Increasing the stability of electrolyte-gated organic synaptic transistors for neuromorphic implants.

Electrolyte-gated organic synaptic transistors (EGOSTs) can have versatile synaptic plasticity in a single device, so they are promising as components of neuromorphic implants that are intended for use in neuroprosthetic electronic nerves that are energy-efficient and have simple system structure. With the advancement in transistor properties of EGOSTs, the commercialization of neuromorphic implants for practical long-term use requires consistent operation, so they must be stable in vivo. This requirement demands strategies that maintain electronic and ionic transport in the devices while implanted in the human body, and that are mechanically, environmentally, and operationally stable. Here, we cover the structure, working mechanisms, and electrical responses of EGOSTs. We then focus on strategies to ensure their stability to maintain these characteristics and prevent adverse effects on biological tissues. We also highlight state-of-the-art neuromorphic implants that incorporate these strategies. We conclude by presenting a perspective on improvements that are needed in EGOSTs to develop practical, neuromorphic implants that are long-term useable.

Support for the Right to Life among Neonatal Intensive Care Nurses in Korea.

The increase of high-risk newborns due to societal changes has presented neonatal intensive care unit nurses with more ethical challenges and heightened their perception of neonatal palliative care. Therefore, this study was a descriptive survey exploring the perceptions of neonatal intensive care unit nurse regarding biomedical ethics and neonatal palliative care in neonatal intensive care units. The research participants were 97 neonatal intensive care unit nurses who had been directly involved with end-of-life care for high-risk babies. Data were collected from November to December 2021 through an online survey. The Korean version of Neonatal Palliative Care Attitude Scale and the tool of biomedical ethics were used. The collected data were analyzed using the T-test, ANOVA, Scheffé test, Pearson correlation coefficient, and multiple regression analysis. The mean score for perception of biomedical ethics in neonatal intensive care unit nurses was 2.89 of 4, and that of neonatal palliative care in neonatal intensive care unit nurses was 3.10 of 5. Existence of a protocol of neonatal palliative care, the experience of patients dying, and the right to life of neonates were factors influencing the perception of neonatal palliative care. The explanatory power was 12.5%. The data support the importance of guidelines regarding systematic neonatal palliative care. Also, developing programs for sharing and supporting experiences of patients dying among colleagues and persistent education about the right to life of neonates for neonatal intensive care unit nurses can improve perception of neonatal palliative care.

Social network position and the Conserved Transcriptional Response to Adversity in older Koreans.

BACKGROUND: Social connections are crucial to human health and well-being. Previous research on molecular mechanisms in health has focused primarily on the individual-level perception of social connections (e.g., loneliness). This study adopted socio-centric social network analysis that includes all social ties from the entire population of interest to examine the group-level social connections and their association with a molecular genomic measure of health. METHODS: Using socio-centric (global) social network data from an entire village in Korea, we investigated how social network characteristics are related to immune cell gene expression among older adults. Blood samples were collected (N = 53, 65-79 years) and mixed effect linear model analyses were performed to examine the association between social network characteristics and Conserved Transcriptional Response to Adversity (CTRA) RNA expression patterns. RESULTS: Social network positions measured by k-core score, the degree of cohesive core positions in an entire village, were significantly associated with CTRA downregulation. Such associations emerged above and beyond the effects of perceived social isolation (loneliness) and biobehavioral risk factors (smoking, alcohol, BMI, etc.). Social network size, defined as degree centrality, was also associated with reduced CTRA gene expression, but its association mimicked that of perceived social isolation (loneliness). CONCLUSIONS: The current findings implicate community-level social network characteristics in the regulation of individual human genome function above and beyond individual-level perceptions of connectedness.

The Effectiveness of Virtual Reality Intervention for COVID-19-Related Psychological Distress: A Systematic Review.

