Publications by authors named "Michael Thomas"

958 Publications

The role of context in verbal humor processing in autism.

J Exp Child Psychol 2021 May 12;209:105166. Epub 2021 May 12.

Developmental Neurocognition Laboratory, Birkbeck College, University of London, London WC1E 7HX, UK.

Difficulties in processing humor have been associated with individuals with autism. The current study investigated whether humor comprehension and appreciation could be augmented in children with autism by providing contextual support suggesting that humor was to be expected. A verbally presented riddle task was used in which participants were assessed for their subjective ratings and comprehension of the materials. They were also filmed to record any smiling or laughing. Both riddles and control stimuli were presented with supporting verbal context and also without it. The results showed that (a) the greater subjective appreciation of riddles than of control stimuli was dependent on the provision of context for the participants with autism and that (b) context statistically equated these ratings of riddles between participants with autism and matched typically developing controls. However, context had no effect on comprehension or affective response. The results of the current study demonstrate that children with autism are, even in the most conservative interpretation, able to use verbal context to recognize verbal humor. This lays the foundation of possible interventions based on training sensitivity to context.
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http://dx.doi.org/10.1016/j.jecp.2021.105166DOI Listing
May 2021

Anticholinergic Medication Burden-Associated Cognitive Impairment in Schizophrenia.

Am J Psychiatry 2021 May 14:appiajp202020081212. Epub 2021 May 14.

Desert Pacific Mental Illness Research, Education, and Clinical Center, VA San Diego Healthcare System, San Diego (Joshi, Braff, MacDonald, Molina, Light, Sprock); Department of Psychiatry, University of California, San Diego, La Jolla (Joshi, Braff, Swerdlow, Greenwood, MacDonald, Molina, Nungaray, Sprock, M.T. Tsuang, Light); Department of Psychology, Colorado State University, Fort Collins (Thomas); Department of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles (Green, Nuechterlein, Sugar); Desert Pacific Mental Illness Research, Education, and Clinical Center, VA Greater Los Angeles Healthcare System, Los Angeles (Green); Department of Psychiatry, University of Pennsylvania, Philadelphia (R.C. Gur, R.E. Gur, Turetsky); Department of Psychiatry, Harvard Medical School, and Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Boston (Stone); Department of Psychiatry and Behavioral Sciences and Department of Biomedical Data Science, Stanford University, Stanford, Calif. (Lazzeroni); Sierra Pacific Mental Illness Research, Education, and Clinical Center, VA Health Care System, Palo Alto, Calif. (Lazzeroni); Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle (Radant, D.W. Tsuang); Northwest Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle (Radant, D.W. Tsuang); Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York (Silverman); Research and Development, James J. Peters VA Medical Center, New York (Silverman); Department of Biostatistics, UCLA School of Public Health, Los Angeles (Sugar).

Objective: Many psychotropic medications used to treat schizophrenia have significant anticholinergic properties, which are linked to cognitive impairment and dementia risk in healthy subjects. Clarifying the impact of cognitive impairment attributable to anticholinergic medication burden may help optimize cognitive outcomes in schizophrenia. The aim of this study was to comprehensively characterize how this burden affects functioning across multiple cognitive domains in schizophrenia outpatients.

Methods: Cross-sectional data were analyzed using inferential statistics and exploratory structural equation modeling to determine the relationship between anticholinergic medication burden and cognition. Patients with a diagnosis of schizophrenia or schizoaffective disorder (N=1,120) were recruited from the community at five U.S. universities as part of the Consortium on the Genetics of Schizophrenia-2. For each participant, prescribed medications were rated and summed according to a modified Anticholinergic Cognitive Burden (ACB) scale. Cognitive functioning was assessed by performance on domains of the Penn Computerized Neurocognitive Battery (PCNB).

Results: ACB score was significantly associated with cognitive performance, with higher ACB groups scoring worse than lower ACB groups on all domains tested on the PCNB. Similar effects were seen on other cognitive tests. Effects remained significant after controlling for demographic characteristics and potential proxies of illness severity, including clinical symptoms and chlorpromazine-equivalent antipsychotic dosage.

Conclusions: Anticholinergic medication burden in schizophrenia is substantial, common, conferred by multiple medication classes, and associated with cognitive impairments across all cognitive domains. Anticholinergic medication burden from all medication classes-including psychotropics used in usual care-should be considered in treatment decisions and accounted for in studies of cognitive functioning in schizophrenia.
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http://dx.doi.org/10.1176/appi.ajp.2020.20081212DOI Listing
May 2021

Point absorbers in Advanced LIGO.

Appl Opt 2021 May;60(13):4047-4063

Small, highly absorbing points are randomly present on the surfaces of the main interferometer optics in Advanced LIGO. The resulting nanometer scale thermo-elastic deformations and substrate lenses from these micron-scale absorbers significantly reduce the sensitivity of the interferometer directly though a reduction in the power-recycling gain and indirect interactions with the feedback control system. We review the expected surface deformation from point absorbers and provide a pedagogical description of the impact on power buildup in second generation gravitational wave detectors (dual-recycled Fabry-Perot Michelson interferometers). This analysis predicts that the power-dependent reduction in interferometer performance will significantly degrade maximum stored power by up to 50% and, hence, limit GW sensitivity, but it suggests system wide corrections that can be implemented in current and future GW detectors. This is particularly pressing given that future GW detectors call for an order of magnitude more stored power than currently used in Advanced LIGO in Observing Run 3. We briefly review strategies to mitigate the effects of point absorbers in current and future GW wave detectors to maximize the success of these enterprises.
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http://dx.doi.org/10.1364/AO.419689DOI Listing
May 2021

Combination of Crizotinib and Osimertinib in T790M+ EGFR-Mutant Non-Small Cell Lung Cancer with Emerging MET Amplification Post-Osimertinib Progression in a 10-Year Survivor: A Case Report.

Case Rep Oncol 2021 Jan-Apr;14(1):477-482. Epub 2021 Mar 18.

Department of Thoracic Oncology, Thoraxklinik, University of Heidelberg, Heidelberg, Germany.

