7 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/08/18

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

7 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2016/08/18

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

From Cues to Nudge: A Knowledge-Based Framework for Surveillance of Healthcare-Associated Infections.

J Med Syst. 2016 Jan;40(1):23

Authors: Shaban-Nejad A, Mamiya H, Riazanov A, Forster AJ, Baker CJ, Tamblyn R, Buckeridge DL

Abstract
We propose an integrated semantic web framework consisting of formal ontologies, web services, a reasoner and a rule engine that together recommend appropriate level of patient-care based on the defined semantic rules and guidelines. The classification of healthcare-associated infections within the HAIKU (Hospital Acquired Infections - Knowledge in Use) framework enables hospitals to consistently follow the standards along with their routine clinical practice and diagnosis coding to improve quality of care and patient safety. The HAI ontology (HAIO) groups over thousands of codes into a consistent hierarchy of concepts, along with relationships and axioms to capture knowledge on hospital-associated infections and complications with focus on the big four types, surgical site infections (SSIs), catheter-associated urinary tract infection (CAUTI); hospital-acquired pneumonia, and blood stream infection. By employing statistical inferencing in our study we use a set of heuristics to define the rule axioms to improve the SSI case detection. We also demonstrate how the occurrence of an SSI is identified using semantic e-triggers. The e-triggers will be used to improve our risk assessment of post-operative surgical site infections (SSIs) for patients undergoing certain type of surgeries (e.g., coronary artery bypass graft surgery (CABG)).

PMID: 26537131 [PubMed - indexed for MEDLINE]

Linezolid in the treatment of drug-resistant tuberculosis: the challenge of its narrow therapeutic index.

Expert Rev Anti Infect Ther. 2016 Aug 17;

Authors: Wasserman S, Meintjes G, Maartens G

Abstract
INTRODUCTION: Linezolid is an oxazolidinone with potent activity against M tuberculosis, and improves culture conversion and cure rates when added to treatment regimens for drug resistant tuberculosis. However, linezolid has a narrow therapeutic window, and the optimal dosing strategy that minimizes the substantial toxicity associated with linezolid's prolonged use in tuberculosis treatment has not been determined, limiting the potential impact of this anti-mycobacterial agent.
AREAS COVERED: This paper aims to review and summarize the current knowledge on linezolid for the treatment of drug-resistant tuberculosis. The focus is on the pharmacokinetic-pharmacodynamic determinants of linezolid's efficacy and toxicity in tuberculosis, and how this relates to defining an optimal dose. Mechanisms of linezolid toxicity and resistance, and the potential role of therapeutic drug monitoring are also covered. Expert commentary: Prospective pharmacokinetic-pharmacodynamic studies are required to define optimal therapeutic targets and to inform improved linezolid dosing strategies for drug-resistant tuberculosis.

PMID: 27532292 [PubMed - as supplied by publisher]

A Skyline Plugin for Pathway-Centric Data Browsing.

J Am Soc Mass Spectrom. 2016 Aug 16;

Authors: Degan MG, Ryadinskiy L, Fujimoto GM, Wilkins CS, Lichti CF, Payne SH

Abstract
For targeted proteomics to be broadly adopted in biological laboratories as a routine experimental protocol, wet-bench biologists must be able to approach selected reaction monitoring (SRM) and parallel reaction monitoring (PRM) assay design in the same way they approach biological experimental design. Most often, biological hypotheses are envisioned in a set of protein interactions, networks, and pathways. We present a plugin for the popular Skyline tool that presents public mass spectrometry data in a pathway-centric view to assist users in browsing available data and determining how to design quantitative experiments. Selected proteins and their underlying mass spectra are imported to Skyline for further assay design (transition selection). The same plugin can be used for hypothesis-driven data-independent acquisition (DIA) data analysis, again utilizing the pathway view to help narrow down the set of proteins that will be investigated. The plugin is backed by the Pacific Northwest National Laboratory (PNNL) Biodiversity Library, a corpus of 3 million peptides from >100 organisms, and the draft human proteome. Users can upload personal data to the plugin to use the pathway navigation prior to importing their own data into Skyline. Graphical Abstract ᅟ.

