tbuckley/cabot-search huggingface dataset:
Natural Variation in a Dendritic Scaffold Protein Remodels Experience-Dependent Plasticity by Altering Neuropeptide Expression
Authors: Isabel Beets, Gaotian Zhang, Lorenz A. Fenk, Changchun Chen, Geoffrey M. Nelson, Marie-Anne Félix, Mario de Bono
Journal: Neuron (2019)

The extent to which behavior is shaped by experience varies between individuals. Genetic differences contribute to this variation, but the neural mechanisms are not understood. Here, we dissect natural variation in the behavioral flexibility of two Caenorhabditis elegans wild strains. In one strain, a memory of exposure to 21% O2 suppresses CO2-evoked locomotory arousal; in the other, CO2 evokes arousal regardless of previous O2 experience. We map that variation to a polymorphic dendritic scaffold protein, ARCP-1, expressed in sensory neurons. ARCP-1 binds the Ca2+-dependent phosphodiesterase PDE-1 and co-localizes PDE-1 with molecular sensors for CO2 at dendritic ends. Reducing ARCP-1 or PDE-1 activity promotes CO2 escape by altering neuropeptide expression in the BAG CO2 sensors. Variation in ARCP-1 alters behavioral plasticity in multiple paradigms. Our findings are reminiscent of genetic accommodation, an evolutionary process by which phenotypic flexibility in response to environmental variation is reset by genetic change.
Bacteria‐Instructed In Situ Aggregation of AuNPs with Enhanced Photoacoustic Signal for Bacterial Infection Bioimaging
Authors: Shi‐Zhao Lu, Xiao‐Yan Guo, Mei‐Shuai Zou, Zi‐Qin Zheng, Yu‐Chuan Li, Xiao‐Dong Li, Li‐Li Li, Hao Wang
Journal: Advanced Healthcare Materials (2019)

Abstract The emergence of drug‐resistant bacteria is becoming the focus of global public health. Early‐stage pathogen bioimaging will offer a unique perspective to obtain infection information in patients. A photoacoustic (PA) contrast agent based on functional peptide modified gold nanoparticles (AuNPs@P1) is developed. These nanoparticles can be specifically tailored surface peptides by bacterial overexpressed enzyme inducing in situ aggregation of the gold nanoparticles. In the meantime, the close aggregation based on the hydrogen bonding, π–π stacking, and hydrophobic interaction of the peptide residues on the surface of gold nanoparticles exhibits a typical redshifted and broadened plasmon band. In addition, this active targeting and following in situ stimuli‐induced aggregation contribute to increased nanoparticle accumulation in the infected site. Finally, the dynamic aggregation of AuNPs@P1 results in dramatically enhanced photoacoustic signals for bioimaging bacterial infection in vivo with high sensitivity and specificity. It is envisioned that this PA contrast agent may provide a new approach for early detection of bacterial infection in vivo.
Intensive Chemotherapy for High-Risk ALL in Children - the Nordic Collaborative Approach
Authors: Atte Nikkilä, Olli Lohi, Ólafur Gísli Jónsson, Bendik Lund, Jonas Abrahamsson, Goda Elizabeta Vaitkeviciene, Kaie Pruunsild, Mats Heyman, Hanne Vibeke Marquart, Kim Vettenranta, Kjeld Schmiegelow
Journal: Blood (2019)
The Loci of Behavioral Evolution: Evidence That Fas2 and tilB Underlie Differences in Pupation Site Choice Behavior between Drosophila melanogaster and D. simulans
Authors: Alison Pischedda, Michael P Shahandeh, Thomas L Turner
Journal: Molecular Biology and Evolution (2019)

