Veterinary echocardiographers' preferences for left atrial size assessment in cats: the BENEFIT project.

INTRODUCTION/OBJECTIVES: Veterinary echocardiographers' preferences for left atrial (LA) size assessment in cats have not been systematically investigated. The primary aim of this prospective exploratory study was to investigate echocardiographers' preferences concerning LA size assessment in cats. A secondary aim was to investigate echocardiographers' preferences for assessing LA size in subgroups based on geographic, demographic, and professional profiles. ANIMALS, MATERIALS, AND METHODS: An online survey instrument was designed, verified, and distributed globally to veterinary echocardiographers. RESULTS: A total of 655 veterinary echocardiographers from six continents and 54 countries, working in specialty practice (56%) and in general practice (38%), provided data. Linear two-dimensional (2D) technique was favored by most echocardiographers (n = 612) for LA size assessment. Most commonly, respondents combined linear 2D with subjective assessment (n = 227), while 209 used linear 2D-based methods alone. Most echocardiographers using linear 2D-based methods preferred the right parasternal short-axis view and to index the LA to the aorta (Ao). Approximately 10% of the respondents obtained LA dimensions from a right parasternal long-axis four-chamber view. Approximately one-third of echocardiographers that made linear measurements from 2D echocardiograms shared the same preferences regarding cat position, acquisition view, indexing method and time point identification for the LA measurement. The responses were comparably homogeneous across geographic location, level of training, years performing echocardiography, and type of practice. DISCUSSION/CONCLUSION: Most veterinary echocardiographers assessed LA size in cats using linear 2D echocardiography from a right parasternal short-axis view, and indexed LA to Ao. Respondents' preferences were similar over geographic, demographic, and professional backgrounds.

Veterinary echocardiographers' preferences for left atrial size assessment in dogs: the BENEFIT project.

INTRODUCTION/OBJECTIVES: Veterinary echocardiographers' preferences for left atrial (LA) size assessment in dogs have never been systematically investigated. The primary aim of this international survey study was to investigate echocardiographers' preferences for LA size assessment in dogs. The secondary aim was to investigate echocardiographers' preferences for assessing LA size in subgroups based on geographic, demographic, and professional profiles. ANIMALS, MATERIALS, AND METHODS: An online survey instrument was designed, verified, and distributed globally to the veterinary echocardiographers. RESULTS: A total of 670 echocardiographers from 54 countries on six continents completed the survey. Most echocardiographers (n = 621) used linear two-dimensional (2D)-based methods to assess LA size, 379 used subjective assessment, and 151 used M-mode-based methods. Most commonly, echocardiographers combined linear 2D-based methods with subjective assessment (n = 222), whereas 191 used linear 2D-based methods alone. Most echocardiographers (n = 436) using linear 2D-based methods preferred the right parasternal short-axis view and indexed the LA to the aorta. Approximately 30% (n = 191) of the echocardiographers who performed linear measurements from 2D echocardiograms shared the same preferences regarding dog position, acquisition view, indexing method, and identification of the time-point used for the measurement. The responses were comparably homogeneous across geographic location, training level, years of performing echocardiography, and type of practice. DISCUSSION/CONCLUSION: Most veterinary echocardiographers assessed LA size in dogs using linear 2D echocardiography from a right parasternal short-axis view, and by indexing the LA to the aorta. The respondents' preferences were similar across geographic, demographic, and professional backgrounds.

A phylogeny for North American Mallocybe (Inocybaceae) and taxonomic revision of eastern North American taxa.

