"It doesn't matter if you are in charge of the trees, you always miss the trees for the forest": Power and the illusion of explanatory depth.

Power can increase overconfidence and illusory thinking. We investigated whether power is also related to the illusion of explanatory depth (IOED), people's tendency to think they understand the world in more detail, coherence, and depth than they actually do. Abstract thinking was reported as a reason for the IOED, and according to the social distance theory of power, power increases abstract thinking. We linked these literatures and tested construal style as a mediator. Further, predispositions can moderate effects of power and we considered narcissism as a candidate because narcissism leads to overconfidence and may thus increase the IOED especially in combination with high power. In three preregistered studies (total N = 607), we manipulated power or measured feelings of power. We found evidence for the IOED (regarding explanatory knowledge about devices). Power led to general overconfidence but had only a small impact on the IOED. Power and narcissism had a small interactive effect on the IOED. Meta-analytical techniques suggest that previous findings on the construal-style-IOED link show only weak evidential value. Implications refer to research on management, power, and overconfidence.

Influence of different conjugation methods for activating antibodies on polymeric nanoparticles: Effects for polyclonal expansion of human CD8+ T cells.

Particle-based systems have become a state-of-the-art method for in vitro expanding cytotoxic T cells by tailoring their surface with activating molecules. However, commonly used methods utilize facile carbodiimide chemistry leading to uncontrolled orientation of the immobilized antibodies on the particle surface that can lead to poor binding to target cells. To address this, selective coupling strategies utilizing regioselective chemical groups such as disulfide bridges offer a simple approach. In this work we present a set of methods to investigate the effect of polymeric nanoparticles, conjugated with either regioselective- or randomly-immobilized antiCD3 and antiCD28 antibodies, on the activation potential, expansion and expression of activation markers in T cells. We show that nanoparticles with well-oriented monovalent antibodies conjugated via maleimide require fewer ligands on the surface to efficiently expand T cells compared to bivalent antibodies randomly-immobilized via carbodiimide conjugation. Analysis of the T cell expression markers reveal that the T cell phenotype can be fine-tuned by adjusting the surface density of well-oriented antibodies, while randomly immobilized antibodies showed no differences despite their ligand density. Both conjugation techniques induced cytotoxic T cells, evidenced by analyzing their Granzyme B secretion. Furthermore, antibody orientation affects the immunological synapse and T cell activation by changing the calcium influx profile upon activation. Nanoparticles with well-oriented antibodies showed lower calcium influx compared to their bivalent randomly-immobilized counterparts. These results highlight the importance of controlling the antibody density and orientation on the nanoparticle surface via controlled coupling chemistries, helping to develop improved particle-based expansion protocols to enhance T cell therapies.

Genome-wide Detection of Chimeric Transcripts in Early-stage Non-small Cell Lung Cancer.

BACKGROUND/AIM: Lung cancer remains the main culprit in cancer-related mortality worldwide. Transcript fusions play a critical role in the initiation and progression of multiple cancers. Treatment approaches based on specific targeting of discovered driver events, such as mutations in EGFR, and fusions in NTRK, ROS1, and ALK genes led to profound improvements in clinical outcomes. The formation of chimeric proteins due to genomic rearrangements or at the post-transcriptional level is widespread and plays a critical role in tumor initiation and progression. Yet, the fusion landscape of lung cancer remains underexplored. MATERIALS AND METHODS: We used the JAFFA pipeline to discover transcript fusions in early-stage non-small cell lung cancer (NSCLC). The set of detected fusions was further analyzed to identify recurrent events, genes with multiple partners and fusions with high predicted oncogenic potential. Finally, we used a generalized linear model (GLM) to establish statistical associations between fusion occurrences and clinicopathological variables. RNA sequencing was used to discover and characterize transcript fusions in 270 NSCLC samples selected from the Glans-Look specimen repository. The samples were obtained during the early stages of disease prior to the initiation of chemo- or radiotherapy. RESULTS: We identified a set of 792 fusions where 751 were novel, and 33 were recurrent. Four of the 33 recurrent fusions were significantly associated with clinicopathological variables. Several of the fusion partners were represented by well-established oncogenes ERBB4, BRAF, FGFR2, and MET. CONCLUSION: The data presented in this study allow researchers to identify, select, and validate promising candidates for targeted clinical interventions.

Risk factors observed in 2-dimensional radiographs for permanent injury of the inferior alveolar nerve after removal of mandibular third molars: a case-control study.

