Cold Spring Harbor perspectives in medicine This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

[PERSPECTIVES] The Persistent Challenge of Developing Addiction Pharmacotherapies
This article will review the development of eight compounds used in the treatment of drug addiction with an emphasis on pharmacological mechanisms and the utility of preclinical animal models of addiction in therapeutic development. In contrast to these successes, animal research has identified a number of promising medications for the treatment of psychostimulant use disorder, none of which have proven to be clinically effective. A specific example of an apparently promising pharmacotherapeutic for cocaine that failed clinically will be examined to determine whether this truly represents a challenge to the predictive vali...
Source: Cold Spring Harbor perspectives in medicine - November 1, 2021 Category: Research Authors: Swinford-Jackson, S. E., O'Brien, C. P., Kenny, P. J., Vanderschuren, L. J. M. J., Unterwald, E. M., Pierce, R. C. Tags: Addiction PERSPECTIVES Source Type: research

[PERSPECTIVES] Host Cell Factors That Interact with Influenza Virus Ribonucleoproteins
Influenza viruses hijack host cell factors at each stage of the viral life cycle. After host cell entry and endosomal escape, the influenza viral ribonucleoproteins (vRNPs) are released into the cytoplasm where the classical cellular nuclear import pathway is usurped for nuclear translocation of the vRNPs. Transcription takes place inside the nucleus at active host transcription sites, and cellular mRNA export pathways are subverted for export of viral mRNAs. Newly synthesized RNP components cycle back into the nucleus using various cellular nuclear import pathways and host-encoded chaperones. Replication of the negative-s...
Source: Cold Spring Harbor perspectives in medicine - November 1, 2021 Category: Research Authors: Staller, E., Barclay, W. S. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research

[PERSPECTIVES] Metabolic Phenotypes, Dependencies, and Adaptation in Lung Cancer
Lung cancer is a heterogeneous disease that is subdivided into histopathological subtypes with distinct behaviors. Each subtype is characterized by distinct features and molecular alterations that influence tumor metabolism. Alterations in tumor metabolism can be exploited by imaging modalities that use metabolite tracers for the detection and characterization of tumors. Microenvironmental factors, including nutrient and oxygen availability and the presence of stromal cells, are a critical influence on tumor metabolism. Recent technological advances facilitate the direct evaluation of metabolic alterations in patient tumor...
Source: Cold Spring Harbor perspectives in medicine - November 1, 2021 Category: Research Authors: DeNicola, G. M., Shackelford, D. B. Tags: Lung Cancer: Disease Biology and Its Potential for Clinical Translation PERSPECTIVES Source Type: research

[PERSPECTIVES] Consequences of Parental Opioid Exposure on Neurophysiology, Behavior, and Health in the Next Generations
Substance abuse and the ongoing opioid epidemic represents a large societal burden. This review will consider the long-term impact of opioid exposure on future generations. Prenatal, perinatal, and preconception exposure are reviewed with discussion of both maternal and paternal influences. Opioid exposure can have long-lasting effects on reproductive function, gametogenesis, and germline epigenetic programming, which can influence embryogenesis and alter the developmental trajectory of progeny. The potential mechanisms by which preconception maternal and paternal opioid exposure produce deleterious consequences on the hea...
Source: Cold Spring Harbor perspectives in medicine - October 1, 2021 Category: Research Authors: Vassoler, F. M., Wimmer, M. E. Tags: Addiction PERSPECTIVES Source Type: research

[PERSPECTIVES] Hemagglutinin Structure and Activities
Hemagglutinins (HAs) are the receptor-binding and membrane fusion glycoproteins of influenza viruses. They recognize sialic acid–containing, cell-surface glycoconjugates as receptors but have limited affinity for them, and, as a consequence, virus attachment to cells requires their interaction with several virus HAs. Receptor-bound virus is transferred into endosomes where membrane fusion by HAs is activated at pH between 5 and 6.5, depending on the strain of virus. Fusion activity requires extensive rearrangements in HA conformation that include extrusion of a buried "fusion peptide" to connect with the endosomal me...
Source: Cold Spring Harbor perspectives in medicine - October 1, 2021 Category: Research Authors: Gamblin, S. J., Vachieri, S. G., Xiong, X., Zhang, J., Martin, S. R., Skehel, J. J. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research

