tbuckley/cabot-search huggingface dataset:
Up‐regulation of thioesterase superfamily member 2 in skeletal muscle promotes hepatic steatosis and insulin resistance in mice
Authors: Norihiro Imai, Hayley T. Nicholls, Michele Alves‐Bezerra, Yingxia Li, Anna A. Ivanova, Eric A. Ortlund, David E. Cohen
Journal: Hepatology (2021)

Background and Aims Thioesterase superfamily member 2 (Them2) is highly expressed in liver and oxidative tissues, where it hydrolyzes long‐chain fatty acyl‐CoA esters to free fatty acids and CoA. Although mice globally lacking Them2 ( Them2 −/− ) are protected against diet‐induced obesity, hepatic steatosis (HS), and insulin resistance (IR), liver‐specific Them2 −/− mice remain susceptible. The aim of this study was to test whether Them2 activity in extrahepatic oxidative tissues is a primary determinant of HS and IR. Approach and Results Upon observing IR and up‐regulation of Them2 in skeletal, but not cardiac, muscle of high‐fat‐diet (HFD)‐fed wild‐type compared to Them2 −/− mice, we created mice with Them2 specifically deleted in skeletal ( S ‐ Them2 −/− ) and cardiac muscle ( C ‐ Them2 −/− ), as well as in adipose tissue ( A ‐ Them2 −/− ). When fed an HFD, S ‐ Them2 −/− , but not C ‐ Them2 −/− or A ‐ Them2 −/− , mice exhibited reduced weight gain and improved glucose homeostasis and insulin sensitivity. Reconstitution of Them2 expression in skeletal muscle of global Them2 −/− mice, using adeno‐associated virus, was sufficient to restore excess weight gain. Increased rates of fatty acid oxidation in skeletal muscle of S ‐ Them2 −/− mice contributed to protection from HFD‐induced HS by increasing VLDL triglyceride secretion rates in response to greater demand. Increases in insulin sensitivity were further attributable to alterations in production of skeletal muscle metabolites, including short‐chain fatty acids, branched‐chain amino acids, and pentose phosphate pathway intermediates, as well as in expression of myokines that modulate insulin responsiveness. Conclusions These results reveal a key role for skeletal muscle Them2 in the pathogenesis of HS and IR and implicate it as a target in the management of NAFLD.
Application of prime editing to the correction of mutations and phenotypes in adult mice with liver and eye diseases
Authors: Hyewon Jang, Dong Hyun Jo, Chang Sik Cho, Jeong Hong Shin, Jung Hwa Seo, Goosang Yu, Ramu Gopalappa, Daesik Kim, Sung-Rae Cho, Jeong Hun Kim, Hyongbum Henry Kim
Journal: Nature Biomedical Engineering (2021)
26415 Regulation of postinflammatory hyperpigmentation by niacinamide through potential modulation of the protease inhibitor, SERPINB3
Authors: Nirmala Nair, Maitreyee Dutta, Johnson Karu, Fei-Ling Lim, Anita Damodaran, Paul-Van-Der Logt
Journal: Journal of the American Academy of Dermatology (2021)
26551 Photothermal therapy using gold nanoparticles on the acne in Asians: Preliminary study
Authors: Hwa Jung Ryu, Dong-Hye Suh, Hyun Joo Kim, Tae Jun Park, Jae Yeong Jeong, Sang Jun Lee, Ko Eun Kim, Jong Heon Park
Journal: Journal of the American Academy of Dermatology (2021)
27460 Teledermatology vs in-person dermatology consultations in the emergency department: A retrospective study of the Mayo Clinic experience from 2015-2019
Authors: Alexander S. Hines, Jacqueline Zayas, David A. Wetter, Alina G. Bridges, Michael J. Camilleri, Marian T. McEvoy, Rokea A. el-Azhary, Mark.D.P. Davis, Julio C. Sartori-Valinotti
Journal: Journal of the American Academy of Dermatology (2021)
25773 A randomized, dose-escalating, double-blind study to evaluate abobotulinumtoxinA for the treatment of moderate-to-severe glabellar lines
Authors: John Joseph, Amir Moradi, Z. Paul Lorenc, Kyle Coleman, Glynis Ablon, Joely Kaufman-Janette, Sue Ellen Cox, Andrew Campbell, Steven Dayan, Girish Munavalli
Journal: Journal of the American Academy of Dermatology (2021)
Dural Arteriovenous Fistula with Retrograde Drainage into the Cortical Veins (Case Report)
Authors: A. S. Filatov, E. I. Kremneva, R. N. Konovalov, V. V. Sin’kova, A. A. Lyaskovik, A. O. Chechetkin, L. A. Dobrynina, M. V. Krotenkova
Journal: Radiology - Practice (2021)

