tbuckley/cabot-search huggingface dataset:
Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer
Authors: Hervé Tiriac, Pascal Belleau, Dannielle D. Engle, Dennis Plenker, Astrid Deschênes, Tim D. D. Somerville, Fieke E. M. Froeling, Richard A. Burkhart, Robert E. Denroche, Gun-Ho Jang, Koji Miyabayashi, C. Megan Young, Hardik Patel, Michelle Ma, Joseph F. LaComb, Randze Lerie D. Palmaira, Ammar A. Javed, Jasmine C. Huynh, Molly Johnson, Kanika Arora, Nicolas Robine, Minita Shah, Rashesh Sanghvi, Austin B. Goetz, Cinthya Y. Lowder, Laura Martello, Else Driehuis, Nicolas LeComte, Gokce Askan, Christine A. Iacobuzio-Donahue, Hans Clevers, Laura D. Wood, Ralph H. Hruban, Elizabeth Thompson, Andrew J. Aguirre, Brian M. Wolpin, Aaron Sasson, Joseph Kim, Maoxin Wu, Juan Carlos Bucobo, Peter Allen, Divyesh V. Sejpal, William Nealon, James D. Sullivan, Jordan M. Winter, Phyllis A. Gimotty, Jean L. Grem, Dominick J. DiMaio, Jonathan M. Buscaglia, Paul M. Grandgenett, Jonathan R. Brody, Michael A. Hollingsworth, Grainne M. O'Kane, Faiyaz Notta, Edward Kim, James M. Crawford, Craig Devoe, Allyson Ocean, Christopher L. Wolfgang, Kenneth H. Yu, Ellen Li, Christopher R. Vakoc, Benjamin Hubert, Sandra E. Fischer, Julie M. Wilson, Richard Moffitt, Jennifer Knox, Alexander Krasnitz, Steven Gallinger, David A. Tuveson
Journal: Cancer Discovery (2018)

Pancreatic cancer is the most lethal common solid malignancy. Systemic therapies are often ineffective, and predictive biomarkers to guide treatment are urgently needed. We generated a pancreatic cancer patient-derived organoid (PDO) library that recapitulates the mutational spectrum and transcriptional subtypes of primary pancreatic cancer. New driver oncogenes were nominated and transcriptomic analyses revealed unique clusters. PDOs exhibited heterogeneous responses to standard-of-care chemotherapeutics and investigational agents. In a case study manner, we found that PDO therapeutic profiles paralleled patient outcomes and that PDOs enabled longitudinal assessment of chemosensitivity and evaluation of synchronous metastases. We derived organoid-based gene expression signatures of chemosensitivity that predicted improved responses for many patients to chemotherapy in both the adjuvant and advanced disease settings. Finally, we nominated alternative treatment strategies for chemorefractory PDOs using targeted agent therapeutic profiling. We propose that combined molecular and therapeutic profiling of PDOs may predict clinical response and enable prospective therapeutic selection.Significance: New approaches to prioritize treatment strategies are urgently needed to improve survival and quality of life for patients with pancreatic cancer. Combined genomic, transcriptomic, and therapeutic profiling of PDOs can identify molecular and functional subtypes of pancreatic cancer, predict therapeutic responses, and facilitate precision medicine for patients with pancreatic cancer. Cancer Discov; 8(9); 1112-29. ©2018 AACR.See related commentary by Collisson, p. 1062This article is highlighted in the In This Issue feature, p. 1047.
Abstract 15060: Protein-Engineered Hydrogels for Improved Efficacy of Stem Cell-Based Injection Therapy in a Murine Model of Peripheral Arterial Disease
Authors: Lei Cai, Ruby Dewi, Zachary Strassberg, Luqia Hou, Abbygail Foster, Sarah C Heilshorn, Ngan F Huang
Journal: Circulation (2015)

