tbuckley/cabot-search huggingface dataset:
A high-salt diet compromises antibacterial neutrophil responses through hormonal perturbation
Authors: Katarzyna Jobin, Natascha E. Stumpf, Sebastian Schwab, Melanie Eichler, Patrick Neubert, Manfred Rauh, Marek Adamowski, Olena Babyak, Daniel Hinze, Sugirthan Sivalingam, Christina Weisheit, Katharina Hochheiser, Susanne V. Schmidt, Mirjam Meissner, Natalio Garbi, Zeinab Abdullah, Ulrich Wenzel, Michael Hölzel, Jonathan Jantsch, Christian Kurts
Journal: Science Translational Medicine (2020)

A high-salt diet in mice and humans impairs neutrophil antibacterial functions by dysregulating immunosuppressive steroid hormones.
Resistance to First-line Osimertinib in EGFR-mutant NSCLC: Tissue is the Issue
Authors: Zofia Piotrowska, Aaron N. Hata
Journal: Clinical Cancer Research (2020)

Matched pre-/posttreatment tissue biopsies from patients with EGFR-mutant non-small cell lung cancer demonstrate that histologic transformations, including both small-cell carcinoma and squamous transformation, are unexpectedly common among patients progressing on first-line osimertinib. The study highlights the key role of tissue testing and underscores the need for innovative therapeutic approaches to prevent, rather than treat, resistance.See related article by Schoenfeld et al., p. 2654.
Abstract P5-04-28: Targeting TIGIT and PD-1 in triple negative breast cancer
Authors: Apurva Kumari Pandey, Joe Marc Chauvin, Adam Brufsky, Ornella Pagliano, Mignane Ka, Carmine Menna, Priscilla McAuliffe, Hassane Zarour
Journal: Cancer Research (2020)

Abstract Background: Triple negative breast cancer is aggressive and has poor prognosis. Tumor infiltrating lymphocytes (TILs) have a prognostic value in triple negative breast cancer. Increased TILs are associated with better disease-free survival and overall survival in triple negative breast cancer (TNBC). Newly approved immunotherapy drug for metastatic triple negative breast cancer patients, Atezolizumab, has shown 10 months improvement in overall survival in for PD-L1 positive group in combination with nab-paclitaxel compared to placebo and paclitaxel. Beyond PD-1 inhibitors, there is a need to improve immunotherapy options in TNBC. TIGIT gene expression in triple negative breast cancer is associated with immune function is linked with improved relapse free survival and overall survival. CD155, a high affinity receptor for TIGIT, is expressed on tumor cells including lung and melanoma. We aim to evaluate the role of TIGIT in regulating immune response to TNBC, TIGIT cooperation with PD-1 in impeding T cell responses to TNBC, and expression of TIGIT ligands on TNBC. Methods: Fresh TNBC tumor samples were obtained from 10 untreated patients and were used for single cell suspension and multi parameter flow cytometry. Results: CD8+ and CD4+ TILs in TNBC exhibited higher PD-1 and TIGIT, yet lower CD226 expression as compared to circulating T cells. LAG-3 and TIM3 were expressed at low frequency in CD 8+ and CD 4+ cells. TNBC Tregs display high expression of TIGIT, PD-1, TIM3 but low CD226 expression. TIGIT interacts with CD155 and CD112 with high affinity and both were found to be highly expressed by TNBC tumor cells and APCs. PD-1−TIGIT+ CD8+ TILs are present at high frequency and appear to represent an activated T cell subset. PD-1+Tim-3+TIGIT+ produced less cytokines including interferon gamma, IL-2, and TNF than other CD8+ T cell subsets, representing a dysfunctional T cell subset. Conclusions: TIGIT is highly upregulated by TNBC CD8+ and CD4+ TILs while the TIGIT ligands are highly expressed by tumor cells and APCs in TNBC. In sharp contrast with metastatic melanoma, high frequency PD-1−TIGIT+CD8+ TILs are present in TNBC. Additional studies will investigate the role of dual PD-1/TIGIT blockade in increasing CD8+ TIL function in TNBC. Such data may support the dual PD-1/TIGIT blockade in TNBCs. Citation Format: Apurva Kumari Pandey, Joe Marc Chauvin, Adam Brufsky, Ornella Pagliano, Mignane Ka, Carmine Menna, Priscilla McAuliffe, Hassane Zarour. Targeting TIGIT and PD-1 in triple negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-04-28.
Endoscopic resection of large “seahorse”-shaped esophageal leiomyoma – stretching the limits of third space endoscopy
Authors: Radhika Chavan, Zaheer Nabi, Mohan Ramchandani, Anuradha Sekharan, Jignesh Reddy, D. Nageshwar Reddy
Journal: Endoscopy (2020)