PMID: 27530777 [PubMed - as supplied by publisher]

Corpus Domain Effects on Distributional Semantic Modeling of Medical Terms.

Bioinformatics. 2016 Aug 16;

Authors: Pakhomov SV, Finley G, McEwan R, Wang Y, Melton GB

Abstract
MOTIVATION: Automatically quantifying semantic similarity and relatedness between clinical terms is an important aspect of text mining from electronic health records, which are increasingly recognized as valuable sources of phenotypic information for clinical genomics and bioinformatics research. A key obstacle to development of semantic relatedness measures is the limited availability of large quantities of clinical text to researchers and developers outside of major medical centers. Text from general English and biomedical literature are freely available; however, their validity as a substitute for clinical domain to represent semantics of clinical terms remains to be demonstrated.
RESULTS: We constructed neural network representations of clinical terms found in a publicly available benchmark dataset manually labeled for semantic similarity and relatedness. Similarity and relatedness measures computed from text corpora in three domains (Clinical Notes, PubMed Central articles, and Wikipedia) were compared using the benchmark as reference. We found that measures computed from full text of biomedical articles in PubMed Central repository (rho = 0.62 for similarity and 0.58 for relatedness) are on par with measures computed from clinical reports (rho = 0.60 for similarity and 0.57 for relatedness). We also evaluated the use of neural network based relatedness measures for query expansion in a clinical document retrieval task and a biomedical term word sense disambiguation task. We found that, with some limitations, biomedical articles may be used in lieu of clinical reports to represent the semantics of clinical terms and that distributional semantic methods are useful for clinical and biomedical natural language processing applications.
CONTACT: pakh0002@umn.edu, gpfinley@umn.edu, rmcewan@umn.edu, wang2258@umn.edu, gmelton@umn.edu.

PMID: 27531100 [PubMed - as supplied by publisher]

9 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/08/17

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

PPARγ agonists promote differentiation of cancer stem cells by restraining YAP transcriptional activity.

Oncotarget. 2016 Aug 12;

Authors: Basu-Roy U, Han E, Rattanakorn K, Gadi A, Verma N, Maurizi G, Gunaratne PH, Coarfa C, Kennedy OD, Garabedian MJ, Basilico C, Mansukhani A

Abstract
Osteosarcoma (OS) is a highly aggressive pediatric bone cancer in which most tumor cells remain immature and fail to differentiate into bone-forming osteoblasts. However, OS cells readily respond to adipogenic stimuli suggesting they retain mesenchymal stem cell-like properties. Here we demonstrate that nuclear receptor PPARγ agonists such as the anti-diabetic, thiazolidinedione (TZD) drugs induce growth arrest and cause adipogenic differentiation in human, mouse and canine OS cells as well as in tumors in mice. Gene expression analysis reveals that TZDs induce lipid metabolism pathways while suppressing targets of the Hippo-YAP pathway, Wnt signaling and cancer-related proliferation pathways. Significantly, TZD action appears to be restricted to the high Sox2 expressing cancer stem cell population and is dependent on PPARγ expression. TZDs also affect growth and cell fate by causing the cytoplasmic sequestration of the transcription factors SOX2 and YAP that are required for tumorigenicity. Finally, we identify a TZD-regulated gene signature based on Wnt/Hippo target genes and PPARγ that predicts patient outcomes. Together, this work highlights a novel connection between PPARγ agonist in inducing adipogenesis and mimicking the tumor suppressive hippo pathway. It also illustrates the potential of drug repurposing for TZD-based differentiation therapy for osteosarcoma.

PMID: 27528232 [PubMed - as supplied by publisher]

Repositioning antipsychotic chlorpromazine for treating colorectal cancer by inhibiting sirtuin 1.

