tbuckley/cabot-search huggingface dataset:
Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site Infection, 2017
Authors: Sandra I. Berríos-Torres, Craig A. Umscheid, Dale W. Bratzler, Brian Leas, Erin C. Stone, Rachel R. Kelz, Caroline E. Reinke, Sherry Morgan, Joseph S. Solomkin, John E. Mazuski, E. Patchen Dellinger, Kamal M. F. Itani, Elie F. Berbari, John Segreti, Javad Parvizi, Joan Blanchard, George Allen, Jan A. J. W. Kluytmans, Rodney Donlan, William P. Schecter
Journal: JAMA Surgery (2017)

The human and financial costs of treating surgical site infections (SSIs) are increasing. The number of surgical procedures performed in the United States continues to rise, and surgical patients are initially seen with increasingly complex comorbidities. It is estimated that approximately half of SSIs are deemed preventable using evidence-based strategies.To provide new and updated evidence-based recommendations for the prevention of SSI.A targeted systematic review of the literature was conducted in MEDLINE, EMBASE, CINAHL, and the Cochrane Library from 1998 through April 2014. A modified Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence and the strength of the resulting recommendation and to provide explicit links between them. Of 5759 titles and abstracts screened, 896 underwent full-text review by 2 independent reviewers. After exclusions, 170 studies were extracted into evidence tables, appraised, and synthesized.Before surgery, patients should shower or bathe (full body) with soap (antimicrobial or nonantimicrobial) or an antiseptic agent on at least the night before the operative day. Antimicrobial prophylaxis should be administered only when indicated based on published clinical practice guidelines and timed such that a bactericidal concentration of the agents is established in the serum and tissues when the incision is made. In cesarean section procedures, antimicrobial prophylaxis should be administered before skin incision. Skin preparation in the operating room should be performed using an alcohol-based agent unless contraindicated. For clean and clean-contaminated procedures, additional prophylactic antimicrobial agent doses should not be administered after the surgical incision is closed in the operating room, even in the presence of a drain. Topical antimicrobial agents should not be applied to the surgical incision. During surgery, glycemic control should be implemented using blood glucose target levels less than 200 mg/dL, and normothermia should be maintained in all patients. Increased fraction of inspired oxygen should be administered during surgery and after extubation in the immediate postoperative period for patients with normal pulmonary function undergoing general anesthesia with endotracheal intubation. Transfusion of blood products should not be withheld from surgical patients as a means to prevent SSI.This guideline is intended to provide new and updated evidence-based recommendations for the prevention of SSI and should be incorporated into comprehensive surgical quality improvement programs to improve patient safety.
Physicians, Industry Payments for Food and Beverages, and Drug Prescribing
Authors: Robert Steinbrook
Journal: JAMA (2017)

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Whole-transcriptome paired-end sequencing and the pancreatic cancer genetic landscape.
Authors: Marina Macchini, Annalisa Astolfi, Valentina Indio, Silvia Vecchiarelli, Elisa Grassi, Carla Serra, Riccardo Casadei, Donatella Santini, Marielda D'Ambra, Claudio Ricci, Francesco Minni, Guido Biasco, Mariacristina Di Marco
Journal: Journal of Clinical Oncology (2013)

4048 Background: A deeper knowledge of the pancreatic cancer (PDAC) biology is needed to improve the prognosis of the disease. Methods: 17 PDAC samples were collected by ultrasound-guided biopsy used for DNA and RNA extraction. 14 samples were analyzed by high resolution copy number analysis (CNA) on Affymetrix SNP array 6.0 and with segmentation algorithm against a reference of 270 Ceu HapMap individuals (Partek Genomic Suite). 17 samples were analyzed by whole transcriptome massively parallel sequencing, performed at 75x2 bp on a HiScanSQ Illumina platform. An average of 7, 3x107 reads per sample were generated, with a mean read depth of 50X. Single nucleotide variants (SNVs) were detected with SNVMix2 and compared with genetic variation databases (dbSNP, 1000genomes, Cosmic). Non-synonimous SNVs were analyzed with the predictors SNPs and GO and PROVEAN. Results: CNA results in 9/14 samples exhibited both macroscopic and cryptic cytogenetic alterations, with a mean of 10 CNA per patient. Most frequent gains were observed in 18q11.2 involving GATA6 (3/14) and 19q13 targeting AKT2 (3/14) while hotspot deletions were found on 18q21 (7/14), 17p13 (6/14), 9p21.3 (6/14), 15q (5/14) and 1q35 (4/14). RNAseq showed that samples exhibited a mean of 145 (range: 61-240) non-synonimous SNVs, of which 16 on average are potentially disease-related. Merging copy number and RNAseq data we highlighted the major oncogenic hits of PDAC, confirming the prevalence (14/17) of KRAS mutations, in one case also NRAS (G13D), and the three oncosuppressor CDKN2A (mutated in 3 cases and deleted in 6 cases, in hetero- or homozygosity), SMAD4 (altered by point mutation or gene deletion in 7/14), and TP53 (lost in 6/14 and mutated in 5/17). The signaling pathways affected were: KRAS/MAPK, TGFbeta and integrin signaling, proliferation and apoptosis, DNA damage response, and epithelial to mesenchymal transition. Moreover we found new oncogenic alterations, such as HMGCR, that displayed mutations in 17% of the analyzed patients (3/17). Conclusions: NGS combined with high resolution cytogenetic analysis can improve the understanding of pancreatic carcinogenesis.
Towards control of the global HIV epidemic: Addressing the middle-90 challenge in the UNAIDS 90–90–90 target
Authors: Collins Iwuji, Marie-Louise Newell
Journal: PLoS Medicine (2017)