OBJECTIVE: The prolonged coronavirus disease-2019 (COVID-19) pandemic is likely to cause psychological distress in people. This systematic review aimed to identify the effectiveness of virtual reality (VR)-based psychological intervention among individuals with psychological distress during the COVID-19 crisis. PubMed, Ovid MEDLINE, Cochrane Library, Web of Science, Embase, and PsycINFO databases were searched for articles published until July 2022. METHODS: The available citations were deduplicated and screened by two authors using the title and abstract information. Eligibility criteria were constructed according to the PICOT guidelines. Empirical studies of all designs and comparator groups were included if they appraised the impact of an immersive VR intervention on any standardized measure indicative of psychological distress (stress, anxiety, depression, and post-traumatic symptoms) or improvements in quality of life in participants, including COVID-19 patients, medical staff working with COVID-19 patients, and people who had experienced strict social distancing during the COVID-19 pandemic. RESULTS: The results were discussed using a narrative synthesis because of the heterogeneity between studies. Seven of the studies met the inclusion criteria. There were two randomized controlled trials and five uncontrolled studies on VR interventions. CONCLUSION: All studies reported significant improvement in a wide range of psychological distress during COVID-19, ranging from stress, anxiety, depression, and post-traumatic symptoms to quality of life, supporting the efficacy of VR-based psychological intervention. Our results suggest that VR intervention has potential to ameliorate COVID-19-related psychological distress with efficacy and safety.

Simultaneous Substitution of Fe and Sr in Beta-Tricalcium Phosphate: Synthesis, Structural, Magnetic, Degradation, and Cell Adhesion Properties.

ß-tricalcium phosphate is a promising bone graft substitute material with biocompatibility and high osteoinductivity. However, research on the ideal degradation and absorption for better clinical application remains a challenge. Now, we focus on modifying physicochemical properties and improving biological properties through essential ion co-substitution (Fe and Sr) in ß-TCPs. Fe- and Sr-substituted and Fe/Sr co-substituted ß-TCP were synthesized by aqueous co-precipitation with substitution levels ranging from 0.2 to 1.0 mol%. The ß-TCP phase was detected by X-ray diffraction and Fourier transform infrared spectroscopy. Changes in Ca-O and P-O bond lengths of the co-substituted samples were observed through X-ray photoelectron spectroscopy. The results of VSM represent the M-H graph having a combination of diamagnetic and ferromagnetic properties. A TRIS-HCl solution immersion test showed that the degradation and resorption functions act synergistically on the surface of the co-substituted sample. Cell adhesion tests demonstrated that Fe enhances the initial adhesion and proliferation behavior of hDPSCs. The present work suggests that Fe and Sr co-substitution in ß-TCP can be a candidate for promising bone graft materials in tissue engineering fields. In addition, the possibility of application of hyperthermia for cancer treatment can be expected.

Genetically programmed alternative splicing of NEMO mediates an autoinflammatory disease phenotype.

Host defense and inflammation are regulated by the NF-κB essential modulator (NEMO), a scaffolding protein with a broad immune cell and tissue expression profile. Hypomorphic mutations in inhibitor of NF-κB kinase regulatory subunit gamma (IKBKG) encoding NEMO typically present with immunodeficiency. Here, we characterized a pediatric autoinflammatory syndrome in 3 unrelated male patients with distinct X-linked IKBKG germline mutations that led to overexpression of a NEMO protein isoform lacking the domain encoded by exon 5 (NEMO-Δex5). This isoform failed to associate with TANK binding kinase 1 (TBK1), and dermal fibroblasts from affected patients activated NF-κB in response to TNF but not TLR3 or RIG-I-like receptor (RLR) stimulation when isoform levels were high. By contrast, T cells, monocytes, and macrophages that expressed NEMO-Δex5 exhibited increased NF-κB activation and IFN production, and blood cells from these patients expressed a strong IFN and NF-κB transcriptional signature. Immune cells and TNF-stimulated dermal fibroblasts upregulated the inducible IKK protein (IKKi) that was stabilized by NEMO-Δex5, promoting type I IFN induction and antiviral responses. These data revealed how IKBKG mutations that lead to alternative splicing of skipping exon 5 cause a clinical phenotype we have named NEMO deleted exon 5 autoinflammatory syndrome (NDAS), distinct from the immune deficiency syndrome resulting from loss-of-function IKBKG mutations.

Nightmares and alexithymia in traumatized North Korean refugees.

