tbuckley/cabot-search huggingface dataset:
Safety and feasibility of laparoscopic and endoscopic cooperative surgery for duodenal neoplasm: a retrospective multicenter study
Authors: Souya Nunobe, Motonari Ri, Kimiyasu Yamazaki, Masanao Uraoka, Ken Ohata, Iwao Kitazono, Masanori Terashima, Yukinori Yamagata, Satoshi Tanabe, Nobutsugu Abe, Toshikatsu Tsuji, Keiko Niimi, Hirofumi Kawakubo, Tomoya Tsukada, Shuji Kitashiro, Naoki Ishizuka, Naoki Hiki
Journal: Endoscopy (2020)

Abstract Background A delayed perforation can often occur after endoscopic treatment for duodenal neoplasms and may be fatal due to leakage of pancreatic and bile juices. We aimed to evaluate the feasibility and safety of laparoscopic and endoscopic cooperative surgery for duodenal neoplasms (D-LECS) in a multicenter, retrospective study. Methods The clinical characteristics and surgical outcomes of 206 patients with duodenal neoplasms in whom D-LECS had initially been attempted at one of 14 institutions were reviewed retrospectively. Results Of the 206 patients, 63 (30.6 %), 128 (62.1 %), and 15 patients (7.3 %) had lesions at the bulb, second portion, and third portion of the duodenum, respectively. The rates of en bloc and R0 resections during D-LECS were 96.1 % and 95.1 %, respectively. Intraoperative and delayed perforations occurred in 10 (4.9 %) and 5 patients (2.4 %), respectively. No cases of recurrence were observed. Surgical duration of ≥ 180 minutes was an independent risk factor for postoperative complications. Conclusions The results revealed that D-LECS was performed with oncological safety and technical feasibility.
First-in-Human Gene Therapy Study of AAVhu37 Capsid Vector Technology in Severe Hemophilia A - BAY 2599023 has Broad Patient Eligibility and Stable and Sustained Long-Term Expression of FVIII
Authors: Steven W. Pipe, Francesca Ferrante, Muriel Reis, Sara Wiegmann, Claudia Lange, Manuela Braun, Lisa A Michaels
Journal: Blood (2020)
Metformin and risk of mortality in patients hospitalised with COVID-19: a retrospective cohort analysis
Authors: Carolyn T Bramante, Nicholas E Ingraham, Thomas A Murray, Schelomo Marmor, Shane Hovertsen, Jessica Gronski, Chace McNeil, Ruoying Feng, Gabriel Guzman, Nermine Abdelwahab, Samantha King, Leonardo Tamariz, Thomas Meehan, Kathryn M Pendleton, Bradley Benson, Deneen Vojta, Christopher J Tignanelli
Journal: The Lancet Healthy Longevity (2020)
AB0781 OPTIMIZATION OF APREMILAST USE IN DAILY PRACTICE BY EXPECTATION MANAGEMENT
Authors: R. Hansildaar, A. Blanken, M. Heslinga, A. Van Kuijk, M. Nurmohamed
Journal: Annals of the Rheumatic Diseases (2020)