OBJECTIVE: To assess whether differences exist in signs observed in 2D radiographs of mandibular third molars between a case group of patients with and a control group without permanent sensory disturbance of the inferior alveolar nerve (IAN) after removal. STUDY DESIGN: Three observers blinded to patient status assessed radiographs from the case group (n=162) and the control group (n=172). Two new signs, craniocaudal relation of the roots and the mandibular canal and position of the canal over the roots; and 4 "classic" signs, interruption of the white borders of the canal, darkening of the roots, narrowing of the canal lumen, and diversion of the canal over the roots were registered. Chi-square tests assessed differences in distribution of radiographic signs between the groups. Odds ratios expressed the association between radiographic signs and permanent sensory disturbance. Inter- and intraobserver reliability values were calculated. RESULTS: We found significantly more teeth with roots positioned inferiorly to the canal borders (P<0.001; OR 4.1-5.3) and with the canal superimposed over the upper or middle third of the roots (P<0.001; OR 2.6-3.9) in the case group than in the control group. Inter- and intraobserver reproducibility was excellent for roots inferior to the canal borders and fair to good for canal superimposition. CONCLUSIONS: Two radiographic signs are valid predictors of permanent sensory disturbance of the IAN in 2D radiographs.

[68Ga]Ga-NODAGA-E[(cRGDyK)]2 angiogenesis PET following myocardial infarction in an experimental rat model predicts cardiac functional parameters and development of heart failure.

BACKGROUND: Angiogenesis has increasingly been a target for imaging and treatment over the last decade. The integrin αvß3 is highly expressed in cells during angiogenesis and are therefore a promising target for imaging. In this study, we aimed to investigate the PET tracer [68Ga]Ga-RGD as a marker of angiogenesis following MI and its ability to predict cardiac functional parameters. METHODS: First, the real-time interaction between [68Ga]Ga-RGD and integrin αvß3 was investigated using surface plasmon resonance (SPR). Second, an animal study was performed to investigate the [68Ga]Ga-RGD uptake in the infarcted area after one and four weeks following MI in a rat model (MI = 68, sham surgery = 36). Finally, the specificity of the [68Ga]Ga-RGD tracer was evaluated ex vivo using histology, autoradiography, gamma counting and flow cytometry. RESULTS: SPR showed that [68Ga]Ga-RGD has a high affinity for integrin αvß3, forming a strong and stable binding. PET/CT showed a significantly higher uptake of [68Ga]Ga-RGD in the infarcted area compared to sham one week (p < 0.001) and four weeks (p < 0.001) after MI. The uptake of [68Ga]Ga-RGD after one week correlated to end diastolic volume (r = 0.74, p < 0.001) and ejection fraction (r = - 0.71, p < 0.001) after four weeks. CONCLUSION: This study demonstrates that [68Ga]Ga-RGD has a high affinity for integrin αvß3, which enables the evaluation of angiogenesis and remodeling. The [68Ga]Ga-RGD uptake after one week indicates that [68Ga]Ga-RGD may be used as an early predictor of cardiac functional parameters and possible development of heart failure after MI. These encouraging data supports the clinical translation and future use in MI patients.

Photodegradation of a bacterial pigment and resulting hydrogen peroxide release enable coral settlement.

The global degradation of coral reefs is steadily increasing with ongoing climate change. Yet coral larvae settlement, a key mechanism of coral population rejuvenation and recovery, is largely understudied. Here, we show how the lipophilic, settlement-inducing bacterial pigment cycloprodigiosin (CYPRO) is actively harvested and subsequently enriched along the ectoderm of larvae of the scleractinian coral Leptastrea purpura. A light-dependent reaction transforms the CYPRO molecules through photolytic decomposition and provides a constant supply of hydrogen peroxide (H2O2), leading to attachment on the substrate and metamorphosis into a coral recruit. Micromolar concentrations of H2O2 in seawater also resulted in rapid metamorphosis, but without prior larval attachment. We propose that the morphogen CYPRO is responsible for initiating attachment while simultaneously acting as a molecular generator for the comprehensive metamorphosis of pelagic larvae. Ultimately, our approach opens a novel mechanistic dimension to the study of chemical signaling in coral settlement and provides unprecedented insights into the role of infochemicals in cross-kingdom interactions.

Peripheral artery disease in patients with schizophrenia as compared to controls.

BACKGROUND: Patients with schizophrenia have an increased prevalence of risk factors for peripheral artery disease (PAD) and is expected to have an increased prevalence of PAD. PAD can be detected utilizing toe-brachial index (TBI) which screens for vascular pathology proximal to the toes. METHODS: Using a cross-sectional design, we defined the subpopulations: (1) Patients diagnosed with schizophrenia less than 2 years before inclusion (SCZ < 2), (2) Psychiatric healthy controls matched to subpopulation 1 on sex, age, and smoking status, and (3) Patients diagnosed with schizophrenia 10 or more years before inclusion (SCZ ≥ 10). TBI was calculated by dividing toe pressures by systolic brachial blood pressure, and PAD was defined by TBI < 0.70. Logistic regression analysis with PAD as outcome and sex, age, smoking status, BMI, skin temperature, diagnosis of schizophrenia, and comorbidities as explanatory variables was conducted. RESULTS: PAD was present in 26.2% of patients diagnosed with SCZ < 2 (17 of 65) and in 18.5% of psychiatric healthy controls (12 of 65) with no statistically significant difference in prevalence rates (p = 0.29). PAD was present in 22.0% of patients diagnosed with SCZ ≥ 10 (31 of 141). In logistic regression, patients diagnosed with SCZ < 2 had an increased odds of PAD with psychiatric healthy controls as reference (Odds ratio = 2.80, 95% confidence interval 1.09-7.23, p = 0.03). The analysis was adjusted for age, sex, smoking status, BMI and comorbidities such as hypertension, diabetes and heart disease. CONCLUSIONS: This study did not find statistically significant increased prevalence rates of PAD in patients with schizophrenia even though patients with SCZ were compared to psychiatric healthy controls using TBI. Utilizing logistic regression PAD was associated with schizophrenia diagnosis within the last 2 years, age and skin temperature. As PAD is initially asymptomatic, screening could be relevant in patients with schizophrenia if other risk factors are prevalent. Further large-scale multicenter studies are warranted to investigate schizophrenia as a potential risk factor for PAD. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02885792.