BACKGROUND: The present study examined the association between nightmare distress and alexithymia in traumatized North Korean (NK) refugees resettled in South Korea and the effects of clinical or subclinical psychiatric symptoms on this association. METHODS: Thirty-eight NK refugees living in South Korea who had traumatic experiences (15 males, 23 females; 29.50 ± 13.11 years of age) were recruited. The Structured Clinical Interview for DSM-IV and the Clinician-Administered Post-Traumatic Stress Disorder (PTSD) Scale were conducted. All participants completed a series of questionnaires on the history of their previous traumatic experiences, the Beck Depression Inventory, the Nightmare Distress Questionnaire (NDQ), the Toronto Alexithymia Scale (TAS), and the Impact of Event Scale. In total, 18 refugees were classified as having nightmare distress based on NDQ scores, and 20 refugees were not. RESULTS: Refugees with nightmares reported significantly higher TAS total scores and Difficulty Identifying Feelings (DIF; a subscale of TAS) scores compared to those without nightmares. In addition, NDQ scores were positively correlated with TAS total scores (r = 0.43, p < 0.01) and DIF scores (r = 0.49, p < 0.01). These correlations remained significant after excluding refugees with current axis I psychiatric disorders or clinical or subclinical depressive symptoms. However, there was no significant correlation between nightmares and alexithymia after excluding refugees with clinical or subclinical trauma-related symptoms. CONCLUSIONS: Nightmares in traumatized refugees were associated with alexithymia even in the absence of current psychiatric disorders or depressive symptoms. Trauma-related symptoms might be a mediating factor between nightmares and alexithymia in traumatized refugees.

Age-Related Retinal Changes in Wild-Type C57BL/6J Mice Between 2 and 32 Months.

Purpose: The purpose of this study was to extend our understanding of how aging affects normal retina function and morphology in wild-type C57BL/6J mice, by analyzing electrophysiological recordings and in vivo and post mortem anatomy. Methods: Electroretinograms (ERGs), spectral domain optical coherence tomography (SD-OCT), and confocal scanning laser ophthalmoscope (cSLO) in vivo images were obtained from mice between the ages of 2 and 32 months in four groups: group 1 (<0.5 years), group 2 (1.0-1.5 years), group 3 (1.5-2.0 years), and group 4 (>2.0 years). Afterward, mouse bodies and eyes were weighed. Eyes were stained with hematoxylin and eosin (H&E) and cell nuclei were quantified. Results: With aging, mice showed a significant reduction in both a- and b-wave ERG amplitudes in scotopic and photopic conditions. Additionally, total retina and outer nuclear layer (ONL) thickness, as measured by SD-OCT images, were significantly reduced in older groups. The cSLO images showed an increase in auto-fluorescence at the photoreceptor-RPE interface as age increases. H&E cell nuclei quantification showed significant reduction in the ONL in older ages, but no differences in the inner nuclear layer (INL) or ganglion cell layer (GCL). Conclusions: By using multiple age groups and extending the upper age limit of our animals to approximately 2.65 years (P970), we found that natural aging causes negative effects on retinal function and morphology in a gradual, rather than abrupt, process. Future studies should investigate the exact mechanisms that contribute to these gradual declines in order to discover pathways that could potentially serve as therapeutic targets.

Polysomnographic Sleep and Attentional Deficits in Traumatized North Korean Refugees.

INTRODUCTION: Attentional deficits and sleep problems are common in refugees who have experienced trauma. In the present study, we used polysomnography (PSG) to investigate the relationship between attentional deficits and objective measures of sleep structure in traumatized North Korean refugees. METHODS: We recruited 32 North Korean refugees (mean age = 33.78 ± 14.33 years) and 39 South Korean participants (mean age = 35.03 ± 11.08 years). Sustained attention and divided attention were assessed using the Computerized Attention Test. We conducted an overnight PSG to objectively assess sleep structure. The participants also completed the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Impact of Event Scale-Revised (IES-R), Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and Insomnia Severity Index (ISI). RESULTS: The North Korean refugees showed more commission errors (CEs, p < 0.05) and a larger standard deviation (SD) of the reaction time (RT) (p < 0.05) in the sustained attention task compared to the South Korean participants. Furthermore, the North Korean refugees showed a shorter period of wake after sleep onset (WASO, p < 0.01), less time spent in N1 (p < 0.05), and more time spent in N2 (p < 0.05). The larger SD of RT in the sustained attention task in the North Korean refugees was positively correlated with WASO (r = 0.62, p < 0.01) and N1 stage (r = 0.47, p < 0.05) after controlling for age, sex, BDI, BAI, and IES-R. CONCLUSION: The North Korean refugees showed poorer performance on the sustained attention task. Nocturnal PSG revealed shorter WASO and time spent in N1 in this population, which are independently associated with the preservation of attentional capacity. These data suggest that traumatized refugees may compensate for attentional deficits induced by their traumatic experiences via increased sleep continuity.