Background: Apremilast is an oral phosphodiesterase 4 inhibitor and approved drug for treatment of Psoriatic Arthritis(PsA). Previous studies show apremilast to be efficacious and safe. (1) However, physician are sometimes reluctant to prescribe apremilast in clinical practice due to its perceived side effects, and relatively small effect size (1). Objectives: In this study we investigated the occurrence and frequencies of adverse events, and the effects of patient expectation management on drug survival for PsA patient starting apremilast. Methods: From March 2017 to December 2019, 21 consecutive patients have been included in the apremilast PsA cohort at Reade in Amsterdam, the Netherlands. The initial high dropout rate that was observed with usual care led to a revision in the baseline visit with more emphasis placed on patient expectation management. Results: From the usual care group (UCG; n=12), 10 patients (83%) stopped apremilast within the first year: 6 (50%) due to adverse events, 4 (33%) due to inefficacy. Only 2 patients (17%) completed one year of follow-up. In contrast, in the expectation management group (EMG; n=9), only 1 patient (11%) dropped out due to adverse events, and none stopped due to inefficacy. 2 patients (22%) completed one year of follow-up, the other 6 patients (67%) are within the first year of treatment (median 5 months, range 1-10; figure 1). In total 55 adverse event were reported during the study, of which 40% were gastro-intestinal (table 1). There was one serious adverse event (within in the EMG group, stroke leading to hospitalization) which was considered not related to apremilast, and the patient remained on drug. Conclusion: The most common adverse event for apremilast are gastrointestinal side effects that subsided during prolonged use. Managing patient expectations before start of apremilast increases drug survival and is helpful for optimizing apremilast use in daily practice. References: [1]Kavanaugh A, Mease PJ, Gomez-Reino JJ, Adebajo AO, Wollenhaupt J, Gladman DD, et al. Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor. Ann Rheum Dis. 2014;73(6):1020-6. Table 1. Patient reported adverse events apremilast Adverse events Mild Moderate Severe SAE Total Gastro-intestinal AE 15 7 0 0 22(40%) Mood complaints 2 1 0 0 3 (5%) Infections 8 1 0 0 9 (17%) Headache 4 1 0 0 5(9%) Others 15 1 1 1 16(29%) Total 44 11 1 1 55(100%) Disclosure of Interests: Romy Hansildaar: None declared, Annelies Blanken: None declared, Maaike Heslinga: None declared, Arno Van Kuijk: None declared, Michael Nurmohamed Grant/research support from: Not related to this research, Consultant of: Not related to this research, Speakers bureau: Not related to this research
Regional Analysis of Coccidioidomycosis Incidence — California, 2000–2018
Authors: Gail L. Sondermeyer Cooksey, Alyssa Nguyen, Duc Vugia, Seema Jain
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Coccidioidomycosis (Valley fever) is an infection caused by the soil-dwelling fungus Coccidioides spp., which usually manifests as a mild self-limited respiratory illness or pneumonia but can result in severe disseminated disease and, rarely, death (1,2). In California, coccidioidomycosis incidence increased nearly 800% from 2000 (2.4 cases per 100,000 population) to 2018 (18.8) (2-4). The California Department of Public Health (CDPH) reports statewide and county-level coccidioidomycosis incidence annually; however, a comprehensive regional analysis has not been conducted. Using California coccidioidomycosis surveillance data during 2000-2018, age-adjusted incidence rates were calculated, and coccidioidomycosis epidemiology was described in six regions. During 2000-2018, a total of 65,438 coccidioidomycosis cases were reported in California; median statewide annual incidence was 7.9 per 100,000 population and varied by region from 1.1 in Northern and Eastern California to 90.6 in the Southern San Joaquin Valley, with the largest increase (15-fold) occurring in the Northern San Joaquin Valley. When analyzing demographic data, which was available for >99% of cases for sex and age and 59% of cases for race/ethnicity, median annual incidence was high among males (10.2) and Black persons (9.0) consistently across all regions; however, incidence varied among Hispanics and adults aged 40-59 years by region. Tracking these surveillance data at the regional level reinforced understanding of where and among what demographic groups coccidioidomycosis rates have been highest and revealed where rates are increasing most dramatically. The results of this analysis influenced the planning of a statewide coccidioidomycosis awareness campaign so that the messaging, including social media and TV and radio segments, focused not only on the general population in the areas with the highest rates, but also in areas where coccidioidomycosis is increasing at the fastest rates and with messaging targeted to groups at highest risk in those areas.
352P Reproductive system disorders following chemotherapy in patients with breast cancer in Yogyakarta, Indonesia
Authors: I. Haris, R. Witaningrum, N.D. Suryani, B. Rifana, B. Leo, M.S. Hardiyanti, K.W. Taroeno-Hariadi, I. Purwanto, J. Kurnianda, Y.S. Prabandari, S.H. Hutajulu
Journal: Annals of Oncology (2020)
16833 Risks by age and sex for thyroid dysfunction in patients with hidradenitis suppurativa: Real-world data from a large urban Midwestern US dermatology patient population
Authors: Henry Bison, Rohail Memon, Anna C. Figueiredo, Eran Gwillim, Dennis P. West, Beatrice Nardone
Journal: Journal of the American Academy of Dermatology (2020)
Polysubstance Involvement in Opioid Overdose Deaths in Adolescents and Young Adults, 1999-2018
Authors: Jamie K. Lim, Joel J. Earlywine, Sarah M. Bagley, Brandon D. L. Marshall, Scott E. Hadland
Journal: JAMA Pediatrics (2020)