We present clinical case of a patient who was referred for brain MRI to clarify the cause of a first-time seizure. MRI examination showed cortical and medullary veins ectasia in the left cerebral hemisphere with multiple cerebral microbleeds around the medullary veins. The revealed changes were considered as a manifestation of regional venous hypertension, however, its cause remained unclear. We decided to perform non-contrast 3D-TOF angiography that revealed a dural arteriovenous fistula between the left occipital artery and the sigmoid venous sinus with retrograde drainage into cortical veins (Borden type II, Cognard type IIb). Early diagnosis and treatment of «aggressive» dural arteriovenous fistulas avoids the development of lifethreatening complications (an annual hemorrhage rate of 8,1%).
Detecting immunoglobulins in processed sputa
Authors: Steven P Cass, Joshua J.C. McGrath, Kiho Son, Katherine Radford, Nicola LaVigne, Ditte K Klein, Sisse B Ditlev, Celeste Porsbjerg, Parameswaran Nair, Martin R. Stampfli, Manali Mukherjee
Journal: Allergy (2021)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Fam20C Regulates Bone Resorption and Breast Cancer Bone Metastasis through Osteopontin and BMP4
Authors: Hao Zuo, Dengbao Yang, Yihong Wan
Journal: Cancer Research (2021)

Fam20C is a kinase that generates the majority of secreted phosphoproteins and regulates biomineralization. However, its potential roles in bone resorption and breast cancer bone metastasis are unknown. Here we show that Fam20C in the myeloid lineage suppresses osteoclastogenesis and bone resorption, during which, osteopontin (OPN) is the most abundant phosphoprotein secreted in a Fam20C-dependent manner. OPN phosphorylation by Fam20C decreased OPN secretion, and OPN neutralization reduced Fam20C deficiency-induced osteoclast differentiation and bone metastasis. In contrast, Fam20C in breast cancer cells promoted bone metastasis by facilitating the phosphorylation and secretion of BMP4, which in turn enhanced osteoclastogenesis. Mutation of the BMP4 phosphorylation site elevated BMP4 lysosomal degradation and reduced BMP4 secretion. In breast cancer cells, BMP4 depletion or treatment with a BMP4 signaling inhibitor diminished osteoclast differentiation and bone metastasis and abolished Fam20C-mediated regulation of these processes. Collectively, this study discovers distinct roles for Fam20C in myeloid cells and breast cancer cells and highlights OPN and BMP4 as potential therapeutic targets for breast cancer bone metastasis. SIGNIFICANCE: Osteoclastogenesis and bone metastasis are suppressed by myeloid-derived Fam20C, but enhanced by breast cancer-associated Fam20C, uncovering novel Fam20C functions and new therapeutic strategies via targeting Fam20C substrates OPN and BMP4.
Retrospective Analysis of the HB A2 Value in Sickle Cell Positive Population in Central Gujarat, India
Authors: Seema S. Bhatwadekar, Parth Shah, Sandip Shah, Harsukh Toprani, Bijal Shah, Devenkumar Desai, Bhagvanji B Zanzarukiya, Tejas S Patel, Tushar Toprani
Journal: Blood (2017)
Primary cytotoxic T-cell lymphomas harbor recurrent targetable alterations in the JAK-STAT pathway
Authors: Katie Lee, Mark G. Evans, Lei Yang, Spencer Ng, Caroline Snowden, Michael Khodadoust, Ryanne A. Brown, Nicholas A. Trum, Christiane Querfeld, Linda T. Doan, Jinming Song, Hailing Zhang, Alejandro A. Gru, Gary S. Wood, David A. Wada, Vignesh Shanmugam, Paul L. Haun, Jon C. Aster, Lyn M. Duncan, Joan Guitart, David M. Weinstock, Valentina Nardi, Jaehyuk Choi
Journal: Blood (2021)
SARS-CoV-2 infection and mortality during the first epidemic wave in Madurai, south India: a prospective, active surveillance study
Authors: Ramanan Laxminarayan, Chandra Mohan B, Vinay T G, K V Arjun Kumar, Brian Wahl, Joseph A Lewnard
Journal: The Lancet Infectious Diseases (2021)