In 2016, just over 2 million people worldwide acquired HIV infection, mostly via heterosexual transmission and mostly in sub-Saharan Africa [1].Antiretroviral treatment (ART) aims to suppress viral load to very low, or undetectable, levels, delaying HIV disease progression [2,3] and reducing the risk of onward transmission [4].Following the 2015 WHO guidelines recommending ART for all HIV-positive people regardless of CD4 count, WHO and the Joint United Nations Programme on HIV/AIDS (UNAIDS) issued the 90-90-90 target, aiming by 2020 to have 90% of infected people knowing their HIV status, 90% of HIV-positive people initiated on ART, and 90% of people treated with ART virally suppressed [5], so as to achieve containment of the HIV epidemic.We commend Richard Hayes and colleagues for their success in navigating the complex logistic challenges in implementing a large-scale universal testing and treatment (UTT) intervention in sub-Saharan Africa, as described in their accompanying research article in PLOS Medicine [6].They report how close they were able to come to reaching the first two stages of the 90-90-90 target in four communities in Zambia after one year of implementing their PopART intervention (comprising home-based HIV testing by Community HIV care Providers [CHiPs] with support for linkage to care, adherence, and retention).Among those consenting to the intervention, 6,197 HIV-positive individuals not on ART (most of whom had never been in care) were referred to care, 42% of whom initiated ART within six months and 53% by 12 months.Extrapolating to the entire population, the estimated percentage of HIV-positive adults who knew their status increased from 52% to 78% (men) and from 56% to 87% (women); percentages of known HIV-positive people on ART increased from 54% to 74% (men) and from 53% to 73% (women).The overall estimated percentage of HIV-positive adults on ART was 61% after 1 y of intervention implementation, compared to the WHO/UNAIDS target of 81% (90% of 90%).We note that many process indicators in the study were based on self-report and, apparently, data from the CHiPs electronic capture system were not verified with clinic data.Further, in this setting, in which nearly 50% of all HIV-positive individuals were ART-naive because they were newly diagnosed, it is likely that most of the 20% of people who migrated out of the area never linked to care or commenced ART.This 20% of people, no longer resident in the PopART communities, was not included in the denominator for the post-CHiPs evaluation at 12 months on linkage to care and ART initiation, which could have resulted in an overestimate of the change observed following the CHiPs intervention.
Impact of Expert Pathologic Review of Lymphoma Diagnosis: Study of Patients From the French Lymphopath Network
Authors: Camille Laurent, Marine Baron, Nadia Amara, Corinne Haioun, Mylène Dandoit, Marc Maynadié, Marie Parrens, Beatrice Vergier, Christiane Copie-Bergman, Bettina Fabiani, Alexandra Traverse-Glehen, Nicole Brousse, Marie-Christine Copin, Patrick Tas, Tony Petrella, Marie-Christine Rousselet, Josette Brière, Fréderic Charlotte, Catherine Chassagne-Clement, Thérèse Rousset, Luc Xerri, Anne Moreau, Antoine Martin, Diane Damotte, Peggy Dartigues, Isabelle Soubeyran, Michel Peoch, Pierre Dechelotte, Jean-François Michiels, Antoine de Mascarel, Françoise Berger, Céline Bossard, Flavie Arbion, Isabelle Quintin-Roué, Jean-Michel Picquenot, Martine Patey, Blandine Fabre, Henri Sevestre, Cécile Le Naoures, Marie-Pierre Chenard-Neu, Claire Bastien, Sylvie Thiebault, Laurent Martin, Manuela Delage, Thomas Filleron, Gilles Salles, Thierry Jo Molina, Georges Delsol, Pierre Brousset, Philippe Gaulard
Journal: Journal of Clinical Oncology (2017)

