF1R inhibition
Authors: Rohit Rao, Rong Han, Sean Ogurek, Chengbin Xue, Lai Man Wu, Liguo Zhang, Li Zhang, Jian Hu, Timothy N Phoenix, Stephen N Waggoner, Q Richard Lu
Journal: Neuro-Oncology (2021)

Tumor-associated macrophages/microglia (TAMs) are prominent microenvironment components in human glioblastoma (GBM) that are potential targets for anti-tumor therapy. However, TAM depletion by CSF1R inhibition showed mixed results in clinical trials. We hypothesized that GBM subtype-specific tumor microenvironment (TME) conveys distinct sensitivities to TAM targeting.We generated syngeneic PDGFB- and RAS-driven GBM models that resemble proneural-like and mesenchymal-like gliomas, and determined the effect of TAM targeting by CSF1R inhibitor PLX3397 on glioma growth. We also investigated the co-targeting of TAMs and angiogenesis on PLX3397-resistant RAS-driven GBM. Using single-cell transcriptomic profiling, we further explored differences in TME cellular compositions and functions in PDGFB- and RAS-driven gliomas.We found that growth of PDGFB-driven tumors was markedly inhibited by PLX3397. In contrast, depletion of TAMs at the early phase accelerated RAS-driven tumor growth and had no effects on other proneural and mesenchymal GBM models. In addition, PLX3397-resistant RAS-driven tumors did not respond to PI3K signaling inhibition. Single-cell transcriptomic profiling revealed that PDGFB-driven gliomas induced expansion and activation of pro-tumor microglia, whereas TAMs in mesenchymal RAS-driven GBM were enriched in pro-inflammatory and angiogenic signaling. Co-targeting of TAMs and angiogenesis decreased cell proliferation and changed the morphology of RAS-driven gliomas.Our work identifies functionally distinct TAM subpopulations in the growth of different glioma subtypes. Notably, we uncover a potential responsiveness of resistant mesenchymal-like gliomas to combined anti-angiogenic therapy and CSF1R inhibition. These data highlight the importance of characterization of the microenvironment landscape in order to optimally stratify patients for TAM-targeted therapy.
CD19-targeted chimeric antigen receptor T-cell therapy for CNS relapsed or refractory acute lymphocytic leukaemia: a post-hoc analysis of pooled data from five clinical trials
Authors: Allison Barz Leahy, Haley Newman, Yimei Li, Hongyan Liu, Regina Myers, Amanda DiNofia, Joseph G Dolan, Colleen Callahan, Diane Baniewicz, Kaitlin Devine, Lisa Wray, Richard Aplenc, Carl H June, Stephan A Grupp, Susan R Rheingold, Shannon L Maude
Journal: The Lancet Haematology (2021)
Vaccine-driven lung TRM cells provide immunity against <i>Klebsiella</i> via fibroblast IL-17R signaling
Authors: Naoki Iwanaga, Kong Chen, Haoran Yang, Shiping Lu, Joseph P. Hoffmann, Alanna Wanek, Janet E. McCombs, Kejing Song, Javier Rangel-Moreno, Elizabeth B. Norton, Jay K. Kolls
Journal: Science Immunology (2021)

A subunit mucosal vaccine conferred protection against heterologous Klebsiella pneumoniae strains, via IL-17R signaling in lung fibroblasts.
ETV6-RUNX1 and RUNX1 directly regulate RAG1 expression: one more step in the understanding of childhood B-cell acute lymphoblastic leukemia leukemogenesis
Authors: Hélène Jakobczyk, Yan Jiang, Lydie Debaize, Benoit Soubise, Stéphane Avner, Aurélien A. Sérandour, Jérémie Rouger-Gaudichon, Anne-Gaëlle Rio, Jason S. Carroll, Hana Raslova, David Gilot, Ziling Liu, Jocelyne Demengeot, Gilles Salbert, Nathalie Douet-Guilbert, Laurent Corcos, Marie-Dominique Galibert, Virginie Gandemer, Marie-Bérengère Troadec
Journal: Leukemia (2021)

