tbuckley/cabot-search huggingface dataset:
CLO22-037: Tumor Lysis Syndrome and Infectious Complications During Induction With Venetoclax Combined With Azacitidine or Decitabine in Patients With Acute Myeloid Leukemia
Authors: Sankalp Arora, Carl Zainaldin, Srilakshmi Bathini, Udita Gupta, Sarah Worth, Kimo Bachiashvili, Ravi Bhatia, Kelly Godby, Omer Jamy, Sravanti Rangaraju, Barry Diamond, Josh D. Oliver, Donna Salzman, Antonio Di Stasi, Pankit Vachhani
Journal: Journal of the National Comprehensive Cancer Network (2022)

"CLO22-037: Tumor Lysis Syndrome and Infectious Complications During Induction With Venetoclax Combined With Azacitidine or Decitabine in Patients With Acute Myeloid Leukemia" published on 31 Mar 2022 by National Comprehensive Cancer Network.
Trends and risk factors for omission of early thromboprophylaxis in Australian and New Zealand ICUs between 2009 and 2020
Authors: Berhe W. Sahle, David Pilcher, Karlheinz Peter, James D. McFadyen, Tracey Bucknall
Journal: Intensive Care Medicine (2022)

Venous thromboembolism (VTE) prophylaxis is effective in reducing VTE events; however, it is underutilized in critically ill patients. We examined trends and risk factors for omission of early thromboprophylaxis within the first 24 h after admission in Australian and New Zealand intensive care units (ICUs) between 2009 and 2020.Retrospective analysis of data from the Australian New Zealand Intensive Care Society Adult Patient Database. Data were obtained for 1,465,020 adult admissions between 2009 and 2020. Mixed effects logistic regression modeling (accounting for the random effects of the contributing ICUs) was used to identify factors associated with omission of early thromboprophylaxis.A total of 107,486 (7.3%) ICU patients did not receive any form of thromboprophylaxis within the first 24 h after ICU admission without obvious reasons. Omission of early thromboprophylaxis declined from 13.7% in 2009 to 4% in 2020 (by 70.8%) (P < 0.001). Younger patients were more like to miss out on VTE prophylaxis (odds ratios (OR)per 10-year increase 0.94, 95% CI 0.95-0.99). A documented process for monitoring VTE prophylaxis (ORs 0.90, 95% CI 0.87-0.93) and having a medical lead, dedicated for coordinating ICU quality (ORper 0.1 increase in full-time equivalent 0.97, 95% CI 0.93-0.99), are associated with less omission of VTE prophylaxis.Omission of thromboprophylaxis within the first 24 h after ICU admission has declined steadily over the past decade. Documented process for monitoring VTE prophylaxis and having a medical lead for coordinating quality of ICU care could be potential targets for sustaining the improvement in VTE prophylaxis use.
Abstract P3-03-22: Use of 64Cu-DOTA trastuzumab positron emission tomography to predict pathologic complete response in locally advanced HER2 positive breast cancer
Authors: Joanne Mortimer, Russell Rockne, Jessica Liu, Yuan Yuan, Daphne Stewart, James Waisman, Paul Frankel, Laura Kruper, Vikram Adhikarla
Journal: Cancer Research (2022)