Oncotarget. 2015 Sep 29;6(29):27580-95

Authors: Lee WY, Lee WT, Cheng CH, Chen KC, Chou CM, Chung CH, Sun MS, Cheng HW, Ho MN, Lin CW

Abstract
Investigating existing drugs for repositioning can enable overcoming bottlenecks in the drug development process. Here, we investigated the effect and molecular mechanism of the antipsychotic drug chlorpromazine (CPZ) and identified its potential for treating colorectal cancer (CRC). Human CRC cell lines harboring different p53 statuses were used to investigate the inhibitory mechanism of CPZ. CPZ effectively inhibited tumor growth and induced apoptosis in CRC cells in a p53-dependent manner. Activation of c-jun N-terminal kinase (JNK) was crucial for CPZ-induced p53 expression and the subsequent induction of tumor apoptosis. Induction of p53 acetylation at lysine382 was involved in CPZ-mediated tumor apoptosis, and this induction was attenuated by sirtuin 1 (SIRT1), a class III histone deacetylase. By contrast, knocking down SIRT1 sensitized tumor cells to CPZ treatment. Moreover, CPZ induced the degradation of SIRT1 protein participating downstream of JNK, and JNK suppression abrogated CPZ-mediated SIRT1 downregulation. Clinical analysis revealed a significant association between high SIRT1 expression and poor outcome in CRC patients. These data suggest that SIRT1 is an attractive therapeutic target for CRC and that CPZ is a potential repositioned drug for treating CRC.

PMID: 26363315 [PubMed - indexed for MEDLINE]

Medical student preparedness for an era of personalized medicine: findings from one US medical school.

Per Med. 2016 Mar;13(2):129-141

Authors: Eden C, Johnson KW, Gottesman O, Bottinger EP, Abul-Husn NS

Abstract
AIM: The objective of this research was to assess medical student preparedness for the use of personalized medicine.
MATERIALS & METHODS: A survey instrument measuring attitude toward personalized medicine, perceived knowledge of genomic testing concepts and perceived ability to apply genomics to clinical care was distributed to students in medical school (MS) years 1-4.
RESULTS: Of 212 participants, 79% felt that it was important to learn about personalized medicine, but only 6% thought that their medical education had adequately prepared them to practice personalized medicine. Attitude did not vary across years; knowledge and ability increased after MS1, but not after MS2.
CONCLUSION: While medical students support the use of personalized medicine, they do not feel prepared to apply genomics to clinical care.

PMID: 27528879 [PubMed - as supplied by publisher]

Pharmacokinetics of bupropion and its pharmacologically active metabolites in pregnancy.

Drug Metab Dispos. 2016 Aug 15;

Authors: Fokina VM, Xu M, Rytting E, Abdel-Rahman SZ, West H, Oncken C, Clark SM, Ahmed MS, Hankins GD, Nanovskaya TN

Abstract
Bupropion sustained release (SR) is used to promote smoking cessation in males and non-pregnant females. However, its efficacy as a smoking cessation aid during pregnancy is not reported. The pregnancy-associated changes in maternal physiology may alter the pharmacokinetics and pharmacodynamics of bupropion, and consequently, its efficacy in pregnant smokers. Therefore, the aims of this study were to determine the steady-state pharmacokinetics of bupropion during pregnancy and the effect of functional genetic variants of CYP2B6 and CYP2C19 on bupropion pharmacokinetics in pregnant women. Plasma and urine concentrations of bupropion and its metabolites hydroxybupropion (OHBUP), threohydrobupropion, and erythrohydrobupropion were determined by liquid chromatography-mass spectrometry. Subjects were genotyped for 5 non-synonymous SNPs that result in 7 CYP2B6 alleles, namely *2, *3, *4, *5, *6, *7, and *9, and for CYP2C19 variants *2, *3, and *17. The present study reports that the isoform-specific effect of pregnancy on bupropion-metabolizing enzymes along with the increase of renal elimination of the drug could collectively result in a slight decrease in exposure to bupropion in pregnancy. On the other hand, pregnancy-induced increase in CYP2B6-catalyzed bupropion hydroxylation did not impact the plasma levels of OHBUP, probably due to a higher rate of OHBUP glucuronidation and renal elimination associated with pregnancy. Therefore, exposure to OHBUP, a pharmacologically active metabolite of the bupropion, appears to be similar to that of the non-pregnant state. The predicted metabolic phenotypes of CYP2B6*6 and variant alleles of CYP2C19 in pregnancy are similar to those in the non-pregnant state.

