tbuckley/cabot-search huggingface dataset:
Endoscopic sleeve gastroplasty: suturing the gastric fundus does not confer benefit
Authors: Jad Farha, Christopher McGowan, Abdellah Hedjoudje, Mohamad I. Itani, Shahem Abbarh, Cem Simsek, Yervant Ichkhanian, Trish Vulpis, Theodore W. James, Lea Fayad, Mouen A. Khashab, Andreas Oberbach, Dilhana Badurdeen, Vivek Kumbhari
Journal: Endoscopy (2020)

BACKGROUND : There is heterogeneity regarding the technical aspects of endoscopic sleeve gastroplasty (ESG), such as applying fundal sutures. Our aim was to determine whether ESG with fundal suturing (ESG-FS) affects weight loss and the serious adverse event (SAE) rate when compared with ESG with no fundal suturing (ESG-NFS). METHODS: We conducted a two-center retrospective analysis of 247 patients who underwent ESG with or without fundal suturing. The primary outcome was percentage excess weight loss (%EWL) at 3, 6, and 12 months post-ESG. The secondary outcomes included the SAE rate and procedure duration. RESULTS: At 3, 6, and 12-months, ESG-NFS had a significantly greater mean %EWL compared with ESG-FS (38.4 % [standard deviation (SD) 15.3 %] vs. 31.2 % [SD 13.9 %], P = 0.001; 54.7 % [SD 19.2 %] vs. 37.7 % [SD 17.3 %], P < 0.001; 65.3 % [SD 21.1 %] vs. 40.6 % [SD 23.5 %], P < 0.001, respectively). There was no statistically significant difference in the SAE rates for ESG-NFS (n = 2; 2.0 %) and ESG-FS (n = 4; 2.6 %; P > 0.99). The mean procedure time was significantly shorter in the ESG-NFS group at 59.1 minutes (SD 32.7) vs. 93.0 minutes (35.5; P < 0.001), and a lower mean number of sutures were used, with 5.7 (SD 1.1) vs. 8.4 (SD 1.6; P < 0.001). CONCLUSION : ESG-NFS demonstrated greater efficacy and shorter procedure duration. Therefore, fundal suturing should not be performed.
Normal and glaucomatous outflow regulation
Authors: Ted S. Acott, Janice A. Vranka, Kate E. Keller, VijayKrishna Raghunathan, Mary J. Kelley
Journal: Progress in Retinal and Eye Research (2020)

Glaucoma remains only partially understood, particularly at the level of intraocular pressure (IOP) regulation. Trabecular meshwork (TM) and Schlemm's canal inner wall endothelium (SCE) are key to IOP regulation and their characteristics and behavior are the focus of much investigation. This is becoming more apparent with time. We and others have studied the TM and SCE's extracellular matrix (ECM) extensively and unraveled much about its functions and role in regulating aqueous outflow. Ongoing ECM turnover is required to maintain IOP regulation and several TM ECM manipulations modulate outflow facility. We have established clearly that the outflow pathway senses sustained pressure deviations and responds by adjusting the outflow resistance correctively to keep IOP within an appropriately narrow range which will not normally damage the optic nerve. The glaucomatous outflow pathway has in many cases lost this IOP homeostatic response, apparently due at least in part, to loss of TM cells. Depletion of TM cells eliminates the IOP homeostatic response, while restoration of TM cells restores it. Aqueous outflow is not homogeneous, but rather segmental with regions of high, intermediate and low flow. In general, glaucomatous eyes have more low flow regions than normal eyes. There are distinctive molecular differences between high and low flow regions, and during the response to an IOP homeostatic pressure challenge, additional changes in segmental molecular composition occur. In conjunction with these changes, the biomechanical properties of the juxtacanalicular (JCT) segmental regions are different, with low flow regions being stiffer than high flow regions. The JCT ECM of glaucomatous eyes is around 20 times stiffer than in normal eyes. The aqueous humor outflow resistance has been studied extensively, but neither the exact molecular components that comprise the resistance nor their exact location have been established. Our hypothetical model, based on considerable available data, posits that the continuous SCE basal lamina, which lies between 125 and 500 nm beneath the SCE basal surface, is the primary source of normal resistance. On the surface of JCT cells, small and highly controlled focal degradation of its components by podosome- or invadopodia-like structures, PILS, occurs in response to pressure-induced mechanical stretching. Sub-micron sized basement membrane discontinuities develop in the SCE basement membrane and these discontinuities allow passage of aqueous humor to and through SCE giant vacuoles and pores. JCT cells then relocate versican with its highly charged glycosaminoglycan side chains into the discontinuities and by manipulation of their orientation and concentration, the JCT and perhaps the SCE cells regulate the amount of fluid passage. Testing this outflow resistance hypothesis is ongoing in our lab and has the potential to advance our understanding of IOP regulation and of glaucoma.
Abstract 37: Computational analysis of the KRAS G13D colorectal cancer response to EGFR inhibition with an alternatively parameterized model
Authors: Thomas McFall, Edward C. Stites
Journal: Clinical Cancer Research (2020)