Leukemiaregulator of the Rag1 promoter and Rag1-Rag2 silencer and antisilencer in mouse T-cells.We aimed to delineate the causative link between the presence of RUNX1, the ETV6-RUNX1 fusion protein and RAG1 upregulation in ETV6-RUNX1 BCP-ALL.Our findings fulfill a missing step in the multi-hit model of ETV6-RUNX1-related leukemogenesis between the ETV6-RUNX1 fusion gene and RAG1 aberrant activity.RAG1 and RUNX1 transcripts levels are positively and significantly correlated exclusively in ETV6-RUNX1 BCP-ALL compared to other childhood BCP-ALL (Fig. 1A, Supplementary Fig. S1A), suggesting
Endoscopic “stenting bridge” to treat combined gastric perforation, jejunal stump dehiscence, and biliodigestive anastomosis leak after duodenopancreatectomy followed by pancreatic totalization
Authors: Alessio Renga, Lorenzo Dioscoridi, Mutaz Massad, Marcello Cintolo, Giulia Bonato, Francesca Aprile, Massimiliano Mutignani
Journal: Endoscopy (2021)

Duodenopancreatectomy is burdened by a high rate of postoperative complications including anastomotic dehiscence. Although repeat surgery is considered the gold standard treatment in these settings [1] [2], it has high morbidity and mortality rates [3] [4]; thus, alternative treatments (i. e. endotherapy) have been investigated to improve clinical outcomes.
Overall and cause specific changes in mortality of patients with myelofibrosis over the last 3 decades
Authors: L. Masarova, P. Bose, N. Pemmaraju, H. Chifotides, L. Zhou, Z. Estrov, H. Kantarjian, S. Verstovsek
Journal: HemaSphere (2021)

Background: Patients with myelofibrosis (MF) have decreased overall survival with a median of 5 years. Leading causes of death are believed to be directly or indirectly related to MF progression or complications, including transformation to acute leukemia (AML) and infections. Aims: We aimed to compare survival, mortality rate and causes of death of MF patients referred to our institution before (≤) and after the years of 2010. Methods: This retrospective study included patients with MF diagnosed within one year prior to their presentation to our institution (between January 1990 and February 2020, 4% presented   2010, respectively, 59% of which were males. Sixty-five percent of patients were ≥60 years. Distribution of age groups between periods was comparable, except for higher proportion of 70+ year old patients > 2010, counterbalanced by lower proportion of   2010, 206 (55%) and 100 (16%) of patients died, respectively (p   2010. In both periods, males COVID-19 (n= 30 PV, n= 30 ET, n= 30 PMF) (45 men, 45 women, mean age 50 years, range 30-60). All patients gave written informed consent for study enrollment. The mean duration of disease was 12 years. All patients were on ASA 100 mg once daily. Concerning presentation and therapy, our MPNs patients with COVID-19 and without COVID-19 had not comorbidities and drug treatment was consistent with therapeutic standards (hydroxyurea, interferon, anagrelide, ruxolitinib). All patients were on ASA 100 mg once daily. IL-6 was measured by multiplex bead array (Millipore Sigma), TF and DD, and TAT by ELISA and Fib by Clauss method. PF4 was determined by ELISA. Whole blood viscoelastic analysis including clotting time (CT), and clot formation time (CFT) were measured by thomboelastometry method. Results: MPNs with COVID-19 had high IL-6 and TF (50±12pg/ml and 1950±500 pg/ml) compared with MPNs without COVID-19 (3±2pg/ml and 19±2 pg/ml), as well as DD, TAT and Fib (549±100 □g/l, 69±10 □g/l and 590±20mg/dl) compared with MPNs without COVID-19 (59±5□g/l, 2±1□g/l and 149±10 mg/l). PF4 was elevated (150.1□62.7 IU/ml) in MPNs with COVID-19 compared with MPNs without COVID-19 (2□1 UI/ml). A positive correlation was found between inflammatory, endothelial and coagulation mediators. A p-value of <.05 was considered statistically significant. Shortened CT (CT, unit: s. n.v. 100-240 s) (40±20 s) and shortened CFT (CFT, unit: s, n.v. 30-160 s (14±10 s) there were in MPNs with COVID-19 compared with MPNs without COVID-19 (CT 99±10 s and CFT 39±5 s). Summary/Conclusion: These data suggest that COVID-19 infection in MPNs patients may increase the thrombotic risk and get worse prognosis. In our opinion, this study can serve as a baseline study of COVID-19 thrombotic risk in MPNs and it is worthy of dissemina ion amongst patients and clinician communities.
BASELINE VLDL-C IS SIGNIFICANTLY ASSOCIATED WITH TRIGLYCERIDE RESPONSE TO TREATMENT WITH FENOFIBRIC ACID, STATINS, OR THEIR COMBINATION
Authors: Szilard Voros, Sarah Rinehart, Parag Joshi, Kamlesh Thakker, Aditya Lele, Carolyn M. Setze, Maureen T. Kelly
Journal: Journal of the American College of Cardiology (2011)
Protein Signatures of NK Cell–Mediated Melanoma Killing Predict Response to Immunotherapies
Authors: Sabrina Cappello, Hsu-Min Sung, Christian Ickes, Christine S. Gibhardt, Adina Vultur, Hilal Bhat, Zhongwen Hu, Patricia Brafford, Andreas Denger, Ioana Stejerean-Todoran, Rixa-Mareike Köhn, Verena Lorenz, Nicolas Künzel, Gabriela Salinas, Hedwig Stanisz, Tobias Legler, Peter Rehling, Michael P. Schön, Karl S. Lang, Volkhard Helms, Meenhard Herlyn, Markus Hoth, Carsten Kummerow, Ivan Bogeski
Journal: Cancer Research (2021)