SARS-CoV-2 has spread substantially within India over multiple waves of the ongoing COVID-19 pandemic. However, the risk factors and disease burden associated with COVID-19 in India remain poorly understood. We aimed to assess predictors of infection and mortality within an active surveillance study, and to probe the completeness of case and mortality surveillance.
Upregulation of C/EBPα Inhibits Suppressive Activity of Myeloid Cells and Potentiates Antitumor Response in Mice and Patients with Cancer
Authors: Ayumi Hashimoto, Debashis Sarker, Vikash Reebye, Sheba Jarvis, Mikael H. Sodergren, Andrew Kossenkov, Emilio Sanseviero, Nina Raulf, Jenni Vasara, Pinelopi Andrikakou, Tim Meyer, Kai-Wen Huang, Ruth Plummer, Cheng E. Chee, Duncan Spalding, Madhava Pai, Shahid Khan, David J. Pinato, Rohini Sharma, Bristi Basu, Daniel Palmer, Yuk-Ting Ma, Jeff Evans, Robert Habib, Anna Martirosyan, Naouel Elasri, Adeline Reynaud, John J. Rossi, Mark Cobbold, Nagy A. Habib, Dmitry I. Gabrilovich
Journal: Clinical Cancer Research (2021)

Abstract Purpose: To evaluate the mechanisms of how therapeutic upregulation of the transcription factor, CCAAT/enhancer-binding protein alpha (C/EBPα), prevents tumor progression in patients with advanced hepatocellular carcinoma (HCC) and in different mouse tumor models. Experimental Design: We conducted a phase I trial in 36 patients with HCC (NCT02716012) who received sorafenib as part of their standard care, and were given therapeutic C/EBPα small activating RNA (saRNA; MTL-CEBPA) as either neoadjuvant or adjuvant treatment. In the preclinical setting, the effects of MTL-CEBPA were assessed in several mouse models, including BNL-1ME liver cancer, Lewis lung carcinoma (LLC), and colon adenocarcinoma (MC38). Results: MTL-CEBPA treatment caused radiologic regression of tumors in 26.7% of HCC patients with an underlying viral etiology with 3 complete responders. MTL-CEBPA treatment in those patients caused a marked decrease in peripheral blood monocytic myeloid-derived suppressor cell (M-MDSC) numbers and an overall reduction in the numbers of protumoral M2 tumor-associated macrophages (TAM). Gene and protein analysis of patient leukocytes following treatment showed CEBPA activation affected regulation of factors involved in immune-suppressive activity. To corroborate this observation, treatment of all the mouse tumor models with MTL-CEBPA led to a reversal in the suppressive activity of M-MDSCs and TAMs, but not polymorphonuclear MDSCs (PMN-MDSC). The antitumor effects of MTL-CEBPA in these tumor models showed dependency on T cells. This was accentuated when MTL-CEBPA was combined with checkpoint inhibitors or with PMN-MDSC–targeted immunotherapy. Conclusions: This report demonstrates that therapeutic upregulation of the transcription factor C/EBPα causes inactivation of immune-suppressive myeloid cells with potent antitumor responses across different tumor models and in cancer patients. MTL-CEBPA is currently being investigated in combination with pembrolizumab in a phase I/Ib multicenter clinical study (NCT04105335).
Notes From a Student
Authors: Kate E. Lee
Journal: Annals of Internal Medicine (2021)