Abstract Controversially, KRAS G13D colorectal cancer patients have been reported to benefit from treatment with the EGFR inhibitor cetuximab. That EGFR inhibitors could somehow reduce signaling through a constitutively active KRAS mutant has been taken as inconsistent with known mechanisms of RAS biology. Through a combination of computational modeling and experimentation, we recently demonstrated that EGFR inhibition results in a reduction of wild-type (HRAS and NRAS) signaling in KRAS G13D colon cancer cells, but not in colon cancer cells with the other common KRAS mutants, G12D and G12V. We demonstrated this in multiple colon cancer cell lines, and we developed the hypothesis originally from our mathematical model of oncogenic RAS signal regulation adapted to biochemical rate constants for the KRAS G13D mutant. Here, we develop and analyze an alternatively parameterized version of the computational model. Analysis of this alternative model similarly suggests that EGFR inhibition causes a greater reduction of wild-type RAS signal in KRAS G13D cancers. This further substantiates our findings, analogous to demonstration in an additional cell line or an additional mouse model. In addition to reinforcing our proposed mechanism, this work also further demonstrates the power of mechanism-based computational models of protein network biochemistry in personalized cancer medicine. Note: This abstract was not presented at the conference. Citation Format: Thomas McFall, Edward C. Stites. Computational analysis of the KRAS G13D colorectal cancer response to EGFR inhibition with an alternatively parameterized model [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr 37.
Chimpanzees' technical reasoning: Taking fieldwork and ontogeny seriously
Authors: Christophe Boesch
Journal: Behavioral and Brain Sciences (2020)

Abstract Following the tradition of comparing humans with chimpanzees placed under unfavorable conditions, the authors suggest many uniquely human technological abilities. However, chimpanzees use spontaneously tools in nature to achieve many different goals demonstrating technological skills and reasoning contradicting the authors contrast. Chimpanzees and humans develop skills through the experiences faced during their upbringing and neglecting this leads to fake conclusions.
Trends in List and Net Prices of Self-administered Systemic Psoriasis Therapies Manufactured by US-Based Pharmaceutical Companies
Authors: Laura K. Ferris, Walid F. Gellad, Inmaculada Hernandez
Journal: JAMA Dermatology (2020)

This economic evaluation reviews the trends in list and net price data from SSR Health for the 2007 to 2019 period of self-administered systemic psoriasis medications manufactured in the United States.
Abstract B08: MSH2 downregulation induces chemoresistance in bladder cancer
Authors: Andrew E. Goodspeed, Annie Jean, James C. Costello
Journal: Clinical Cancer Research (2020)

Abstract Treatment of muscle-invasive bladder cancer has seen little improvement in three decades. The objective of this study is to identify genes and pathways that associate with cisplatin resistance in bladder cancer. A whole-genome, CRISPR-based screen was performed in the MGHU4 bladder cancer cell line treated with cisplatin to identify genes that mediate resistance to cisplatin. Targeted validation was performed in vitro in another bladder cancer cell line, 253J. MSH2 and MLH1 are prominent components of the mismatch repair. These are the top two genes that have the largest effect on cisplatin resistance according to our synthetic lethal screen. Bladder cancer cells with an MSH2 knockdown are resistant to cisplatin in vitro, in part due to a reduction in apoptosis. MSH2 was also investigated in a publicly available bladder cancer dataset containing 340 bladder cancer patients with treatment, protein, and survival information. Bladder cancer patients with low protein levels of MSH2 have poorer overall survival when treated with cisplatin- or carboplatin-based therapy. If confirmed in follow-up studies, MSH2 protein level may serve as a prospective biomarker of chemotherapy response in this cancer type. Note: This abstract was not presented at the conference. Citation Format: Andrew E. Goodspeed, Annie Jean, James C. Costello. MSH2 downregulation induces chemoresistance in bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr B08.
Negative tests for SARS‐CoV‐2 infection do not rule out its responsibility for chilblains: reply from the authors
Authors: L. Le Cleach, S. Fourati, E. Sbidian, M. Beylot‐Barry
Journal: British Journal of Dermatology (2020)