A multigene phylogenetic assessment of North American species of Mallocybe is presented based on analyses of rpb1, rpb2, ITS, and 28S rDNA nucleotide data. This framework enables a systematic revision of the genus for 16 eastern North American species and captures taxonomic and phylogenetic diversity in a global context. A grade of two unusual and poorly known North American species stems from the most recent common ancestor of the genus that gives rise to three core subgroups named here as clades Unicolores, Nothosperma, and Mallocybe. The grade of taxa includes the poorly known Lepista praevillosa from Florida and a new species from the southern Appalachians, M. montana, both of which appear to be narrow-range endemics. Clade Nothosperma is characterized by Australian and New Zealand species, whereas clade Unicolores is composed of six species from eastern North America and East Asia. Clade Mallocybe is dominated by numerous north temperate taxa and constitutes the sister group to clade Nothosperma. These major clades are distinguished by a combination of phylogeny, morphology, geographic distribution, and ecology. In addition, four North American species are described as new: M. leucothrix, M. luteobasis, M. montana, and M. tomentella. Several names originating in North America, long ignored or misunderstood in the literature, are revitalized and established by type comparisons and modern reference material collected from or near type localities. In addition, 11 species were subjected to mass spectrometry muscarine assays, none of which contained detectable amounts of muscarine except for two: M. sabulosa and M. praevillosa. This confirms a diffuse phylogenetic distribution of muscarine within the genus. Taxonomic descriptions are presented for 16 species, several synonymies proposed, and four new combinations made. A key to species of eastern North American Mallocybe is presented, along with illustrations of important diagnostic features. Citation: Matheny PB, Kudzma LV, Graddy MG, Mardini SM, Noffsinger CR, Swenie RA, Walker NC, Campagna SR, Halling R, Lebeuf R, Kuo M, Lewis DP, Smith ME, Tabassum M, Trudell SA, Vauras J (2023). A phylogeny for North American Mallocybe (Inocybaceae) and taxonomic revision of eastern North American taxa. Fungal Systematics and Evolution 12: 153-201. doi: 10.3114/fuse.2023.12.09.

Study of Water Relative Permeability in Fractures Using Well Tests and Radon: Gas Bubbles Effect.

Few published data are available for two-phase flow in fractures from field studies. All measurements of relative permeability reported in the literature were done in laboratory-scale. The in situ water saturations are normally not known for multiphase flow in natural fractures; therefore, the direct measurements of relative permeability are difficult in field-scale. With the help of a case study before and after the 2008 Mw 5.4 Antung earthquake, groundwater radon was used as a tracer to determine the gas and water saturations in a small naturally fractured aquifer. Well tests were also conducted to estimate aquifer transmissivity before and after the 2008 Antung earthquake. Anomalous declines in both groundwater radon concentration and transmissivity were observed precursory to the 2008 Antung earthquake. Both declines are two precursory phenomena having a common effect of gas bubbles. Using the data from well tests and radon tracer, one data point of water relative permeability can be obtained for in situ fractures. This data point reveals strong phase interference between water and gas bubbles for multiphase flow in natural fractures. Both the data of well tests and radon tracer are essential to gain an improved understanding of mass transfer behavior of groundwater-dissolved gases between water and gas phases.

Cytokines profile in neonatal and adult wild-type mice post-injection of U. S. pediatric vaccination schedule.