Perceptions of Black Children's Narrative Language: A Mixed-Methods Study.

Purpose In this mixed-methods study, we address two aims. First, we examine the impact of language variation on the ratings of children's narrative language. Second, we identify participants' ideologies related to narrative language and language variation. Method Forty adults listened to and rated six Black second-grade children on the quality of 12 narratives (six fictional, six personal). Adults then completed a quantitative survey and participated in a qualitative interview. Results Findings indicated that adults rated students with less variation from mainstream American English (MAE) more highly than students with greater variation from MAE for fictional narratives, but not for personal narratives. Personal narratives tended to be evaluated more favorably by parents than teachers. Black raters tended to assign higher ratings of narrative quality than did White raters. Thematic analysis and conversation analysis of qualitative interviews supported quantitative findings and provided pertinent information about participants' beliefs. Conclusion Taken together, quantitative and qualitative results point to a shared language ideology among adult raters of variation from MAE being more acceptable in informal contexts, such as telling a story of personal experience, and less acceptable in more formal contexts, such as narrating a fictional story prompted by a picture sequence.

Rapid detection of deformed wing virus in honeybee using ultra-rapid qPCR and a DNA-chip.

Fast and accurate detection of viral RNA pathogens is important in apiculture. A polymerase chain reaction (PCR)-based detection method has been developed, which is simple, specific, and sensitive. In this study, we rapidly (in 1 min) synthesized cDNA from the RNA of deformed wing virus (DWV)-infected bees (Apis mellifera), and then, within 10 min, amplified the target cDNA by ultra-rapid qPCR. The PCR products were hybridized to a DNA-chip for confirmation of target gene specificity. The results of this study suggest that our method might be a useful tool for detecting DWV, as well as for the diagnosis of RNA virus-mediated diseases on-site.

Factors associated with fatigue in patients with insomnia.

Although fatigue is common in insomnia, the clinical associates of fatigue in patients with insomnia are largely unknown. We aimed to investigate the clinical associates of fatigue in patients with insomnia. Patients visiting the Stanford Sleep Medicine Center completed the Insomnia Severity Index (ISI), Insomnia Symptom Questionnaire (ISQ), the Fatigue Severity Scale (FSS), the Epworth Sleepiness Scale (ESS), and the Patient Health Questionnaire (PHQ-9). Among 6367 patients, 2024 were diagnosed with insomnia (age 43.06 ±â€¯15.19 years; 1110 women and 914 men) according to the ISI and the ISQ. Insomnia patients with severe fatigue (n = 1306) showed higher insomnia symptoms, daytime sleepiness, depression and longer habitual sleep duration than those without severe fatigue (n = 718). Higher insomnia symptoms, daytime sleepiness and depressive symptoms, and longer habitual sleep duration, independently predicted higher fatigue scores. Among insomnia patients with daytime sleepiness (ESS≥10), only habitual sleep duration and depression predicted fatigue scores. The interaction between insomnia severity and daytime sleepiness significantly predicted the severity of fatigue. Depression was a significant mediator between insomnia and fatigue. For 598 insomnia patients undergoing overnight polysomnography (PSG), no significant correlations were found between fatigue and any PSG parameters. The current study suggests that managing insomnia or depression may reduce the fatigue of insomnia patients, whereas arbitrary efforts to prolong sleep duration may worsen their fatigue.

Determination of the Absolute Enantiomeric Excess of the Carbon Nanotube Ensemble by Symmetry Breaking Using the Optical Titration Method.

Symmetry breaking of single-walled carbon nanotubes (SWNTs) has profound effects on their optoelectronic properties that are essential for fundamental study and applications. Here, we show that isomeric SWNTs that exhibit identical photoluminescence (PL) undergo symmetry breaking by flavin mononucleotide (FMN) and exhibit dual PLs and different binding affinities (Ka). Increasing the FMN concentration leads to systematic PL shifts of SWNTs according to structural modality and handedness due to symmetry breaking. Density gradient ultracentrifugation using a FMN-SWNT dispersion displays PL shifts and different densities according to SWNT handedness. Using the optical titration method to determine the PL-based Ka of SWNTs against an achiral surfactant as a titrant, left- and right-handed SWNTs display two-step PL inflection corresponding to respective Ka values with FMN, which leads to the determination of the enantiomeric excess (ee) of the SWNT ensemble that was confirmed by circular dichroism measurement. Decreasing the FMN concentration for the SWNT dispersion leads to enantiomeric selection of SWNTs. The titration-based ee determination of the widely used sodium cholate-based SWNT dispersion was also demonstrated by using FMN as a cosurfactant.