Abstract Use of 64Cu-DOTA trastuzumab Positron Emission Tomography to predict pathologic complete response in locally advanced HER2 positive breast cancer. Background: We have demonstrated that 64Cu-DOTA trastuzumab is an effective PET imaging agent of HER2 positive breast cancer and correlated with HER2 status by IHC. Methods: Patients with locally advanced breast cancer were eligible if they had biopsy confirmed HER2 + disease, locally advanced disease and were to be treated with neoadjuvant therapy. Pretreatment staging included a breast MRI, 18F-FDG-PET/CT and 64Cu-trastuzumab-PET/CT (64CuT-PET). Prior to injection of 64Cu-trastuzumab, patients received 50 mg of cold trastuzumab per our previously established protocol. 64CuT-PET was obtained at 21-25 h over fields of view chosen in reference to MRI. Uptake in lesions was measured in terms of body wt-normalized SUV. Lesions with intensity &amp;gt; adjacent tissue were considered positive on PET. Breast MRI was obtained after 4 cycles of chemotherapy and preoperatively. Response to therapy was determined on the surgical specimen. Results: Eighteen women have completed study and are evaluable for treatment response. The median age was 56 years (Range 32-62); 5 were ER- and PR-; 13 ER+/- PR+. One patient had increased 64CuT-PET uptake at T4 which was not appreciated on conventional imaging and subsequent biopsy confirmed metastatic disease. She is included in the analysis as she ultimately underwent surgical management of the breast. Complete pathologic response was seen in 14/18 patients - 11/14 ER+/- PR + and 3/4 ER-/PR-. Four patient had residual disease at surgery; 3 of 4 were HER2 negative and 1 was HER2+. Uptake on 64CuT-PET correlated with increased uptake on 18F-FDG-PET. The ratio of 64CuT-PET: 18F-FDG-PET ≥ 0.7 was associated with complete pathologic response at surgery.Conclusions: The ratio of 64CuT-PET to 18F-FDG-PET ≥ 0.7 was associated with complete pathologic response in women undergoing neoadjuvant chemotherapy for locally advanced HER2+ breast cancer. Residual disease after HER2-directed therapy was frequently HER2 negative. Citation Format: Joanne Mortimer, Russell Rockne, Jessica Liu, Yuan Yuan, Daphne Stewart, James Waisman, Paul Frankel, Laura Kruper, Vikram Adhikarla. Use of 64Cu-DOTA trastuzumab positron emission tomography to predict pathologic complete response in locally advanced HER2 positive breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-03-22.
SENP3‐mediated TIP60 deSUMOylation is required for DNA‐PKcs activity and DNA damage repair
Authors: Yang Han, Xin Huang, Xiaoyu Cao, Yuchen Li, Lei Gao, Jin Jia, Gang Li, Hejiang Guo, Xiaochang Liu, Hongling Zhao, Hua Guan, Pingkun Zhou, Shanshan Gao
Journal: MedComm (2022)