INTRODUCTION: A recent study from our laboratory demonstrated a number of neurobehavioral abnormalities in mice colony injected with a mouse-weight equivalent dose of all vaccines that are administered to infants in their first 18 months of life according to the U. S. pediatric vaccination schedule.Cytokines have been studied extensively as blood immune and inflammatory biomarkers, and their association with neurodevelopmental disorders. Given the importance of cytokines in early neurodevelopment, we aimed to investigate the potential post-administration effects of the U. S. pediatric vaccines on circulatory cytokines in a mouse model.In the current study, cytokines have been assayed at early and late time points in mice vaccinated early in postnatal life and compared with placebo controls. MATERIALS AND METHODS: Newborn mouse pups were divided into three groups: i) vaccine (V1), ii) vaccine â€‹× â€‹3 (V3) and iii) placebo control. V1 group was injected with mouse weight-equivalent of the current U. S. pediatric vaccine schedule. V3 group was injected with same vaccines but at triple the dose and the placebo control was injected with saline. Pups were also divided according to the sampling age into two main groups: acute- and chronic-phase group. Blood samples were collected at postnatal day (PND) 23, two days following vaccine schedule for the acute-phase group or at 67 weeks post-vaccination for the chronic-phase groups. Fifteen cytokines were analyzed: GM-CSF, IFN-γ, IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-13, IL-17A, MCP-1, TNF-α, and VEGF-A. Wilcoxon Rank Sum test or unpaired Student's t-test was performed where applicable. RESULTS: IL-5 levels in plasma were significantly elevated in the V1 and V3 group compared with the control only in the acute-phase group. The elevation of IL-5 levels in the two vaccine groups were significant irrespective of whether the sexes were combined or analyzed separately. Other cytokines (VEGF-A, TNF-α, IL-10, MCP-1, GM-CSF, IL-6, and IL-13) were also impacted, although to a lesser extent and in a sex-dependent manner. In the acute-phase group, females showed a significant increase in IL-10 and MCP-1 levels and a decrease in VEGF-A levels in both V1 and V3 group compared to controls. In the acute-phase, a significant increase in MCP-1 levels in V3 group and CM-CSF levels in V1 and V3 group and decrease in TNF-α levels in V1 group were observed in treated males as compared with controls. In chronic-phase females, levels of VEGF-A in V1 and V3 group, TNF-α in V3 group, and IL-13 in V1 group were significantly decreased in contrast with controls. In chronic-phase males, TNF-α levels were significantly increased in V1 group and IL-6 levels decreased in V3 group in comparison to controls. The changes in levels of most tested cytokines were altered between the early and the late postnatal assays. CONCLUSIONS: IL-5 levels significantly increased in the acute-phase of the treatment in the plasma of both sexes that were subjected to V1 and V3 injections. These increases had diminished by the second test assayed at week 67. These results suggest that a profound, albeit transient, effect on cytokine levels may be induced by the whole vaccine administration supporting our recently published observations regarding the behavioral abnormalities in the same mice. These observations support the view that the administration of whole pediatric vaccines in a neonatal period may impact at least short-term CNS functions in mice.

Validation of the Chinese Version of Dementia Quality of Life Measure - Proxy in Care Home Residents with Dementia.

OBJECTIVE: To evaluate psychometric properties of the Chinese version of Dementia Quality of Life Measure - Proxy (C-DEMQoL-Proxy). METHODS: Care home residents aged ≥60 years who were diagnosed with dementia or demonstrated impairment in cognition were recruited from four care facilities in Hong Kong. Caregivers of these participants were also invited to participate. The original DEMQoL-Proxy was translated into Chinese (Cantonese) by a trained translator. The forward-translated version was reviewed by an expert panel of six experienced healthcare professionals. Revisions were made based on comments. The instrument was back-translated to English to check whether further changes were necessary. Demographic data (age, sex, type and severity of dementia, and Mini-Mental State Examination [MMSE] score) were collected from medical records of participants with dementia. Caregivers were interviewed by an occupational therapist or personnel supervised by the occupational therapist using the C-DEMQoL-Proxy and the Chinese version of Quality of Life-Alzheimer's Disease-Proxy (C-QoL-AD-Proxy). Acceptability, reliability, and validity of the C-DEMQoL-Proxy were evaluated using standard psychometric methods. RESULTS: 90 individuals (82.2% women) with dementia aged 72 to 102 years were included. Their diagnosis included Alzheimer's disease (23.3%), vascular dementia (15.6%), mixed and other types of dementias (51.1%), and missing (10%). Severity was mild in 12.2%, moderate in 62.2%, and severe in 25.6%. The mean MMSE score was 12.0 ± 4.9. 20% of the caregivers were family members and the rest were professional carers. The C-DEMQoL-Proxy had good acceptability, with no floor or ceiling effects or missing data. It had good internal consistency (Cronbach alpha = 0.91) and test-retest reliability (intraclass correlation coefficients = 0.83). It was mildly correlated with C-QoL-AD-Proxy (r = 0.29, p < 0.01). Age and sex were not correlated with C-DEMQoL-Proxy scores. C-DEMQoL-Proxy scores were not significantly different between dementia types, severity levels, or between those with higher or lower MMSE scores. CONCLUSION: The C-DEMQoL-Proxy is a valid and reliable instrument to assess health-related quality of life in individuals with dementia.