Abstract Despite impressive advances in melanoma-directed immunotherapies, resistance is common and many patients still succumb to metastatic disease. In this context, harnessing natural killer (NK) cells, which have thus far been sidelined in the development of melanoma immunotherapy, could provide therapeutic benefits for cancer treatment. To identify molecular determinants of NK cell–mediated melanoma killing (NKmK), we quantified NK-cell cytotoxicity against a panel of genetically diverse melanoma cell lines and observed highly heterogeneous susceptibility. Melanoma protein microarrays revealed a correlation between NKmK and the abundance and activity of a subset of proteins, including several metabolic factors. Oxidative phoshorylation, measured by oxygen consumption rate, negatively correlated with melanoma cell sensitivity toward NKmK, and proteins involved in mitochondrial metabolism and epithelial–mesenchymal transition were confirmed to regulate NKmK. Two- and three-dimensional killing assays and melanoma xenografts established that the PI3K/AKT/mTOR signaling axis controls NKmK via regulation of NK cell–relevant surface proteins. A “protein-killing-signature” based on the protein analysis predicted NKmK of additional melanoma cell lines and the response of patients with melanoma to anti-PD-1 checkpoint therapy. Collectively, these findings identify novel NK cell–related prognostic biomarkers and may contribute to improved and personalized melanoma-directed immunotherapies. Significance: NK-cell cytotoxicity assays and protein microarrays reveal novel biomarkers of NK cell–mediated melanoma killing and enable development of signatures to predict melanoma patient responsiveness to immunotherapies.
Impact of sustaining SDAI remission for preventing incident of bone fragility fracture in patient with rheumatoid arthritis
Authors: Ichiro Yoshii, Naoya Sawada, Tatsumi Chijiwa, Shohei Kokei
Journal: Annals of the Rheumatic Diseases (2021)

It is well known that rheumatoid arthritis (RA) has a determinant risk for bone fragility, and patient with RA has a seriously high risk for bone fragility fracture (BFF).1 On the other hand, the BFF risks in the patient with RA owe disease activity.2 3 We hypothesised that if disease activity is successfully controlled and achieved clinical remission, adverse effects on bone metabolism would be minimised, resulting in a lower incidence of BFF.4 We therefore statistically examined whether there was a difference in the incidence of BFF between patients with and without RA who achieved clinical remission.