Abstract The activation of DNA‐dependent kinase (DNA‐PKcs) upon DNA damage contains a cascade of reactions, covering acetylation by TIP60, binding with Ku70/80, and autophosphorylation. However, how cells regulate TIP60‐mediated acetylation of DNA‐PKcs and the following DNA‐PKcs activation upon DNA damage remains obscure. This present study reported that TIP60 is hyper‐SUMOylated in normal conditions, but upon irradiation‐induced DNA damage, small ubiquitin‐like modifier (SUMO)‐specific protease 3 (SENP3)‐mediated deSUMOylation of TIP60 promoted its interaction with DNA‐PKcs to form the TIP60‐DNA‐PKcs complex. We show that TIP60 SUMOylation is reduced quickly in response to DNA damage and the deSUMOylation of TIP60 by SENP3 is required for DNA‐PKcs acetylation and its autophosphorylation. Comet and γH2AX immunofluorescence assay showed that knockdown of SENP3 impaired DNA damage repair. Using the NHEJ report system, we found that knockdown of SENP3 affected the efficiency of NHEJ. Further exploration using clonogenic survival assay, cell viability assay and cytoflow assay suggested that leaking SENP3 increased the sensitivity of tumour cells to serval DNA damage treatment. Overall, our findings revealed a previously unidentified role of SENP3 in regulating DNA‐PKcs activity and DNA damage repair.
Microbiota-dependent activation of the myeloid calcineurin-NFAT pathway inhibits B7H3- and B7H4-dependent anti-tumor immunity in colorectal cancer
Authors: Kenneth Peuker, Anne Strigli, Daniele V.F. Tauriello, Alexander Hendricks, Witigo von Schönfels, Greta Burmeister, Mario Brosch, Alexander Herrmann, Sandra Krüger, Jessica Nitsche, Lea Južnić, Marc Marius Geissler, Andreas Hiergeist, André Gessner, Jakob Wirbel, Ruby Priyadarshini Ponnudurai, Antje Tunger, Rebekka Wehner, Daniel E. Stange, Jürgen Weitz, Daniela E. Aust, Gustavo B. Baretton, Marc Schmitz, Christoph Röcken, Jochen Hampe, Sebastian Hinz, Georg Zeller, Triantafyllos Chavakis, Clemens Schafmayer, Eduard Batlle, Sebastian Zeissig
Journal: Immunity (2022)
ADULT DILATED CARDIOMYOPATHY DUE TO SEPTAL PREEXCITATION IN WOLFF-PARKINSONWHITE (WPW) SYNDROME MANAGED WITH RADIOFREQUENCY CATHETER ABLATION
Authors: Omar J. Baqal, Vatsal Mukesh Ladia, Hicham Z. El Masry
Journal: Journal of the American College of Cardiology (2022)
FEASIBILITY AND SAFETY OF SAME-DAY DISCHARGE FOLLOWING TRANSFEMORAL TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Toshiaki Isogai, Amar Krishnaswamy, Ankit Agrawal, Shashank Shekhar, Rishi Puri, Grant W. Reed, James Yun, Shinya Unai, Daniel Burns, Patrick R. Vargo, Samir R. Kapadia
Journal: Journal of the American College of Cardiology (2022)
PROGNOSTIC VALUE OF TRICUSPID REGURGITANT VOLUME TO RIGHT VENTRICLE END-DIASTOLIC VOLUME RATIO BY MAGNETIC RESONANCE IMAGING FOR ISOLATED SECONDARY TRICUSPID REGURGITATION
Authors: Tom Kai Ming Wang, Reza Reyaldeen, Emmanuel Akintoye, Zoran Popovic, Gosta Pettersson, A. Marc Gillinov, Scott D. Flamm, Brian P. Griffin, Milind Y. Desai
Journal: Journal of the American College of Cardiology (2022)
PERFORMANCE OF A MULTIPLE PROTEIN BIOMARKER PANEL FOR PREDICTION OF CARDIOVASCUALR EVENTS IN PATIENTS WITH DIABETES MELLITUS
Authors: Reza Mohebi, Cian P. McCarthy, Craig A Magaret, Grady Barnes, Rhonda Rhyne, Celine Peters, Hanna Kim Gaggin, James L. Januzzi
Journal: Journal of the American College of Cardiology (2022)
Errors in Byline, Author Affiliations, and Author Contributions
Journal: JAMA Network Open (2022)

Jenell Stewart, DO, MPH; Meighan L. Krows, BA; Torin T. Schaafsma, MPH; Kate B. Heller, MS; Elizabeth R. Brown, ScD; Jim Boonyaratanakornkit, MD, PhD; Clare E. Brown, MS; Hannah Leingang, MPH; Caroline Liou, MA; Anna Bershteyn, PhD; Mark D. Schwartz, MD; Vaidehi Agrawal, PhD; DeAnna Friedman-Klabanoff, MD; Stephen Eustace, BA; Helen C. Stankiewicz Karita, MD; Michael K. Paasche-Orlow, MD, MA, MPH; Patricia Kissinger, PhD; Sybil G. Hosek, PhD; Helen Y. Chu, MD, MPH; Connie Celum, MD, MPH; Jared M. Baeten, MD, PhD; Anna Wald, MD, MPH; Christine Johnston, MD, MPH; Ruanne V. Barnabas, MBChB, MSc, DPhil
IgA Nephropathy in a Patient With Metastatic Carcinoma of Unknown Primary
Authors: Shuhui Huang, Zhibing Qi, Rui Huang, Minggang Su
Journal: Clinical Nuclear Medicine (2022)

A 35-year-old man with mesenteric metastases of unknown primary was referred for 18F-FDG PET/MRI. The images demonstrated that FDG accumulated in the chest, abdomen, bilateral kidneys, and external genitalia. Renal and testicular metastases were suspected. The primary tumor was still not found. In addition, kidney biopsy findings indicated a diagnosis of IgA nephropathy.
Reply to: “COVID-19 vaccination in IMID patients receiving rituximab: A personalized regimen should be formulated”
Authors: Vartan Pahalyants, William S. Murphy, Nikolai Klebanov, Chen Lu, Nicholas Theodosakis, Monina R. Klevens, Hossein Estiri, Evelyn Lilly, Maryam Asgari, Yevgeniy R. Semenov
Journal: Journal of the American Academy of Dermatology (2022)
Shunt-type plexiform lesions identified in the Sugen5416/hypoxia rat model of pulmonary arterial hypertension using synchrotron-based phase-contrast micro-CT
Authors: Oscar van der Have, Christian Westöö, Filip Ahrné, Xuefei Tian, Kenzo Ichimura, Till Dreier, Christian Norvik, Maya E. Kumar, Edda Spiekerkoetter, Karin Tran-Lundmark
Journal: European Respiratory Journal (2022)