Ad LibitumAugust 2021Notes From a StudentKate E. Lee, BAKate E. Lee, BAVagelos College of Physicians and Surgeons, Columbia University New York, New YorkSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M21-0309 Audio Reading - “Notes From a Student” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads “Notes From a Student” by Kate E. Lee, BA Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Let me introduce you to our kind.We whisper our opinions in the shadows.You can hear those at the top rumble,But you cannot hear us at the bottom;We are silent, agreeable, anonymous.Once I had a patient with diabetes.We opened a white cast on his foot andOcherous maggots greeted us a swarmingWelcome from a raw rotting crater.In January the revelries of Georgia were eclipsed by the terrors of Washington,The white Capitol a broken cast, surroundedBy ocherous fumes, seizedBy a brewing boiling myiasis.We whisper our opinions in the shadows.We chatter in the dark, unbeknownst to all;We are silent, agreeable, anonymous.... Author, Article, and Disclosure InformationAffiliations: Vagelos College of Physicians and Surgeons, Columbia University New York, New YorkCurrent Author Address: Kate E. Lee, BA, Vagelos College of Physicians and Surgeons, Columbia University, 622 W. 168th Street, PH9-105C, New York, NY 10032; e-mail, [email protected]columbia.edu. PreviousarticleNextarticle Advertisement Audio Reading - “Notes From a Student” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads “Notes From a Student” by Kate E. Lee, BA Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics August 2021Volume 174, Issue 8Page: 1196 ePublished: 17 August 2021 Issue Published: August 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 17000: Concomitant Transthyretin Cardiac Amyloidosis and Aortic Stenosis: A Systematic Review and Meta-Analysis
Authors: Jose Sleiman, Mohammad S Khan, Muhammad S Usman, Ezequiel Munoz, Sagar Ranka, Hassan N Muhammad, Anthonia Ijeli, Kaneez Fatima, Sajjad Raza, Salil Deo
Journal: Circulation (2018)

Background: Concomitant aortic stenosis (AS) and transthyretin cardiac amyloidosis (TTR-CA) in elderly population remains poorly described. Moreover, prognosis in patients with TTR-CA who undergo aortic valve replacement (AVR) is uncertain. We conducted a systematic review and meta-analysis to gain further insight. Methods: Medline, Scopus and Embase were searched from inception of these databases to May 2018 for studies reporting prevalence of TTR-CA in AS patients (surgical or trans-catheter) or prognosis of TTR-CA patients who received AVR. Pooled estimates were calculated using a random-effects model. Results: Eight studies comprising of 598 patients with AS (mean age: 75.1; males: 57.5%) were included. 63 cases had concomitant TTR-CA, with a pooled prevalence of 11.5% [6.6, 17.4]; I 2 =74%. Four studies (mean age: 76.5; males: 72.7%)] reported prognosis in patients with TTR-CA after AVR. Over a mean follow-up duration of 2.4 years, 14 of 37 patients suffered all-cause mortality (pooled incidence of mortality: 37.5% [22.8, 53.4]; I 2 =0%). Conclusion: Current meta-analysis suggests that TTR-CA in AS patients is relatively common, and has high risk of all-cause mortality after AVR. However, low event rates with wide confidence interval limit us from making conclusive statements. Further studies are needed to explore this association.
Updated USPSTF Screening Recommendations for Diabetes
Authors: Richard W. Grant, Anjali Gopalan, Marc G. Jaffe
Journal: JAMA Internal Medicine (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Association of Increased Serum Lipopolysaccharide, But Not Microbial Dysbiosis, With <scp>Obesity‐Related</scp> Osteoarthritis
Authors: Richard F. Loeser, Liubov Arbeeva, Kathryn Kelley, Anthony A. Fodor, Shan Sun, Veronica Ulici, Lara Longobardi, Yang Cui, Delisha A. Stewart, Susan J. Sumner, M. Andrea Azcarate‐Peril, R. Balfour Sartor, Ian M. Carroll, Jordan B. Renner, Joanne M. Jordan, Amanda E. Nelson
Journal: Arthritis & Rheumatology (2021)