A 71-year-old man presented with intermittent dysphagia to solids for 5 months. Gastroscopy showed a large globular swelling in the lower esophagus ([Fig. 1]). Computed tomography showed a large intraluminal polypoidal soft-tissue density lesion causing luminal narrowing in the distal esophagus extending to the gastroesophageal junction ([Fig. 2]). Endoscopic ultrasound showed a large homogenous non-vascular hypoechoic lesion arising from the muscularis propria. He underwent a submucosal tunneling endoscopic resection. The procedure was performed under general anesthesia with the patient in the supine position. Steps for the resection were as follows: 1) a mucosal bleb was created 2 cm above the bulge; 2) a mucosal incision was made using a triangle tip jet knife (TTJ knife; Olympus, Tokyo, Japan); 3) submucosal tunneling extending to the lower end of the lesion; 4) dissection of the lesion from surrounding attachments to the muscularis layer ([Fig. 3], [Fig. 4] and [Fig. 5]) removal of the lesion using a standard polypectomy snare ([Fig. 5]). In this case, the mucosal incision had to be extended for removal of the tumor. The lesion was approximately 11 × 3.5 cm in size (video image). Finally, the mucosal incision was closed with multiple endoclips. There were no significant intra-operative adverse events. Histopathological examination showed features of leiomyoma.
ALPPS improves survival compared with TSH in patients affected of CRLM – Survival analysis from the randomized controlled trial LIGRO
Authors: Kristina Hasselgren, Bård I. Røsok, Peter N. Larsen, Ernesto Sparrelid, Gert Lindell, Nicolai A. Schultz, Bjorn A. Bjørnbeth, Bengt Isaksson, Anna Lindhoff Larsson, Magnus Rizell, Bergthor Björnsson, Per Sandström
Journal: International Journal of Surgery (2020)
Abstract B44: Clinical utility of semiquantitative evaluation of progesterone receptor immunohistochemistry in neuroendocrine tumors of the pancreas
Authors: Sonya Purushothaman, Simona De Michele, Dorothy Low, Helen E. Remotti
Journal: Cancer Research (2019)

Abstract Purpose: Progesterone receptor (PR) is expressed strongly in a subset of neuroendocrine cells in the pancreas. Tamoxifen has long been used in adjuvant endocrine therapy of steroid hormone receptor–positive breast cancer, and currently clinical trials are assessing its use in pancreatic neuroendocrine tumors (NET) that show variable PR expression. Prior studies have reported receptor status as “positive” or “negative,” using 1% or 10% positive nuclei as a cutoff. In this study, we assessed PR immunohistochemical expression in a cohort of NET and other pancreatic nonexocrine carcinomas. Theoretically, tumors with highest PR expression are more likely to respond to adjuvant tamoxifen. Experimental Design: Immunohistochemical staining for PR was performed on tissue microarrays of 54 well-differentiated neuroendocrine tumors of the pancreas and 8 poorly differentiated carcinomas of the pancreas, including 4 acinar cell carcinomas, 2 neuroendocrine carcinomas, and 2 small-cell neuroendocrine carcinomas. A minimum of 4 separate 2-mm tumor cores were sampled on each case. Results: PR expression in non-neoplastic pancreatic islets was used for positive control. PR staining was evaluated using a semiquantitative H-score method. Positive PR staining (defined as greater than 1%) was identified in 61% (33 of 54 cases) of well-differentiated NET (mean H-score 100) and 0% (0 of 8 cases) of poorly differentiated carcinomas of the pancreas. Of the 33 PR positive cases of well-differentiated NET, 3 cases had less than 10% nuclear staining (mean H-score 7), 8 cases had 10% to less than 50% nuclear staining (mean H-score 44), and 22 cases had 50% or greater nuclear staining (mean H-score 229). Conclusions: Based on these findings, we suggest analysis of NET tumor PR expression should include a quantitative or semiquantitative score rather than dichotomized immunohistochemical evaluation of hormone receptors, particularly in the evaluation of patients’ response to clinical trials with tamoxifen. High-grade endocrine and acinar carcinomas showed no PR expression and are less likely to derive benefit from adjuvant endocrine therapy. Citation Format: Sonya Purushothaman, Simona De Michele, Dorothy Low, Helen E. Remotti. Clinical utility of semiquantitative evaluation of progesterone receptor immunohistochemistry in neuroendocrine tumors of the pancreas [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B44.
Facial Erythema in an Elderly Man
Authors: Cristian Navarrete-Dechent, Klaus J. Busam, Alina Markova
Journal: JAMA Dermatology (2020)

