tbuckley/cabot-search huggingface dataset:
Incidence and Determinants of Intraocular Lens Implantation in Type 2 Diabetes: The Fremantle Diabetes Study Phase II
Authors: Jocelyn J. Drinkwater, Timothy M.E. Davis, Angus W. Turner, David G. Bruce, Wendy A. Davis
Journal: Diabetes Care (2018)

To compare the incidence of intraocular lens (IOL) implantation for cataracts between people with and without type 2 diabetes and to determine associated risk factors in those with type 2 diabetes.Participants with type 2 diabetes (n = 1,499) from the community-based observational Fremantle Diabetes Study Phase II (FDS2) were age, sex, and zip code matched 1:4 with residents without diabetes. IOL implantation status was ascertained between entry (2008-2011) and the end of 2016 using validated data linkage. Age-specific incidence rates and incidence rate ratios (IRRs) for cataract surgery were calculated. Predictors of IOL implantation in FDS2 participants were assessed using proportional hazards and competing risk regression modeling.The crude IRR (95% CI) for cataract surgery in FDS2 participants (mean ± SD age 62.8 ± 10.8 years at entry) versus the matched group without diabetes was 1.50 (1.32-1.71), with the highest relative risk in those aged 45-54 years at the time of surgery (7.12 [2.05-27.66]). Competing risk analysis showed that age at entry, diabetes duration, serum HDL cholesterol, serum triglycerides, a severe hypoglycemic episode in the past year, and Asian and southern European ethnicity increased the risk of cataract surgery in participants with type 2 diabetes (P ≤ 0.025).People with type 2 diabetes, especially those in younger age-groups, are at a significantly increased risk of cataract surgery than matched people without diabetes. Multifaceted prevention strategies should be incorporated as part of routine care. As well as limiting ultraviolet light exposure, these might include lipid-modifying treatment and strategies to avoid severe hypoglycemia.
Reply to Alba Fiorentino, Angelo Errico, and Marcello Scarcia's Letter to the Editor re: Marco Moschini, Emanuele Zaffuto, Pierre I. Karakiewicz, et al. External Beam Radiotherapy Increases the Risk of Bladder Cancer When Compared with Radical Prostatectomy in Patients Affected by Prostate Cancer: A Population-based Analysis. Eur Urol 2019;75:319–28
Authors: Marco Moschini, Emanuele Zaffuto, Agostino Mattei, Pierre I. Karakiewicz, Shahrokh F. Shariat
Journal: European Urology (2018)
Paradoxical pulmonary event under tocilizumab treatment for systemic sclerosis-associated usual interstitial pneumonia
Authors: Ana Luisa Oliveira, Carina Ruano, Nuno Riso, José Cepeda Ribeiro, Maria Francisca Moraes-Fontes
Journal: Annals of the Rheumatic Diseases (2018)

We read with interest, the results of the faSScinate trial1 suggesting tocilizumab had a good safety profile in the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD). SSc-ILD is, however, a heterogeneous condition classified according to radiological and histopathological findings. Usual interstitial pneumonia (UIP) is much less frequent than non-specific interstitial pneumonia (approximately 10% and 75% respectively), with no difference in prognosis and survival reported between these two main entities.2 An earlier report in tocilizumab-treated patients with severe SSc-lung fibrosis reported respiratory function stabilisation in two but slight deterioration in one of the patients.3 Based on this evidence, we treated one patient in breast cancer remission, with clinical and functional respiratory deterioration and a UIP pattern of SSc-ILD, with off-label tocilizumab. We, hereby, report a reversible life-threatening episode of acute alveolitis that led to treatment discontinuation.