Interventions to improve children's access to mental health care: a systematic review and meta-analysis.

AIMS: Mental disorders in children are a significant and growing cause of morbidity worldwide. Although interventions to help overcome barriers along the pathway to accessing health care for children with mental disorders exist, there is no overview of randomised controlled trials (RCTs) on these interventions as yet. This study aimed to systematically identify RCTs of interventions to improve access to mental health care for children and synthesise them using a conceptual framework of access to health care. METHODS: This systematic review was performed following a predefined protocol registered with PROSPERO (ID: CRD42018081714). We searched the databases MEDLINE, EMBASE, PsycINFO and CENTRAL for RCTs up to 15 May 2019 using terms related to the concepts 'young people,' 'mental disorders' and 'help-seeking interventions' and scanned reference lists from relevant studies. Two reviewers independently screened all identified articles in a two-stage process, extracted results on outcomes of interest (knowledge, attitudes, intentions, help-seeking, accessing care, mental health outcomes and satisfaction), assessed the risk of bias and conducted meta-analyses where deemed appropriate. RESULTS: After screening 5641 identified articles, 34 RCTs were eligible for inclusion. Eighty per cent of universal school-based interventions measuring knowledge (n = 5) and 67% measuring attitudes (n = 6) reported significantly better results compared with controls on those outcomes, whereas 20% measuring access to care (n = 5) and none measuring mental health outcomes (n = 7) did. In contrast, 71% of interventions targeting at-risk individuals (n = 21) reported better access to care compared with controls, while just 33% (n = 6) did for mental health outcomes. For satisfaction with care, this proportion was 80% (n = 5). Meta-analyses of interventions measuring initial appointment attendance yielded combined odds ratios of 3.11 (2.07-4.67) for appointment reminder interventions and 3.51 (2.02-6.11) for treatment engagement interventions. The outcomes for universal school-based interventions were heterogeneous and could not be summarised quantitatively through meta-analysis. CONCLUSIONS: To have a population-level effect on improving children's access to mental health care, two-stage interventions that identify those in need and then engage them in the health-care system may be necessary. We need more evidence on interventions to target contextual factors such as affordability and infrastructural barriers.

Standardized MR Perfusion Scoring System for Evaluation of Sequential Perfusion Changes and Surgical Outcome of Moyamoya Disease.

BACKGROUND AND PURPOSE: Simple-but-precise evaluation of cerebral perfusion is crucial for the treatment of Moyamoya disease. We aimed to develop a standardized scoring system for MR perfusion suitable for Moyamoya disease evaluation and investigate the postoperative serial changes and outcome predictors. MATERIALS AND METHODS: From January 2013 to December 2016, patients diagnosed with Moyamoya disease and receiving indirect revascularization were recruited prospectively. Clinical data and serial imaging studies were analyzed. The TTP maps were standardized using cerebellar reference values. We developed a scoring system of standardized TTP maps: 14 points for each hemisphere with higher points indicating better perfusion. RESULTS: In total, 24 children (4-17 years of age, 41 hemispheres) and 20 adults (18-51 years of age, 34 hemispheres) were included. The mean preoperative TTP scores were higher in children (7.34 ± 3.90) than in adults (4.88 ± 3.24). The standardized TTP maps revealed dynamic improvement with an increase in the corresponding scores at the 1-, 3-, and 6-month postoperative follow-ups; the scores stabilized after 6 months. The mean improvement in the 6-month scores of the pediatric and adult groups was 4.15 ± 3.55 and 6.03 ± 3.04, respectively. The 6-month TTP score improvements were associated with Matsushima grades. If we took score improvement as the outcome, the preoperative TTP score was the only significant predictor in multivariable analysis. CONCLUSIONS: The standardized TTP maps and scoring system facilitated the quantification of the sequential perfusion changes during Moyamoya disease treatment. The preoperative perfusion status was the only predictor of indirect revascularization outcome.