We recently described four distinct types of plexiform lesions in human idiopathic and familial pulmonary arterial hypertension (PAH) [1], visualising the three-dimensional lesion structure using synchrotron-based phase-contrast micro-computed tomography (SPµCT). Two types, 1 and 2, are shunt-type lesions that connect pulmonary arteries to the bronchial circulation: type 1 to the vasa vasorum, and type 2 to peribronchial vessels. Type 3 lesions are found peripherally in the lung as spherical structures abruptly terminating the distal pulmonary artery/arteriole, and type 4 lesions are characterised by recanalisation of an occluded artery/arteriole. Our observation of type 1 and type 2 lesions in PAH supports previous work that demonstrated intrapulmonary bronchopulmonary anastomoses (IBAs) connected to plexiform lesions in human PAH, suggesting that shunting of blood can occur within lesions in the setting of supra-systemic pulmonary arterial pressure [2]. Further haemodynamic studies of distinct subtypes of plexiform lesions have been hampered by the lack of available animal models with plexiform lesions representative of the full range of lesion types found in human disease. Plexiform lesions have previously been described in the Sugen5416/hypoxia rat model of pulmonary hypertension when time until sacrifice following hypoxia is extended to 13–14 weeks. Initially plexiform lesions were identified within the pulmonary artery, as well as in the form of aneurysm-like lesions projecting outside the vessel lumen [3], and recently the latter type was shown to form in supernumerary arteries [4]. However, neither study observed plexiform lesions communicating with the bronchial circulation, possibly because of methodological limitations of the histological analysis. Human like plexiform lesions identified in the prolonged Sugen5416/hypoxia rat model, visualised by synchrotron tomography imaging https://bit.ly/3KQvDHg We acknowledge the Paul Scherrer Institute, Villigen, Switzerland, for provision of synchrotron radiation beamtime at the X02DA TOMCAT beamline of the Swiss Light Source and Anne Bonnin for excellent technical assistance. We also acknowledge Phan-Kiet Tran for schematic illustrations.
LESS IS MORE···ADVERSE OUTCOMES: AN OBESITY PARADOX IN TAVR PATIENTS
Authors: Manoj Ambalavanan, Pranati Sreepathy, Aamir Twing, Helena Dickens, David Tiu, Jonathan D. Meyer, Brody Slostad, Mayank Kansal, Khalil Ibrahim, Adhir Ramesh Shroff
Journal: Journal of the American College of Cardiology (2022)
ACUTE ST-ELEVATION MYOCARDIAL INFARCTION: A CASE OF CORONARY ARTERY ECTASIA AND INTRACORONARY THROMBOLYSIS
Authors: Sachit Singal, Sanchita Singal Parulkar, Anshul B. Parulkar, Christopher Tuohy, Marwan Saad
Journal: Journal of the American College of Cardiology (2022)
Multiple Mechanisms of Photoreceptor Spectral Tuning in<i>Heliconius</i>Butterflies
Authors: Kyle J. McCulloch, Aide Macias-Muñoz, Ali Mortazavi, Adriana D. Briscoe
Journal: Molecular Biology and Evolution (2022)