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Heritable arrhythmias associated with abnormal function of cardiac potassium channels
Authors: Lia Crotti, Katja E Odening, Michael C Sanguinetti
Journal: Cardiovascular Research (2020)

Cardiomyocytes express a surprisingly large number of potassium channel types. The primary physiological functions of the currents conducted by these channels are to maintain the resting membrane potential and mediate action potential repolarization under basal conditions and in response to changes in the concentrations of intracellular sodium, calcium, and ATP/ADP. Here, we review the diversity and functional roles of cardiac potassium channels under normal conditions and how heritable mutations in the genes encoding these channels can lead to distinct arrhythmias. We briefly review atrial fibrillation and J-wave syndromes. For long and short QT syndromes, we describe their genetic basis, clinical manifestation, risk stratification, traditional and novel therapeutic approaches, as well as insights into disease mechanisms provided by animal and cellular models.
The burden of non‐cardiac comorbidities and association with clinical outcomes in an acute heart failure trial – insights from ASCEND‐HF
Authors: Ankeet S. Bhatt, Andrew P. Ambrosy, Allison Dunning, Adam D. DeVore, Javed Butler, Shelby Reed, Adriaan Voors, Randall Starling, Paul W. Armstrong, Justin A. Ezekowitz, Marco Metra, Adrian F. Hernandez, Christopher M. O'Connor, Robert J. Mentz
Journal: European Journal of Heart Failure (2020)
Abstract P5-05-15: Activation of osteocytes connexin43 hemichannels suppresses breast cancer bone metastasis, a potential therapeutic target
Authors: Manuel A. Riquelme, Sumin Gu, Jeffery B. Chavez, Zhiqiang An, Jean X. Jiang
Journal: Cancer Research (2020)

Abstract Bone is a fertile place for metastasized breast cancer cell (BCC), however, mechanical loading is reported to inhibit BCC growth. Osteocytes, representing over 95% of bone cells, are mechanosensitive; they coordinate bone remodeling and modulate the extracellular environment. Mechanical loading activates osteocityc connexin 43 (Cx43) hemichannels, which mediates communication between the intracellular and extracellular space with message of molecules below 1 kDa. We have shown that ATP released by osteocytic hemichannels through the activation of BCC P2X7 receptor, inhibits BCC growth and migration. Here, we evaluate if activation of Cx43 hemichannels in osteocytes plays a critical role in inhibiting breast cancer bone metastasis. Our lab develops a monoclonal antibody, MHC2, which binds to extracellular domain of Cx43 and increases the activity of osteocytic hemichannels. This antibody was immune-reactive in HeLa cells transfected with Cx43 and osteocytes cell line MLO-Y4. It also labeled mouse osteocytes in situ. MHC2 antibody enhanced the activity of Cx43 hemichannels in cells and in vivo osteocytes and promoted the ATP release from osteocytic MLO-Y4 cells. Moreover, conditioned media collected from MHC2-treated osteocytes reduced BCC migration in vitro. The weekly injection of MHC2 reduced the breast cancer growth in bone in WT mice, but not in specific osteocyte Cx43 knockout mice. MHC2 antibody increase levels of lymphocytes T cytotoxic (CD3+/CD8+) and helper (CD3+/CD4+) in tumor and draining lymph nodes. Moreover, the weekly injection of MHC2, in intracardiac injected tumor cells model, in both immunocompetent and immune-compromised mice increased survival rate and reduced tumor spreading. As is known, osteocytic Cx43 hemichannels are permeable to ATP. We showed that P2X7 specific agonist benzoyl ATP reduced in vitro breast cancer cell migration, increased cytoplasmic free Ca2+ and induced formation of tubulin bundles, an indicator of cytoskeleton reorganization. The effect of benzoyl ATP required activation of CamKII in breast cancer cells. Our results suggest that Cx43 hemichannels are likely a potential therapeutic target in treating breast cancer growth and metastasizing to the bone, probably through the enhancement of the extracellular ATP level and the activation of P2X7/CamKII axis. Citation Format: Manuel A. Riquelme, Sumin Gu, Jeffery B. Chavez, Zhiqiang An, Jean X. Jiang. Activation of osteocytes connexin43 hemichannels suppresses breast cancer bone metastasis, a potential therapeutic target [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-05-15.
Response to: ‘Can sexual dimorphism in rheumatoid arthritis be attributed to the different abundance of<i>Gardnerella</i>?’ by Liu<i>et al</i>
Authors: Toshihiro Kishikawa, Yuichi Maeda, Takuro Nii, Yukinori Okada
Journal: Annals of the Rheumatic Diseases (2020)