Tyrosine kinase inhibitors (TKIs) represent the standard treatment for patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. The duration of the response is, however, limited in time owing to the development of resistance mechanisms to both first- and second-generation agents such as oncogene amplification. This report describes the successful results obtained with the combination of the third-generation TKI osimertinib with the multitargeted TKI and MET inhibitor crizotinib in a patient with EGFR-mutant NSCLC with emerging MET amplification with a tolerable toxicity profile.
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http://dx.doi.org/10.1159/000513904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077408PMC
March 2021

Feasibility and Challenges for Sequential Treatments in ALK-Rearranged Non-Small-Cell Lung Cancer.

Front Oncol 2021 20;11:670483. Epub 2021 Apr 20.

Department of Thoracic Oncology, Thoraxklinik and National Center for Tumor diseases (NCT) at Heidelberg University Hospital, Heidelberg, Germany.

Background: Anaplastic lymphoma kinase-rearranged non-small-cell lung cancer (ALK NSCLC) is a model disease for use of targeted therapies (TKI), which are administered sequentially to maximize patient survival.

Methods: We retrospectively analyzed the flow of 145 consecutive TKI-treated ALK NSCLC patients across therapy lines. Suitable patients that could not receive an available next-line therapy ("attrition") were determined separately for various treatments, based on the approval status of the respective targeted drugs when each treatment failure occurred in each patient.

Results: At the time of analysis, 70/144 (49%) evaluable patients were still alive. Attrition rates related to targeted treatments were approximately 25-30% and similar for administration of a second-generation (2G) ALK inhibitor (22%, 17/79) or any subsequent systemic therapy (27%, 27/96) after crizotinib, and for the administration of lorlatinib (27%, 6/22) or any subsequent systemic therapy (25%, 15/61) after any 2G TKI. The rate of chemotherapy implementation was 67% (62/93). Both administration of additional TKI (median overall survival [mOS] 59 41 months for multiple one TKI lines, logrank p=0.002), and chemotherapy (mOS 41 vs. 16 months, logrank p<0.001) were significantly associated with longer survival. Main reason for patients foregoing any subsequent systemic treatment was rapid clinical deterioration (n=40/43 or 93%) caused by tumor progression. In 2/3 of cases (29/43), death occurred under the first failing therapy, while in 11/43 the treatment was switched, but the patient did not respond, deteriorated further, and died within 8 weeks.

Conclusions: Despite absence of regulatory obstacles and no requirement for specific acquired mutations, 25-30% of ALK NSCLC patients forego subsequent systemic therapy due to rapid clinical deterioration, in several cases (approximately 1/3) associated with an ineffective first next-line choice. These results underline the need for closer patient monitoring and broader profiling in order to support earlier and better directed use of available therapies.
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http://dx.doi.org/10.3389/fonc.2021.670483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096170PMC
April 2021

Detecting the Inverted-U in fMRI Studies of Schizophrenia: A Comparison of Three Analysis Methods.

J Int Neuropsychol Soc 2021 May 5:1-12. Epub 2021 May 5.

Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.

Objective: Cognitive tasks are used to probe neuronal activity during functional magnetic resonance imaging (fMRI) to detect signs of aberrant cognitive functioning in patients diagnosed with schizophrenia (SZ). However, nonlinear (inverted-U-shaped) associations between neuronal activity and task difficulty can lead to misinterpretation of group differences between patients and healthy comparison subjects (HCs). In this paper, we evaluated a novel method for correcting these misinterpretations based on conditional performance analysis.

Method: Participants included 25 HCs and 27 SZs who performed a working memory (WM) task (N-back) with 5 load conditions while undergoing fMRI. Neuronal activity was regressed onto: 1) task load (i.e., parametric task levels), 2) marginal task performance (i.e., performance averaged over all load conditions), or 3) conditional task performance (i.e., performance within each load condition).

Results: In most regions of interest, conditional performance analysis uniquely revealed inverted-U-shaped neuronal activity in both SZs and HCs. After accounting for conditional performance differences between groups, we observed few difference in both the pattern and level of neuronal activity between SZs and HCs within regions that are classically associated with WM functioning (e.g., posterior dorsolateral prefrontal and parietal association cortices). However, SZs did show aberrant activity within the anterior dorsolateral prefrontal cortex.

Conclusions: Interpretations of differences in neuronal activity between groups, and of associations between neuronal activity and performance, should be considered within the context of task performance. Whether conditional performance-based differences reflect compensation, dedifferentiation, or other processes is not a question that is easily resolved by examining activation and performance data alone.
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http://dx.doi.org/10.1017/S1355617721000424DOI Listing
May 2021

Role of Synaptophysin, Chromogranin and CD56 in adenocarcinoma and squamous cell carcinoma of the lung lacking morphological features of neuroendocrine differentiation: a retrospective large-scale study on 1170 tissue samples.

BMC Cancer 2021 May 1;21(1):486. Epub 2021 May 1.

Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, Heidelberg, Germany.

Background: Synaptophysin, chromogranin and CD56 are recommended markers to identify pulmonary tumors with neuroendocrine differentiation. Whether the expression of these markers in pulmonary adenocarcinoma and pulmonary squamous cell carcinoma is a prognostic factor has been a matter of debate. Therefore, we investigated retrospectively a large cohort to expand the data on the role of synaptophysin, chromogranin and CD56 in non-small cell lung cancer lacking morphological features of neuroendocrine differentiation.

Methods: A cohort of 627 pulmonary adenocarcinomas (ADC) and 543 squamous cell carcinomas (SqCC) lacking morphological features of neuroendocrine differentiation was assembled and a tissue microarray was constructed. All cases were stained with synaptophysin, chromogranin and CD56. Positivity was defined as > 1% positive tumor cells. Data was correlated with clinico-pathological features including overall and disease free survival.

Results: 110 (18%) ADC and 80 (15%) SqCC were positive for either synaptophysin, chromogranin, CD56 or a combination. The most commonly positive single marker was synaptophysin. The least common positive marker was chromogranin. A combination of ≤2 neuroendocrine markers was positive in 2-3% of ADC and 0-1% of SqCC. There was no significant difference in overall survival in tumors with positivity for neuroendocrine markers neither in ADC (univariate: P = 0.4; hazard ratio [HR] = 0.867; multivariate: P = 0.5; HR = 0.876) nor in SqCC (univariate: P = 0.1; HR = 0.694; multivariate: P = 0.1, HR = 0.697). Likewise, there was no significant difference in disease free survival.

Conclusions: We report on a cohort of 1170 cases that synaptophysin, chromogranin and CD56 are commonly expressed in ADC and SqCC and that their expression has no impact on survival, supporting the current best practice guidelines.
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http://dx.doi.org/10.1186/s12885-021-08140-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088012PMC
May 2021

Making Room for Wisdom.