In June 2009, a previously healthy 43-year-old female smoker of Portuguese ancestry experienced Raynaud phenomenon (RP). Three months later, an oestrogen-receptor-positive ductal breast carcinoma was diagnosed and treated by tumorectomy, axillary lymphadenectomy, radiotherapy and tamoxifen. Twelve months after the onset of RP, she developed severely pruritic and diffusely progressive skin thickening, dyspnoea, gastro-oesophageal reflux, recurrent digital ulceration and large joint arthritis. By July 2010, the modified …
Acquisition of tenofovir-susceptible, emtricitabine-resistant HIV despite high adherence to daily pre-exposure prophylaxis: a case report
Authors: Stephanie E Cohen, Darpun Sachdev, Sulggi A Lee, Susan Scheer, Oliver Bacon, Miao-Jung Chen, Hideaki Okochi, Peter L Anderson, Mary F Kearney, Susa Coffey, Hyman Scott, Robert M Grant, Diane Havlir, Monica Gandhi
Journal: The Lancet HIV (2018)
Integration and delivery of palliative and supportive care.
Authors: Fredrick Otieno Okinyi, Joshua Dower, Germaine Serubuga Makory, Christy Orndorff, Jarred Gallegos, Edwin Indalo, Helena Musau, Catharine Adhiambo, Catherine Wangechi, Rosemary Rochford, Brigid Sirengo, Scot C. Remick, Walter Mwanda
Journal: Journal of Clinical Oncology (2018)

97 Background: Pediatric palliative care (PC) and end-of-life (EoL) planning and support for children, families, and providers are under-developed in Kenya. PC providers in Kenya want to build advocacy and teams to support children with life-threatening or limiting diseases and their families. Methods: KEHPCA in collaboration with UoN/KNH and US pediatric PC providers solicited applications from across the country to participate in a weeklong “train-the-trainer” workshop. The program was entirely devoted to pediatric PC and EoL care and is the “first-like” workshop to our knowledge. The program incorporated a variety of teaching and training tools that were used to support children, their families and caregivers suitable for the Kenyan setting. The cases of 7 children (7 mos. to 11 yrs) served as the focal point for training including extensive role-play scenarios. Results: The workshop convened 9-13 th July 2018 in Nairobi. KEHPCA selected 31 providers from among 130 across Kenya to participate and included medical officers, nurses, pharmacists, psychosocial workers, spiritual care, and a school teacher. Expectations were identified by participants at the start, pre- and post-conference surveys were completed, and the identical survey was submitted twice to more than 5,000 physicians listed in the Kenya Board of Medicine directory. There is a lack of awareness of the importance of PC by physicians listed in the directory responding to the same survey. The workshop was well received and ways forward identified. Conclusions: There is consensus among participants that there are five critical gaps in pediatric PC in Kenya: 1) PC requires an interdisciplinary team; 2) interdisciplinary family visits are seldom done; 3) there is a need to facilitate EoL and serious illness conversations with families/guardians and children as appropriate (adolescents in particular); 4) identify ways to support the legacy of infants and young children who pass away; and 5) a clear desire to support the healthcare team. These observations will form a solid departure point for developing programs and ways forward for Kenyan children with life-threatening illnesses. [Supported in part by: KEHPCA and NIH grant nos.: D43 TW009333.]
Radiolabeling of cell membrane-based nano-vesicles with 14C-linoleic acid for robust and sensitive quantification of their biodistribution
Authors: Nitzan Letko Khait, Natali Malkah, Galoz Kaneti, Lital Fried, Noa Cohen Anavy, Tomer Bronshtein, Marcelle Machluf