Purpose To prospectively assess the clinical impact of expert review of lymphoma diagnosis in France. Materials and Methods From January 2010 to December 2013, 42,145 samples from patients with newly diagnosed or suspected lymphomas were reviewed, according to the 2008 WHO classification, in real time by experts through the Lymphopath Network. Changes in diagnosis between referral and expert review were classified as major or minor according to their potential impact on patient care. Results The 42,145 reviewed samples comprised 36,920 newly diagnosed mature lymphomas, 321 precursor lymphoid neoplasms, 314 myeloid disorders, and 200 nonhematopoietic neoplasms, with 4,390 benign lesions. There were 4,352 cutaneous and 32,568 noncutaneous lymphomas. The most common mature noncutaneous lymphomas were diffuse large B-cell lymphomas (32.4%), follicular lymphomas (15.3%), classic Hodgkin lymphomas (13%), peripheral T-cell lymphomas (6.3%) of which angioimmunoblastic T-cell lymphomas (2.3%) were the most frequent, and mucosa-associated lymphoid tissue lymphomas (5.8%). A diagnostic change between referral and expert review occurred in 19.7% of patients, with an estimated impact on patient care for 17.4% of patients. This rate was significantly higher for patients sent with a provisional diagnosis seeking expert second opinion (37.8%) than for patients sent with a formal diagnosis (3.7%). The most frequent discrepancies were misclassifications in lymphoma subtype (41.3%), with 12.3% being misclassifications among small B-cell lymphoma entities. Fewer than 2% of changes were between benign and malignant lymphoid conditions. Minor changes (2.3%) mostly consisted of follicular lymphoma misgrading and diffuse large B-cell lymphoma subtype misclassification. Conclusion To our knowledge, this study provides the largest ever description of the distribution of lymphoma entities in a western country and highlights how expert review significantly contributes to a precise lymphoma diagnosis and optimal clinical management in a proportion of patients.
Reminder devices seem not to improve drug compliance, trial finds
Authors: Jacqui Wise
Journal: BMJ (2017)

A trial comparing three low cost devices designed to help patients remember to take their pills has found that they did not improve adherence.1

The REMIND trial included 53 480 patients who were taking one to three oral medicines for long term use and who had been suboptimally adherent to their prescribed treatments in the previous year. The mean age was 45, and 56% were female.

The patients were randomly …
Ex-Vivo Drug Response Profiling for Precision Medicine Approaches in Acute Myeloid Leukemia with the Open Microwell Microfluidic Platform
Authors: Laura Rocchi, Andrea Faenza, Laura Rambelli, Viviana Guadagnuolo, Giovanni Marconi, Giorgia Simonetti, Cristina Papayannidis, Antonella Padella, Nicola Pecorari, Luca Giulianelli, Dario Biscarini, Giovanni Martinelli, Roberto Guerrieri, Massimo Bocchi
Journal: Blood (2016)
Metabolomic analysis as a tool to identify breast cancer (BC) cell lines resistant to palbociclib (PD)
Authors: M. Bonechi, C. Guarducci, G. Meoni, L. Tenori, C. Biagioni, R. Schiff, C.K. Osborne, C. Luchinat, L. Malorni, I. Migliaccio
Journal: Annals of Oncology (2017)
Correction: Routine HIV Testing in Botswana: A Population-Based Study on Attitudes, Practices, and Human Rights Concerns
Authors: Sheri D Weiser, Michele Heisler, Karen Leiter, Fiona Percy-de Korte, Sheila Tlou, Sonya DeMonner, Nthabiseng Phaladze, David R Bangsberg, Vincent Iacopino
Journal: PLoS Medicine (2006)