Patients who matched the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria under the T2T since August 2010, have been treating RA and were measured bone mineral density (BMD) with dual-energy X-ray absorptiometry, were recruited. The initial target of therapy is the attainment of remission with a Simplified Disease Activity Index (SDAI) within 6 months of initiation.5 The primary outcome was incident BFF. Follow-up started at BMD measurement (baseline) and continued until the development of the first fracture or censoring at death, loss to follow-up or end of the study. Kaplan-Meier survival curves were determined for incident BFF incidence up to the last observation. Risks for the incidence of BFF were classified as RA specific and general candidate. In general candidate, comorbidities that might affect the incidence of BFF, such as lifestyle-related diseases,6 and increased ability to fall or a disorder were included. Candidate risk factors …
Identifying barriers to equitable biomarker testing in underserved patients with NSCLC: A mixed-methods study to inform quality improvement opportunities.
Authors: Leigh Boehmer, Upal Kunal Basu Roy, Janelle Schrag, Nikki A. Martin, Gregory D. Salinas, Brandon Coleman, Alexandra Howson, Latha Shivakumar
Journal: Journal of Clinical Oncology (2021)

123 Background: Despite recent advances in cancer precision medicine, patients from underserved communities do not have equal access to biomarker testing and targeted therapies. This study used a mixed-methods approach to identify barriers to equitable precision medicine access among underserved patients with non-small cell lung cancer (NSCLC). Methods: Paired national surveys (one clinician-facing and one patient-facing) were developed respectively by the Association of Community Cancer Centers (ACCC) and LUNGevity Foundation. Administered online in spring/summer 2020, the surveys were designed to identify key attitudes/barriers related to biomarker testing, resource needs, and current practice patterns for pertinent stakeholders. Survey data was triangulated with data from focus groups (2 clinician and 6 patient) conducted in fall 2020. The study was approved by Advarra IRB. Results: A total of 99 clinicians responded, with 67% (66/99) representing oncologists from community cancer programs. 248 patients responded to the LUNGevity survey, with 161 coming from the general population and 87 from the LUNGevity network (patients with relatively high income and education levels). Most clinicians surveyed indicated they were “very” (34%) or “extremely” likely (44%) to discuss biomarker testing with NSCLC patients. Academic clinicians, however, were more likely than community-based clinicians to order testing at the time of initial biopsy (76% vs 52%, P =.02). Academic clinicians were also more likely to involve the patient’s family in biomarker testing discussions (85% vs 59%, P =.009). Patient survey results identified that medical oncologists are the primary source of biomarker testing information; 64% of LUNGevity-connected and 37% of underserved patients. Eighty-five percent of LUNGevity-connected patients receive biomarker testing versus 52% for general patients (p &lt; 0.05). Notably, more than a quarter (27%) of underserved patients who have undergone biomarker testing do not know their results. Clinician focus group participants corroborated survey findings that most clinicians receive testing results in 7-14 days, but for 23% of community and 6% of academic clinicians the process can take over 2 weeks. They identified disparities in offering biomarker testing and results to patients with known or presumed low socioeconomic status (SES) and/or health literacy. This was supported by patient survey data, which showed biomarker testing was proactively offered to only 40% of low-SES patients. Conclusions: This study identifies key areas of ongoing need related to equitable biomarker testing. Quality-improvement opportunities exist to address both clinician and patient barriers to guideline-concordant biomarker testing for underserved patients with NSCLC.
Correction to: Genome-wide sequencing as a first-tier screening test for short tandem repeat expansions
Authors: Indhu-Shree Rajan-Babu, Junran J Peng, Readman Chiu, Imagine Study, Causes Study, Chenkai Li, Arezoo Mohajeri, Egor Dolzhenko, Michael A Eberle, Inanc Birol, Jan M Friedman
Journal: Genome Medicine (2021)
The Bihormonal Bionic Pancreas Improves Glycemic Control in Individuals With Hyperinsulinism and Postpancreatectomy Diabetes: A Pilot Study
Authors: Arpana Rayannavar, Lauren M. Mitteer, Courtney A. Balliro, Firas H. El-Khatib, Katherine L. Lord, Colin P. Hawkes, Lance S. Ballester, Edward R. Damiano, Steven J. Russell, Diva D. De León
Journal: Diabetes Care (2021)