Correspondence responseand RA-associated Prevotella had a symbiotic relationship in gut microbiome.Further studies are required to reveal the role of the G. vaginalis in the gut microbiome of patients with RA.Liu et al also mentioned that female patients with RA confer more severe inflammation profiles (i.e., 28-joint Disease Activity Score (DAS28)) than male patients. 8Assessing whether Gardnerella is responsible for the sexual difference of RA severity, we performed association tests between the relative abundance of G. vaginalis and DAS28-CRP, but no significant association was found (P=0.91,r=-0.013).This result indicates that Gardnerella in gut microbiome may not be related to RA severity in female samples.We hoped that researches focusing on G. vaginalis would lead to further clarification of aetiology of RA.
RED-S: not just a female phenomenon
Authors: Doug Bentall
Journal: British Journal of Sports Medicine (2020)

I ran as a schoolboy at both cross-country and middle distance athletics. After a knee injury at university, a school friend introduced me to the pleasures of cycling as a leisure pursuit. In my mid-30s, I joined my local cycle club and I continued to ride for leisure. My peak weight in my early 40s was around 73 kg. At the age of 48, I regained my interest in cycling and started doing club time trials again. My performances were considerably slower after a 12-year break, and after another, year I decided to look for the help of a cycle trainer.

Working with a trainer completely transformed my training and approach to cycling. My weight was now around 65 kg; however, after a year of gradually increased training load, my weight dipped as low as 62.5 kg. I did not make any effort to lose weight and I took advantage of the fact that I could eat more. I also did not really pay attention to the nutritional needs of being a competitive cyclist. After my first full year of training, I could beat my personal bests from my mid-30s, and investment in better cycle equipment helped to cut my times even further (figure 1).



Figure 1 
On my bike at …
Leflunomide–hydroxychloroquine combination therapy in patients with primary Sjögren's syndrome (RepurpSS-I): a placebo-controlled, double-blinded, randomised clinical trial
Authors: Eefje Hanna Martine van der Heijden, Sofie Liny Marie Blokland, Maarten Reinier Hillen, Ana Paula Pinheiro Lopes, Fréderique Marie van Vliet-Moret, Antoine Johan Wilhelm Peter Rosenberg, Nard Gabriëlle Janssen, Paco Mattheus Jacobus Welsing, Valentina Iannizzotto, Weiyang Tao, Aridaman Pandit, Francesca Barone, Aike Albert Kruize, Timothy Ruben Dirk Jan Radstake, Joel Adrianus Gijsbert van Roon
Journal: The Lancet Rheumatology (2020)
Fighting covid-19 outbreaks in prisons
Authors: Hong Yang, Julian R Thompson
Journal: BMJ (2020)

Poor prison healthcare has been reported by Armstrong.1 Improving prison health services is critical for fighting epidemics such as covid-19.

