tbuckley/cabot-search huggingface dataset:
Trichoderma longibrachiatum: an unusual pathogen of fungal pericarditis
Authors: R. Recio, M.Á. Meléndez-Carmona, M.C. Martín-Higuera, V. Pérez, E. López, F. López-Medrano, A. Pérez-Ayala
Journal: Clinical Microbiology and Infection (2019)
Serious Ethical Violations in Medicine: A Statistical and Ethical Analysis of 280 Cases in the United States From 2008–2016
Authors: James M. DuBois, Emily E. Anderson, John T. Chibnall, Jessica Mozersky, Heidi A. Walsh
Journal: The American Journal of Bioethics (2019)

Serious ethical violations in medicine, such as sexual abuse, criminal prescribing of opioids, and unnecessary surgeries, directly harm patients and undermine trust in the profession of medicine. We review the literature on violations in medicine and present an analysis of 280 cases. Nearly all cases involved repeated instances (97%) of intentional wrongdoing (99%), by males (95%) in nonacademic medical settings (95%), with oversight problems (89%) and a selfish motive such as financial gain or sex (90%). More than half of cases involved a wrongdoer with a suspected personality disorder or substance use disorder (51%). Despite clear patterns, no factors provide readily observable red flags, making prevention difficult. Early identification and intervention in cases requires significant policy shifts that prioritize the safety of patients over physician interests in privacy, fair processes, and proportionate disciplinary actions. We explore a series of 10 questions regarding policy, oversight, discipline, and education options. Satisfactory answers to these questions will require input from diverse stakeholders to help society negotiate effective and ethically balanced solutions.
High subclonal fraction of 17p deletion is associated with poor prognosis in multiple myeloma
Authors: Anjan Thakurta, Maria Ortiz, Pedro Blecua, Fadi Towfic, Jill Corre, Natalya V. Serbina, Erin Flynt, Zhinuan Yu, Zhihong Yang, Antonio Palumbo, Meletios A. Dimopoulos, Norma C. Gutierrez, Hartmut Goldschmidt, Pieter Sonneveld, Herve Avet-Loiseau
Journal: Blood (2019)
Abstract 20169: A Novel Early Warning System to Predict Critical Events in Children With Congenital Heart Disease
Authors: Andrew Y Shin, Rui Liu, Vamsi Yarlagadda, Doff McElhinney, Christopher Almond, Xuefeng Ling
Journal: Circulation (2015)

Background: The outcome of hospitalized patients suffering clinical decline is contingent upon timely recognition. Current algorithms utilize select clinical variables for predictive modeling but have generally excluded congenital heart disease due to heterogeneity of patient and disease. The purpose of this study is to develop a model to predict decline in congenital heart disease patients. Methods: We analyzed all patients admitted to the Heart Center at Stanford Children’s Health between 9/1/2009 and 12/31/2012. We profiled the phenotypic changes in the EMR and measured entropy defined as the degree of fluctuation in all EMR values at 3-hour intervals. Predictive modeling was performed to identify temporal and directional relationships between entropy and the occurrence of a critical event, compared to the entropy of matched control patients. The entropy index was derived retrospectively in the first two-thirds of patients, and applied prospectively in the final third to determine predictability. Results: A total of 2,658 encounters occurred. A total of 71 (2.6%) critical events were observed as defined by calls for rapid response team, code blue, and ECMO. Peak entropy within the EMR was observed at mean of 15 (±5.4) hours prior to critical events (Figure). In the prospective arm, the area under the ROC curve for predicting critical events was 0.80 (95% confidence interval [CI]: 0.75-0.83). The sensitivity and specificity derived from the ROC curve was 68.4% and 74.6%, respectively. Only 2% of EMR variables were found in all cases and 14% of all critical events shared 3 or more common variables. Conclusion: Common EMR variables that cluster uniquely in relation to critical events among children hospitalized for cardiac disease are rare, which poses a challenge to early warning systems that are based on specific variables. Leveraging the EMR to detect increased entropy as a novel predictor of crisis event in this population merits further investigation.
A cumulative meta-analysis of endoscopic papillary balloon dilation versus endoscopic sphincterotomy for removal of common bile duct stones
Authors: Alberto Tringali, Matteo Rota, Marta Rossi, Cesare Hassan, Douglas G. Adler, Massimiliano Mutignani
Journal: Endoscopy (2019)