The evolution of color vision is often studied through the lens of receptor gain relative to an ancestor with fewer spectral classes of photoreceptor. For instance, in Heliconius butterflies, a genus-specific UVRh opsin duplication led to the evolution of UV color discrimination in Heliconius erato females, a rare trait among butterflies. However, color vision evolution is not well understood in the context of loss. In Heliconius melpomene and Heliconius ismenius lineages, the UV2 receptor subtype has been lost, which limits female color vision in shorter wavelengths. Here, we compare the visual systems of butterflies that have either retained or lost the UV2 photoreceptor using intracellular recordings, ATAC-seq, and antibody staining. We identify several ways these butterflies modulate their color vision. In H. melpomene, chromatin reorganization has downregulated an otherwise intact UVRh2 gene, whereas in H. ismenius, pseudogenization has led to the truncation of UVRh2. In species that lack the UV2 receptor, the peak sensitivity of the remaining UV1 photoreceptor cell is shifted to longer wavelengths. Across Heliconius, we identify the widespread use of filtering pigments and co-expression of two opsins in the same photoreceptor cells. Multiple mechanisms of spectral tuning, including the molecular evolution of blue opsins, have led to the divergence of receptor sensitivities between species. The diversity of photoreceptor and ommatidial subtypes between species suggests that Heliconius visual systems are under varying selection pressures for color discrimination. Modulating the wavelengths of peak sensitivities of both the blue- and remaining UV-sensitive photoreceptor cells suggests that Heliconius species may have compensated for UV receptor loss.
Single-cell transcriptomics reveals a distinct developmental state of KMT2A-rearranged infant B-cell acute lymphoblastic leukemia
Authors: Eleonora Khabirova, Laura Jardine, Tim H. H. Coorens, Simone Webb, Taryn D. Treger, Justin Engelbert, Tarryn Porter, Elena Prigmore, Grace Collord, Alice Piapi, Sarah A. Teichmann, Sarah Inglott, Owen Williams, Olaf Heidenreich, Matthew D. Young, Karin Straathof, Simon Bomken, Jack Bartram, Muzlifah Haniffa, Sam Behjati
Journal: Nature Medicine (2022)

Abstract KMT2A- rearranged infant ALL is an aggressive childhood leukemia with poor prognosis. Here, we investigated the developmental state of KMT2A -rearranged infant B-cell acute lymphoblastic leukemia (B-ALL) using bulk messenger RNA (mRNA) meta-analysis and examination of single lymphoblast transcriptomes against a developing bone marrow reference. KMT2A -rearranged infant B-ALL was uniquely dominated by an early lymphocyte precursor (ELP) state, whereas less adverse NUTM1 -rearranged infant ALL demonstrated signals of later developing B cells, in line with most other childhood B-ALLs. We compared infant lymphoblasts with ELP cells and revealed that the cancer harbored hybrid myeloid–lymphoid features, including nonphysiological antigen combinations potentially targetable to achieve cancer specificity. We validated surface coexpression of exemplar combinations by flow cytometry. Through analysis of shared mutations in separate leukemias from a child with infant KMT2A -rearranged B-ALL relapsing as AML, we established that KMT2A rearrangement occurred in very early development, before hematopoietic specification, emphasizing that cell of origin cannot be inferred from the transcriptional state.
An Office-Based, Point-of-Care Test Predicts Treatment Outcomes With Community-Based Pelvic Floor Physical Therapy in Patients With Chronic Constipation
Authors: Eric D Shah, Elizabeth A Pelletier, Carol Greeley, Emily E Sieglinger, Jamie D Sanchez, Kayla A Northam, Jessica A Perrone, Michael A Curley, Christopher M Navas, Tracy L Ostler, Aimee R Burnett Greeley, Pablo Martinez-Camblor, Jason R Baker, Adrienne Harris, Corey A Siegel, William D Chey
Journal: Clinical Gastroenterology and Hepatology (2022)
Diminished androgen levels are linked to irritable bowel syndrome and cause bowel dysfunction in mice
Authors: Daniella Rastelli, Ariel Robinson, Valentina N. Lagomarsino, Lynley T. Matthews, Rafla Hassan, Kristina Perez, William Dan, Peter D. Yim, Madison Mixer, Aleksandra Prochera, Amy Shepherd, Liang Sun, Kathryn Hall, Sarah Ballou, Anthony Lembo, Judy Nee, Meenakshi Rao
Journal: Journal of Clinical Investigation (2021)