PMID: 27528039 [PubMed - as supplied by publisher]

HLA-B*51:01 is strongly associated with clindamycin-related cutaneous adverse drug reactions.

Pharmacogenomics J. 2016 Aug 16;

Authors: Yang Y, Chen S, Yang F, Zhang L, Alterovitz G, Zhu H, Xuan J, Yang X, Luo H, Mu J, He L, Luo X, Xing Q

Abstract
Clindamycin causes cutaneous adverse drug reactions (cADRs), sometimes with the mechanisms of pathogenicity or risk factors unknown. This study aims to assess whether HLA alleles are associated with clindamycin-related cADRs in the Han Chinese population. We performed an association study of 12 subjects with clindamycin-related cADRs, 279 controls and 26 clindamycin-tolerant subjects. Subjects who received clindamycin through intravenous drip were analyzed separately. Unbiased, in silico docking was conducted. We found 6 out of 12 clindamycin-induced cADR patients carried HLA-B*51:01, and all of them received clindamycin via intravenous drip (6/9). The carrier frequency of HLA-B*51:01 is significantly higher compared with the control group (P=0.0006; OR=9.731, 95% CI: 2.927-32.353) and the clindamycin-tolerant group (OR=24.000, 95% CI: 3.247-177.405). In silico docking showed clindamycin is potentially more stable inside HLA-B*51:01 protein. Our results suggested, for the first time, that HLA-B*51:01 is a risk allele for clindamycin-related cADRs in Han Chinese, especially when clindamycin is administered via intravenous drip.The Pharmacogenomics Journal advance online publication, 16 August 2016; doi:10.1038/tpj.2016.61.

PMID: 27527109 [PubMed - as supplied by publisher]

Regulation of the Coxsackie and Adenovirus Receptor Expression is Dependent on CFTR in Airway Epithelial Cells.

Cell Microbiol. 2016 Aug 16;

Authors: Sharma A, Xu Y, Sung B, Vincent TC, Worgall T, Worgall S

Abstract
The coxsackievirus and adenovirus receptor (CAR), in addition to serving as viral receptor, is a component of tight junctions and plays an important role in tissue homeostasis. Defects in the cystic fibrosis transmembrane regulator (CFTR) in lung epithelial cells are linked to inflammation and susceptibility for respiratory tract infections. Here we demonstrate that CAR expression and infectivity with adenovirus (Ad) are increased in cystic fibrosis (CF) airway epithelial cells. Inhibition of CFTR or histone deacetylase (HDAC) enhanced CAR expression while CFTR overexpression or restoration of the diminished HDAC activity in CF cells reduced CAR expression. This connects the CFTR to CAR expression and infectivity with Ad through HDAC.

PMID: 27527752 [PubMed - as supplied by publisher]

Life in a bubble.

Lancet Respir Med. 2015 Oct;3(10):759

Authors: Ranscombe P

PMID: 26477554 [PubMed - indexed for MEDLINE]

The complexity of silk under the spotlight of synthetic biology.

Biochem Soc Trans. 2016 Aug 15;44(4):1151-7

Authors: Vollrath F

Abstract
For centuries silkworm filaments have been the focus of R&D innovation centred on textile manufacture with high added value. Most recently, silk research has focused on more fundamental issues concerning bio-polymer structure-property-function relationships. This essay outlines the complexity and fundamentals of silk spinning, and presents arguments for establishing this substance as an interesting and important subject at the interface of systems biology (discovery) and synthetic biology (translation). It is argued that silk is a generic class of materials where each type of silk presents a different embodiment of emergent properties that combine genetically determined (anticipatory) and environmentally responsive components. In spiders' webs the various silks have evolved to form the interactive components of an intricate fabric that provides an extended phenotype to the spider's body morphology.

PMID: 27528763 [PubMed - in process]

The gain and loss of long noncoding RNA associated-competing endogenous RNAs in prostate cancer.