NMDA Receptor-Mediated Motor Cortex Plasticity After 20 Hz Transcranial Alternating Current Stimulation.

Transcranial alternating current stimulation (tACS) has been shown to modulate neural oscillations and excitability levels in the primary motor cortex (M1). These effects can last for more than an hour and an involvement of N-methyl-d-aspartate receptor (NMDAR) mediated synaptic plasticity has been suggested. However, to date the cortical mechanisms underlying tACS after-effects have not been explored. Here, we applied 20 Hz beta tACS to M1 while participants received either the NMDAR antagonist dextromethorphan or a placebo and the effects on cortical beta oscillations and excitability were explored. When a placebo medication was administered, beta tACS was found to increase cortical excitability and beta oscillations for at least 60 min, whereas when dextromethorphan was administered, these effects were completely abolished. These results provide the first direct evidence that tACS can induce NMDAR-mediated plasticity in the motor cortex, which contributes to our understanding of tACS-induced influences on human motor cortex physiology.

Correction to: CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation.

Following publication of their article "CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation", the authors reported an error in Fig.6b. α-Tubulin image of rCCN2 treatment  (upper panel in CL1-5) only showed eight lanes, when there should be nine.

Cost Analysis and Determinants of Living Donor Liver Transplantation in Taiwan.

BACKGROUND: Liver transplantation (LT) has become established therapy for end-stage liver disease and small-cell hepatocellular carcinoma (HCC), relying mainly on living donor LT (LDLT) in Taiwan. The cost of LDLT varies in different countries depending on the insurance system, the costs of the facility, and staff. In this study we aimed to investigate cost outcomes and determinants of LDLT in Taiwan. METHODS: From January 2014 to December 2015, 184 LDLT patients were enrolled in a study performed at the Kaohsiung Chang Gung Memorial Hospital. Patients' transplantation costs were defined as expense from immediately after surgery to discharge during hospitalization for LDLT. Antiviral therapy and hepatitis B immunoglobulin (HBIG) for prevention of hepatitis B virus (HBV) were included, but direct-acting antiviral (DAA) therapy for hepatitis C (HCV) was excluded. RESULTS: The median total, intensive care unit (ICU), and ward costs of LT were US$64,250, $43,357, and $16,138 (currency ratio 1:30), respectively. HBV significantly increased the total cost of LT, followed by postoperative reintubation and bile duct complications. CONCLUSION: The charges associated with anti-HBV viral therapy and HBIG increase the cost of LDLT. Disease severity of liver cirrhosis showed less importance in predicting cost. Postoperative complications such as reintubation or bile duct complications should be avoided to reduce the cost of LT.

The Risk Factors of mTORi-Associated Posttransplant Proteinuria.

Treatment with mammalian target of rapamycin inhibitors (mTORi) has been associated with an increased incidence of proteinuria after kidney transplantation as compared to other immunosuppressive agents. Proteinuria after mTORi use may occur in different clinical conditions and the precise mechanism remains unclear. The objective of this study was to investigate the related risk factors for proteinuria after mTORi treatment in kidney transplant recipients. This retrospective observational study population consisted of kidney transplant recipients followed up in a medical center in Southern Taiwan from January 1999 to April 2016. The baseline characteristics and transplantation-related profiles were collected at the time of enrollment. We examined risk factors for mTORi-associated proteinuria using a multivariate logistic regression analysis. P < .05 was considered as statistically significant. Hyperlipidemia and obesity at the initiation of mTORi treatment were strong predictors for proteinuria. Earlier identification of these risk factors may assist physicians in deciding the best candidate for mTORi conversion in order to optimize transplantation outcomes.

New insights into the correlation structure of DSM-IV depression symptoms in the general population v. subsamples of depressed individuals.