Loss-of-function screens of druggable targetome against cancer stem-like cells.

Cancer stem-like cells (CSLCs) contribute to the initiation and recurrence of tumors and to their resistance to conventional therapies. In this study, small interfering RNA (siRNA)-based screening of ∼4800 druggable genes in 3-dimensional CSLC cultures in comparison to 2-dimensional bulk cultures of U87 glioma cells revealed 3 groups of genes essential for the following: survival of the CSLC population only, bulk-cultured population only, or both populations. While diverse biologic processes were associated with siRNAs reducing the bulk-cultured population, CSLC-eliminating siRNAs were enriched in a few functional categories, such as lipid metabolism, protein metabolism, and gene expression. Interestingly, siRNAs that selectively reduced CSLC only were found to target genes for cholesterol and unsaturated fatty acid synthesis. The lipidomic profile of CSLCs revealed increased levels of monounsaturated lipids. Pharmacologic blockage of these target pathways reduced CSLCs, and this effect was eliminated by addition of downstream metabolite products. The present CSLC-sensitive target categories provide a useful resource that can be exploited for the selective elimination of CSLCs.-Song, M., Lee, H., Nam, M.-H., Jeong, E., Kim, S., Hong, Y., Kim, N., Yim, H. Y., Yoo, Y.-J., Kim, J. S., Kim, J.-S., Cho, Y.-Y., Mills, G. B., Kim, W.-Y., Yoon, S. Loss-of-function screens of druggable targetome against cancer stem-like cells.

Affinity-mediated sorting order reversal of single-walled carbon nanotubes in density gradient ultracentrifugation.

Sorted single-walled carbon nanotubes (SWNTs) are of paramount importance for their utilization in high-end optoelectronic applications. Sodium cholate (SC)-based density gradient ultracentrifugation (DGU) has been instrumental in isolating small diameter (d t) SWNTs. Here, we show that SWNTs wrapped by flavin mononucleotide (FMN) as a dispersing agent are sorted in DGU, and show sorting order reversal behavior, departing from prototypical SC-SWNT trends. Larger d t SWNTs are sorted in lower density (ρ), and buoyant ρ distribution of FMN-SWNT ranges from 1.15-1.25 g cm(-3). Such a nanotube layering pattern originates from both the binding affinity between FMN and SWNT and the less-susceptible hydrated volume of remote phosphate sidechains of FMN according to nanotube d t change.

Selective Dispersion of Highly Pure Large-Diameter Semiconducting Carbon Nanotubes by a Flavin for Thin-Film Transistors.

Scalable and simple methods for selective extraction of pure, semiconducting (s) single-walled carbon nanotubes (SWNTs) is of profound importance for electronic and photovoltaic applications. We report a new, one-step procedure to obtain respective large-diameter s- and metallic (m)-SWNT enrichment purity in excess of 99% and 78%, respectively, via interaction between the aromatic dispersing agent and SWNTs. The approach utilizes N-dodecyl isoalloxazine (FC12) as a surfactant in conjunction with sonication and benchtop centrifugation methods. After centrifugation, the supernatant is enriched in s-SWNTs with less carbonaceous impurities, whereas precipitate is enhanced in m-SWNTs. In addition, the use of an increased centrifugal force enhances both the purity and population of larger diameter s-SWNTs. Photoinduced energy transfer from FC12 to SWNTs is facilitated by respective electronic level alignment. Owing to its peculiar photoreduction capability, FC12 can be employed to precipitate SWNTs upon UV irradiation and observe absorption of higher optical transitions of SWNTs. A thin-film transistor prepared from a dispersion of enriched s-SWNTs was fabricated to verify electrical performance of the sorted sample and was observed to display p-type conductance with an average on/off ratio over 10(6) and an average mobility over 10 cm(2)/V·s.

Evaluation of Bone Regeneration on Polyhydroxyethyl-polymethyl Methacrylate Membrane in a Rabbit Calvarial Defect Model.