The behaviors of closely related species can be remarkably different, and these differences have important ecological and evolutionary consequences. Although the recent boom in genotype-phenotype studies has led to a greater understanding of the genetic architecture and evolution of a variety of traits, studies identifying the genetic basis of behaviors are, comparatively, still lacking. This is likely because they are complex and environmentally sensitive phenotypes, making them difficult to measure reliably for association studies. The Drosophila species complex holds promise for addressing these challenges, as the behaviors of closely related species can be readily assayed in a common environment. Here, we investigate the genetic basis of an evolved behavioral difference, pupation site choice, between Drosophila melanogaster and D. simulans. In this study, we demonstrate a significant contribution of the X chromosome to the difference in pupation site choice behavior between these species. Using a panel of X-chromosome deficiencies, we screened the majority of the X chromosome for causal loci and identified two regions associated with this X-effect. We then collect gene disruption and RNAi data supporting a single gene that affects pupation behavior within each region: Fas2 and tilB. Finally, we show that differences in tilB expression correlate with the differences in pupation site choice behavior between species. This evidence associating two genes with differences in a complex, environmentally sensitive behavior represents the first step toward a functional and evolutionary understanding of this behavioral divergence.
Hybrid diamond/ carbon fiber microelectrodes enable multimodal electrical/chemical neural interfacing
Authors: Maryam A. Hejazi, Wei Tong, Alastair Stacey, Artemio Soto-Breceda, Michael R. Ibbotson, Molis Yunzab, Matias I. Maturana, Ali Almasi, Young Jun Jung, Shi Sun, Hamish Meffin, Jian Fang, Melanie E.M. Stamp, Kumaravelu Ganesan, Kate Fox, Aaqil Rifai, Athavan Nadarajah, Samira Falahatdoost, Steven Prawer, Nicholas V. Apollo, David J. Garrett
Journal: Biomaterials (2019)
A stress-responsive enhancer induces dynamic drug resistance in acute myeloid leukemia
Authors: Mark S. Williams, Fabio M.R. Amaral, Fabrizio Simeoni, Tim C.P. Somervaille
Journal: Journal of Clinical Investigation (2019)

The drug efflux pump ABCB1 is a key driver of chemoresistance, and high expression predicts treatment failure in acute myeloid leukemia (AML). In this study, we identified and functionally validated the network of enhancers that controls expression of ABCB1. We show that exposure of leukemia cells to daunorubicin activated an integrated stress response-like transcriptional program to induce ABCB1 through remodeling and activation of an ATF4-bound, stress-responsive enhancer. Protracted stress primed enhancers for rapid increases in activity following re-exposure of cells to daunorubicin, providing an epigenetic memory of prior drug treatment. In primary human AML, exposure of fresh blast cells to daunorubicin activated the stress-responsive enhancer and led to dose-dependent induction of ABCB1. Dynamic induction of ABCB1 by diverse stressors, including chemotherapy, facilitated escape of leukemia cells from targeted third-generation ABCB1 inhibition, providing an explanation for the failure of ABCB1 inhibitors in clinical trials. Stress-induced upregulation of ABCB1 was mitigated by combined use of the pharmacologic inhibitors U0126 and ISRIB, which inhibit stress signaling and have potential for use as adjuvants to enhance the activity of ABCB1 inhibitors.
Targeting CD70 with Cusatuzumab Eliminates Acute Myeloid Leukemia Stem Cells in Humans
Authors: Adrian F Ochsenbein, Thomas Pabst, Sabine Höpner, Vera Ulrike Bacher, Magdalena Hinterbrandner, Yara Banz, Rouven Müller, Markus G. Manz, Walid Gharib, David Francisco, Rémy Bruggmann, Luc Van Rompaey, Mahan Moshir, Tim Delahaye, Domenica Gandini, Ellen Erzeel, Anna Hultberg, Samson Fung, Hans De Haard, Nicolas Leupin, Carsten Riether
Journal: Blood (2019)
Problems following treatment for cancer: Building a picture and pathways for Manchester Cancer (UK) 2015-2018.
Authors: Claire Emily Higham, Lindsey Wilby, Claire O'Rourke, Wendy Makin
Journal: Journal of Clinical Oncology (2019)