Introduction: Stem cell injection is a minimally invasive approach for treatment of cardiovascular diseases including peripheral arterial disease (PAD), which affects over 8 million patients in the US. However, poor cell survival and low cell retention at injection site are critical bottlenecks to the efficacy of stem cell therapy. We developed a shear-thinning and self-healing hydrogel system with controllable rigidity for stem cell encapsulation so as to enhance transplant cell viability. Hypothesis: The injectable hydrogel system will prolong cell survival under ischemic conditions and maintain cellular phenotype, in comparison to cell injection in saline. Methods: We developed a hydrogel comprised of two complementary engineered proteins that self-assemble upon simple mixing. The hydrogel network incorporates a polyethylene glycol physical crosslinker that modulates hydrogel stiffness and degradation. Bioluminescently-labeled human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) were encapsulated within the hydrogel with controllable stiffness (G'~10-800 Pa) under conditions of hypoxia (1% O2). The cells within hydrogel were then subjected to an in vitro model of injection and assayed for cell survival, proliferation, and endothelial phenotype for up to 14 days. To verify these results in an experimental model of PAD, 10^6 cells were injected in saline or in 400 Pa hydrogel into the ischemic limb in SCID mice. Results: Acutely after injection, the survival of iPSC-ECs in saline was 65%, whereas survival of iPSC-ECs in hydrogels with stiffnesses of 10, 100, 400, and 800 Pa was 94%. Bioluminescence imaging of cell viability in hypoxia for 14 days demonstrated the highest proliferation in the hydrogel with 400 Pa stiffness. In the 400 Pa hydrogel, iPSC-ECs maintained elongated morphology with robust expression of endothelial phenotypic marker, CD31. In the ischemic hindlimb, iPSC-EC retention was markedly increased with hydrogel encapsulation, compared to saline delivery. Conclusions: These findings demonstrate that stem cell encapsulation within this protein hydrogel improves cell viability, which may have therapeutic benefit for treatment of PAD and broadly to myocardial ischemia.
Prenatal Mancozeb Exposure, Excess Manganese, and Neurodevelopment at 1 Year of Age in the Infants’ Environmental Health (ISA) Study
Authors: Ana María Mora, Leonel Córdoba, Juan Camilo Cano, David Hernandez-Bonilla, Larissa Pardo, Lourdes Schnaas, Donald R. Smith, José A. Menezes-Filho, Donna Mergler, Christian H. Lindh, Brenda Eskenazi, Berna van Wendel de Joode
Journal: Environmental Health Perspectives (2018)

Background: Although growing evidence suggests that early-life excess manganese (Mn) impairs neurodevelopment, data on the neurodevelopmental effects of mancozeb, a fungicide containing Mn, and its main metabolite ethylenethiourea (ETU) are limited. Objective: We examined whether prenatal mancozeb exposure and excess Mn were associated with neurodevelopment in 355 1-y-old infants living near banana plantations with frequent aerial mancozeb spraying in Costa Rica. Methods: We measured urinary ETU, hair Mn, and blood Mn concentrations in samples collected 1–3 times during pregnancy from mothers enrolled in the Infants’ Environmental Health (ISA) study. We then assessed neurodevelopment in their 1-y-old infants using the Bayley Scales of Infant and Toddler Development, 3rd edition (BSID-III). We estimated exposure–outcome associations using linear regression models adjusted for maternal education, parity, gestational age at birth, child age, Home Observation for Measurement of the Environment score, and location of neurodevelopmental assessment. Results: Median (P25–P75) urinary ETU, hair Mn, and blood Mn measured during pregnancy were 3.3μg/L (2.4–4.9; specific gravity–corrected), 1.7μg/g (0.9–4.1), and 24.0μg/L (20.3–28.0), respectively. Among girls, higher ETU was associated with lower social-emotional scores [β per 10-fold increase=−7.4 points (95% CI: −15.2, 0.4)], whereas higher hair Mn was associated with lower cognitive scores [−3.0 (−6.1, 0.1)]. Among boys, higher hair Mn was associated with lower social-emotional scores [−4.6 (−8.5, −0.8)]. We observed null associations for blood Mn, language, and motor outcomes. Conclusions: Our findings indicate that maternal exposure to mancozeb and excess Mn during pregnancy may have adverse and sex-specific effects on infant neurodevelopment. https://doi.org/10.1289/EHP1955
Syphilis and gonorrhoea cases rose by a fifth in England last year
Authors: Gareth Iacobucci
Journal: BMJ (2018)

England saw a spike in cases of syphilis and gonorrhoea last year, with cases rising by a fifth, official figures have shown.