With great interest, we read Battesti and Descamps comment on our recently published study in this journal. Their comment is based on their findings that histological and immunostaining of skin biopsy of 7 cases of “epidemic chilblains” with negative SARS‐CoV‐2 RT‐PCR and repeated serology was similar to those of a historical series of 11 cases of chilblains lupus notably for high expression of CD123 and MxA a type‐I interferon (IFN‐I)‐induced protein in both groups1.
Retraction: Effectiveness of Surgical and Cotton Masks in Blocking SARS-CoV-2: A Controlled Comparison in 4 Patients (Annals of internal medicine (2020))
Authors: S. Bae, M. C. Kim, J. Y. Kim, H. H. Cha, J. S. Lim, J. Jung, M. J. Kim, D. K. Oh, M. K. Lee, S. H. Choi, M. Sung, S. B. Hong, J. W. Chung, S. H. Kim
Journal: Annals of Internal Medicine (2020)
Bleeding Events and Safety Outcomes in Pediatric Persons with Hemophilia A with Inhibitors: The First Non-Interventional Study (NIS) from a Real-World Setting
Authors: Johannes Oldenburg, Midori Shima, Rebecca Kruse-Jarres, Elena Santagostino, Johnny Mahlangu, Nives Selak Bienz, Sammy Chebon, Elina Asikanius, Gallia G. Levy
Journal: Blood (2017)
Evaluation of the Cost-effectiveness of Infection Control Strategies to Reduce Hospital-Onset <i>Clostridioides difficile</i> Infection
Authors: Anna K. Barker, Elizabeth Scaria, Nasia Safdar, Oguzhan Alagoz
Journal: JAMA Network Open (2020)

<h3>Importance</h3> <i>Clostridioides difficile</i>infection is the most common hospital-acquired infection in the United States, yet few studies have evaluated the cost-effectiveness of infection control initiatives targeting<i>C difficile</i>. <h3>Objective</h3> To compare the cost-effectiveness of 9<i>C difficile</i>single intervention strategies and 8 multi-intervention bundles. <h3>Design, Setting, and Participants</h3> This economic evaluation was conducted in a simulated 200-bed tertiary, acute care, adult hospital. The study relied on clinical outcomes from a published agent-based simulation model of<i>C difficile</i>transmission. The model included 4 agent types (ie, patients, nurses, physicians, and visitors). Cost and utility estimates were derived from the literature. <h3>Interventions</h3> Daily sporicidal cleaning, terminal sporicidal cleaning, health care worker hand hygiene, patient hand hygiene, visitor hand hygiene, health care worker contact precautions, visitor contact precautions,<i>C difficile</i>screening at admission, and reduced intrahospital patient transfers. <h3>Main Outcomes and Measures</h3> Cost-effectiveness was evaluated from the hospital perspective and defined by 2 measures: cost per hospital-onset<i>C difficile</i>infection averted and cost per quality-adjusted life-year (QALY). <h3>Results</h3> In this agent-based model of a simulated 200-bed tertiary, acute care, adult hospital, 5 of 9 single intervention strategies were dominant, reducing cost, increasing QALYs, and averting hospital-onset<i>C difficile</i>infection compared with baseline standard hospital practices. They were daily cleaning (most cost-effective, saving $358 268 and 36.8 QALYs annually), health care worker hand hygiene, patient hand hygiene, terminal cleaning, and reducing intrahospital patient transfers. Screening at admission cost $1283/QALY, while health care worker contact precautions and visitor hand hygiene interventions cost $123 264/QALY and $5 730 987/QALY, respectively. Visitor contact precautions was dominated, with increased cost and decreased QALYs. Adding screening, health care worker hand hygiene, and patient hand hygiene sequentially to the daily cleaning intervention formed 2-pronged, 3-pronged, and 4-pronged multi-intervention bundles that cost an additional $29 616/QALY, $50 196/QALY, and $146 792/QALY, respectively. <h3>Conclusions and Relevance</h3> The findings of this study suggest that institutions should seek to streamline their infection control initiatives and prioritize a smaller number of highly cost-effective interventions. Daily sporicidal cleaning was among several cost-saving strategies that could be prioritized over minimally effective, costly strategies, such as visitor contact precautions.
Promoting Apoptosis with Venetoclax — A Benefit for Older Patients with AML
Authors: Charles A. Schiffer
Journal: New England Journal of Medicine (2020)