[PERSPECTIVES] Induction and Evasion of Type-I Interferon Responses during Influenza A Virus Infection
Influenza A viruses (IAVs) are contagious pathogens and one of the leading causes of respiratory tract infections in both humans and animals worldwide. Upon infection, the innate immune system provides the first line of defense to neutralize or limit the replication of invading pathogens, creating a fast and broad response that brings the cells into an alerted state through the secretion of cytokines and the induction of the interferon (IFN) pathway. At the same time, IAVs have developed a plethora of immune evasion mechanisms in order to avoid or circumvent the host antiviral response, promoting viral replication. Herein,...
Source: Cold Spring Harbor perspectives in medicine - October 1, 2021 Category: Research Authors: Munoz-Moreno, R., Martinez-Romero, C., Garcia-Sastre, A. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research

[PERSPECTIVES] Radiation Therapy in Non-Small-Cell Lung Cancer
The management of non-small-cell lung cancer (NSCLC) varies according to stage. Surgical resection is reserved for operable patients with early-stage NSCLC, while high-dose target radiation—stereotactic body radiation therapy (SBRT)—is reserved for patients whose comorbidities prohibit them from a major surgical procedure. The treatment of locally advanced NSCLC (LA-NSCLC) is stratified according to resectability. Those with resectable disease may require additional treatments such as chemotherapy and radiation, while patients with unresectable disease will require definitive chemoradiation therapy with adjuvan...
Source: Cold Spring Harbor perspectives in medicine - October 1, 2021 Category: Research Authors: Dohopolski, M., Gottumukkala, S., Gomez, D., Iyengar, P. Tags: Lung Cancer: Disease Biology and Its Potential for Clinical Translation PERSPECTIVES Source Type: research

[PERSPECTIVES] The Meaning of "Cause" in Genetics
Causation has multiple distinct meanings in genetics. One reason for this is meaning slippage between two concepts of the gene: Mendelian and molecular. Another reason is that a variety of genetic methods address different kinds of causal relationships. Some genetic studies address causes of traits in individuals, which can only be assessed when single genes follow predictable inheritance patterns that reliably cause a trait. A second sense concerns the causes of trait differences within a population. Whereas some single genes can be said to cause population-level differences, most often these claims concern the effects of...
Source: Cold Spring Harbor perspectives in medicine - September 1, 2021 Category: Research Authors: Lynch, K. E. Tags: Combining Human Genetics and Causal Inference to Understand Human Disease and Development PERSPECTIVES Source Type: research

[PERSPECTIVES] Opioid Modulation of the Gut-Brain Axis in Opioid-Associated Comorbidities
Growing evidence from animal and human studies show that opioids have a major impact on the composition and function of gut microbiota. This leads to disruption in gut permeability and altered microbial metabolites, driving both systemic and neuroinflammation, which in turn impacts central nervous system (CNS) homeostasis. Tolerance and dependence are the major comorbidities associated with prolonged opioid use. Inflammatory mediators and signaling pathways have been implicated in both opioid tolerance and dependence. We provide evidence that targeting the gut microbiome during opioid use through prebiotics, probiotics, an...
Source: Cold Spring Harbor perspectives in medicine - September 1, 2021 Category: Research Authors: Zhang, L., Roy, S. Tags: Addiction PERSPECTIVES Source Type: research

[PERSPECTIVES] Live Attenuated Cold-Adapted Influenza Vaccines
Live attenuated, cold-adapted influenza vaccines exhibit several desirable characteristics, including the induction of systemic, mucosal, and cell-mediated immunity resulting in breadth of protection, ease of administration, and yield. Seasonal live attenuated influenza vaccines (LAIVs) were developed in the United States and Russia and have been used in several countries. In the last decade, following the incorporation of the 2009 pandemic H1N1 strain, the performance of both LAIVs has been variable and the U.S.-backbone LAIV was less effective than the corresponding inactivated influenza vaccines. The cause appears to be...
Source: Cold Spring Harbor perspectives in medicine - September 1, 2021 Category: Research Authors: Subbarao, K. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research