This study was conducted to evaluate the capacity of guiding bone regeneration of polyhydroxyethyl-polymethyl methacrylate (PHEMA-PMMA) membrane as a guided tissue regeneration membrane for bone defects. Two 8-mm diameter transosseous round defects were made at the parietal bone of 18 New Zealand White rabbits. Defects were covered with or without PHEMA-PMMA membrane. Radiological and histological evaluation revealed that the bone tissue over the defect was more regenerated with time in both groups. However, there was significantly more bone regeneration at 8 weeks in the experimental group than the control group (p<0.05). There was no sign of membrane degradation or tissue inflammation and no invasion of muscle and fibrous tissue into defects. PHEMA-PMMA is a potential material for guided tissue regeneration membrane as it induces no adverse tissue reaction and effectively supports selective bone regeneration.

Cardiac glycosides display selective efficacy for STK11 mutant lung cancer.

Although STK11 (LKB1) mutation is a major mediator of lung cancer progression, targeted therapy has not been implemented due to STK11 mutations being loss-of-function. Here, we report that targeting the Na(+)/K(+)-ATPase (ATP1A1) is synthetic lethal with STK11 mutations in lung cancer. The cardiac glycosides (CGs) digoxin, digitoxin and ouabain, which directly inhibit ATP1A1 function, exhibited selective anticancer effects on STK11 mutant lung cancer cell lines. Restoring STK11 function reduced the efficacy of CGs. Clinically relevant doses of digoxin decreased the growth of STK11 mutant xenografts compared to wild type STK11 xenografts. Increased cellular stress was associated with the STK11-specific efficacy of CGs. Inhibiting ROS production attenuated the efficacy of CGs, and STK11-AMPK signaling was important in overcoming the stress induced by CGs. Taken together, these results show that STK11 mutation is a novel biomarker for responsiveness to CGs. Inhibition of ATP1A1 using CGs warrants exploration as a targeted therapy for STK11 mutant lung cancer.

Differential regulation and synthetic lethality of exclusive RB1 and CDKN2A mutations in lung cancer.

Genetic alterations in lung cancer are distinctly represented in non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC). Mutation of the RB1 and CDKN2A genes, which are tightly associated with cell cycle regulation, is exclusive to SCLC and NSCLC cells, respectively. Through the systematic analysis of transcriptome and proteome datasets for 318 cancer cell lines, we characterized differential gene expression and protein regulation in RB1-mutant SCLC and CDKN2A-mutant NSCLC. Many of the genes and proteins associated with RB1-mutant SCLC cell lines belong to functional categories of gene expression and transcription, whereas those associated with CDKN2A-mutant NSCLC cell lines were enriched in gene sets of the extracellular matrix and focal adhesion. These results indicate that the loss of RB1 and CDKN2A function induces distinctively different signaling cascades in SCLC and NSCLC cells. In addition, knockdown of the RB1 gene in CKDN2A-mutant cell lines (and vice versa) synergistically inhibits cancer cell proliferation. The present study on the exclusive role of RB1 and CDKN2A mutations in lung cancer subtypes demonstrates a synthetic lethal strategy for cancer regulation.

Integrated analysis of transcriptomes of cancer cell lines and patient samples reveals STK11/LKB1-driven regulation of cAMP phosphodiesterase-4D.

The recent proliferation of data on large collections of well-characterized cancer cell lines linked to therapeutic drug responses has made it possible to identify lineage- and mutation-specific transcriptional markers that can help optimize implementation of anticancer agents. Here, we leverage these resources to systematically investigate the presence of mutation-specific transcription markers in a wide variety of cancer lineages and genotypes. Sensitivity and specificity of potential transcriptional biomarkers were simultaneously analyzed in 19 cell lineages grouped into 228 categories based on the mutational genotypes of 12 cancer-related genes. Among a total of 1,455 category-specific expression patterns, the expression of cAMP phosphodiesterase-4D (PDE4D) with 11 isoforms, one of the PDE4(A-D) subfamilies, was predicted to be regulated by a mutant form of serine/threonine kinase 11 (STK11)/liver kinase B1 (LKB1) present in lung cancer. STK11/LKB1 is the primary upstream kinase of adenine monophosphate-activated protein kinase (AMPK). Subsequently, we found that the knockdown of PDE4D gene expression inhibited proliferation of STK11-mutated lung cancer lines. Furthermore, challenge with a panel of PDE4-specific inhibitors was shown to selectively reduce the growth of STK11-mutated lung cancer lines. Thus, we show that multidimensional analysis of a well-characterized large-scale panel of cancer cell lines provides unprecedented opportunities for the identification of unexpected oncogenic mechanisms and mutation-specific drug targets.