Int Psychogeriatr 2021 Apr 30:1-5. Epub 2021 Apr 30.

Department of Psychology, Colorado State University, Fort Collins, CO, United States.

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http://dx.doi.org/10.1017/S1041610221000600DOI Listing
April 2021

Validation of the T Descriptor (TNM-8) in T3N0 Non-Small-Cell Lung Cancer Patients; a Bicentric Cohort Analysis with Arguments for Redefinition.

Cancers (Basel) 2021 Apr 10;13(8). Epub 2021 Apr 10.

Department of Thoracic Surgery, Thoraxklinik, Heidelberg University Hospital, Roentgenstrasse 1, 69126 Heidelberg, Germany.

The current pT3N0 category represents a heterogeneous subgroup involving tumor size, separate tumor nodes in one lobe, and locoregional growth pattern. We aim to validate outcomes according to the eighth edition of the TNM staging classification. A total of 281 patients who had undergone curative lung cancer surgery staged with TNM-7 in two German centers were retrospectively analyzed. The subtypes tumor size >7 cm and multiple nodules were grouped as T3a, and the subtypes parietal pleura invasion and mixed were grouped as T3b. We stratified survival by subtype and investigated the relative benefit of adjuvant chemotherapy according to subtype. The 5-year overall survival (OS) rates differed between the different subtypes tumor diameter >7 cm (71.5%), multiple nodules in one lobe (71.0%) (grouped as T3a), parietal pleura invasion (59.%), and mixed subtype (5-year OS 50.3%) (grouped as T3b), respectively. The cohort as a whole did not gain significant OS benefit from adjuvant chemotherapy. In contrast, adjuvant chemotherapy significantly improved OS in the T3b subgroup (logrank = 0.03). This multicenter cohort analysis of pT3N0 patients identifies a new prognostic mixed subtype. Tumors >7 cm should not be moved to pT4. Patients with T3b tumors have significantly worse survival than patients with T3a tumors.
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http://dx.doi.org/10.3390/cancers13081812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068959PMC
April 2021

Scaffold-Hopping Strategy on a Series of Proteasome Inhibitors Led to a Preclinical Candidate for the Treatment of Visceral Leishmaniasis.

J Med Chem 2021 May 27;64(9):5905-5930. Epub 2021 Apr 27.

Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry, University of Dundee, Dundee DD1 5EH, U.K.

There is an urgent need for new treatments for visceral leishmaniasis (VL), a parasitic infection which impacts heavily large areas of East Africa, Asia, and South America. We previously reported on the discovery of GSK3494245/DDD01305143 () as a preclinical candidate for VL and, herein, we report on the medicinal chemistry program that led to its identification. A hit from a phenotypic screen was optimized to give a compound with efficacy, which was hampered by poor solubility and genotoxicity. The work on the original scaffold failed to lead to developable compounds, so an extensive scaffold-hopping exercise involving medicinal chemistry design, profiling, and subsequent synthesis was utilized, leading to the preclinical candidate. The compound was shown to act via proteasome inhibition, and we report on the modeling of different scaffolds into a cryo-EM structure and the impact this has on our understanding of the series' structure-activity relationships.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00047DOI Listing
May 2021

Versus Secondary Metastatic -Mutated Non-Small-Cell Lung Cancer.

Front Oncol 2021 9;11:640048. Epub 2021 Apr 9.

Department of Thoracic Oncology, Thoraxklinik at Heidelberg University Hospital, Heidelberg, Germany.

Background: Metastatic epidermal growth factor receptor-mutated (EGFR) non-small-cell lung cancer (NSCLC) can present or following previous nonmetastatic disease (secondary). Potential differences between these two patient subsets are unclear at present.

Methods: We retrospectively analyzed characteristics of tyrosine kinase inhibitor (TKI)-treated patients with vs. secondary metastatic EGFR NSCLC until December 2019 (n = 401).

Results: metastatic disease was 4× more frequent than secondary (n = 83/401), but no significant differences were noted regarding age (median 66 vs. 70 years), sex (65% vs. 65% females), smoking history (67% vs. 62% never/light-smokers), and histology (both >95% adenocarcinoma). Patients with secondary metastatic disease showed a better ECOG performance status (PS 0-1 67%-32% vs. 46%-52%, p = 0.003), fewer metastatic sites (mean 1.3 vs. 2.0, p < 0.001), and less frequent brain involvement (16% vs. 28%, p = 0.022) at the time of stage IV diagnosis. Progression-free survival (PFS) under TKI (median 17 for secondary vs. 12 months for , p = 0.26) and overall survival (OS, 29 vs. 25 months, respectively, p = 0.47) were comparable. alterations (55% vs. 60% exon 19 deletions), mutation rate at baseline (47% vs. 43%, n = 262), and T790M positivity at the time of TKI failure (51% vs. 56%, n = 193) were also similar. OS according to differing characteristics, e.g., presence or absence of brain metastases (19-20 or 30-31 months, respectively, p = 0.001), and ECOG PS 0 or 1 or 2 (32-34 or 20-23 or 5-7 months, respectively, p < 0.001), were almost identical for and secondary metastatic disease.

Conclusions: Despite the survival advantage reported in the pre-TKI era for relapsed NSCLC, molecular features and outcome of TKI-treated metastatic EGFR tumors are currently independent of preceding nonmetastatic disease. This simplifies design of outcome studies and can assist prognostic considerations in everyday management of patients with secondary metastatic EGFR tumors.
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http://dx.doi.org/10.3389/fonc.2021.640048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063726PMC
April 2021

Deep learning can accelerate and quantify simulated localized correlated spectroscopy.

Sci Rep 2021 Apr 22;11(1):8727. Epub 2021 Apr 22.