From 1999 to 2016, opioid-related mortality among adolescents and young adults aged 13 to 25 years (referred to as youth) increased 3-fold. 1 Opioid overdose deaths in adult populations often involve other substances, particularly benzodiazepines and, increasingly, stimulants. 2,3 Little is known about polysubstance involvement in opioid overdose deaths among youth.In this cross-sectional study, we examined national trends in polysubstance-involved opioid overdose deaths among youth in the US.
Repolarization Alternans in Dilated Pulsing Atria: A Preventable “Prelude” to Atrial Fibrillation?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Jérôme Kalifa, Masatoshi Yamazaki
Journal: Journal of the American College of Cardiology (2011)
Copper-64-Labeled Daratumumab As a PET Imaging Tracer for Multiple Myeloma: Potential Use for Minimal Residual Disease Detection
Authors: Enrico Caserta, Junie Chea, Megan Minnix, Domenico Viola, Steven Vonderfecht, Jonathan J Keats, James F Sanchez, David Colcher, John E. Shively, Amrita Krishnan, Flavia Pichiorri
Journal: Blood (2017)
Evidence for a protective role of placental growth factor in cardiovascular disease
Authors: Yihong Chen, Anna Hultgårdh Nilsson, Isabel Goncalves, Andreas Edsfeldt, Gunnar Engström, Olle Melander, Marju Orho-Melander, Uwe Rauch, Christoffer Tengryd, Shreenidhi M. Venuraju, Avijit Lahiri, Chun Liang, Jan Nilsson
Journal: Science Translational Medicine (2020)

Placental growth factor is expressed in response to cellular stress and lowers cardiovascular risk by stimulating vascular repair.
CERKL is upregulated in cutaneous squamous cell carcinoma and maintains cellular sphingolipids and resistance to oxidative stress*
Authors: J.M. Meyer, E. Lee, A. Celli, K. Park, R. Cho, W. Lambert, M. Pitchford, M. Gordon, K. Tsai, J. Cleaver, S.T. Arron, T.M. Mauro
Journal: British Journal of Dermatology (2021)

Ceramide kinase-like protein (CERKL) was originally described in retinal tissue. CERKL has been shown to protect cells from oxidative stress, and mutations in CERKL underlie the inherited disease retinitis pigmentosa. CERKL expression maintains cellular sphingolipids via an unknown mechanism.To determine whether CERKL is expressed in epidermis and cutaneous squamous cell carcinoma (cSCC) and whether CERKL expression affects cSCC sphingolipid metabolism and susceptibility to oxidative stress.CERKL expression was determined by RNA-Seq, quantitative polymerase chain reaction and immunohistochemistry. CERKL was knocked down in cSCC cells using small interfering RNA. Sphingolipid content was analysed by liquid chromatography-mass spectrometry. Oxidative stress was induced by treatment with H2 O2 , and apoptosis was measured using flow cytometry to determine annexin V binding.CERKL mRNA and protein are highly expressed in actinic keratosis and cSCC in comparison with normal epidermis. CERKL is also expressed in metabolically active epithelial cells in normal hair bulbs and sebaceous glands. CERKL knockdown in cultured cSCC cells reduces cellular sphingolipid content and enhances susceptibility to oxidative stress.These findings suggest that CERKL may be important in cSCC progression and could lead to novel strategies for prevention and treatment of cSCC.
“Positive Contrast” Inversion-Recovery With Oxide Nanoparticles-Resonant Water Suppression Magnetic Resonance Imaging: A Change for the Better?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Michael J. Lipinski, Karen C. Briley-Saebo, Venkatesh Mani, Zahi A. Fayad
Journal: Journal of the American College of Cardiology (2008)
Abstract 16681: Ability of the Intermountain Risk Score Measured in 2019 (pre-COVID) to Predict Major Adverse Health Events in Patients Positive for SARS-CoV-2 in 2020
Authors: Benjamin D Horne, Joseph B Muhlestein, Joseph R Bledsoe, Heidi T May, John F Carlquist, Ithan D Peltan, Brandon J Webb, Sterling T Bennett, Susan Rea, Tami L Bair, Stacey Knight, Brianna S Ronnow, Viet T Le, Kirk U Knowlton, Jeffrey L Anderson
Journal: Circulation (2020)