Journal: Journal of Controlled Release (2018)
Immunotherapy utilizing the combination of natural killer– and antibody dependent cellular cytotoxicity (ADCC)–mediating agents with poly (ADP-ribose) polymerase (PARP) inhibition
Authors: Kathleen E. Fenerty, Michelle Padget, Benjamin Wolfson, Sofia R. Gameiro, Zhen Su, John H. Lee, Shahrooz Rabizadeh, Patrick Soon-Shiong, James W. Hodge
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Poly (ADP-ribose) polymerase inhibitors (PARPi) prevent single-stranded DNA repair. Olaparib is a PARPi approved for the treatment of BRCA mutant ovarian and breast carcinoma. Emerging clinical data suggest a benefit of combining olaparib with immunotherapy in prostate cancer patients both with and without somatic BRCA mutations. <h3>Methods</h3> We examined if olaparib, when combined with IgG<sub>1</sub> antibody-dependent cellular cytotoxicity (ADCC)-mediating monoclonal antibodies (mAbs) cetuximab (anti-EGFR), or avelumab (anti-PD-L1), would increase tumor cell sensitivity to killing by natural killer (NK) cells independently of BRCA status or mAb target upregulation. BRCA mutant and BRCA wildtype (WT) prostate carcinoma cell lines were pretreated with olaparib and then exposed to NK cells in the presence or absence of cetuximab or avelumab. <h3>Results</h3> NK-mediated killing was significantly increased in both cell lines and was further increased using the ADCC-mediating mAbs. Pre-exposure of NK cells to recombinant IL-15/IL-15Rα further increased the lysis of olaparib treated tumor cells. In addition, olaparib treated tumor cells were killed to a significantly greater degree by engineered high-affinity NK cells (haNK). We show here for the first time that (a) olaparib significantly increased tumor cell sensitivity to NK killing and ADCC in both BRCA WT and BRCA mutant prostate carcinoma cells, independent of PD-L1 or EGFR modulation; (b) mechanistically, treatment with olaparib upregulated death receptor TRAIL-R2; and (c) olaparib significantly enhanced NK killing of additional tumor types, including breast, non-small cell lung carcinoma, and chordoma. <h3>Conclusions</h3> These studies support the combined use of NK- and ADCC-mediating agents with correctly timed PARP inhibition.
Long-Term Follow-up of SWOG S0816: Response-Adapted Therapy for Stage III/IV Hodgkin Lymphoma Demonstrates Limitations of PET-Adapted Approach
Authors: Deborah M. Stephens, Hongli Li, Heiko Schoder, David J. Straus, Craig H. Moskowitz, Michael L. Leblanc, Lisa M. Rimsza, Nancy L. Bartlett, Andrew M. Evens, Ann S. LaCasce, Paul Barr, Michael V. Knopp, Eric D. Hsi, John P. Leonard, Brad S Kahl, Sonali M. Smith, Jonathan W. Friedberg
Journal: Blood (2018)
Loss of Microbiota Diversity after Autologous Stem Cell Transplant Is Comparable to Injury in Allogeneic Stem Cell Transplant
Authors: Niloufer Khan, Jonathan U. Peled, Antonio LC Gomes, Sean M Devlin, Carlos Rondon-Clavo, Annelie Clurman, John B. Slingerland, Ann E. Slingerland, Molly Maloy, Anthony D. Sung, Nelson J. Chao, Craig S. Sauter, Heather J. Landau, Doris Ponce, Boglarka Gyurkocza, Gunjan L. Shah, Michael Scordo, Parastoo B. Dahi, Miguel-Angel Perales, Robert R. Jenq, Sergio Giralt, Eric G. Pamer, Marcel R.M. van den Brink
Journal: Blood (2018)
Noncoding regions are the main source of targetable tumor-specific antigens
Authors: Céline M. Laumont, Krystel Vincent, Leslie Hesnard, Éric Audemard, Éric Bonneil, Jean-Philippe Laverdure, Patrick Gendron, Mathieu Courcelles, Marie-Pierre Hardy, Caroline Côté, Chantal Durette, Charles St-Pierre, Mohamed Benhammadi, Joël Lanoix, Suzanne Vobecky, Elie Haddad, Sébastien Lemieux, Pierre Thibault, Claude Perreault
Journal: Science Translational Medicine (2018)