Under the section heading "Expected Death Toll during a Present-Day Mass Vaccination Campaign," the numbers of expected deaths that were computed for a mass vaccination campaign were displayed as per million; they should be absolute numbers.The corrected text should be: "Under those assumptions, in the Netherlands mass vaccination with NYCBH would lead to 9.8 deaths (95% CI [0, 30]), mass vaccination with Lister to 55.1 deaths (95% CI [7, 182]), and mass vaccination with Bern would lead to 303.5 deaths (95% CI [19, 1093]).In Germany mass vaccination with NYCBH would lead to 46.2 deaths (95% CI [6, 142]), mass vaccination with Lister would lead to 268.5 deaths (95% CI [39, 875]), and mass vaccination with Bern would lead to 1,381 deaths (95% CI [94, 4909]).
Noisy knees may be early sign of knee osteoarthritis
Authors: Jacqui Wise
Journal: BMJ (2017)

Patients who report that they hear grating, cracking, or popping sounds in or around the knee joint may be at increased risk of developing knee osteoarthritis, a study published in Arthritis Care & Research has found.1

Patients frequently ask doctors whether crepitus—such sounds in or around a joint—is a problem. The researchers said that theirs is the first study to find an association between self reported crepitus and incident symptomatic knee osteoarthritis.

The …
Outcomes of Autologous Stem Cell Transplantation in Elderly Mexican Patients
Authors: Brenda Lizeth Lizeth Acosta-Maldonado, Liliana Rivera-Fong., Juan Francisco Zazueta Pozos., Jaime Eduardo Dulón Tarqui., José Guadalupe Ríos., Luis Manuel Valero-Saldaña., Silvia Rivas-Vera
Journal: Blood (2016)
Addressing a Yellow Fever Vaccine Shortage — United States, 2016–2017
Authors: Mark D. Gershman, Kristina M. Angelo, Julian Ritchey, David P. Greenberg, Riyadh D. Muhammad, Gary Brunette, Martin S. Cetron, Mark J. Sotir
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Recent manufacturing problems resulted in a shortage of the only U.S.-licensed yellow fever vaccine. This shortage is expected to lead to a complete depletion of yellow fever vaccine available for the immunization of U.S. travelers by mid-2017. CDC, the Food and Drug Administration (FDA), and Sanofi Pasteur are collaborating to ensure a continuous yellow fever vaccine supply in the United States. As part of this collaboration, Sanofi Pasteur submitted an expanded access investigational new drug (eIND) application to FDA in September 2016 to allow for the importation and use of an alternative yellow fever vaccine manufactured by Sanofi Pasteur France, with safety and efficacy comparable to the U.S.-licensed vaccine; the eIND was accepted by FDA in October 2016. The implementation of this eIND protocol included developing a systematic process for selecting a limited number of clinic sites to provide the vaccine. CDC and Sanofi Pasteur will continue to communicate with the public and other stakeholders, and CDC will provide a list of locations that will be administering the replacement vaccine at a later date.
Integrin-targeted cancer immunotherapy elicits protective adaptive immune responses
Authors: Byron H. Kwan, Eric F. Zhu, Alice Tzeng, Harun R. Sugito, Ahmed A. Eltahir, Botong Ma, Mary K. Delaney, Patrick A. Murphy, Monique J. Kauke, Alessandro Angelini, Noor Momin, Naveen K. Mehta, Alecia M. Maragh, Richard O. Hynes, Glenn Dranoff, Jennifer R. Cochran, K. Dane Wittrup
Journal: The Journal of Experimental Medicine (2017)

Certain RGD-binding integrins are required for cell adhesion, migration, and proliferation and are overexpressed in most tumors, making them attractive therapeutic targets. However, multiple integrin antagonist drug candidates have failed to show efficacy in cancer clinical trials. In this work, we instead exploit these integrins as a target for antibody Fc effector functions in the context of cancer immunotherapy. By combining administration of an engineered mouse serum albumin/IL-2 fusion with an Fc fusion to an integrin-binding peptide (2.5F-Fc), significant survival improvements are achieved in three syngeneic mouse tumor models, including complete responses with protective immunity. Functional integrin antagonism does not contribute significantly to efficacy; rather, this therapy recruits both an innate and adaptive immune response, as deficiencies in either arm result in reduced tumor control. Administration of this integrin-targeted immunotherapy together with an anti–PD-1 antibody further improves responses and predominantly results in cures. Overall, this well-tolerated therapy achieves tumor specificity by redirecting inflammation to a functional target fundamental to tumorigenic processes but expressed at significantly lower levels in healthy tissues, and it shows promise for translation.
Podocytes regulate the glomerular basement membrane protein nephronectin by means of miR-378a-3p in glomerular diseases
Authors: Janina Müller-Deile, Jan Dannenberg, Patricia Schroder, Meei-Hua Lin, Jeffrey H. Miner, Rongjun Chen, Jan-Hinrich Bräsen, Thomas Thum, Jenny Nyström, Lynne Beverly Staggs, Hermann Haller, Jan Fiedler, Johan M. Lorenzen, Mario Schiffer
Journal: Kidney International (2017)
Rac1 activation in podocytes induces the spectrum of nephrotic syndrome
Authors: Richard Robins, Cindy Baldwin, Lamine Aoudjit, Jean-François Côté, Indra R. Gupta, Tomoko Takano
Journal: Kidney International (2017)