145 Background: Greater Manchester Cancer (GMC) is the cancer program for Greater Manchester’s (GM) devolved health and social care system. 13 tumor-specific (TPB’s) and 7 cross-cutting (inc Living With and Beyond Cancer (LWBCPB)) pathway boards were formed to support this. Aims:The LWBCPB tasked the TPB’s to describe late consequences of treatment, define current care pathways/resources and highlight service gaps. Methods: Questionnaires were sent to all TPB’s. Returned questionnaires (11/13) from 2015-18 were analysed quantitatively (Excel) and qualitatively (Nvivo). Results: Frequent cross cutting long term effects were fatigue(9/11 TPB’s), psychological distress(7/11), sexual dysfunction(6/11), memory loss(5/11), neuropathy(5/11). Management strategies were described; eg, for fatigue; specific workshops(11/11), verbal +/- written advice(7/11), referral to other HCP(6/11). Tumour specific long term effects included a mix of clinical and psychosocial issues; with all TPB’s providing information to patients; only 6/11 to Primary Care. Limited evidence was given for active screening for long term effects. Resources offered included national websites, charities, local services and support groups. For specific clinical issues eg cardiac; referral was mainly to local services; despite identification of clinicians with an interest in LWBC offering specialist services within GM. Lack of resource was the commonly cited reason for absence of care pathways. Identified gaps in current approaches to management were; lack of access to specific resources(11/11) (psychology(7/11), specialist nurse(2/11), hospice care(2/11); inequity of access to resources(7/11); need for specific pathways and referral guidance(3/11). Conclusions: Long term consequences of cancer treatments are cross-cutting. GMC PB’s are an opportunity to use these baseline data to define and implement locally appropriate LWBC pathways including optimal referral, screening and communication with primary care.
Pakistan attracts 700 female doctors back into practice through online service
Authors: Ashfaq Yusufzai
Journal: BMJ (2019)

A digital medical service launched by one of Pakistan’s oldest universities has attracted 700 female doctors back into practice and helped 100 000 patients, often in the most deprived and remote parts of the country, to receive medical care.

The eDoctor initiative, which is led by gynaecologist Jehan Ara Ainuddin from Dow University of Health Sciences in Karachi, is targeting 35 000 women doctors who trained in Pakistani medical schools but have never entered clinical practice, often because of the restrictions placed on women by …
Implantable Neural Interfaces and Wearable Tactile Systems for Bidirectional Neuroprosthetics Systems
Authors: Annarita Cutrone, Silvestro Micera
Journal: Advanced Healthcare Materials (2019)

Abstract Neuroprosthetics and neuromodulation represent a promising field for several related applications in the central and peripheral nervous system, such as the treatment of neurological disorders, the control of external robotic devices, and the restoration of lost tactile functions. These actions are allowed by the neural interface, a miniaturized implantable device that most commonly exploits electrical energy to fulfill these operations. A neural interface must be biocompatible, stable over time, low invasive, and highly selective; the challenge is to develop a safe, compact, and reliable tool for clinical applications. In case of anatomical impairments, neuroprosthetics is bound to the need of exploring the surrounding environment by fast‐responsive and highly sensitive artificial tactile sensors that mimic the natural sense of touch. Tactile sensors and neural interfaces are closely interconnected since the readouts from the first are required to convey information to the neural implantable apparatus. The role of these devices is pivotal hence technical improvements are essential to ensure a secure system to be eventually adopted in daily life. This review highlights the fundamental criteria for the design and microfabrication of neural interfaces and artificial tactile sensors, their use in clinical applications, and future enhancements for the release of a second generation of devices.
Age-Related Dopaminergic Innervation Augments T Helper 2-Type Allergic Inflammation in the Postnatal Lung
Authors: Wei Wang, Jonathan A. Cohen, Antonia Wallrapp, Kenneth G. Trieu, Juliana Barrios, Fengzhi Shao, Nandini Krishnamoorthy, Vijay K. Kuchroo, Matthew R. Jones, Alan Fine, Yan Bai, Xingbin Ai
Journal: Immunity (2019)
HIV infections and HIV testing during pregnancy, Germany, 1993 to 2016
Authors: Ulrich Marcus
Journal: Eurosurveillance (2019)