Acute myeloid leukemia (AML) is a molecularly heterogeneous disorder characterized by symptoms related to pancytopenia and by an accumulation of immature myeloid precursors that is a consequence of a blockage in normal cellular differentiation. Although the therapeutic approach to AML has remained largely unchanged for the past few decades, it is notable that more than 30% of children and young adults with this disease are cured after receiving chemotherapy alone (with variations in the combination of an anthracycline and cytarabine — the "3 and 7" regimen), without stem-cell transplantation. The outcome in adults older than 60 years of age is . . .
Insights into self-healing behavior and mechanism of dicalcium phosphate dihydrate coating on biomedical Mg
Authors: Qiangsheng Dong, Xingxing Zhou, Yuanjia Feng, Kun Qian, Huan Liu, Mengmeng Lu, Chenglin Chu, Feng Xue, Jing Bai
Journal: Bioactive Materials (2020)

Self-healing coatings have been developed as smart surface coatings for Mg and its alloys to retain local corrosion from the coating damages. In this study, we prepared dicalcium phosphate dihydrate (DCPD) coating on biomedical Mg, and found that the artificial scratches in DCPD coating can be efficiently sealed by anti-corrosive products in both Hank's and normal saline (NS) solutions. Besides, the in-depth study revealed that DCPD was served as not only a physical barrier but also a self-healing agent, demonstrating an autonomous self-healing coating without embedded extra corrosion inhibitors. Moreover, Hank's solution provided foreign-aid film-forming ions to promote self-healing behavior. The findings might offer new opportunities for further studies and applications of efficient self-healing coatings on biodegradable Mg implants.
FRI0102 The outcome of lupus nephritis in malaysian patients with systemic lupus erythematosus
Authors: SS Yeap, SI Asarudin, SK Chow, CT Chua, LC Lai
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Renal disease is a common manifestation of systemic lupus erythematosus (SLE). However, there continues to be debate about the best therapeutic option(s). <h3>Objectives</h3> This objective of this study was to look at the response rate and complications of previous treatment(s) given for their lupus nephritis. <h3>Methods</h3> A retrospective cross-sectional survey of the case notes of SLE patients under current follow-up at University Hospital, Kuala Lumpur, from June to August 2000 was undertaken. <h3>Results</h3> A total of 103 patients (97F, 6M) were studied of whom 48 (46.6%) had renal involvement at presentation. The WHO classification of the first renal biopsy was: class I – 6(5.8%), class II – 10(9.7%), class III – 4(3.9%), class IV – 58(56.3%), class V – 18(17.5%). We present the results for class IV disease (Table 1). Six patients had prednisolone only of whom 2 went into remission, 3 patients had IV Cyclophosphamide (CPM) followed by oral CPM and all went into remission. Drug-related complications were noted in 63 (61.2%) patients. Prednisolone, oral CPM, IV CPM and Azathioprine (Aza) were responsible for 36.5%, 28.6%, 17.5% and 12.7% of complications respectively. <h3>Conclusion</h3> In this cohort of class IV lupus nephritis patients, IV CPM, closely followed by oral CPM, are the agents of choice in inducing remission, but this is associated with a higher complication rate than Aza alone.
Distinguishing between type 1 and type 2 diabetes
Authors: Alexandra E Butler, David Misselbrook
Journal: BMJ (2020)