Oncotarget. 2016 Aug 9;

Authors: Liu D, Yu X, Wang S, Dai E, Jiang L, Wang J, Yang Q, Yang F, Zhou S, Jiang W

Abstract
Prostate cancer (PC) is one of the most common solid tumors in men. However, the molecular mechanism of PC remains unclear. Numerous studies have demonstrated that long noncoding RNA (lncRNA) can act as microRNA (miRNA) sponge, one type of competing endogenous RNAs (ceRNAs), which offers a novel viewpoint to elucidate the mechanisms of PC. Here, we proposed an integrative systems biology approach to infer the gain and loss of ceRNAs in PC. First, we re-annotated exon microarray data to obtain lncRNA expression profiles of PC. Second, by integrating mRNA and miRNA expression, as well as miRNA targets, we constructed lncRNA-miRNA-mRNA ceRNA networks in cancer and normal samples. The lncRNAs in these two ceRNA networks tended to have a longer transcript length and cover more exons than the lncRNAs not involved in ceRNA networks. Next, we further extracted the gain and loss ceRNA networks in PC. We found that the gain ceRNAs in PC participated in cell cycle, and the loss ceRNAs in PC were associated with metabolism. We also identified potential prognostic ceRNA pairs such as MALAT1-EGR2 and MEG3-AQP3. Finally, we inferred a novel mechanism of known drugs, such as cisplatin, for the treatment of PC through gain and loss ceRNA networks. The potential drugs such as 1,2,6-tri-O-galloyl-beta-D-glucopyranose (TGGP) could modulate lncRNA-mRNA competing relationships, which may uncover new strategy for treating PC. In summary, we systematically investigated the gain and loss of ceRNAs in PC, which may prove useful for identifying potential biomarkers and therapeutics for PC.

PMID: 27528026 [PubMed - as supplied by publisher]

Validation of a network-based strategy for the optimization of combinatorial target selection in breast cancer therapy: siRNA knockdown of network targets in MDA-MB-231 cells as an in vitro model for inhibition of tumor development.

Oncotarget. 2016 Aug 4;

Authors: Tilli TM, Carels N, Tuszynski JA, Pasdar M

Abstract
Network-based strategies provided by systems biology are attractive tools for cancer therapy. Modulation of cancer networks by anticancer drugs may alter the response of malignant cells and/or drive network re-organization into the inhibition of cancer progression. Previously, using systems biology approach and cancer signaling networks, we identified top-5 highly expressed and connected proteins (HSP90AB1, CSNK2B, TK1, YWHAB and VIM) in the invasive MDA-MB-231 breast cancer cell line. Here, we have knocked down the expression of these proteins, individually or together using siRNAs. The transfected cell lines were assessed for in vitro cell growth, colony formation, migration and invasion relative to control transfected MDA-MB-231, the non-invasive MCF-7 breast carcinoma cell line and the non-tumoral mammary epithelial cell line MCF-10A. The knockdown of the top-5 upregulated connectivity hubs successfully inhibited the in vitro proliferation, colony formation, anchorage independence, migration and invasion in MDA-MB-231 cells; with minimal effects in the control transfected MDA-MB-231 cells or MCF-7 and MCF-10A cells. The in vitro validation of bioinformatics predictions regarding optimized multi-target selection for therapy suggests that protein expression levels together with protein-protein interaction network analysis may provide an optimized combinatorial target selection for a highly effective anti-metastatic precision therapy in triple-negative breast cancer. This approach increases the ability to identify not only druggable hubs as essential targets for cancer survival, but also interactions most susceptible to synergistic drug action. The data provided in this report constitute a preliminary step toward the personalized clinical application of our strategy to optimize the therapeutic use of anti-cancer drugs.

PMID: 27527857 [PubMed - as supplied by publisher]

AID/APOBEC-network reconstruction identifies pathways associated with survival in ovarian cancer.