On 20 February 2020, over 500 new covid-19 cases in five prisons ended 16 days of continuous decline in new cases in China (excluding Hubei province).2 Over half were in Hubei, including 230 at Wuhan Women’s Prison and 41 at …
Abstract P3-02-11: Topographical ues overlaid with fructose-like molecules to assess breast cancer recruitment in nanofiber scaffolds
Authors: Carolynn Que, Samerender Nagam Hanumantharao, Brennan Vogl, Marina Tanasova, Smitha Rao
Journal: Cancer Research (2020)

Abstract Tumorigenesis is a complex process involving numerous cellular signaling cascades and environmental factors. While 2D cultures for stiffness measurements and more recently 3D cultures to demonstrate differences in cell structures have been reported, very little is known about the impact of sugars in cell recruitment. In this study, we report the fabrication of 3D-scaffolds with different morphologies obtained by electrospinning with fluorescent fructose-like molecular probes to study cancer cell proliferation and migration. Using a FDA approved, biocompatible and biodegradable polymer Polycaprolactone (PCL), we electrospun nanofiber scaffolds having random, aligned, and honeycomb morphologies. Scaffolds with similar morphology without the fructose mimicking analogs were fabricated and used as controls. The degradation rate of the scaffolds was also characterized to ensure long-term availability of probes and mechanical stability of PCL. Cell viability, cell morphology, formation of colonies with changes in morphology were investigated. The changes in biophysical properties of tumor microenvironment with change in morphology of the scaffolds were investigated. In vitro tests for proliferation, alignment and migration of normal breast epithelial cells (184B5), adenocarcinoma (MCF-7), pre-malignant (MCF10AneoT) and triple-negative (MDAMB231 on the scaffolds on days 1, 2, and 3 were carried out. The morphology of the scaffolds was characterized using FE-SEM; cell proliferation was assessed using CellTiter-Blue® Viability Assay; migration and cell-scaffold interactions were investigated using phalloidin for F-Actin and fructose response was determined by immunostaining for facilitative fructose transporter GLUT-5. Our data indicates that while topographical features affected cell adhesion and proliferation, cell lines that responded to the fructose-like probes tended to be more invasive. Furthermore, the preference to a specific scaffold was greatly altered by the presence of the probes with MDAMB231 showing least preference after 72 hours and pre-malignant AneoT showing highest preference. However, there was no significant difference in the cell numbers between scaffolds with probes and those without for the pre-malignant cells while this difference was noticeable in the control cell lines. Further investigation into specific response to glucose and fructose uptake through their major transporters GLUT2 and GLUT5 are currently ongoing. Citation Format: Carolynn Que, Samerender Nagam Hanumantharao, Brennan Vogl, Marina Tanasova, Smitha Rao. Topographical ues overlaid with fructose-like molecules to assess breast cancer recruitment in nanofiber scaffolds [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-02-11.
Abstract 104: Metabolic Effect of Temperature Manipulation in Healthy Individuals
Authors: Jon C Rittenberger, Katharyn Flickinger, David Hopkins, Jonathan Elmer, Frank Guyette, Cameron Dezfulian, Alexandra Weissman
Journal: Circulation (2019)

Introduction: Temperature manipulation to decrease metabolism is commonly after acute brain injury. Preclinical data suggest metabolism decreases 7-8% for each degree C drop in core temperature. We hypothesized similar results would be found in healthy individuals. Methods: Following informed consent and physical screening, we administered a 1mcg/kg bolus of dexmedetomidine followed by 20cc/kg of cold (4C) saline bolus. We cooled subjects using surface pads (emcools (Austria)). Dexmedetomidine infusion was titrated to effect (max dose &lt;1.5mcg/kg/hr). We recorded vital signs, Richmond Agitation Sedation Scale, Bedside Shivering Assessment Scale and sensation of cold every 15 minutes. We measured resting metabolism at baseline and after each 1 C decrease in temperature thereafter using indirect calorimetry and a ventilated canopy system. We analyzed data using analysis of variance. Results: Median age in the 9 enrolled subjects was 30 (SD 10) years and most (78%) were male. Median height was 173 (IQR 168, 180) cm and median weight was 77 (IQR 72, 83) kg. Baseline VO2 was 3.4 (IQR 3.0, 3.8) ml/kg/min and baseline energy expenditure was 1692 (IQR 1579, 1845) kcal/day. Both VO2 and energy expenditure decreased with core temperature (p=0.017 and p=0.027) (Table). Conclusion: Metabolic rate decreases with core temperature manipulation. The largest change occurs between 37C and 36C with smaller changes thereafter.