### What you need to know A 33 year old man with no notable medical history attends his general practitioner reporting two months of fatigue, with no other symptoms. His mother has hypothyroidism. His body mass index is 25 kg/m2 and he has a pulse rate of 72 beats/min and blood pressure 135/88 mmHg with no postural drop. Examination is unremarkable. A random blood glucose test shows 14 mmol/L (250 mg/dL). Urinalysis is normal. The next day the patient returns, and a repeat fasting glucose test finds 14 mmol/L . This article is intended to help primary care doctors to differentiate between type 1 and type 2 diabetes when first diagnosing diabetes in a patient where the distinction is unclear. For people who fit the classic pattern of type 2 diabetes (table 1), and where two glucose test results are in the diabetic range (box 1), no further testing is required for diagnosis, and management should follow current guidelines.1 Follow-up testing of glycated haemoglobin (HbA1c) is useful to assess glycaemia over time and to tailor treatment.1 View this table: Table 1 Clinical features at presentation that help to distinguish type 1 and type 2 diabetes Box 1 ### Criteria for the diagnosis of diabetes (all types) as determined by the World Health Organization and the American Diabetes Association17RETURN TO TEXT
O-GlcNAcylation of SIX1 enhances its stability and promotes Hepatocellular Carcinoma Proliferation
Authors: Yi Chu, Mingzuo Jiang, Nan Wu, Bing Xu, Wenjiao Li, Haiming Liu, Song Su, Yanting Shi, Hao Liu, Xiaoliang Gao, Xin Fu, Di Chen, Xiaowei Li, Weijie Wang, Jie Liang, Yongzhan Nie, Daiming Fan
Journal: Theranostics (2020)

It is universally accepted that aberrant metabolism facilitates tumor growth. However, how cancer cells coordinate glucose metabolism and tumor proliferation is largely unknown. Sine oculis homeobox homolog 1 (SIX1) is a transcription factor that belongs to the SIX family and is believed to play an important role in the regulation of the Warburg effect in tumors. However, whether the role of SIX1 and the molecular mechanisms that regulate its activity are similar in hepatocellular carcinoma (HCC) still needs further investigation. Methods: Western blotting was performed to determine the levels of SIX1 and O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) in HCC tissues. Cell Counting Kit 8 (CCK8), colony formation and mouse tumor model assays were used to establish the role of SIX1 and O-GlcNAcylation in HCC processes. Mass spectrometry, immunoprecipitation and site-directed mutagenesis were performed to confirm the O-GlcNAcylation of SIX1. Results: Here, we demonstrated that SIX1, the key transcription factor regulating the Warburg effect in cancer, promotes HCC growth in vitro and in vivo. Furthermore, we revealed that SIX1 could also enhance the levels of a posttranslational modification called O-GlcNAcylation. Importantly, we found that SIX1 was also highly modified by O-GlcNAcylation and that O-GlcNAcylation inhibited the ubiquitination degradation of SIX1. In addition, site-directed mutagenesis at position 276 (T276A) decreased the O-GlcNAcylation level and reversed the protumor effect of SIX1. Conclusions: We conclude that O-GlcNAcylation of SIX1 enhances its stability and promotes HCC proliferation. Our findings illustrate a novel feedback loop of SIX1 and O-GlcNAcylation and show that O-GlcNAcylation of SIX1 is an important way to coordinate glucose metabolism and tumor progression.
The IDEAL framework for ensuring safety and effectiveness of medical devices
Authors: Peter McCulloch
Journal: BMJ (2020)

The report of the Cumberlege review documents the suffering caused by three treatments that ended up injuring many.12 The review’s recommendations include the establishment of a better voice for the patient, improved informed consent procedures, and remedies for those who have experienced harm. The most important of its objectives is to ensure that the story is not repeated. In the case …
Reply to Fenton <i>et al.</i>: An Expanded COVID-19 Telemedicine Intermediate Care Model Using Repurposed Hotel Rooms
Authors: Teresa Bruni, Ajit Lalvani, Luca Richeldi
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

To date, our jurisdiction has had great success with social distancing, self-isolation, and robust contact tracing in containing COVID-19.At the time of writing this, we have had a total of 962 cases with 15 deaths and enjoy an effective reproductive number of approximately 2.3 (recently increased from ,1.0 because of a localized and contained outbreak).Fortunately, to date, our hospitals have not been overwhelmed like some of our Canadian and international peers.As such, we have not yet had to activate this model of care.We highly appreciate the data presented by our Italian colleagues that supports the feasibility of the convalescent part of our model.It remains to be seen how our multientry point model performs relative to theirs.In summary, we applaud Bruni and colleagues (1) on their work and present a similar but more comprehensive hotel-based model of COVID-19 care.
Abstract 10700: Does Ones Socioeconomic Status Predispose to the Development of Stress Induced Cardiomyopathy?
Authors: Kareem Niazi, Stavros Zinonos, John B Kostis, William J Kostis, John Kassotis
Journal: Circulation (2019)

Introduction: Stress-induced cardiomyopathy (SIC), known as Takotsubo Cardiomyopathy, presents with chest pain and ECG changes suggestive of an acute myocardial infarction, triggered by physical or...