A proteogenomic method identifies potentially actionable tumor-specific antigens and shows that most of them are not coded by classic exons.
Abstract 15051: True Public Access Defibrillator Coverage is Overestimated
Authors: Christopher L Sun, Derya Demirtas, Steven C Brooks, Laurie J Morrison, Timothy C Chan
Journal: Circulation (2015)

Background: Out-of-hospital cardiac arrests (OHCAs) occur at all times of the day and night. Immediate access to an AED increases survival. However, most public-location AEDs are placed in buildings without 24 hour access. Objective: To measure fixed-location public AED coverage of OHCAs by time of day and day of week in a Canadian urban setting. Methods: We identified all atraumatic public OHCAs occurring in Toronto, Canada from Jan. 2006 – Aug. 2014. We obtained a list of registered AEDs from Toronto Emergency Medical Services as of March 2015 and determined the hours that each AED was available based on operating hours of the building housing the AED. We counted the number of OHCAs that occurred within 100 m of an AED (“assumed 24/7 coverage”) and the number that occurred both within 100 m of an AED and when the AED was available (“actual coverage”). Statistical analysis was performed using a χ 2 test. Results: We identified 2440 atraumatic public OHCAs and 737 registered AED locations. A total of 451 OHCAs were covered under assumed 24/7 coverage. In terms of actual coverage, 354 OHCAs were covered, representing a coverage loss of 25.5%. The figure shows coverage decreased by 8.6% during the day (8am-3:59pm), 28.6% in the evening (4pm-11:59pm), and 48.4% at night (12am-7:59am); the differences were statistically significant (p&lt;0.001). During the evenings, nights, and weekends the coverage loss was 31.6%, which is when the majority (66.1%) of the OHCAs occurred. The largest coverage losses were found in schools (39.7%), industrial facilities (39.3%), recreation facilities (37.1%), and offices (35.7%). Transportation facilities, long term care homes and homeless shelters had no coverage loss. Conclusion: One out of every four OHCAs in proximity of an AED occurs when that AED is inaccessible due to lack of 24/7 access. When deciding on candidate locations for placement of AEDs, temporal access should be considered to maximize the number of lives saved.
Abstract 358: Aortic Balloon Occlusion Augments the Efficacy of External Cardiopulmonary Resuscitation After Traumatic Cardiac Arrest in Swine
Authors: Jiefeng Xu, Peng Shen, Senlin Xia, Yuzhi Gao, Shaoyun Liu, Zilong Li, Mao Zhang
Journal: Circulation (2018)

Introduction: Following hemorrhage-induced traumatic cardiac arrest (TCA), the effectiveness of standard cardiopulmonary resuscitation (CPR) would be weakened or lost due to an inadequate circulating volume. Previous investigations demonstrated that aortic balloon occlusion (ABO) could control the bleeding and increase proximal organ perfusion during severe traumatic hemorrhage. In this study, we investigated the effect of ABO on the efficacy of CPR in a swine model of TCA. Hypothesis: ABO initiated during CPR would increase cardiac and cerebral perfusion so as to improve the outcomes of resuscitation after TCA in swine. Methods: Twenty-seven male domestic swine weighing 33±4 kg were utilized. Forty percent of estimated blood volume was removed within 20 mins. The animals were then subjected to 5 mins of untreated ventricular fibrillation and 5 mins of CPR. Coincident with the start of CPR, the animals were randomized to receive ABO (n=15) or control (n=12). Meanwhile, normal saline was intravenously infused at a speed of 0.7 ml/kg/min in all animals. Results: During CPR, significantly greater coronary perfusion pressure, regional cerebral oxygen saturation and end-tidal CO 2 were observed in animals treated with ABO when compared with the control group (Table). Consequently, the rate of resuscitation success was significantly higher in the ABO group than in the control group (15/15 vs. 9/12, p = 0.040). Additionally, shorter duration of CPR (5.1±0.5 vs. 7.5±4.5 min, p = 0.054) and less number of shocks (1.1±0.3 vs. 2.0±1.8, p = 0.058) were required for establishing spontaneous circulation in the ABO group compared to the control group. Conclusion: The implementation of ABO during CPR significantly increased cardiac and cerebral perfusion and improved the outcomes of resuscitation in TCA following massive hemorrhage.
Lrig2 and Hpse2, mutated in urofacial syndrome, pattern nerves in the urinary bladder
Authors: Neil A. Roberts, Emma N. Hilton, Filipa M. Lopes, Subir Singh, Michael J. Randles, Natalie J. Gardiner, Karl Chopra, Riccardo Coletta, Zunera Bajwa, Robert J. Hall, Wyatt W. Yue, Franz Schaefer, Stefanie Weber, Roger Henriksson, Helen M. Stuart, Håkan Hedman, William G. Newman, Adrian S. Woolf
Journal: Kidney International (2019)

Mutations in leucine-rich-repeats and immunoglobulin-like-domains 2 (LRIG2) or in heparanase 2 (HPSE2) cause urofacial syndrome, a devastating autosomal recessive disease of functional bladder outlet obstruction. It has been speculated that urofacial syndrome has a neural basis, but it is unknown whether defects in urinary bladder innervation are present. We hypothesized that urofacial syndrome features a peripheral neuropathy of the bladder. Mice with homozygous targeted Lrig2 mutations had urinary defects resembling those found in urofacial syndrome. There was no anatomical blockage of the outflow tract, consistent with a functional bladder outlet obstruction. Transcriptome analysis revealed differential expression of 12 known transcripts in addition to Lrig2, including 8 with established roles in neurobiology. Mice with homozygous mutations in either Lrig2 or Hpse2 had increased nerve density within the body of the urinary bladder and decreased nerve density around the urinary outflow tract. In a sample of 155 children with chronic kidney disease and urinary symptoms, we discovered novel homozygous missense LRIG2 variants that were predicted to be pathogenic in 2 individuals with non-syndromic bladder outlet obstruction. These observations provide evidence that a peripheral neuropathy is central to the pathobiology of functional bladder outlet obstruction in urofacial syndrome, and emphasize the importance of LRIG2 and heparanase 2 for nerve patterning in the urinary tract.
Elimination of the Moratorium on Gun Research Is Not Enough
Authors: Katherine He, Joseph V. Sakran
Journal: JAMA Surgery (2018)