Endoscopic papillary balloon dilation (EPBD) was introduced to overcome the risk of adverse events associated with endoscopic sphincterotomy in the removal of common bile duct (CBD) stones. We performed a meta-analysis of randomized controlled trials (RCTs) comparing efficacy and safety of EPBD vs. endoscopic sphincterotomy, focusing on stone size, balloon diameter, and balloon dilation time.A multiple database search was performed, including MEDLINE, EMBASE and Cochrane Library, from their inception date until October 2017. RCTs comparing the efficacy and safety of EPBD vs. endoscopic sphincterotomy in the removal of CBD stones were included. Cumulative meta-analyses over time, and subgroup analyses according to stone size, and balloon diameter and dilation time were carried out.25 RCTs met the inclusion criteria. Despite the cumulative meta-analysis showing a trend over time in favor of endoscopic sphincterotomy in studies published up to 2004, the conventional meta-analysis revealed that EPBD was equally efficacious compared with endoscopic sphincterotomy in stone removal at first attempt (odds ratio [OR] 0.95, 95 % confidence interval [CI] 0.65 - 1.38). Endoscopic sphincterotomy was superior to EPBD in terms of overall stone clearance (OR 0.65, 95 %CI 0.43 - 0.99) in studies published since 2002, but no differences emerged in studies using large ( ≥ 10 mm) balloons (OR 1.37, 95 %CI 0.72 - 2.62). No statistically significant difference in pancreatitis occurrence emerged between EPBD and endoscopic sphincterotomy (OR 1.35, 95 %CI 0.90 - 2.03). Pancreatitis was more common with EPBD than with endoscopic sphincterotomy in studies using balloons < 10 mm (OR 1.78, 95 %CI 1.07 - 2.97), whereas no difference emerged in studies using large balloons (OR 0.84, 95 %CI 0.46 - 1.53). EPBD had lower rates of bleeding and cholecystitis.Our latest data confirm that EPBD is currently inferior to endoscopic sphincterotomy in terms of overall stone clearance. However, EPBD using large balloons (≥ 10 mm) was as effective as endoscopic sphincterotomy, both in stone clearance and the need for endoscopic mechanical lithotripsy, without carrying an increased risk of pancreatitis.
Heart and Sole — Of Metatarsals, Meaning, and Medicine
Authors: Lisa Rosenbaum
Journal: New England Journal of Medicine (2019)

Of Metatarsals, Meaning, and Medicine The world outside medicine can be full of unscripted caring from people who are happy for the mere opportunity to help. Many of us become doctors precisely for such opportunities. So why has it become so hard to translate this impulse into truly caring for patients?
Chronic lymphocytic leukemia cells impair mitochondrial fitness in CD8+ T cells and impede CAR T-cell efficacy
Authors: Jaco A. C. van Bruggen, Anne W. J. Martens, Joseph A. Fraietta, Tom Hofland, Sanne H. Tonino, Eric Eldering, Mark-David Levin, Peter J. Siska, Sanne Endstra, Jeffrey C. Rathmell, Carl H. June, David L. Porter, J. Joseph Melenhorst, Arnon P. Kater, Gerritje J. W. van der Windt
Journal: Blood (2019)
Nutrition and exercise patterns in survivors of esophageal and gastroesophageal junction (EGEJ) cancers.
Authors: Rishi Jain, Chethan Ramamurthy, Jennifer Y. Sheng, Evgenia Granina, Xiaoning Lu, Daohai Yu, Abbas E. Abbas, Joshua E. Meyer, Efrat Dotan, Carolyn Y Fang, Crystal S. Denlinger
Journal: Journal of Clinical Oncology (2019)