Functional gastrointestinal disorders (FGIDs) have prominent sex differences in incidence, symptoms, and treatment response that are not well understood. Androgens are steroid hormones present at much higher levels in males than females and could be involved in these differences. In adults with irritable bowel syndrome (IBS), a FGID that affects 5% to 10% of the population worldwide, we found that free testosterone levels were lower than those in healthy controls and inversely correlated with symptom severity. To determine how this diminished androgen signaling could contribute to bowel dysfunction, we depleted gonadal androgens in adult mice and found that this caused a profound deficit in gastrointestinal transit. Restoring a single androgen hormone was sufficient to rescue this deficit, suggesting that circulating androgens are essential for normal bowel motility in vivo. To determine the site of action, we probed androgen receptor expression in the intestine and discovered, unexpectedly, that a large subset of enteric neurons became androgen-responsive upon puberty. Androgen signaling to these neurons was required for normal colonic motility in adult mice. Taken together, these observations establish a role for gonadal androgens in the neural regulation of bowel function and link altered androgen levels with a common digestive disorder.
The regulation of cardiac intermediary metabolism by NADPH oxidases
Authors: Adam A Nabeebaccus, Christina M Reumiller, Jie Shen, Anna Zoccarato, Celio X C Santos, Ajay M Shah
Journal: Cardiovascular Research (2022)

Abstract NADPH oxidases (NOXs), enzymes whose primary function is to generate reactive oxygen species, are important regulators of the heart’s physiological function and response to pathological insults. The role of NOX-driven redox signalling in pathophysiological myocardial remodelling, including processes such as interstitial fibrosis, contractile dysfunction, cellular hypertrophy, and cell survival, is well recognized. While the NOX2 isoform promotes many detrimental effects, the NOX4 isoform has attracted considerable attention as a driver of adaptive stress responses both during pathology and under physiological states such as exercise. Recent studies have begun to define some of the NOX4-modulated mechanisms that may underlie these adaptive responses. In particular, novel functions of NOX4 in driving cellular metabolic changes have emerged. Alterations in cellular metabolism are a recognized hallmark of the heart’s response to physiological and pathological stresses. In this review, we highlight the emerging roles of NOX enzymes as important modulators of cellular intermediary metabolism in the heart, linking stress responses not only to myocardial energetics but also other functions. The novel interplay of NOX-modulated redox signalling pathways and intermediary metabolism in the heart is unravelling a new aspect of the fascinating biology of these enzymes which will inform a better understanding of how they drive adaptive responses. We also discuss the implications of these new findings for therapeutic approaches that target metabolism in cardiac disease.
P2Y12 INHIBITORS VERSUS ASPIRIN FOR LONG-TERM SECONDARY PREVENTION OF ATHEROSCLEROSIS - A META-ANALYSIS
Authors: Ahmad Al-Abdouh, Qais Radaideh, Waiel Abusnina, Mohammed Mhanna, Ahmad Jabri, Anan Abu Rmilah, Mahmoud Barbarawi, Khaldun Obeidat, Hossam Alzu’bi, Mohamed Farhan Nasser, Talal Alnabelsi, Timir K. Paul
Journal: Journal of the American College of Cardiology (2022)
ESGE news and upcoming events April 2022
Journal: Endoscopy (2022)

If you haven’t already, be sure to secure your registration for the essential international event in the endoscopy calendar. Those who can’t join us in the beautiful city of Prague can make the most of our state-of-the-art hybrid event – carefully structured to give the best possible experience to all our delegates. There is so much on offer to enrich your endoscopy practice:
FEASIBILITY OF ENROLLMENT AND INTERIM SAFETY ANALYSIS OF IL-1 BLOCKADE IN THE MULTIMODALITY ASSESSMENT OF GRANULOMAS IN CARDIAC SARCOIDOSIS - ANAKINRA RANDOMIZED TRIAL (MAGIC-ART)
Authors: Jordana Kron, Thomas Crawford, Virginia Mihalick, Todd Koelling, Frank Bogun, Emily Federmann, Huzaefah Syed, Aamer Syed, Thomas Iden, Kelly Polly, Sangeeta Lathkar-Pradhan, Kirsta Bray, Kenneth A. Ellenbogen, Benjamin Van Tassell, Greg Hundley, Jennifer H. Jordan, Antonio Abbate
Journal: Journal of the American College of Cardiology (2022)