Public Health England’s (PHE) latest report into rates of sexually transmitted infections (STIs) showed a 20% rise in syphilis cases from 2016 to 2017 (up from 5955 to 7137) and a 22% rise in gonorrhoea cases (from 36 577 to 44 676).1

The overall rates of STIs remained stable in 2016-17. The highest rates of diagnoses across …
Mapping of genomic EGFRvIII deletions in glioblastoma: insight into rearrangement mechanisms and biomarker development
Authors: Tomoyuki Koga, Bin Li, Javier M Figueroa, Bing Ren, Clark C Chen, Bob S Carter, Frank B Furnari
Journal: Neuro-Oncology (2018)

Epidermal growth factor receptor (EGFR) variant III (vIII) is the most common oncogenic rearrangement in glioblastoma (GBM), generated by deletion of exons 2 to 7 of EGFR. The proximal breakpoints occur in variable positions within the 123-kb intron 1, presenting significant challenges in terms of polymerase chain reaction (PCR)–based mapping. Molecular mechanisms underlying these deletions remain unclear. We determined the presence of EGFRvIII and its breakpoints for 29 GBM samples using quantitative PCR, arrayed PCR mapping, Sanger sequencing, and whole genome sequencing (WGS). Patient-specific breakpoint PCR was performed on tumors, plasma, and cerebrospinal fluid (CSF) samples. The breakpoint sequences and single nucleotide polymorphisms (SNPs) were analyzed to elucidate the underlying biogenic mechanism. PCR mapping and WGS independently unveiled 8 EGFRvIII breakpoints in 6 tumors. Patient-specific primers yielded EGFRvIII PCR amplicons in matched tumors and in cell-free DNA (cfDNA) from a CSF sample, but not in cfDNA or extracellular-vesicle DNA from plasma. The breakpoint analysis revealed nucleotide insertions in 4 samples, an insertion of a region outside of the EGFR locus in 1, microhomologies in 3, as well as a duplication or an inversion accompanied by microhomologies in 2, suggestive of distinct DNA repair mechanisms. In the GBM samples that harbored distinct breakpoints, the SNP compositions of EGFRvIII and amplified non-vIII EGFR were identical, suggesting that these rearrangements arose from amplified non-vIII EGFR. Our approach efficiently "fingerprints" each sample's EGFRvIII breakpoints. Breakpoint sequence analyses suggest that independent breakpoints arose from precursor amplified non-vIII EGFR through different DNA repair mechanisms.
Evaluating Outcomes in Trauma After Medicaid Expansion Under The Affordable Care Act
Authors: Joseph V. Sakran
Journal: JAMA Surgery (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Thromboembolic events in advanced pancreatic cancer: A systematic review.
Authors: Mann Muhsin, Omar Dabbous, Blake Morrison, Piet Vervaet, Dimitrios Chondros
Journal: Journal of Clinical Oncology (2018)

461 Background: Pancreatic ductal adenocarcinoma (PDA) is highly associated with thromboembolic events (TEs). There is no consensus for prophylaxis of TEs across thromboprophylactic guidelines in ambulatory patient settings. Published ASCO (2014) and ESMO (2011) guidelines recommend use of primary thromboprophylaxis in pancreatic cancer outpatients at high risk of TEs. This systematic review investigated TE rates and prophylaxis among advanced PDA patients. Methods: A literature review identified clinical trials and observational studies reporting TE rates with and without thromboprophylaxis in PDA patients undergoing chemotherapy. A search was conducted using electronic databases including Medline, Medline In-Process, and Embase; limited to English language and publication between 1990 and April 2017. Retrieved articles were cross-referenced and scrutinized to identify additional publications. Results: Seven studies were identified; 2 randomized clinical trials (RCTs) and 5 observational/retrospective studies met the stated criteria. The TE rate in PDA in the 5 observational studies without prophylaxis ranged from 9.6% to 36.0%. Thromboprophylaxis was used in the 2 RCTs and was associated with lower TE rates. Conclusions: This comprehensive literature review shows that PDA patients face a substantial risk of TE after chemotherapy. The high rates of TEs in PDA, and the effectiveness of thromboprophylaxis in patients with PDA, highlight the importance of having consensus for prophylaxis of TEs across thromboprophylactic guidelines in ambulatory patient settings as a critical early preventive measure during the treatment of patients with advanced PDA. [Table: see text]
The impact of a breast cancer diagnosis on women’s work status.
Authors: Lucinda Barry, Leanne Storer, Meron Pitcher
Journal: Journal of Clinical Oncology (2018)