To test the hypothesis that an altered gut microbiota (dysbiosis) plays a role in obesity-associated osteoarthritis (OA).
27533 Comparative efficacy and safety of systemic therapies used in adult and adolescent moderate-to-severe atopic dermatitis (AD): A systematic literature review (SLR) and network meta-analysis (NMA)
Authors: Jonathan I. Silverberg, Jacob P. Thyssen, Kyle Fahrbach, Kristin Mickle, Joseph C. Cappelleri, William Romero, Michael C. Cameron, Daniela E. Myers, Claire Clibborn
Journal: Journal of the American Academy of Dermatology (2021)
Pharmacokinetics, Safety, and Efficacy of Trastuzumab Deruxtecan with Concomitant Ritonavir or Itraconazole in Patients with HER2-Expressing Advanced Solid Tumors
Authors: Shunji Takahashi, Masato Karayama, Masato Takahashi, Junichiro Watanabe, Hironobu Minami, Noboru Yamamoto, Ichiro Kinoshita, Chia-Chi Lin, Young-Hyuck Im, Issei Achiwa, Emi Kamiyama, Yasuyuki Okuda, Caleb Lee, Yung-Jue Bang
Journal: Clinical Cancer Research (2021)

To evaluate drug-drug interactions between the human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate trastuzumab deruxtecan (T-DXd; DS-8201a) and the OATP1B/CYP3A inhibitor ritonavir or the strong CYP3A inhibitor itraconazole.Patients with HER2-expressing advanced solid tumors were enrolled in this phase I, open-label, single-sequence crossover study (NCT03383692) and received i.v. T-DXd 5.4 mg/kg every 3 weeks. Patients received ritonavir (cohort 1) or itraconazole (cohort 2) from day 17 of cycle 2 through the end of cycle 3. Primary endpoints were maximum serum concentration (Cmax) and partial area under the concentration-time curve from beginning of cycle through day 17 (AUC17d) for T-DXd and deruxtecan (DXd) with (cycle 3) and without (cycle 2) ritonavir or itraconazole treatment.Forty patients were enrolled (cohort 1, n = 17; cohort 2, n = 23). T-DXd Cmax was similar whether combined with ritonavir [cohort 1, cycle 3/cycle 2; 90% confidence interval (CI): 1.05 (0.98-1.13)] or itraconazole [cohort 2, 1.03 (0.96-1.09)]. T-DXd AUC17d increased from cycle 2 to 3; however, the cycle 3/cycle 2 ratio upper CI bound remained at ≤1.25 for both cohorts. For DXd (cycle 3/cycle 2), Cmax ratio was 0.99 (90% CI, 0.85-1.14) for cohort 1 and 1.04 (0.92-1.18) for cohort 2; AUC17d ratio was 1.22 (1.08-1.37) and 1.18 (1.11-1.25), respectively. The safety profile of T-DXd plus ritonavir or itraconazole was consistent with previous studies of T-DXd monotherapy. T-DXd demonstrated promising antitumor activity across HER2-expressing solid-tumor types.T-DXd was safely combined with ritonavir or itraconazole without clinically meaningful impact on T-DXd or DXd pharmacokinetics.
Prolonged solitary confinement of UK immigration detainees during the pandemic
Authors: Rachel Bingham, Hilary Pickles
Journal: BMJ (2021)