Medical Artificial Intelligence and Automation Laboratory, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

Nuclear magnetic resonance spectroscopy (MRS) allows for the determination of atomic structures and concentrations of different chemicals in a biochemical sample of interest. MRS is used in vivo clinically to aid in the diagnosis of several pathologies that affect metabolic pathways in the body. Typically, this experiment produces a one dimensional (1D) H spectrum containing several peaks that are well associated with biochemicals, or metabolites. However, since many of these peaks overlap, distinguishing chemicals with similar atomic structures becomes much more challenging. One technique capable of overcoming this issue is the localized correlated spectroscopy (L-COSY) experiment, which acquires a second spectral dimension and spreads overlapping signal across this second dimension. Unfortunately, the acquisition of a two dimensional (2D) spectroscopy experiment is extremely time consuming. Furthermore, quantitation of a 2D spectrum is more complex. Recently, artificial intelligence has emerged in the field of medicine as a powerful force capable of diagnosing disease, aiding in treatment, and even predicting treatment outcome. In this study, we utilize deep learning to: (1) accelerate the L-COSY experiment and (2) quantify L-COSY spectra. All training and testing samples were produced using simulated metabolite spectra for chemicals found in the human body. We demonstrate that our deep learning model greatly outperforms compressed sensing based reconstruction of L-COSY spectra at higher acceleration factors. Specifically, at four-fold acceleration, our method has less than 5% normalized mean squared error, whereas compressed sensing yields 20% normalized mean squared error. We also show that at low SNR (25% noise compared to maximum signal), our deep learning model has less than 8% normalized mean squared error for quantitation of L-COSY spectra. These pilot simulation results appear promising and may help improve the efficiency and accuracy of L-COSY experiments in the future.
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http://dx.doi.org/10.1038/s41598-021-88158-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062502PMC
April 2021

Migration after union dissolution in the United States: The role of non-resident family.

Soc Sci Res 2021 May 13;96:102539. Epub 2021 Feb 13.

Department of Geography, University of Connecticut, 215 Glenbrook Road, U-4148, Storrs, CT 06269, 4148, United States. Electronic address:

Separation from a spouse or cohabiting partner is associated with a high likelihood of moving, even over long distances. In this paper, we use longitudinal data from the Panel Study of Income Dynamics for the United States to analyze the role of non-resident family in the migration of separated people immediately after and in the years following union dissolution. We explore both migration in general and return migration among separated people, drawing comparisons to married and never-married people. We find that having parents, children, or siblings living close by substantially deters migration, especially among separated people. We also find marked positive effects of having family members in the county where the respondent grew up on the likelihood of returning there. Separated people are especially likely to return, compared to others, if they have parents in their county of origin. Furthermore, a lack of an effect of years of education on migration, and a negative effect of this variable on return migration, suggest that migration after separation is less related to human-capital considerations than other types of migration.
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http://dx.doi.org/10.1016/j.ssresearch.2021.102539DOI Listing
May 2021

[Heidelberg Milestones Communication (HeiMeKOM) - Experiences, Best Practice Examples and Recommendations from the Final Symposium on January 30 and 31 in 2020].

Gesundheitswesen 2021 Apr 16. Epub 2021 Apr 16.

Abteilung Internistische Onkologie, Thoraxklinik am Universitätsklinikum Heidelberg, Translational Lung Research Center Heidelberg (TLRC-H), Mitglied des Deutschen Zentrums für Lungenforschung (DZL), Heidelberg, Deutschland.

The National Cancer Plan emphasises the importance of medical communication and calls for its integration into medical education and training. In this context, the Milestone Communication Approach meets the communicative challenges in dealing with lung cancer patients. Interprofessional tandems, consisting of doctors and nurses, conduct structured conversations at defined moments with patients and their relatives. The concept aims at shared decision making, continuity in the care of lung cancer patients and the early integration of palliative care. During the symposium on the Heidelberg Milestone Communication in January 2020, recommendations on the care situation of lung cancer patients in advanced stages were developed. In addition, the further adaptability of HeiMeKOM to other settings and hospitals and to other diseases was discussed as well as the possibility of implementing such a concept in standard care. This article presents the experiences, best practice examples and recommendations discussed during the symposium in order to enable their extrapolation to other similarly oriented projects. The long-term goal is to transfer the milestone concept to other hospital, primarily certified lung cancer centers, and to ensure permanent funding. For further dissemination of the concept and, above all, to have it established in standard care, health policy awareness and support are required in addition to the integration of the concept in competence catalogues of continuing medical and nursing education.
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http://dx.doi.org/10.1055/a-1375-0922DOI Listing
April 2021

Effects of an Interprofessional Communication Approach on Support Needs, Quality of Life, and Mood of Patients with Advanced Lung Cancer: A Randomized Trial.

Oncologist 2021 Apr 16. Epub 2021 Apr 16.

Department of General Practice and Health Services Research, University Hospital Heidelberg, Heidelberg, Germany.

Background: To address the support needs of newly diagnosed patients with lung cancer with limited prognosis, the Milestone Communication Approach (MCA) was developed and implemented. The main elements of the MCA are situation-specific conversations along the disease trajectory conducted by an interprofessional tandem of physician and nurse. The aim of the study was to evaluate the effects of MCA on addressing support needs, quality of life, and mood as compared with standard oncological care.

Patients And Methods: A randomized trial was conducted with baseline assessment and follow-up assessments at 3, 6, and 9 months in outpatients with newly diagnosed lung cancer stage IV at a German thoracic oncology hospital. The primary outcome was the Health System and Information Needs subscale of the Short Form Supportive Care Needs Survey (SCNS-SF34-G) at 3-month follow-up. Secondary outcomes included the other subscales of the SCNS-SF34-G, the Schedule for the Evaluation of Individual Quality of Life, the Functional Assessment of Cancer Therapy lung module, the Patient Health Questionnaire for Depression and Anxiety, and the Distress Thermometer.

Results: At baseline, 174 patients were randomized, of whom 102 patients (MCA: n = 52; standard care: n = 50) provided data at 3-month follow-up. Patients of the MCA group reported lower information needs at 3-month follow-up (mean ± SD, 33.4 ± 27.5; standard care, 43.1 ± 29.9; p = .033). No effects were found for secondary outcomes.

Conclusion: MCA lowered patient-reported information needs but did not have other effects. MCA contributed to tailored communication because an adequate level of information and orientation set the basis for patient-centered care.

Implications For Practice: By addressing relevant issues at predefined times, the Milestone Communication Approach provides individual patient-centered care facilitating the timely integration of palliative care for patients with a limited prognosis. The needs of patients with lung cancer must be assessed and addressed throughout the disease trajectory. Although specific topics may be relevant for all patients, such as information about the disease and associated health care, situations of individual patients and their families must be considered. Additionally, using the short form of the Supportive Care Needs Survey in clinical practice to identify patients' problems might support individually targeted communication and preference-sensitive care.
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http://dx.doi.org/10.1002/onco.13790DOI Listing
April 2021

[When to test in biomarker-stratified therapy of non-small cell lung cancer - Biomarker-stratified therapy of Non-small cell lung cancer: when and what to test?]