Background Elimination of mother-to-child transmission (MTCT) of HIV by 2020 is a goal of the World Health Organization (WHO) action plan for the European Region. However, data to monitor progress towards MTCT elimination are not readily available in Germany. Aim We aimed to estimate the number of pregnant women with HIV and MTCT rates in Germany. Methods We triangulated retrospectively obtained data from: (i) healthcare reimbursement for HIV screening tests, (ii) a statutory health insurance subsample of prevalent and incident HIV diagnoses among pregnant women, (iii) a mathematical model of the German HIV epidemic with number, region of origin and risk factors for women of childbearing age, and (iv) the statutory anonymous HIV registry on children infected through HIV MTCT. Results The number of women aged 15–49 years with HIV increased from ca 6,000 in 1993 to ca 11,000 in 2016. Risk of injecting drug use (IDU) declined from 65% in 1993 to 16% in 2016. The annual proportion of women living with HIV giving live birth increased from a mean of 1.9% during 1993 to 1998 to 4.9% in 2011 to 2015. HIV screening rates during pregnancy increased from ca 50% in 2001 to ca 90% in 2016. The HIV MTCT rate dropped from 6.8% in 2001 to 1.1% in 2016. Conclusions The population of women living with HIV in Germany shifted from predominantly IDU-associated infections to predominantly sexually acquired infections, while fertility rates more than doubled. MTCT rates dropped, mainly because of improved detection and management of HIV in pregnancy.
CAR T Cells Derived from Healthy Mice Lead to Cytokine Release Syndrome (CRS) in the TCL1 Chronic Lymphocytic Leukemia Model; Mice with CLL Treated with Acalabrutinib or Ibrutinib Have Improved CAR T Cell Function without Increasing the Cytokines of CRS
Authors: Robin Sanderson, Arantxa Romero-Toledo, John G. Gribben
Journal: Blood (2019)
An Atlas of Clinically-Distinct Tumor Cellular Ecosystems in Diffuse Large B Cell Lymphoma
Authors: Chloe B. Steen, Bogdan A. Luca, Mohammad Shahrokh Esfahani, Barzin Y. Nabet, Brian Sworder, Farshad Farshidfar, Kiarash Shamardani, David M. Kurtz, Chih Long Liu, Ranjana H Advani, Yasodha Natkunam, June Helen Myklebust, Maximilian Diehn, Andrew Gentles, Aaron M Newman, Ash A. Alizadeh
Journal: Blood (2019)
Beneficial effects of endurance exercise training on skeletal muscle microvasculature in sickle cell disease patients
Authors: Angèle N. Merlet, Laurent A. Messonnier, Cécile Coudy-Gandilhon, Daniel Béchet, Barnabas Gellen, Thomas Rupp, Frédéric Galactéros, Pablo Bartolucci, Léonard Féasson
Journal: Blood (2019)
Safety and Efficacy of Orelabrutinib Monotherapy in Chinese Patients with Relapsed or Refractory Mantle Cell Lymphoma: A Multicenter, Open-Label, Phase II Study
Authors: Yuqin Song, Yongping Song, Lihong Liu, Mingzhi Zhang, Zhiming Li, Chunyan Ji, Wei Xu, Ting Liu, Bing Xu, Xin Wang, Sujun Gao, Huilai Zhang, Yu Hu, Yan Li, Ying Cheng, Haiyan Yang, Junning Cao, Zunmin Zhu, Jianda Hu, Wei Zhang, Hongmei Jing, Kaiyang Ding, Zhengguang Lu, Bin Zhang, Renbin Zhao, Zhixin Xu, Jun Zhu
Journal: Blood (2019)
Prevalence of prognostic uncertainty and impact on prognostic discussions in thoracic oncology.
Authors: Anand Habib, Zilu Zhang, Anna Tanasijevic, Richard Chen, Mark M. Awad, Oreofe Olukemi Odejide, Gregory A. Abel
Journal: Journal of Clinical Oncology (2019)