23 Background: The diagnosis and treatment of cancer often causes financial stress, partly by impacting on the ability to continue in paid employment. Our aim was to identify changes in work status 12 months after a diagnosis of breast cancer. Methods: An audit of the medical records of women who presented to the Western Health (Victoria, Australia) nurse led breast cancer Survivorship Clinic (SC) between October 2015 and October 2016 was performed to identify employment status at diagnosis and at their review at SC 12 months later. Results: 111 records were reviewed. The mean age was 55 (range 28-82yrs). 84 of these women (76%) were 65 years of younger at the time of diagnosis. 46 of the 84 women ≤65 years were in paid employment at diagnosis (55%), and 38 (83%) were still working in some capacity at review in the SC. Of the 38 still working, 28 were working in the same capacity, 8 were working reduced hours, and 2 were working increased hours. Women who had axillary dissections were most likely to have changed work status. Financial stress was reported by 8/19 of women who stopped working or had changed work hours, including 9 no longer in paid employment and 10 with changed hours. 2/28 women working in the same capacity reported financial stress. 65% of those who reported financial stress (11/17) had chemotherapy as part of their treatment. Conclusions: A breast cancer diagnosis has the ability to influence a woman's work status one year after diagnosis. Health professionals should appreciate the potential work concerns and financial stresses continuing to affect their patients.
Rapid HIV RNA rebound after antiretroviral treatment interruption in persons durably suppressed in Fiebig I acute HIV infection
Authors: Donn J. Colby, Lydie Trautmann, Suteeraporn Pinyakorn, Louise Leyre, Amélie Pagliuzza, Eugène Kroon, Morgane Rolland, Hiroshi Takata, Supranee Buranapraditkun, Jintana Intasan, Nitiya Chomchey, Roshell Muir, Elias K. Haddad, Sodsai Tovanabutra, Sasiwimol Ubolyam, Diane L. Bolton, Brandie A. Fullmer, Robert J. Gorelick, Lawrence Fox, Trevor A. Crowell, Rapee Trichavaroj, Robert O’Connell, Nicolas Chomont, Jerome H. Kim, Nelson L. Michael, Merlin L. Robb, Nittaya Phanuphak, Jintanat Ananworanich
Journal: Nature Medicine (2018)
The influence of an androgen deprivation therapy educational program on dyadic quality and intimacy for prostate cancer patients and their partners.
Authors: Erik Wibowo, Richard J Wassersug, John W Robinson, Andrew Matthew, Deborah L McLeod, Lauren M Walker
Journal: Journal of Clinical Oncology (2018)

178 Background: Androgen deprivation therapy (ADT) is a common treatment for advanced prostate cancer (PCa), but ADT typically impairs men’s sexual function and couples’ relationships. We offer an educational program to help PCa patients and their partners manage ADT related side effects and to maintain a strong dyadic relationship while the patient is on ADT. Methods: Patients and partners attended a one time 1.5 hour ADT Class. Patients received a copy of the book Androgen Deprivation Therapy: An essential guide for men with prostate cancer and their partners (DEMOS Health, NY), which covers how to manage ADT side effects and make healthy lifestyle changes. We emphasize the importance of physical exercise in preventing or reducing many of the side effects of ADT. 79 couples (patients = 68.8±7.5 years old, partners = 64.9±8.8 years old; relationship duration = 34.6±16.4 years) completed the Dyadic Adjustment Scale, the Personal Assessment of Intimacy in Relationships, and the Godin Leisure-Time Exercise questionnaires at baseline and again 2-3 months later to assess their relational intimacy and dyadic quality. At baseline 73% of patients either had not started or been on ADT for &lt; 3 weeks. Results: Attending the ADT Educational Program was associated with improved dyadic adjustment and relational intimacy but age, relationship duration, baseline strain in the relationship and physical exercise all influence these effects. Specifically, dyadic cohesion improved in patients ≥68 years old. Recreational intimacy increased in patients ≤60 years old and for those in a relationship ≥50 years. Recreational intimacy also improved in partners who had been in a 20-49 years relationship or those reporting at baseline little strain in their relationship. Dyadic cohesion was maintained in participants who increased their frequency of physical exercise. For the above results, all P &lt; 0.05. Conclusions: The ADT Educational Program improves dyadic cohesion and relational intimacy for some patients and partners but age, relationship duration, baseline quality of the relationship, and physical exercise frequency appear to influence the effectiveness of the program.
A natural killer T-cell subset that protects against airway hyperreactivity
Authors: Ya-Ting Chuang, Krystle Leung, Ya-Jen Chang, Rosemarie H. DeKruyff, Paul B. Savage, Richard Cruse, Christophe Benoit, Dirk Elewaut, Nicole Baumgarth, Dale T. Umetsu
Journal: Journal of Allergy and Clinical Immunology (2018)
Psychomotor function measured via online activity predicts motor vehicle fatality risk
Authors: Tim Althoff, Eric Horvitz, Ryen W. White
Journal: npj Digital Medicine (2017)