89 Background: While obesity is a risk factor for EGEJ, malnutrition is common at diagnosis (dx) and can be exacerbated by neoadjuvant therapy (NAT) and esophagectomy. Little is known regarding nutrition and exercise patterns of EGEJ cancer survivors. Methods: A survey of EGEJ survivors &gt; 12 months from esophagectomy was conducted. Pts were identified using institutional tumor registry. The Dillman mailed survey method was used. Questionnaires regarding health behaviors were employed: Godin Leisure-Time Exercise [GLTQ], Cancer Appetite and Symptom [CASQ], Nutritional Self-Efficacy (NSEQ). Chart review included demographics, pt characteristics and therapy received. Spearman correlation, Wilcoxon and Fisher’s tests assessed relationships between groups or variables. Results: Forty one of 140 eligible pts (29%) returned questionnaires and had surgery between 1991-2014. Median age was 69 and 78% were male. Most (83%) had adenocarcinoma. On presentation, 73% had clinical stage II or III disease and 76% received NAT. Median time from dx was 5 years (range 2-25). Mean weight loss from dx to current was 38 lbs. Mean BMI (kg/m 2 ) was 29.52 at dx and 24.15 at most recent clinic visit. Obesity was present in 37% of pts at dx, but only 7% of survivors. Mean health behavior scores (SD): GLTQ 22.10 (22.93), CASQ 31.74 (6.66), and NSEQ 11.39 (4.03). Age, marital status, gender, education, and income were not associated with GLTQ, CASQ or NSEQ. Sedentary lifestyle (SL) with GTLQ score &lt; 14 was present in 46% of survivors and associated with overweight BMI (mean 26.7 for SL vs 23.7 for non-SL; p = 0.04). There was a significant positive correlation between current BMI and NSEQ score (r = 0.68; p = 0.03). Conclusions: Many EGEJ cancer pts present with obesity but subsequently lose weight after curative therapy. The mean CASQ score in our population is similar to other GI cancer populations, suggesting that residual symptoms persist years after treatment ends. There is a high prevalence of SL in survivors which is associated with being overweight. Higher levels of nutrition self-efficacy were also associated with a higher current BMI. Future studies should define strategies to optimize nutrition and exercise habits in EGEJ cancer survivors.
Role of the microbiome in human development
Authors: Maria Gloria Dominguez-Bello, Filipa Godoy-Vitorino, Rob Knight, Martin J Blaser
Journal: Gut (2019)

The host-microbiome supraorganism appears to have coevolved and the unperturbed microbial component of the dyad renders host health sustainable. This coevolution has likely shaped evolving phenotypes in all life forms on this predominantly microbial planet. The microbiota seems to exert effects on the next generation from gestation, via maternal microbiota and immune responses. The microbiota ecosystems develop, restricted to their epithelial niches by the host immune system, concomitantly with the host chronological development, providing early modulation of physiological host development and functions for nutrition, immunity and resistance to pathogens at all ages. Here, we review the role of the microbiome in human development, including evolutionary considerations, and the maternal/fetal relationships, contributions to nutrition and growth. We also discuss what constitutes a healthy microbiota, how antimicrobial modern practices are impacting the human microbiota, the associations between microbiota perturbations, host responses and diseases rocketing in urban societies and potential for future restoration.
Tuberculous meningitis in children.
Authors: E M LINCOLN, S V SORDILLO, P A DAVIES
Journal: BMJ (1971)