Background: The Intermountain Risk Sore (IMRS) is a general health clinical decision tool based on the complete blood count (CBC) and basic metabolic profile (BMP). IMRS was developed to predict all-cause mortality. IMRS was validated previously in patients from the US and elsewhere, including in general medical and surgical patients and in diagnosis-specific populations. IMRS has been implemented at Intermountain Healthcare to guide clinical care in hospital settings. IMRS has not been tested as a predictor of major adverse health events after diagnosis of novel coronavirus disease (COVID)-19. Methods: Intermountain patients (ages ≥18 years) with a CBC and BMP measured in 2019 and with a COVID-positive test in 2020 (N=1,025) were evaluated to determine if the pre-2020 IMRS predicted a composite of hospitalization or mortality. All study subjects tested positive for COVID between March 3 and June 8, 2020. IMRS was calculated using original sex-specific variable weightings (see Horne BD et al, Am J Med 2009). Results: Overall, 55 females and 54 males had a composite endpoint, respectively (5 and 10 deaths; 52 and 46 hospitalizations), with c-statistics of c=0.748 for females and c=0.669 for males using IMRS calculations from 2019 (see Table). For n=170 patients, IMRS was also calculated from 2020 CBC/BMP panels obtained at the time of COVID diagnosis, and it also predicted the composite endpoint at that timepoint (for females and males combined, odds ratios= 4.05, 2.46, and 1.53 for high-, moderate-, and mild-risk categories vs. low-risk; see Table for category thresholds). Conclusion: IMRS measured using 2019 CBC and BMP lab results predicted major adverse health events for patients diagnosed with COVID in 2020. Use of IMRS may empower population health with anticipation of COVID outcomes; for higher risk patients, the IMRS result may lead to enhanced preventive measures if the patient is free of COVID and, if COVID is diagnosed, it may lead to earlier, more aggressive care.
The Wearable Cardioverter-Defibrillator: Lifesaving Attire or “Fashion Faux Pas?”**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Ralph J. Verdino
Journal: Journal of the American College of Cardiology (2010)
Abstract PO-044: Epigenetic silencing of SLC17A7 promotes osteosarcoma growth
Authors: Niveditha Nerlakanti, Jeremy McGuire, Diana Yu, Damon R. Reed, Conor C. Lynch
Journal: Cancer Research (2020)

Abstract Osteosarcoma is an orphan disease with only 900 patients diagnosed each year in US. Most patients are adolescents with small number of older patients. The 5-survival rates for those with metastatic disease is only 30%. Frustratingly, there has been little change in treatment options (chemotherapy, surgery and radiotherapy) due to the difficulty of conducting clinical trials in this rare but deadly cancer. To address this, strong pre-clinical trial information is required to motivate clinical trial design. In vitro and in vivo, we identified that the pan-HDAC inhibitor, panobinostat is highly effective in limiting osteosarcoma growth and metastasis. Panobinostat is approved for the treatment of other malignancies but has noted toxicities. Therefore, to identify therapeutic targets, we explored the HDACs responsible for driving osteosarcoma metastasis and the specific genes through which those HDACs mediated their effects. Our data shows that HDAC1 and HDAC2 are key for osteosarcoma survival using siRNA approaches. Use of the HDAC1/2 selective inhibitor romidepsin in vitro and in vivo supported this finding. To identify targets being regulated by HDAC1/2, we performed microarray and proteomics analyses on romidepsin treated osteosarcoma cells. We found and validated independently that, SLC17A7, a metabolic vesicular glutamate transporter to be highly induced in response to romidepsin treatment; &amp;gt;100 fold more than base line in multiple osteosarcoma cell lines. Functionally, SLC17A7 allows entry of glutamate into the synaptic vesicles from cytoplasm and releases the glutamate from the cells via exocytosis. In our studies, we have seen that romidepsin treatment leads to reduced glutamate levels in the conditioned media and cell death indicating key roles for SLC17A7 in driving osteosarcoma progression and metastasis. In conclusion, our data shows that HDAC1/2 suppression of SLC17A7 is a novel means of promoting osteosarcoma progression and metastasis. Citation Format: Niveditha Nerlakanti, Jeremy McGuire, Diana Yu, Damon R. Reed, Conor C. Lynch. Epigenetic silencing of SLC17A7 promotes osteosarcoma growth [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PO-044.
The Unstoppable Attraction for Induced Pluripotent Stem Cells: Are They the Magic Bullet for Modeling Inherited Arrhythmogenic Diseases?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Massimiliano Gnecchi, Peter J. Schwartz
Journal: Journal of the American College of Cardiology (2012)
Vaccine-Induced Intratumoral Lymphoid Aggregates Correlate with Survival Following Treatment with a Neoadjuvant and Adjuvant Vaccine in Patients with Resectable Pancreatic Adenocarcinoma
Authors: Lei Zheng, Ding Ding, Barish H. Edil, Carol Judkins, Jennifer N. Durham, Dwayne L. Thomas, Katherine M. Bever, Guanglan Mo, Sara E. Solt, Jessica A. Hoare, Raka Bhattacharya, Qingfeng Zhu, Arsen Osipov, Beth Onner, Katrina A. Purtell, Hongyan Cai, Rose Parkinson, Amy Hacker-Prietz, Joseph M. Herman, Dung T. Le, Nilofer S. Azad, Ana M.C. De Jesus-Acosta, Alex B. Blair, Victoria Kim, Kevin C. Soares, Lindsey Manos, John L. Cameron, Martin A. Makary, Matthew J. Weiss, Richard D. Schulick, Jin He, Christopher L. Wolfgang, Elizabeth D. Thompson, Robert A. Anders, Elizabeth Sugar, Elizabeth M. Jaffee, Daniel A. Laheru
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Immunotherapy is currently ineffective for nearly all pancreatic ductal adenocarcinomas (PDAC), largely due to its tumor microenvironment (TME) that lacks antigen-experienced T effector cells (Teff). Vaccine-based immunotherapies are known to activate antigen-specific Teffs in the peripheral blood. To evaluate the effect of vaccine therapy on the PDAC TME, we designed a neoadjuvant and adjuvant clinical trial of an irradiated, GM-CSF-secreting, allogeneic PDAC vaccine (GVAX). Patients and Methods: Eighty-seven eligible patients with resectable PDAC were randomly assigned (1:1:1) to receive GVAX alone or in combination with two forms of low-dose cyclophosphamide. Resected tumors following neoadjuvant immunotherapy were assessed for the formation of tertiary lymphoid aggregates (TLA) in response to treatment. The clinical endpoints are disease-free survival (DFS) and overall survival (OS). Results: The neoadjuvant treatment with GVAX either alone or with two forms of low-dose cyclophosphamide is safe and feasible without adversely increasing the surgical complication rate. Patients in Arm A who received neoadjuvant and adjuvant GVAX alone had a trend toward longer median OS (35.0 months) than that (24.8 months) in the historical controls who received adjuvant GVAX alone. However, Arm C, who received low-dose oral cyclophosphamide in addition to GVAX, had a significantly shorter DFS than Arm A. When comparing patients with OS &amp;gt; 24 months to those with OS &amp;lt; 15 months, longer OS was found to be associated with higher density of intratumoral TLA. Conclusions: It is safe and feasible to use a neoadjuvant immunotherapy approach for PDACs to evaluate early biologic responses. In-depth analysis of TLAs is warranted in future neoadjuvant immunotherapy clinical trials.
A Two-Locus System with Strong Epistasis Underlies Rapid Parasite-Mediated Evolution of Host Resistance
Authors: Camille Ameline, Yann Bourgeois, Felix Vögtli, Eevi Savola, Jason Andras, Jan Engelstädter, Dieter Ebert
Journal: Molecular Biology and Evolution (2020)