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Reply to ‘Mosaic loss of chromosome Y in leukocytes matters’
Authors: Weiyin Zhou, Mitchell J. Machiela, Neal D. Freedman, Nathaniel Rothman, Nuria Malats, Casey Dagnall, Neil Caporaso, Lauren T. Teras, Mia M. Gaudet, Susan M. Gapstur, Victoria L. Stevens, Kevin B. Jacobs, Joshua Sampson, Demetrius Albanes, Stephanie Weinstein, Jarmo Virtamo, Sonja Berndt, Robert N. Hoover, Amanda Black, Debra Silverman, Jonine Figueroa, Montserrat Garcia-Closas, Francisco X. Real, Julie Earl, Gaelle Marenne, Benjamin Rodriguez-Santiago, Margaret Karagas, Alison Johnson, Molly Schwenn, Xifeng Wu, Jian Gu, Yuanqing Ye, Amy Hutchinson, Margaret Tucker, Luis A. Perez-Jurado, Michael Dean, Meredith Yeager, Stephen J. Chanock
Journal: Nature Genetics (2018)
Abstract P142: Daily Chocolate Consumption is Inversely Associated with Insulin Resistance and Liver Enzymes in Adults: The Observation of Cardiovascular Risk Factors Study
Authors: Ala’a Alkerwi, Nicolas Sauvageot, Georgina E. Crichton, Merrill F. Elias, Saverio Stranges, Saverio Stranges
Journal: Circulation (2016)

Introduction: Research into the health effects of cocoa has received much attention over the past few years. Several systematic reviews and meta-analyses of existing studies have generally agreed on a potentially beneficial association between chocolate consumption and risk for cardiometabolic disorders. However, evidence regarding a potential role of chocolate consumption in insulin resistance and hepatic biomarkers, from human epidemiological studies, is lacking. Hypothesis: We assessed the hypothesis that daily chocolate consumption would be inversely associated with insulin resistance and hepatic biomarkers in appraently healthy adults. Methods: A random sample of 1153 individuals, aged 18-69 years, was recruited between 2007 and 2009 to participate in the Observation of Cardiovascular Risk Factors (ORISCAV-LUX) study. Chocolate consumption in g/day was obtained from a semi-quantitative food-frequency questionnaire. Blood glucose and insulin were used for the homeostasis model assessment of insulin resistance (HOMA-IR). Hepatic biomarkers, namely serum γ-glutamyl-transpeptidase (γ-GT), serum Aspartate Transaminase (AST) and serum Alanine Transaminase (ALT) in mg/l were assessed using standard laboratory assays. Results: Chocolate consumers (81.8 %) were more likely to be younger, physically active, affluent people with higher education levels and have fewer chronic comorbidities. After exclusion of subjects taking antidiabetic medications, higher chocolate consumption was associated with lower HOMA-IR (β= -0.16, P=0.004), serum insulin levels (β= -0.16, P=0.003), and liver enzymes, including γGT (β= -0.12, P=0.009) and ALT (β= -0.09, P=0.004) after adjustment for age, sex, education, lifestyle (smoking status and physical activity) and dietary confounding factors, including daily energy intake, consumption of fruit and vegetables, alcohol, as well as polyphenol-rich coffee, and tea. Conclusion: This is the first population-based study reporting an independent inverse relationship between daily chocolate consumption and levels of insulin, HOMA-IR and liver enzymes in adults.. Small dietary changes with respect to chocolate consumption may improve liver enzymes and protect against insulin resistance, a well-established risk factor for cardiometabolic disorders.