Dtsch Med Wochenschr 2021 Apr 14;146(8):559-561. Epub 2021 Apr 14.

Therapy of non-small cell lung cancer (NSCLC) should be based on biomarker test results in the palliative setting. To this end, testing of all patients in stage IV and in the future also in the earlier stages will be important. In a conference with the patronage of the German Cancer Society, the question of "reflex testing", i.e. independently of tumor stage, was discussed but not deemed to be acceptable. The current report summarizes the results of the consensus conference and discusses possible paths to efficent biomarker testing in NSCLC.
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http://dx.doi.org/10.1055/a-1383-5231DOI Listing
April 2021

Validation of a highly realistic embryo transfer simulator and trainer.

Fertil Steril 2021 Apr;115(4):879-880

Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, Cincinnati, Ohio.

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http://dx.doi.org/10.1016/j.fertnstert.2021.01.019DOI Listing
April 2021

Skills-based intervention to enhance collaborative decision-making: systematic adaptation and open trial protocol for veterans with psychosis.

Pilot Feasibility Stud 2021 Mar 29;7(1):89. Epub 2021 Mar 29.

VA Desert Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), San Diego, CA, USA.

Background: Collaborative decision-making is an innovative decision-making approach that assigns equal power and responsibility to patients and providers. Most veterans with serious mental illnesses like schizophrenia want a greater role in treatment decisions, but there are no interventions targeted for this population. A skills-based intervention is promising because it is well-aligned with the recovery model, uses similar mechanisms as other evidence-based interventions in this population, and generalizes across decisional contexts while empowering veterans to decide when to initiate collaborative decision-making. Collaborative Decision Skills Training (CDST) was developed in a civilian serious mental illness sample and may fill this gap but needs to undergo a systematic adaptation process to ensure fit for veterans.

Methods: In aim 1, the IM Adapt systematic process will be used to adapt CDST for veterans with serious mental illness. Veterans and Veteran's Affairs (VA) staff will join an Adaptation Resource Team and complete qualitative interviews to identify how elements of CDST or service delivery may need to be adapted to optimize its effectiveness or viability for veterans and the VA context. During aim 2, an open trial will be conducted with veterans in a VA Psychosocial Rehabilitation and Recovery Center (PRRC) to assess additional adaptations, feasibility, and initial evidence of effectiveness.

Discussion: This study will be the first to evaluate a collaborative decision-making intervention among veterans with serious mental illness. It will also contribute to the field's understanding of perceptions of collaborative decision-making among veterans with serious mental illness and VA clinicians, and result in a service delivery manual that may be used to understand adaptation needs generally in VA PRRCs.

Trial Registration: ClinicalTrials.gov Identifier: NCT04324944.
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http://dx.doi.org/10.1186/s40814-021-00820-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005669PMC
March 2021

Shoulder Pain Diagnosis, Treatment and Referral Guidelines for Primary, Community and Intermediate Care.

Shoulder Elbow 2021 Feb 23;13(1):5-11. Epub 2021 Feb 23.

These care pathway guidelines for the shoulder have been written in collaboration with the NHS Evidence Based Interventions (EBI) programme. The EBI programme is a partnership between the Academy of Medical Royal Colleges, NHS Clinical Commissioners, the National Institute for Health and Care Excellence, as well as NHS England and Improvement.
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http://dx.doi.org/10.1177/1758573220984471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905504PMC
February 2021

The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes: Thematic Review Series: Biology of Lipid Rafts.

J Lipid Res 2020 05 7;61(5):676-686. Epub 2020 Nov 7.

Department of Medicine, Division of Endocrinology and Molecular Medicine,Medical College of Wisconsin, Milwaukee, WI 53226; Cardiovascular Center,Medical College of Wisconsin, Milwaukee, WI 53226; Department of Pharmacology and Toxicology,Medical College of Wisconsin, Milwaukee, WI 53226. Electronic address:

Cellular membranes are not homogenous mixtures of proteins; rather, they are segregated into microdomains on the basis of preferential association between specific lipids and proteins. These microdomains, called lipid rafts, are well known for their role in receptor signaling on the plasma membrane (PM) and are essential to such cellular functions as signal transduction and spatial organization of the PM. A number of disease states, including atherosclerosis and other cardiovascular disorders, may be caused by dysfunctional maintenance of lipid rafts. Lipid rafts do not occur only in the PM but also have been found in intracellular membranes and extracellular vesicles (EVs). Here, we focus on discussing newly discovered functions of lipid rafts and microdomains in intracellular membranes, including lipid and protein trafficking from the ER, Golgi bodies, and endosomes to the PM, and we examine lipid raft involvement in the production and composition of EVs. Because lipid rafts are small and transient, visualization remains challenging. Future work with advanced techniques will continue to expand our knowledge about the roles of lipid rafts in cellular functioning.
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http://dx.doi.org/10.1194/jlr.TR119000383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193959PMC
May 2020

A Human-Based Functional NMJ System for Personalized ALS Modeling and Drug Testing.

Adv Ther (Weinh) 2020 Nov 11;3(11). Epub 2020 Aug 11.

NanoScience Technology Center, University of Central Florida, 12424 Research Parkway, Suite 400, Orlando, FL 32826, USA.

Loss of the neuromuscular junction (NMJ) is an early and critical hallmark in all forms of ALS. The study design was to develop a functional NMJ disease model by integrating motoneurons (MNs) differentiated from multiple ALS-patients' induced pluripotent stem cells (iPSCs) and primary human muscle into a chambered system. NMJ functionality was tested by recording myotube contractions while stimulating MNs by field electrodes and a set of clinically relevant parameters were defined to characterize the NMJ function. Three ALS lines were analyzed, 2 with SOD1 mutations and 1 with a FUS mutation. The ALS-MNs reproduced pathological phenotypes, including increased axonal varicosities, reduced axonal branching and elongation and increased excitability. These MNs formed functional NMJs with wild type muscle, but with significant deficits in NMJ quantity, fidelity and fatigue index. Furthermore, treatment with the Deana protocol was found to correct the NMJ deficits in all the ALS mutant lines tested. Quantitative analysis also revealed the variations inherent in each mutant lines. This functional NMJ system provides a platform for the study of both fALS and sALS and has the capability of being adapted into subtype-specific or patient-specific models for ALS etiological investigation and patient stratification for drug testing.
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http://dx.doi.org/10.1002/adtp.202000133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942691PMC
November 2020

Symptom Burden and Palliative Care Needs of Patients with Incurable Cancer at Diagnosis and During the Disease Course.