AIMS: Previous research failed to uncover a replicable dimensional structure underlying the symptoms of depression. We aimed to examine two neglected methodological issues in this research: (a) adjusting symptom correlations for overall depression severity; and (b) analysing general population samples v. subsamples of currently depressed individuals. METHODS: Using population-based cross-sectional and longitudinal data from two nations (Switzerland, 5883 young men; USA, 2174 young men and 2244 young women) we assessed the dimensions of the nine DSM-IV depression symptoms in young adults. In each general-population sample and each subsample of currently depressed participants, we conducted a standardised process of three analytical steps, based on exploratory and confirmatory factor and bifactor analysis, to reveal any replicable dimensional structure underlying symptom correlations while controlling for overall depression severity. RESULTS: We found no evidence of a replicable dimensional structure across samples when adjusting symptom correlations for overall depression severity. In the general-population samples, symptoms correlated strongly and a single dimension of depression severity was revealed. Among depressed participants, symptom correlations were surprisingly weak and no replicable dimensions were identified, regardless of severity-adjustment. CONCLUSIONS: First, caution is warranted when considering studies assessing dimensions of depression because general population-based studies and studies of depressed individuals generate different data that can lead to different conclusions. This problem likely generalises to other models based on the symptoms' inter-relationships such as network models. Second, whereas the overall severity aligns individuals on a continuum of disorder intensity that allows non-affected individuals to be distinguished from affected individuals, the clinical evaluation and treatment of depressed individuals should focus directly on each individual's symptom profile.

A composite of exhaled LTB4 , LXA4 , FeNO, and FEV1 as an "asthma classification ratio" characterizes childhood asthma.

BACKGROUND: Aberrant generation of eicosanoids is associated with asthma, but the evidence remains incomplete and its potential utility as biomarkers is unclear. Major eicosanoids in exhaled breath condensates (EBCs) were assessed as candidate markers for childhood asthma. METHODS: Ten exhaled eicosanoid species was evaluated using ELISA in the discovery phase, followed by prediction model-building and validation phases. RESULTS: Exhaled LTB4 , LTE4 , PGE2, and LXA4 showed significant difference between asthmatics (N = 60) and controls (N = 20). For validation, an expanded study population consisting of 626 subjects with asthma and 161 healthy controls was partitioned into a training subset to establish a prediction model and a test sample subset for validation. Receiver operating characteristic (ROC) analyses of the training subset revealed the level of exhaled LTB4 to be the most discriminative among all parameters, including FeNO, and a composite of exhaled LTB4 , LXA4 , together with FeNO and FEV1 , distinguishing asthma with high sensitivity and specificity. Further, the Youden index (J) indicated the cut point value of 0.598 for this composite of markers as having the strongest discriminatory ability (sensitivity = 85.2% and specificity = 83.6%). The predictive algorithm as "asthma classification ratio" was further validated in an independent test sample with sensitivity and specificity being 84.4% and 84.8%, respectively. CONCLUSIONS: In a pediatric study population in Taiwan, the levels of exhaled LTB4 , LTE4 , LXA4, and PGE2 in asthmatic children were significantly different from those of healthy controls, and the combination of exhaled LTB4 and LXA4 , together with FeNO and FEV1 , best characterized childhood asthma.

The MNS glycophorin variant GP.Mur affects differential erythroid expression of Rh/RhAG transcripts.