[PERSPECTIVES] Structure and Function of Influenza Polymerase
Influenza polymerase (FluPol) plays a key role in the viral infection cycle by transcribing and replicating the viral genome. FluPol is a multifunctional, heterotrimeric enzyme with cap-binding, endonuclease, RNA-dependent RNA polymerase and polyadenylation activities. It performs its functions in the context of the viral ribonucleoprotein particle (RNP), wherein the template viral RNA is coated by multiple copies of viral nucleoprotein. Moreover, it interacts with a number of host proteins that are essential cofactors and, consequently, adaptive mutations in the polymerase are required for crossing the avian–human s...
Source: Cold Spring Harbor perspectives in medicine - September 1, 2021 Category: Research Authors: Wandzik, J. M., Kouba, T., Cusack, S. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research

[PERSPECTIVES] Early Diagnosis and Screening for Lung Cancer
Cancer interception refers to actively blocking the cancer development process by preventing progression of premalignancy to invasive disease. The rate-limiting steps for effective lung cancer interception are the incomplete understanding of the earliest molecular events associated with lung carcinogenesis, the lack of preclinical models of pulmonary premalignancy, and the challenge of developing highly sensitive and specific methods for early detection. Recent advances in cancer interception are facilitated by developments in next-generation sequencing, computational methodologies, as well as the renewed emphasis in preci...
Source: Cold Spring Harbor perspectives in medicine - September 1, 2021 Category: Research Authors: Kadara, H., Tran, L. M., Liu, B., Vachani, A., Li, S., Sinjab, A., Zhou, X. J., Dubinett, S. M., Krysan, K. Tags: Lung Cancer: Disease Biology and Its Potential for Clinical Translation PERSPECTIVES Source Type: research

[PERSPECTIVES] Triangulating Evidence through the Inclusion of Genetically Informed Designs
Much research effort is invested in attempting to determine causal influences on disease onset and progression to inform prevention and treatment efforts. However, this is often dependent on observational data that are prone to well-known limitations, particularly residual confounding and reverse causality. Several statistical methods have been developed to support stronger causal inference. However, a complementary approach is to use design-based methods for causal inference, which acknowledge sources of bias and attempt to mitigate these through the design of the study rather than solely through statistical adjustment. G...
Source: Cold Spring Harbor perspectives in medicine - August 2, 2021 Category: Research Authors: Munafo, M. R., Higgins, J. P. T., Smith, G. D. Tags: Combining Human Genetics and Causal Inference to Understand Human Disease and Development PERSPECTIVES Source Type: research

[PERSPECTIVES] Animal Models of the Behavioral Symptoms of Substance Use Disorders
To more effectively manage substance use disorders, it is imperative to understand the neural, genetic, and psychological underpinnings of addictive behavior. To contribute to this understanding, considerable efforts have been made to develop translational animal models that capture key behavioral characteristics of addiction on the basis of DSM5 criteria of substance use disorders. In this review, we summarize empirical evidence for the occurrence of addiction-like behavior in animals. These symptoms include escalation of drug use, neurocognitive deficits, resistance to extinction, exaggerated motivation for drugs, increa...
Source: Cold Spring Harbor perspectives in medicine - August 2, 2021 Category: Research Authors: Vanderschuren, L. J. M. J., Ahmed, S. H. Tags: Addiction PERSPECTIVES Source Type: research

[TECHNIQUE] Application of Radiomics and Artificial Intelligence for Lung Cancer Precision Medicine
Medical imaging is the standard-of-care for early detection, diagnosis, treatment planning, monitoring, and image-guided interventions of lung cancer patients. Most medical images are stored digitally in a standardized Digital Imaging and Communications in Medicine format that can be readily accessed and used for qualitative and quantitative analysis. Over the several last decades, medical images have been shown to contain complementary and interchangeable data orthogonal to other sources such as pathology, hematology, genomics, and/or proteomics. As such, "radiomics" has emerged as a field of research that involves the pr...
Source: Cold Spring Harbor perspectives in medicine - August 2, 2021 Category: Research Authors: Tunali, I., Gillies, R. J., Schabath, M. B. Tags: Lung Cancer: Disease Biology and Its Potential for Clinical Translation TECHNIQUE Source Type: research