Oncologist 2021 Mar 9. Epub 2021 Mar 9.

Leipzig University Medical Center, University Cancer Center Leipzig, Leipzig, Germany.

Background: Although current guidelines advocate early integration of palliative care, symptom burden and palliative care needs of patients at diagnosis of incurable cancer and along the disease trajectory are understudied.

Material And Methods: We assessed distress, symptom burden, quality of life, and supportive care needs in patients with newly diagnosed incurable cancer in a prospective longitudinal observational multicenter study. Patients were evaluated using validated self-report measures (National Comprehensive Cancer Network Distress Thermometer [DT], Functional Assessment of Cancer Therapy [FACT], Schedule for the Evaluation of Individual Quality of Life [SEIQoL-Q], Patients Health Questionnaire-4 [PHQ-4], modified Supportive Care Needs Survey [SCNS-SF-34]) at baseline (T0) and at 3 (T1), 6 (T2), and 12 months (T3) follow-up.

Results: From October 2014 to October 2016, 500 patients (219 women, 281 men; mean age 64.2 years) were recruited at 20 study sites in Germany following diagnosis of incurable metastatic, locally advanced, or recurrent lung (217), gastrointestinal (156), head and neck (55), gynecological (57), and skin (15) cancer. Patients reported significant distress (DT score ≥ 5) after diagnosis, which significantly decreased over time (T0: 67.2%, T1: 51.7%, T2: 47.9%, T3: 48.7%). The spectrum of reported symptoms was broad, with considerable variety between and within the cancer groups. Anxiety and depressiveness were most prevalent early in the disease course (T0: 30.8%, T1: 20.1%, T2: 14.7%, T3: 16.9%). The number of patients reporting unmet supportive care needs decreased over time (T0: 71.8 %, T1: 61.6%, T2: 58.1%, T3: 55.3%).

Conclusion: Our study confirms a variable and mostly high symptom burden at the time of diagnosis of incurable cancer, suggesting early screening by using standardized tools and underlining the usefulness of early palliative care.

Implications For Practice: A better understanding of symptom burden and palliative care needs of patients with newly diagnosed incurable cancer may guide clinical practice and help to improve the quality of palliative care services. The results of this study provide important information for establishing palliative care programs and related guidelines. Distress, symptom burden, and the need for support vary and are often high at the time of diagnosis. These findings underscore the need for implementation of symptom screening as well as early palliative care services, starting at the time of diagnosis of incurable cancer and tailored according to patients' needs.
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http://dx.doi.org/10.1002/onco.13751DOI Listing
March 2021

Targeting rare and non-canonical driver variants in NSCLC - An uncharted clinical field.

Lung Cancer 2021 04 19;154:131-141. Epub 2021 Feb 19.

Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany; Translational Lung Research Center Heidelberg (TLRC-H), Heidelberg, Member of the German Center for Lung Research (DZL), Germany; German Cancer Consortium (DKTK), Berlin, Munich and Heidelberg Partner Sites, Germany. Electronic address:

Objectives: Implementation of tyrosine kinase inhibitors (TKI) and other targeted therapies was a main advance in thoracic oncology with survival gains ranging from several months to years for non-small-cell lung cancer (NSCLC) patients. High-throughput comprehensive molecular profiling is of key importance to identify patients that can potentially benefit from these novel treatments.

Material And Methods: Next-generation sequencing (NGS) was performed on 4500 consecutive formalin-fixed, paraffin-embedded specimens of advanced NSCLC (n = 4172 patients) after automated extraction of DNA and RNA for parallel detection of mutations and gene fusions, respectively.

Results And Conclusion: Besides the 24.9 % (n = 1040) of cases eligible for approved targeted therapies based on the presence of canonical alterations in EGFR exons 18-21, BRAF, ROS1, ALK, NTRK, and RET, an additional n = 1260 patients (30.2 %) displayed rare or non-canonical mutations in EGFR (n = 748), BRAF (n = 135), ERBB2 (n = 30), KIT (n = 32), PIK3CA (n = 221), and CTNNB1 (n = 94), for which targeted therapies could also be potentially effective. A systematic literature search in conjunction with in silico evaluation identified n = 232 (5.5 %) patients, for which a trial of targeted treatment would be warranted according to available evidence (NCT level 1, i.e. published data showing efficacy in the same tumor entity). In conclusion, a sizeable fraction of NSCLC patients harbors rare or non-canonical alterations that may be associated with clinical benefit from currently available targeted drugs. Systematic identification and individualized management of these cases can expand applicability of precision oncology in NSCLC and extend clinical gain from established molecular targets. These results can also inform clinical trials.
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http://dx.doi.org/10.1016/j.lungcan.2021.02.022DOI Listing
April 2021

Relationship of parity and prior cesarean delivery to levonorgestrel 52 mg intrauterine system expulsion over 6 years.

Contraception 2021 Jun 28;103(6):444-449. Epub 2021 Feb 28.

Department of Obstetrics and Gynecology, University of California, Davis, Sacramento, CA, United States. Electronic address:

Objective: Assess the relationship between parity and prior route of delivery to levonorgestrel 52 mg intrauterine system (IUS) expulsion during the first 72 months of use.

Study Design: We evaluated women enrolled in the ACCESS IUS multicenter, Phase 3, open-label clinical trial of the Liletta levonorgestrel 52 mg IUS. Investigators evaluated IUS presence at 3 and 6 months after placement and then every 6 months and during unscheduled visits. We included women with successful placement and at least one follow-up assessment. We evaluated expulsion rates based on obstetric history; for prior delivery method subanalyses, we excluded 12 participants with missing delivery data. We determined predictors of expulsion using multivariable regression analyses.