33 Background: Recent advances for late-stage lung cancer may have led to a shift from therapeutic ‘nihilism’ to ‘optimism’ (Temel, JCO 2016). It is not known whether this shift has increased prognostic uncertainty nor whether oncologists’ tolerance of uncertainty affects their prognostic discussion practices. Methods: In October 2018, we sent a 34-item survey by FedEx to a random sample of thoracic oncologists (n=444) listed in the publicly-available ASCO directory. The survey assessed professional training, perceptions of prognostic uncertainty for advanced lung cancer, prognostic discussion practices, uncertainty tolerance using an adapted Physicians’ Reactions to Uncertainty (PRU) scale (Gerrity , Motivation and Emotion 1995), and presented a clinical vignette. Results: We received 178 completed surveys from thoracic oncologists in 36 states (response rate: 40.4%). Median duration of practice was 29 years, and 56.7% endorsed an academic affiliation. 52.3% agreed that “there is more prognostic uncertainty in the management of lung cancer now than there was 10 years ago,” and 36.4% noted difficulty “staying up-to-date on the most recent science” in lung cancer management. Surprisingly, only 78.4% reported discussing prognosis with the vast majority (&gt;95%) of their patients. In univariable logistic regression analyses, respondents had lower odds of reporting discussing prognosis with &gt;95% of their patients if they scored highly on the PRU ‘anxious due to uncertainty’ subscale (OR=0.39 [0.18,0.83]), the PRU’s ‘reluctant to disclose uncertainty’ subscale (OR=0.43 [0.20,0.93]) or were male (OR=0.28 [0.08,0.97). Those with higher reluctant to disclose uncertainty scores were also less likely to agree that they would discuss life expectancy when first meeting a patient with stage IV NSCLC presented in the vignette (p=0.014). Conclusions: Data from this geographically diverse cohort of lung cancer oncologists suggest there is increasing prognostic uncertainty within thoracic oncology, and that many find it challenging to stay current with practice changes. Moreover, oncologists’ personal characteristics including gender and uncertainty tolerance may affect their propensity to discuss prognosis.
A single-cell atlas of entorhinal cortex from individuals with Alzheimer’s disease reveals cell-type-specific gene expression regulation
Authors: Alexandra Grubman, Gabriel Chew, John F. Ouyang, Guizhi Sun, Xin Yi Choo, Catriona McLean, Rebecca K. Simmons, Sam Buckberry, Dulce B. Vargas-Landin, Daniel Poppe, Jahnvi Pflueger, Ryan Lister, Owen J. L. Rackham, Enrico Petretto, Jose M. Polo
Journal: Nature Neuroscience (2019)
Response: The most fundamental change in asthma management in 30 years?
Authors: Helen K. Reddel
Journal: European Respiratory Journal (2019)