Alan Mitchell, the first doctor to be elected president of the European Committee for the Prevention of Torture, emphasises the impact of increased restrictions in prisons during the pandemic, including cells being locked for prolonged periods.1 In the UK, confinement alone or with a cellmate has extended to 22-24 hours each day.2

A recent joint report from the charities Medical Justice and Bail for Immigration Detainees describes the effects of such isolation on people …
Updates in the Treatment of Multiple Myeloma
Authors: Shaji K. Kumar
Journal: Journal of the National Comprehensive Cancer Network (2021)

The treatment of multiple myeloma is marked by many recent advances, but for newly diagnosed patients the standard of care for induction remains the combination of a proteasome inhibitor, immunomodulatory drug, and dexamethasone. The role of a 4-drug induction regimen is still being defined, but can be considered for patients with high-risk disease. For patients who are eligible to undergo stem cell transplant, this approach remains the preferred option, but transplant can be delayed until relapse if patients prefer. In those who are not eligible for transplant, based on impressive data with daratumumab/lenalidomide/dexamethasone, this triplet should be considered as initial therapy. In patients with relapsed disease, it is important to switch treatment to new drug classes; for this, multiple combinations can be recommended. Updated guidelines now include new drugs for refractory disease: selinexor and belantamab mafodotin, both listed as “other regimens” in the NCCN Guidelines, can be considered.
Jean Ross Colston
Authors: Michael Shipley
Journal: BMJ (2021)

Jean Colston was a highly respected consultant rheumatologist at the Central Middlesex Hospital from 1975 until her retirement in 1995. She was born in central London to Eric and Cathie (nee Ross) Colston. She, then 8, and her two younger brothers, Ian and Colin were evacuated to North Canton, Ohio, USA, where the headquarters of the Hoover Company was based. Their father was managing director of Hoover in the UK. They and their nanny, Ivy, set sail from Southampton in 1940 and remained happily in North America until August 1944, six weeks after D-Day. Jean and Ian were moved to boarding school in Canada in 1943 …
Atezolizumab Plus Chemotherapy for First-Line Treatment of Non-Squamous Non-Small Cell Lung Cancer: Results From the Randomized Phase III IMpower132 Trial.
Authors: Makoto Nishio, Fabrice Barlesi, Howard West, Simon Ball, Rodolfo Bordoni, Manuel Cobo, Pascale Dubray Longeras, Jerome Goldschmidt, Silvia Novello, Francisco Orlandi, Rachel E Sanborn, Zsuzsanna Szalai, Grigoriy Ursol, Diana Mendus, Lijia Wang, Xiaohui Wen, Mark McCleland, Tien Hoang, See Phan, Mark A Socinski
Journal: Journal of Thoracic Oncology (2020)
INFIMA leverages multi-omics model organism data to identify effector genes of human GWAS variants
Authors: Chenyang Dong, Shane P. Simonett, Sunyoung Shin, Donnie S. Stapleton, Kathryn L. Schueler, Gary A. Churchill, Leina Lu, Xiaoxiao Liu, Fulai Jin, Yan Li, Alan D. Attie, Mark P. Keller, Sündüz Keleş
Journal: Genome biology (2021)

Abstract Genome-wide association studies reveal many non-coding variants associated with complex traits. However, model organism studies largely remain as an untapped resource for unveiling the effector genes of non-coding variants. We develop INFIMA, In tegrative Fi ne- Ma pping, to pinpoint causal SNPs for diversity outbred (DO) mice eQTL by integrating founder mice multi-omics data including ATAC-seq, RNA-seq, footprinting, and in silico mutation analysis. We demonstrate INFIMA’s superior performance compared to alternatives with human and mouse chromatin conformation capture datasets. We apply INFIMA to identify novel effector genes for GWAS variants associated with diabetes. The results of the application are available at http://www.statlab.wisc.edu/shiny/INFIMA/ .