Results: Of 1714 women with IUS placement, 1710 had at least one follow-up assessment. The total population included 986 (57.7%) nulliparous women. Sixty-five (3.8%) women experienced expulsion within 72 months, 50 (76.9%) within the first 12 months. Expulsion rates among nulliparous women (22/986 [2.2%]) or parous women with any pregnancy ending with a Cesarean delivery (6/195 [3.1%]) differed from parous women who only experienced vaginal deliveries (37/517 [7.2%]) (p < 0.001). In multivariable regression, obesity (adjusted odds ratio [aOR] 2.2, 95% confidence interval [CI] 1.3-3.7), parity (aOR 2.2, 95% CI 1.2-4.1), and non-white race (aOR 1.8, 95% CI 1.1-3.2) predicted expulsion. Among parous women, obesity (aOR 2.2, 95% CI 1.2-4.2) increased the odds and having ever had a cesarean delivery (aOR 0.4, 95% CI 0.1-0.9) decreased the odds of expulsion.

Conclusion: IUS expulsion occurs in less than 4% of users over the first 6 years of use and occurs mostly during the first year. Expulsion is more likely among obese and parous women.

Implications: Levonorgestrel 52 mg intrauterine system expulsion occured more commonly in parous than nulliparous women; the increase in parous women is primarily in women who had vaginal deliveries only. The association between obesity, delivery route, and IUS expulsion needs further elucidation.
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http://dx.doi.org/10.1016/j.contraception.2021.02.013DOI Listing
June 2021

Patch augmentation surgery for rotator cuff repair: the PARCS mixed-methods feasibility study.

Health Technol Assess 2021 Feb;25(13):1-138

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Background: A rotator cuff tear is a common, disabling shoulder problem. Symptoms may include pain, weakness, lack of shoulder mobility and sleep disturbance. Many patients require surgery to repair the tear; however, there is a high failure rate. There is a need to improve the outcome of rotator cuff surgery, and the use of patch augmentation (on-lay or bridging) to provide support to the healing process and improve patient outcomes holds promise. Patches have been made using different materials (e.g. human/animal skin or tissue and synthetic materials) and processes (e.g. woven or mesh).

Objectives: The aim of the Patch Augmented Rotator Cuff Surgery (PARCS) feasibility study was to determine the design of a definitive randomised controlled trial assessing the clinical effectiveness and cost-effectiveness of a patch to augment surgical repair of the rotator cuff that is both acceptable to stakeholders and feasible.

Design: A mixed-methods feasibility study of a randomised controlled trial.

Data Sources: MEDLINE, EMBASE and the Cochrane Library databases were searched between April 2006 and August 2018.

Methods: The project involved six stages: a systematic review of clinical evidence, a survey of the British Elbow and Shoulder Society's surgical membership, a survey of surgeon triallists, focus groups and interviews with stakeholders, a two-round Delphi study administered via online questionnaires and a 2-day consensus meeting. The various stakeholders (including patients, surgeons and industry representatives) were involved in stages 2-6.

Results: The systematic review comprised 52 studies; only 15 were comparative and, of these, 11 were observational (search conducted in August 2018). These studies were typically small (median number of participants 26, range 5-152 participants). There was some evidence to support the use of patches, although most comparative studies were at a serious risk of bias. Little to no published clinical evidence was available for a number of patches in clinical use. The membership survey of British Elbow and Shoulder surgeons [105 (21%) responses received] identified a variety of patches in use. Twenty-four surgeons (77%) completed the triallist survey relating to trial design. Four focus groups were conducted, involving 24 stakeholders. Differing views were held on a number of aspects of trial design, including the appropriate patient population (e.g. patient age) to participate. Agreement on the key research questions and the outline of two potential randomised controlled trials were achieved through the Delphi study [29 (67%)] and the consensus meeting that 22 participants attended.

Limitations: The main limitation was that the findings were influenced by the participants, who are not necessarily representative of the views of the relevant stakeholder groups.

Conclusion: The need for further clinical studies was clear, particularly given the range and number of different patches available.

Future Work: Randomised comparisons of on-lay patch use for completed rotator cuff repairs and bridging patch use for partial rotator cuff repairs were identified as areas for further research. The value of an observational study to assess safety concerns of patch use was also highlighted. These elements are included in the trial designs proposed in this study.

Study Registration: The systematic review is registered as PROSPERO CRD42017057908.

Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 25, No. 13. See the NIHR Journals Library website for further project information.
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http://dx.doi.org/10.3310/hta25130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958078PMC
February 2021

Safety of dexmedetomidine in the cardiac intensive care unit.

Eur Heart J Acute Cardiovasc Care 2020 Aug 28. Epub 2020 Aug 28.

Division of Cardiology, Department of Medicine, University of Michigan,1500 East Medical Center Drive, Ann Arbor, MI 48109, USA.

Aims: Dexmedetomidine is one of the sedative agents recommended by the Society of Critical Care Medicine as a preferred option over benzodiazepines in critically ill, mechanically ventilated patients. Little data exists describing sedation in the cardiac intensive care unit (CICU). The purpose of this study was to determine the prevalence of adverse events in CICU patients treated with dexmedetomidine.

Methods And Results: This was a retrospective cohort analysis of patients >18 years old admitted to the University of Michigan CICU from June 2014 to October 2019 who received dexmedetomidine therapy. The primary outcome was the composite of adverse events including bradycardia, hypotension, increasing vasopressor/inotrope requirements, and asystole. Secondary outcomes included individual components of the primary outcome. Patients that experienced adverse events were compared to those that did not experience adverse events to identify risk factors for adverse events. A total of 197 patients were included. There were 116 adverse events in 106 patients. Hypotension was the most common adverse event, making up 60.3% of adverse events reported. Increased vasopressor requirement and bradycardia both occurred in 22 patients (18.9%). Asystole occurred in two patients. B-type natriuretic peptide (BNP) levels were significantly higher in those experiencing an adverse event (848 pg/mL vs. 431 pg/mL; P = 0.03).

Conclusions: Patients admitted to the CICU experienced a high rate of adverse events with dexmedetomidine use. Those experiencing adverse events were more likely to have a higher BNP. Future studies should explore the safety of alternative sedative agents to ascertain safe pharmacological options for patients admitted to the CICU.
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http://dx.doi.org/10.1093/ehjacc/zuaa009DOI Listing
August 2020

KRAS G12C-mutated advanced non-small cell lung cancer: A real-world cohort from the German prospective, observational, nation-wide CRISP Registry (AIO-TRK-0315).

Lung Cancer 2021 04 13;154:51-61. Epub 2021 Feb 13.

Pius-Hospital Oldenburg, Universitätsklinik für Innere Medizin, Oldenburg, Germany.