BACKGROUND: The band 3 macrocomplex (also known as the ankyrin-associated complex) on the red cell membrane comprises two interacting subcomplexes: a band 3/glycophorin A subcomplex, and a Rh/RhAG subcomplex. Glycophorin B (GPB) is a component of the Rh/RhAG subcomplex that is also structurally associated with glycophorin A (GPA). Expression of glycophorin B-A-B hybrid GP.Mur enhances band 3 expression and is associated with lower levels of Rh-associated glycoprotein (RhAG) and Rh polypeptides. The goal of this study was to determine whether GP.Mur influenced erythroid Rh/RhAG expression at the transcript level. MATERIALS AND METHODS: GP.Mur was serologically determined in healthy participants from Taitung County, Taiwan. RNA was extracted from the reticulocyte-enriched fraction of peripheral blood, followed by reverse transcription and quantitative PCR for RhAG, RhD and RhCcEe. RESULTS: Quantification by real-time PCR revealed significantly fewer RhAG and RhCcEe transcripts in the reticulocytes from subjects with homozygous GYP*Mur. Independent from GYP.Mur, both RhAG and RhD transcript levels were threefold or higher than that of RhCcEe. Also, in GYP.Mur and the control samples alike, direct quantitative associations were observed between the transcript levels of RhAG and RhD, but not between that of RhAG and RhCcEe. CONCLUSION: Erythroid RhD and RhCcEe were differentially expressed at the transcript levels, which could be related to their different degrees of interaction or sensitivity to RhAG. Further, the reduction or absence of glycophorin B in GYP.Mur erythroid cells affected transcript expressions of RhAG and RhCcEe. Thus, GPB and GP.Mur differentially influenced Rh/RhAG expressions prior to protein translation.

Relationship of Metabolic Alterations and PD-L1 Expression in Cisplatin Resistant Lung Cancer.

Despite numerous reports on immune checkpoint inhibitor for the treatment of non-small cell lung cancer (NSCLC), the response rate remains low but durable. Thus cisplatin still plays a major role in the treatment of NSCLC. While there are many mechanisms involved in cisplatin resistance, alteration in metabolic phenotypes with elevated levels of reactive oxygen species (ROS) are found in several cisplatin resistant tumors. These resistant cells become more reliant on mitochondria oxidative metabolism instead of glucose. Consequently, high ROS and metabolic alteration contributed to epithelial-mesenchymal transition (EMT). Importantly, recent findings indicated that EMT has a crucial role in upregulating PD-L1 expression in cancer cells. Thus, it is very likely that cisplatin resistance will lead to high expression of PD-L1/PD-1 which makes them vulnerable to anti PD-1 or anti PD-L1 antibody treatment. An understanding of the interactions between cancer cells metabolic reprogramming and immune checkpoints is critical for combining metabolism targeted therapies with immunotherapies.

B-cell lymphoma/leukemia 10 promotes oral cancer progression through STAT1/ATF4/S100P signaling pathway.

This corrects the article DOI: 10.1038/onc.2014.43.

Compromised neuroplasticity in cigarette smokers under nicotine withdrawal is restituted by the nicotinic α4ß2-receptor partial agonist varenicline.

Nicotine modulates neuroplasticity and improves cognitive functions in animals and humans. In the brain of smoking individuals, calcium-dependent plasticity induced by non-invasive brain stimulation methods such as transcranial direct current stimulation (tDCS) and paired associative stimulation (PAS) is impaired by nicotine withdrawal, but partially re-established after nicotine re-administration. In order to investigate the underlying mechanism further, we tested the impact of the α4ß2-nicotinic receptor partial agonist varenicline on focal and non-focal plasticity in smokers during nicotine withdrawal, induced by PAS and tDCS, respectively. We administered low (0.3 mg) and high (1.0 mg) single doses of varenicline or placebo medication before stimulation over the left motor cortex of 20 healthy smokers under nicotine withdrawal. Motor cortex excitability was monitored by single-pulse transcranial magnetic stimulation-induced motor evoked potential amplitudes for 36 hours after plasticity induction. Stimulation-induced plasticity was absent under placebo medication, whereas it was present in all conditions under high dose. Low dose restituted only tDCS-induced non-focal plasticity, producing no significant impact on focal plasticity. High dose varenicline also prolonged inhibitory plasticity. These results are comparable to the impact of nicotine on withdrawal-related impaired plasticity in smokers and suggest that α4ß2 nicotinic receptors are relevantly involved in plasticity deficits and restitution in smokers.

Cytosolic PKM2 stabilizes mutant EGFR protein expression through regulating HSP90-EGFR association.

This corrects the article DOI: 10.1038/onc.2015.397.