Tuberculous Meningitis in ChildrenTuberculous meningitis has become relatively rare in countries with advanced social and medical standards.With modem treatment almost 100% recovery can be achieved without sequelae if it is begun before the child becomes unconscious.'But among underdeveloped peoples the disease is of much graver import.For example, in a recent South African series I. Freiman and J. Geefhuysen2 treated 131 African children of whom two-thirds were unconscious at the beginning of therapy.About 40% of all the patients had died within a year, and more than half the survivors had serious sequelae.Early diagnosis makes all the difference in this disease.Listlessness, irritability, anorexia and vomiting, loss of weight, refusal to smile or play, or photophobia may all indicate the onset of tuberculous meningitis in an infant or child.Older children will complain of headache.The persistence and the combination of several of these symptoms should alert the doctor to the possibility of tuberculous meningitis before the appearance of neck stiffness, focal neurological signs, dis- turbance of consciousness, or convulsions.A positive contact history is important but is now rarely obtained.More often the discovery of tuberculosis in a child followed by an im- mediate search will lead to the detection of an unsuspected active case in the household, or among relatives or friends, or in the school.The discovery of such a contact is a useful diagnostic aid.An intradermal tuberculin test (Mantoux 1:1,000) should be carried out at once, but in advanced cases a negative result does not rule out tuberculous meningitis.Tuberculin testing of all children should still be a routine in hospitals, for to omit it may lead to delay in diagnosis.Choroidal tubercles are present at the onset in about half the cases3 4 and provide an immediate diagnostic clue.They are easily found in a well- sedated child whose pupils are fully dilated.A radiograph of the chest may show hilar glands, a primary complex, or miliary tuberculosis.In suspected cases at least 10 ml of cerebrospinal fluid should be obtained and the deposit examined for tubercle bacilli.These can be detected in the NO.
Dimethyl fumarate, a two‐edged drug: Current status and future directions
Authors: Nathaniel Edward Bennett Saidu, Niloufar Kavian, Karen Leroy, Claus Jacob, Carole Nicco, Frédéric Batteux, Jérôme Alexandre
Journal: Medicinal Research Reviews (2019)

Abstract Dimethyl fumarate (DMF) is a fumaric acid ester registered for the treatment of relapsing‐remitting multiple sclerosis (RRMS). It induces protein succination leading to inactivation of cysteine‐rich proteins. It was first shown to possess cytoprotective and antioxidant effects in noncancer models, which appeared related to the induction of the nuclear factor erythroid 2 (NF‐E2)–related factor 2 (NRF2) pathway. DMF also displays antitumor activity in several cellular and mice models. Recently, we showed that the anticancer mechanism of DMF is dose‐dependent and is paradoxically related to the decrease in the nuclear translocation of NRF2. Some other studies performed indicate also the potential role of DMF in cancers, which are dependent on the NRF2 antioxidant and cellular detoxification program, such as KRAS‐mutated lung adenocarcinoma. It, however, seems that DMF has multiple biological effects as it has been shown to also inhibit the transcription factor nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB), thus blocking downstream targets that may be involved in the development and progression of inflammatory cascades leading to various disease processes, including tumors, lymphomas, diabetic retinopathy, arthritis, and psoriasis. Herein, we present the current status and future directions of the use of DMF in various diseases models with particular emphases on its targeting of specific intracellular signal transduction cascades in cancer; to shed some light on its possible mode of action.
Impact of neoadjuvant radiation on survival in patients with pancreatic cancer undergoing neoadjuvant chemotherapy followed by pancreatectomy.
Authors: Francis Igor Macedo, Basem Azab, Omar Picado, Danny Yakoub, Alan S Livingstone, Dido Franceschi, Vikas Dudeja, Nipun B. Merchant
Journal: Journal of Clinical Oncology (2019)