BMC Genomics. 2016;17(1):643

Authors: Svoboda M, Meshcheryakova A, Heinze G, Jaritz M, Pils D, Castillo-Tong DC, Hager G, Thalhammer T, Jensen-Jarolim E, Birner P, Braicu I, Sehouli J, Lambrechts S, Vergote I, Mahner S, Zimmermann P, Zeillinger R, Mechtcheriakova D

Abstract
BACKGROUND: Building up of pathway-/disease-relevant signatures provides a persuasive tool for understanding the functional relevance of gene alterations and gene network associations in multifactorial human diseases. Ovarian cancer is a highly complex heterogeneous malignancy in respect of tumor anatomy, tumor microenvironment including pro-/antitumor immunity and inflammation; still, it is generally treated as single disease. Thus, further approaches to investigate novel aspects of ovarian cancer pathogenesis aiming to provide a personalized strategy to clinical decision making are of high priority. Herein we assessed the contribution of the AID/APOBEC family and their associated genes given the remarkable ability of AID and APOBECs to edit DNA/RNA, and as such, providing tools for genetic and epigenetic alterations potentially leading to reprogramming of tumor cells, stroma and immune cells.
RESULTS: We structured the study by three consecutive analytical modules, which include the multigene-based expression profiling in a cohort of patients with primary serous ovarian cancer using a self-created AID/APOBEC-associated gene signature, building up of multivariable survival models with high predictive accuracy and nomination of top-ranked candidate/target genes according to their prognostic impact, and systems biology-based reconstruction of the AID/APOBEC-driven disease-relevant mechanisms using transcriptomics data from ovarian cancer samples. We demonstrated that inclusion of the AID/APOBEC signature-based variables significantly improves the clinicopathological variables-based survival prognostication allowing significant patient stratification. Furthermore, several of the profiling-derived variables such as ID3, PTPRC/CD45, AID, APOBEC3G, and ID2 exceed the prognostic impact of some clinicopathological variables. We next extended the signature-/modeling-based knowledge by extracting top genes co-regulated with target molecules in ovarian cancer tissues and dissected potential networks/pathways/regulators contributing to pathomechanisms. We thereby revealed that the AID/APOBEC-related network in ovarian cancer is particularly associated with remodeling/fibrotic pathways, altered immune response, and autoimmune disorders with inflammatory background.
CONCLUSIONS: The herein study is, to our knowledge, the first one linking expression of entire AID/APOBECs and interacting genes with clinical outcome with respect to survival of cancer patients. Overall, data propose a novel AID/APOBEC-derived survival model for patient risk assessment and reconstitute mapping to molecular pathways. The established study algorithm can be applied further for any biologically relevant signature and any type of diseased tissue.

PMID: 27527602 [PubMed - as supplied by publisher]

The T helper type 17/regulatory T cell paradigm in pregnancy.

Immunology. 2016 May;148(1):13-21

Authors: Figueiredo AS, Schumacher A

Abstract
T helper type 17 (Th17) and regulatory T (Treg) cells are active players in the establishment of tolerance and defence. These attributes of the immune system enmesh to guarantee the right level of protection. The healthy immune system, on the one hand, recognizes and eliminates dangerous non-self pathogens and, on the other hand, protects the healthy self. However, there are circumstances where this fine balance is disrupted. In fact, in situations such as in pregnancy, the foreign fetal antigens challenge the maternal immune system and Treg cells will dominate Th17 cells to guarantee fetal survival. In other situations such as autoimmunity, where the Th17 responses are often overwhelming, the immune system shifts towards an inflammatory profile and attacks the healthy tissue from the self. Interestingly, autoimmune patients have meliorating symptoms during pregnancy. This connects with the antagonist role of Th17 and Treg cells, and their specific profiles during these two immune challenging situations. In this review, we put into perspective the Th17/Treg ratio during pregnancy and autoimmunity, as well as in pregnant women with autoimmune conditions. We further review existing systems biology approaches that study specific mechanisms of these immune cells using mathematical modelling and we point out possible future directions of investigation. Understanding what maintains or disrupts the balance between these two opponent yet reciprocal cells in healthy physiological settings, sheds light into the development of innovative pharmacological approaches to fight pregnancy loss and autoimmunity.

PMID: 26855005 [PubMed - indexed for MEDLINE]

30 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/08/16

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.