Objectives: After decades of unsuccessful efforts in inhibiting KRAS, promising clinical data targeting the mutation subtype G12C emerge. Since little is known about outcome with standard treatment of patients with G12C mutated non-small cell lung cancer (NSCLC), we analyzed a large, representative, real-world cohort from Germany.

Patients And Methods: A total of 1039 patients with advanced KRAS-mutant or -wildtype NSCLC without druggable alterations have been recruited in the prospective, observational registry CRISP from 12/2015 to 06/2019 by 98 centers in Germany. Details on treatment, best response, and outcome were analyzed for patients with KRAS wildtype, G12C, and non-G12C mutations.

Results: Within the study population, 160 (15.4 %) patients presented with KRAS G12C, 251 (24.2 %) with non-G12C mutations, 628 (60.4 %) with KRAS wildtype. High PD-L1 expression (Tumor Proportion Score, TPS > 50 %) was documented for 28.0 %, 43.5 %, and 28.9 % (wildtype, G12C, non-G12C) of the tested patients; 68.8 %, 89.3 %, and 87.7 % of the patients received first-line treatment combined with an immune checkpoint-inhibitor in 2019. TPS > 50 % vs. TPS < 1 % was associated with a significantly decreased risk of mortality in a multivariate Cox model (HR 0.39, 95 % CI 0.26-0.60, p=<0.001). There were no differences in clinical outcome between KRAS wildtype, G12C or non-G12C mutations and KRAS mutational status was not prognostic in the model.

Conclusion: Here we describe the so far largest prospectively recruited cohort of patients with advanced NSCLC and KRAS mutations, with special focus on the G12C mutation. These data constitute an extremely valuable historical control for upcoming clinical studies that employ KRAS inhibitors.
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http://dx.doi.org/10.1016/j.lungcan.2021.02.005DOI Listing
April 2021

Separation and Elevated Residential Mobility: A Cross-Country Comparison.

Eur J Popul 2021 Mar 29;37(1):121-150. Epub 2020 May 29.

Population Research Centre, Faculty of Spatial Sciences, University of Groningen, Groningen, The Netherlands.

This study investigates the magnitude and persistence of elevated post-separation residential mobility (i.e. residential instability) in five countries (Australia, Belgium, Germany, the Netherlands, and the UK) with similar levels of economic development, but different welfare provisions and housing markets. While many studies examine residential changes related to separation in selected individual countries, only very few have compared patterns across countries. Using longitudinal data and applying Poisson regression models, we study the risk of a move of separated men and women compared with cohabiting and married individuals. We use time since separation to distinguish between moves due to separation and moves of separated individuals. Our analysis shows that separated men and women are significantly more likely to move than cohabiting and married individuals. The risk of a residential change is the highest shortly after separation, and it decreases with duration since separation. However, the magnitude of this decline varies by country. In Belgium, mobility rates remain elevated for a long period after separation, whereas in the Netherlands, post-separation residential instability appears brief, with mobility rates declining rapidly. The results suggest that housing markets are likely to shape the residential mobility of separated individuals. In countries, where mortgages are easy to access and affordable rental properties are widespread, separated individuals can rapidly adjust their housing to new family circumstances; in contrast, in countries with limited access to homeownership and small social rental markets, separated individuals experience a prolonged period of residential instability.
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http://dx.doi.org/10.1007/s10680-020-09561-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865036PMC
March 2021

DNA methylation profiles of bronchoscopic biopsies for the diagnosis of lung cancer.

Clin Epigenetics 2021 Feb 17;13(1):38. Epub 2021 Feb 17.

Institute of Human Genetics, University Medical Center Ulm, Albert-Einstein-Allee 11, 89081, Ulm, Germany.

Background: Lung cancer is the leading cause of cancer-related death in most western countries in both, males and females, accounting for roughly 20-25% of all cancer deaths. For choosing the most appropriate therapy regimen a definite diagnosis is a prerequisite. However, histological characterization of bronchoscopic biopsies particularly with low tumor cell content is often challenging. Therefore, this study aims at (a) determining the value of DNA methylation analysis applied to specimens obtained by bronchoscopic biopsy for the diagnosis of lung cancer and (b) at comparing aberrantly CpG loci identified in bronchoscopic biopsy with those identified by analyzing surgical specimens.

Results: We report the HumanMethylation450-based DNA methylation analysis of paired samples of bronchoscopic biopsy specimens either from the tumor side or from the contralateral tumor-free bronchus in 37 patients with definite lung cancer diagnosis and 18 patients with suspicious diagnosis. A differential DNA methylation analysis between both biopsy sites of patients with definite diagnosis identified 1303 loci. Even those samples were separated by the set of 1303 loci in which histopathological analysis could not unambiguously define the dignity. Further differential DNA methylation analyses distinguished between SCLC and NSCLC. We validated our results in an independent cohort of 40 primary lung cancers obtained by open surgical resection and their corresponding controls from the same patient as well as in publically available DNA methylation data from a TCGA cohort which could also be classified with high accuracy.

Conclusions: Considering that the prognosis correlates with tumor stage at time of diagnosis, early detection of lung cancer is vital and DNA methylation analysis might add valuable information to reliably characterize lung cancer even in histologically ambiguous sample material.
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http://dx.doi.org/10.1186/s13148-021-01024-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890863PMC
February 2021

Iodide-Mediated Rapid and Sensitive Surface Etching of Gold Nanostars for Biosensing.

Angew Chem Int Ed Engl 2021 04 24;60(18):9891-9896. Epub 2021 Mar 24.

Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK.

Iodide-mediated surface etching can tailor the surface plasmon resonance of gold nanostars through etching of the high-energy facets of the nanoparticle protrusions in a rapid and sensitive way. By exploring the underlying mechanisms of this etching and the key parameters influencing it (such as iodide, oxygen, pH, and temperature), we show its potential in a sensitive biosensing system. Horseradish peroxidase-catalyzed oxidation of iodide enables control of the etching of gold nanostars to spherical gold nanoparticles, where the resulting spectral shift in the surface plasmon resonance yields a distinct color change of the solution. We further develop this enzyme-modulated surface etching of gold nanostars into a versatile platform for plasmonic immunoassays, where a high sensitivity is possible by signal amplification via magnetic beads and click chemistry.
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http://dx.doi.org/10.1002/anie.202017317DOI Listing
April 2021