453 Background: Pancreatic adenocarcinoma (PDAC) carries a dismal prognosis. Neoadjuvant chemoradiation therapy (NACR) has been introduced to enhance the outcomes of patients with borderline resectable and locally advanced PDAC, however the role of radiation therapy remains largely unknown. Methods: The National Cancer Database (NCDB) was queried for patients with stage I-III PDAC who underwent surgical resection from 2004 to 2014. Patients undergoing NACR were compared to those undergoing neoadjuvant chemotherapy (NAC) alone. The association between clinical characteristics and overall survival (OS) was assessed using the Kaplan-Meier method and multivariable Cox regression model. Results: Of 3,133 patients, 2,351 (75%) patients underwent NACR and 782 (25%), NAC alone. Most patients were Caucasians (84%), treated at academic institutions (67%) and underwent pancreaticoduodenectomy (74%). Median follow-up time was 32 months (IQR, 22-50 months). Median number of lymph nodes examined (LNE) and number of positive nodes (NPN) were significantly decreased in NACR (13 vs. 16, p &lt; 0.001 and 0 vs. 1, p &lt; 0.001, respectively). Rates of margin positivity, median OS and 5-year OS were similar between 2 groups (NACR vs. NAC: 15% vs. 17%, p = 0.545; 25.7 months (95% CI 24.4–26.7) vs. 25.1 months (95% CI: 23.9–27.5), and 20% vs. 22%, p = 0.616, respectively, Figure 1). Subgroup analysis of high-risk features (R1/R2 and N1) also showed no difference in survival outcomes. Neoadjuvant radiation was not an independent predictor associated with OS, whereas advanced age, R1/R2, T3/T4, N1, and poorly differentiated histology were independent negative prognostic factors. Conclusions: NACR is associated with lower rates of lymph node positivity, however this did not translate in survival or margin positivity benefit compared to NAC alone. The role of radiotherapy in PDAC continues to evolve, however no convincing data is currently available to advocate the widespread use of radiotherapy in the neoadjuvant setting. Further evidence with prospective clinical trials is still warranted to confirm these findings.
Simultaneous Global Phase I Studies of a Differentiated BTK Inhibitor, Dtrmwxhs-12, in Relapsed/Refractory Patients with Chronic Lymphocytic Leukemia and B-Cell Lymphomas
Authors: Yuqin Song, Stephen J. Schuster, Wei He, Jun Zhu, Lijuan Deng, Yingli Sun, Ning Ding, Xiaogan Wang, Jennifer Gill, Elizabeth T Chatburn, Kaitlin Kennard, Barry Douglas Anderson, Sunita Dwivedy Nasta, Daniel J. Landsburg, David L Porter, Ellen Napier, Mitchell E. Hughes, Tanya Latorre, Kristy Walsh, Colleen Dorsey, Jakub Svoboda, Victoria Addis, Anthony R. Mato
Journal: Blood (2017)
Factor Xa Inhibitory Profile of Apixaban, Betrixaban, Edoxaban and Rivaroxaban Does Not Fully Reflect Their Biologic Spectrum
Authors: Fakiha Siddiqui, Siddharth Mehrotra, Vishnu Venkitasubramony, Rithik Raina, Lorenzo Storino Ramacciotti, Jack Bontekoe, Omer Iqbal, Debra Hoppensteadt, Walter Jeske, Jawed Fareed
Journal: Blood (2018)
The association of novel recurrent in-frame gene fusions with prognosis of diffuse gastric cancer.
Authors: Hark K. Kim
Journal: Journal of Clinical Oncology (2019)