Abstract Parasites are a major evolutionary force, driving adaptive responses in host populations. Although the link between phenotypic response to parasite-mediated natural selection and the underlying genetic architecture often remains obscure, this link is crucial for understanding the evolution of resistance and predicting associated allele frequency changes in the population. To close this gap, we monitored the response to selection during epidemics of a virulent bacterial pathogen, Pasteuria ramosa, in a natural host population of Daphnia magna. Across two epidemics, we observed a strong increase in the proportion of resistant phenotypes as the epidemics progressed. Field and laboratory experiments confirmed that this increase in resistance was caused by selection from the local parasite. Using a genome-wide association study, we built a genetic model in which two genomic regions with dominance and epistasis control resistance polymorphism in the host. We verified this model by selfing host genotypes with different resistance phenotypes and scoring their F1 for segregation of resistance and associated genetic markers. Such epistatic effects with strong fitness consequences in host–parasite coevolution are believed to be crucial in the Red Queen model for the evolution of genetic recombination.
Aldosterone Blockade in Metabolic Syndrome: Hitting the Target or Still Missing Some Links?⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: Dominic Y. Leung
Journal: JACC. Cardiovascular imaging (2011)
15989 Safety of tildrakizumab in psoriatic arthritis: An interim analysis from a randomized, double-blind, placebo-controlled phase 2b trial
Authors: Christopher T. Ritchlin, Vibeke Strand, Rocco Ballerini, Richard Chou, Stephen J. Rozzo, Alan M. Mendelsohn, Arthur Kavanaugh
Journal: Journal of the American Academy of Dermatology (2020)
Improving Surgical Cancer Care: A Rising Tide May Lift All Boats, Yet Inequity Persists
Authors: Michelle C. Salazar, Cary P. Gross
Journal: JAMA Network Open (2020)

Miranda B. Lam, MD, MBA; Katherine Raphael, BA; Winta T. Mehtsun, MD, MPH; Jessica Phelan, MA; E. John Orav, PhD; Ashish K. Jha, MD, MPH; Jose F. Figueroa, MD, MPH