<b>GINA recommends against treating asthma in adults and adolescents with SABAs alone. Large studies support as-needed low dose ICS–formoterol, which is available in several formulations, as a feasible solution to reduce risk in mild asthma.</b>http://bit.ly/2l5X0H4
Trends in Diabetic Retinopathy, Visual Acuity, and Treatment Outcomes for Patients Living With Diabetes in a Fundus Photograph–Based Diabetic Retinopathy Screening Program in Bangladesh
Authors: Mahiul M. K. Muqit, Nick Kourgialis, Meredith Jackson-deGraffenried, Zaman Talukder, Erica R. Khetran, Arifur Rahman, Weng Onn Chan, Fakrhul A. Chowdury, Dipak Nag, Jasmin Ahmad, David S. Friedman
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Diabetic retinopathy (DR) is the leading cause of low vision among working-age adults. An estimated 6.9 million people in Bangladesh were living with diabetes in 2017, which is projected to increase to more than 10 million people in 2025. Currently, no standardized and/or large-scale DR screening program exists in Bangladesh. <h3>Objective</h3> To develop a novel fundus photograph–based eye screening model for early detection of DR to prevent vision loss in Bangladeshi individuals with diabetes. <h3>Design, Setting, and Participants</h3> In this cross-sectional study, 49 264 patients with diabetes underwent opportunistic eye screening at 2 eye hospitals and 1 diabetic hospital in Bangladesh between June 1, 2010, and September 30, 2017. The data set was analyzed from April 8 to December 30, 2018. Technicians were trained to obtain 2-field digital fundus photographs and to grade each according to a standardized DR severity scale. Each patient was counseled and triaged for treatment using defined DR referral criteria. <h3>Main Outcomes and Measures</h3> Primary DR grading outcomes, visual acuity, and treatment outcomes. <h3>Results</h3> A total of 49 264 patients (54.3% male; mean [SD] age, 50.8 [12.3] years) underwent DR screening during a 7-year period. The DR prevalence rate across all 3 sites was 33% (95% CI, 33%-33%). Prevalence rates varied by center (Chittagong, 64.6% [95% CI, 64.0%-65.0%]; Dhaka, 39.8% [95% CI, 39.0%-41.0%]; and Feni, 13.0% [95% CI, 13.0%-14.0%]). Across all age groups, male patients were at higher risk of prevalent DR than female patients (odds ratio, 1.99; 95% CI, 1.90-2.07). The prevalence was 3.9% for preproliferative DR, 7.8% for proliferative DR, and 19.2% for maculopathy. Individuals with DR had significantly worse visual acuity than those with no DR (best-corrected visual acuity, 0.35 vs 0.21 logMAR;<i>P</i> &lt; .001). The rate of moderate visual impairment was 12.2%, and the rate of blindness was 2.5%. Primary treatments included laser photocoagulation (n = 1637), intravitreal injection (n = 1440), and vitrectomy (n = 309). <h3>Conclusions and Relevance</h3> Screening Bangladeshi individuals known to have diabetes using fundus photography identified large numbers of patients with sight-threatening proliferative DR, maculopathy, and visual impairment or blindness. Expansion of eye screening services in Bangladesh is warranted as part of a national government eye care and diabetes health policy.
Abstract 27: Machine Learning Models for Outcome Prediction of Out-Of-Hospital Cardiac Arrest of Presumed Cardiac Cause Using the All-Japan Utstein Registry
Authors: Tomohisa Seki, Tomoyoshi Tamura, Kazuhiko Ohe, Masaru Suzuki
Journal: Circulation (2019)

Background: Outcome prediction for patients with out-of-hospital cardiac arrest (OHCA) using prehospital information has been one of the major challenges in resuscitation medicine. Recently, machine learning techniques have been shown to be highly effective in predicting outcomes using clinical registries. In this study, we aimed to establish a prediction model for outcomes of OHCA of presumed cardiac cause using machine learning techniques. Methods: We analyzed data from the All-Japan Utstein Registry of the Fire and Disaster Management Agency between 2005 and 2016. Of 1,423,338 cases, data of OHCA patients aged ≥18 years with presumed cardiac etiology were retrieved and divided into two groups: training set, n = 584,748 (between 2005 and 2013) and test set, n = 223,314 (between 2014 and 2016). The endpoints were neurologic outcome at 1-month and survival at 1-month. Of 47 variables evaluated during the prehospital course, 19 variables (e.g.,sex, age, ECG waveform, and practice of bystander CPR) were used for outcome prediction. Performances of logistic regression, random forests, and deep neural network were examined in this study. Results: For prediction of neurologic outcomes (cerebral performance category 1 or 2) using the test set, the generated models showed area under the receiver operating characteristic curve (AUROC) values of 0.942 (95% confidence interval [CI] 0.941-0.943), 0.947 (95% CI 0.946-0.948), and 0.948 (95% CI 0.948-0.950) in logistic regression, random forest, and deep neural network, respectively. For survival prediction, the generated models showed AUROC values of 0.901 (95% CI 0.900-0.902), 0.913 (95% CI 0.912-0.914), and 0.912 (95% CI 0.911-0.913) in logistic regression, random forest, and deep neural network, respectively. Conclusions: Machine learning techniques using prehospital variables showed favorable prediction capability for 1-month neurologic outcome and survival in OHCA of presumed cardiac cause.