Impaired psychomotor performance severely increases the risk of fatal and non-fatal car accidents. However, we currently lack methods to continuously and non-intrusively monitor psychomotor performance. We show we can estimate psychomotor function at population scale from 16 billion observations of typing speeds during the input of web search queries. We show that these estimates exhibit diurnal variation with a substantial increase during typical sleep times, matching published accident risk rates. Further, we show that psychomotor impairment, as measured by keystroke timing, predicts motor vehicle fatality risk on a population level (Spearman ρ = 0.61; p « 10-10). The methods and results highlight a promising direction of harnessing ambient streams of data, such as patterns of interactions with devices, as large-scale sensors to continuously and non-intrusively monitor human psychomotor performance at population scale.
Abstract 17472: Impact of Do-Not-Resuscitate Status on Hospital Risk-adjusted Mortality for Heart Failure
Authors: Jeffrey T Bruckel, Anuj Mehta, Brahmajee K Nallamothu, Sabu Thomas, Steven M Bradley, Allan J Walkey
Journal: Circulation (2016)

Introduction:  Risk-adjusted mortality following heart failure hospitalization is used by payers to adjust reimbursement and incentivize improvements. This risk-adjusted measure does not account for variation in hospital rates of do not resuscitate (DNR) on admission, which may impact measure validity.   Methods:  California Healthcare Cost and Utilization Project data identifies patients with DNR within 24 hours of admission. We included all adults admitted with primary diagnosis of heart failure during 2011. We determined hospital-level in-hospital mortality, before and after accounting for admission DNR, from hierarchical logistic regression adjusting for Hierarchical Clinical Condition variables. We generated hospital risk-adjusted Predicted-to-Expected mortality ratios (P/E ratios). We determined the effect of accounting for DNR on patient-level mortality risk, and on changes in hospital P/E ratio quartiles.   Results:  Among 55,865 hospitalized heart failure patients at 290 hospitals, the overall DNR rate was 12.1% (6,755). Median hospital DNR rate was 8.7% (IQR 3.9% to 20.0%). Median hospital mortality rate was 2.9% (IQR 1.8 - 4.1). At the patient-level, DNR status was associated with increased in-hospital mortality (OR 3.50, 95% CI 3.11 - 3.94, p   Conclusion:  DNR on admission rates vary widely between hospitals and DNR predicts in-hospital mortality. Adjustment for DNR alters hospital risk-adjusted mortality classification and may be useful for risk-adjusted mortality measures.
Peripapillary Ovoid Hyperreflectivity in Optic Disc Edema and Pseudopapilledema
Authors: Lasse Malmqvist, Patrick A. Sibony, Clare L. Fraser, Marianne Wegener, Steffen Heegaard, Marie Skougaard, Steffen Hamann, Valérie Biousse, Lulu Bursztyn, Fiona Costello, Alison Crum, Kathleen B. Digre, J. Alexander Fraser, Clare L. Fraser, Steffen Hamann, Bradley Katz, Mitchell Lawlor, Lasse Malmqvist, Nancy J. Newman, Jason H. Peragallo, Axel Petzold, Patrick A. Sibony, Prem S. Subramanian, Judith Warner, Marianne Wegener, Sui H. Wong
Journal: Ophthalmology (2018)