OBJECTIVE To determine whether the bihormonal bionic pancreas (BHBP) improves glycemic control and reduces hypoglycemia in individuals with congenital hyperinsulinism (HI) and postpancreatectomy diabetes (PPD) compared with usual care (UC). RESEARCH DESIGN AND METHODS Ten subjects with HI and PPD completed this open-label, crossover pilot study. Coprimary outcomes were mean glucose concentration and time with continuous glucose monitoring (CGM) glucose concentration &amp;lt;3.3 mmol/L. RESULTS Mean (SD) CGM glucose concentration was 8.3 (0.7) mmol/L in the BHBP period versus 9 (1.8) mmol/L in the UC period (P = 0.13). Mean (SD) time with CGM glucose concentration &amp;lt;3.3 mmol/L was 0% (0.002) in the BHBP period vs. 1.3% (0.018) in the UC period (P = 0.11). CONCLUSIONS Relative to UC, the BHBP resulted in comparable glycemic control in our population.
Natriuretic Peptides and Risk of Type 2 Diabetes: Results From the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium
Authors: Chaterina Sujana, Veikko Salomaa, Frank Kee, Simona Costanzo, Stefan Söderberg, Jens Jordan, Pekka Jousilahti, Charlotte Neville, Licia Iacoviello, Viktor Oskarsson, Dirk Westermann, Wolfgang Koenig, Kari Kuulasmaa, Jaakko Reinikainen, Stefan Blankenberg, Tanja Zeller, Christian Herder, Ulrich Mansmann, Annette Peters, Barbara Thorand
Journal: Diabetes Care (2021)

Natriuretic peptide (NP) concentrations are increased in cardiovascular diseases (CVDs) but are associated with a lower diabetes risk. We investigated associations of N-terminal pro-B-type NP (NT-proBNP) and midregional proatrial NP (MR-proANP) with incident type 2 diabetes stratified by the presence of CVD.Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium, we included 45,477 participants with NT-proBNP measurements (1,707 developed type 2 diabetes over 6.5 years of median follow-up; among these, 209 had CVD at baseline) and 11,537 participants with MR-proANP measurements (857 developed type 2 diabetes over 13.8 years of median follow-up; among these, 106 had CVD at baseline). The associations were estimated using multivariable Cox regression models.Both NPs were inversely associated with incident type 2 diabetes (hazard ratios [95% CI] per 1-SD increase of log NP: 0.84 [0.79; 0.89] for NT-proBNP and 0.77 [0.71; 0.83] for MR-proANP). The inverse association between NT-proBNP and type 2 diabetes was significant in individuals without CVD but not in individuals with CVD (0.81 [0.76; 0.86] vs. 1.04 [0.90; 1.19]; P multiplicative interaction = 0.001). There was no significant difference in the association of MR-proANP with type 2 diabetes between individuals without and with CVD (0.75 [0.69; 0.82] vs. 0.81 [0.66; 0.99]; P multiplicative interaction = 0.236).NT-proBNP and MR-proANP are inversely associated with incident type 2 diabetes. However, the inverse association of NT-proBNP seems to be modified by the presence of CVD. Further investigations are warranted to confirm our findings and to investigate the underlying mechanisms.
Sure Start children’s centres did so much more than prevent paediatric admissions
Authors: Gemma N Simons
Journal: BMJ (2021)

I was thrilled to see the long term data on the impact of Sure Start centres on health outcomes.1 I was lucky enough to have my children during the period the centres were available and cannot praise the scheme highly enough. They gave me a reason to get out of the house, walk for an hour, and …