Hyper-activation of Rac1, a small GTPase, in glomerular podocytes has been implicated in the pathogenesis of familial proteinuric kidney diseases. However, the role of Rac1 in acquired nephrotic syndrome is unknown. To gain direct insights into this, we generated a transgenic mouse model expressing a doxycycline-inducible constitutively active form of Rac1 (CA-Rac1) in podocytes. Regardless of the copy number, proteinuria occurred rapidly within five days, and the histology resembled minimal change disease. The degree and severity of proteinuria were dependent on the transgene copy number. Upon doxycycline withdrawal, proteinuria resolved completely (one copy) or nearly completely (two copy). After one month of doxycycline treatment, two-copy mice developed glomerulosclerosis that resembled focal segmental glomerulosclerosis (FSGS) with urinary shedding of transgene-expressing podocytes. p38 MAPK was activated in podocytes upon CA-Rac1 induction while a p38 inhibitor attenuated proteinuria, podocyte loss, and glomerulosclerosis. Mechanistically, activation of Rac1 in cultured mouse podocytes reduced adhesiveness to laminin and induced redistribution of β1 integrin, and both were partially reversed by the p38 inhibitor. Activation of Rac1 in podocytes was also seen in kidney biopsies from patients with minimal change disease and idiopathic FSGS by immunofluorescence while sera from the same patients activated Rac1 in cultured human podocytes. Thus, activation of Rac1 in podocytes causes a spectrum of disease ranging from minimal change disease to FSGS, due to podocyte detachment from the glomerular basement membrane that is partially dependent on p38 MAPK.
Current and emerging techniques for antibiotic susceptibility tests
Authors: Karan Syal, Manni Mo, Hui Yu, Rafael Iriya, Wenwen Jing, Sui Guodong, Shaopeng Wang, Thomas E. Grys, Shelley E. Haydel, Nongjian Tao
Journal: Theranostics (2017)

Infectious diseases caused by bacterial pathogens are a worldwide burden. Serious bacterial infection-related complications, such as sepsis, affect over a million people every year with mortality rates ranging from 30% to 50%. Crucial clinical microbiology laboratory responsibilities associated with patient management and treatment include isolating and identifying the causative bacterium and performing antibiotic susceptibility tests (ASTs), which are labor-intensive, complex, imprecise, and slow (taking days, depending on the growth rate of the pathogen). Considering the life-threatening condition of a septic patient and the increasing prevalence of antibiotic-resistant bacteria in hospitals, rapid and automated diagnostic tools are needed. This review summarizes the existing commercial AST methods and discusses some of the promising emerging AST tools that will empower humans to win the evolutionary war between microbial genes and human wits.
The French LOC Network for Primary CNS Lymphoma (PCNSL) Patients: What Can We Learn from a Large National Database?
Authors: Carole Soussain, Caroline Houillier, Herve Ghesquieres, Pierre Soubeyran, Olivier Chinot, Luc Taillandier, Roch Houot, Guido Ahle, Emmanuel Gyan, Cécile Chabrot, Marie-Pierre Moles, Sylvain Choquet, Philippe Agape, Vincent Delwail, Fabrice Jardin, Annie Brion, Gandhi Damaj, Olivier Casanovas, Luc Mathieu Fornecker, Michel Fabbro, Valerie Touitou, Nathalie Cassoux, Remy Gressin, Adrian Tempescul, Arnaud Jaccard, Pascal Bourquard, Franck Morschhauser, Khê Hoang-Xuan
Journal: Blood (2016)
Predicting Response to Immunosuppressive Therapy in Patients with Acquired Aplastic Anemiausing EGFR and TWIST1 Expression Levels
Authors: Sharat Damodar, Varun Bafna, Arati Khanna-Gupta, Shilpa Prabhu, Nataraj KS, Durga Sarvepalli, Snigdha Majumder, Coral Karunakaran, Malini Manoharan, Sakthivel Murugan, Chirantan Bose, Ravi Gupta, Arkasubhra Ghosh
Journal: Blood (2016)