34 Background: Among the two histologic subtype of gastric cancer (GC), diffuse gastric cancer (DGC) is increasingly being considered distinct from intestinal type gastric cancer (IGC). Despite the relative importance of DGC, few whole transcriptomic analyses have been performed for this histological subtype. We therefore conducted an RNA-sequencing study to search for novel driver fusions in DGC. Methods: We conducted a whole transcriptomic and targeted RNA sequencing study of 384 Korean DGCs to identify gene fusions that may be novel prognostic markers or therapeutic targets. Targeted DNA sequencing and SNP6.0 array analyses were conducted in parallel. Results: Whole transcriptomic analyses were conducted in 80 discovery dataset tumors collected from young patients with DGC who had not been treated with chemotherapy or radiation. Twenty-five in-frame fusions were associated with DGC, four of which were recurrent in 384 DGCs based on targeted RNA sequencing and RT-PCR sequencing analyses. Three of the four recurrent fusions contained a RhoGAP domain in their 3’ partner genes. Patients with one of these three fusions have a significantly worse prognosis than those without (HR, 2.8 [95% CI, 1.5‒5.3]). The fusion that harbored a PAP2 domain in the 3’ partner gene was also identified as recurrent and poor prognostic in-frame fusions. Overall, RhoGAP and PAP2 domain-containing fusions were present in 7.5% of DGCs, but not in adjacent normal tissue, and clearly defined the worst prognosis subgroup. Their prognostic impact (adjusted HR 4.1 [95% CI, 2.1‒7.9]) was higher than, and independent of, chromosomal instability (CIN) and CDH1 mutation, which we previously identified as the strongest adverse prognostic genomic abnormalities in DGCs (adjusted HRs, 2.5 (1.5‒4.4) and 2.4 (1.3‒4.4), respectively). Our comprehensive in-frame fusion screen also identified several clinically-actionable fusions amenable to ALK or FGFR inhibition, which had not been previously associated with gastric cancer. Conclusions: Our findings may provide novel genomic insights guiding future personalized strategies for managing DGCs, given the strong prognostic impact of RhoGAP and PAP2 domain-containing gene fusions.
Oxidative Balance in Fetal Life and Allergic Disease Risk in Adolescence: Investigating the role of Prenatal Nutrient Intakes and Potential Sources of Oxidative Stress in Utero
Authors: Joanne Sordillo, Sheryl L. Rifas-Shiman, Karen Switkowski, Brent Coull, Heike Gibson, Mary Rice, Thomas A.E. Platts-Mills, Augusto A. Litonjua, Diane R. Gold, Emily Oken
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 18340: Alternatively Spliced Tissue Factor Promotes Atherosclerosis by Increasing Foam Cell Formation via LOX-1 and SR-A1 up-regulation
Authors: Daniel Alicea, Saboor Hekmaty, David T Rodriguez, Peter Bhandari, Dong Kwong Yang, Dongtak Jeong, Jason C Kovacic, Johan L Bjorkegren, Juan J Badimon, Thomas Weber, Roger J Hajjar, Valentin Fuster, Chiara Giannarelli
Journal: Circulation (2015)

Introduction: Alternatively Spliced Tissue Factor (asTF) is an isoform of tissue factor that is expressed in human atherosclerotic plaques and promotes plaque progression in experimental atherosclerosis (Giannarelli C, Circulation 2014). Hypothesis: asTF is the isoform of tissue factor that most strongly promotes atherosclerosis by increasing foam cell formation. Methods: ApoE-/- mice (8 weeks old) were fed a Western-type diet starting 2 weeks before surgery. Immediately after transluminal wire injury of the left common carotid artery (LCCA), LCCA was incubated with lentivirus encoding asTF-GFP (asTF+;n=10), fl-TF-GFP (fl-TF+, n=10) or GFP (controls; n=5). Four weeks after, LCCA was removed and processed for the quantification of plaque size (H&amp;E) and lipid accumulation (Oil-Red O). The effect of asTF on foam cell formation was tested in vitro by treating THP-1 derived macrophages with oxLDL (75μg/ml), with asTF (10nM) or vehicle. Total cholesterol (TC) and cholesterol esters (CE) were measured in lipid cell extracts. The mRNA levels of the oxLDL scavenger receptors LOX-1, SR-A1 and CD36 in macrophages and foam cells were assessed using qRT-PCR. Results: Plaque size and lipid accumulation were significantly greater in asTF+ vs. fl-TF+ and control mice (Fig.1, A-D). In vitro results showed that asTF promotes TC and CE accumulation in foam cells (Fig.1, E,F). Gene expression studies showed that asTF significantly increased the mRNA expression of scavenger receptors LOX-1, SR-A1 in both macrophages and foam cells (Fig.1, G-I). An increase in mRNA levels of CD36 (1.4-fold) was only detected in asTF-treated foam cells. Conclusions: In vivo results suggest that asTF promote plaque progression and lipid accumulation. In vitro studies imply that asTF promotes foam cell formation by increasing the expression of oxLDL scavenger receptors implicated in lipoprotein uptake by macrophages. These studies suggest a functional role for asTF in atherosclerotic plaque progression.