Transplacental transfer of SARS-CoV-2 antibodies: a cohort study.

The purpose of this study was to examine the transfer rate of SARS-CoV-2 IgG antibodies in pregnancy and newborns. Two Danish labor wards screened all women for SARS-CoV-2 by PCR upon arrival. Women (n = 99) with a SARS-CoV-2 PCR-positive nasopharyngeal (NP) swab or with a household member with a positive swab at labor or any time during pregnancy, or COVID-19 symptoms upon admission (November 2020 through August 2021), were included. Mother and infant were tested by NP swabs at delivery, and maternal and infant (umbilical cord) venous blood samples were collected. We obtained clinical information including previous PCR test results from the medical records. SARS-Cov-2 IgM and quantified IgG antibodies were measured by enzyme-linked immunosorbent assay and transfer ratios of IgG. We detected IgG antibodies in 73 women and 65 cord blood sera and found a strong correlation between SARS-CoV-2 IgG concentrations in maternal and umbilical cord sera (r = 0.9; p < 0.05). Transfer ratio was > 1.0 in 51 out of 73 (69%) infants and > 1.5 in 26 (35%). We found that transfer was proportional to time from a positive SARS-CoV-2 PCR NP swab to delivery (r = 0.5; p < 0.05). Transfer ratios of SARS-CoV-2 antibodies were associated with time from infection to delivery with transfer ratios of more than 1.0 in the majority of seropositive mother-infant dyads.

The clinical consequences of routine 68Ga-PSMA-11 PET/CT in patients with newly diagnosed prostate cancer, ISUP grade 5 and no metastases based on standard imaging - preliminary results.

AIM: To evaluate the clinical consequences of prostate specific membrane antigen (PSMA) PET/CT for primary staging in patients with ISUP grade 5 (Gleason score ≥9) prostate cancer (PCa), and no definitive distant metastases based on standard imaging. METHODS: At our tertial referral center, PSMA PET/CT became standard of care from August 2018 for primary staging of prostate cancer given the following criteria: (1) no prior treatment for prostate cancer, (2) ISUP grade 5, (3) no definitive metastases on standard imaging (contrast enhanced CT and bone scintigraphy), and (4) deemed suitable for treatment with curative intent based on comorbidity and life expectancy. We present the preliminary results of first six months recruitment with 12 months of follow-up. RESULTS: Forty-eight patients (mean age 69 years, median PSA 13.0 ng/mL, 20 patients with locally advanced PCa) were included. CT was positive in pelvic lymph nodes in two patients, bone scintigraphy was equivocal in three patients. PSMA PET/CT showed pathological uptake outside the prostatic bed in 22 patients (46%) of which 13 patients (27%) showed lesions confined to regional lymph nodes, and nine patients (19%) showed nonregional lymph node metastases and/or bone metastases. PSMA PET/CT changed the treatment strategy from curatively intended treatment to palliative treatment in 18 patients (38%). CONCLUSION: PMSA PET/CT revealed pathological uptake in a large proportion of high-risk patients at primary staging among patients with no definite metastases on standard imaging leading to change of patient management in 38% of the patients.

Influence of Prior Imaging Information on Diagnostic Accuracy for Focal Skeletal Processes-A Retrospective Analysis of the Consistency between Biopsy-Verified Imaging Diagnoses.

INTRODUCTION: Comparing imaging examinations with those previously obtained is considered mandatory in imaging guidelines. To our knowledge, no studies are available on neither the influence, nor the sequence, of prior imaging and reports on diagnostic accuracy using biopsy as the reference standard. Such data are important to minimize diagnostic errors and to improve the preparation of diagnostic imaging guidelines. The aim of our study was to provide such data. MATERIALS AND METHODS: A retrospective cohort of 216 consecutive skeletal biopsies from patients with at least 2 different imaging modalities (X-ray, CT and MRI) performed within 6 months of biopsy was identified. The diagnostic accuracy of the individual imaging modality was assessed. Finally, the possible influence of the sequence of imaging modalities was investigated. RESULTS: No significant difference in the accuracy of the imaging modalities was shown, being preceded by another imaging modality or not. However, the sequence analyses indicate sequential biases, particularly if MRI was the first imaging modality. CONCLUSION: The sequence of the imaging modalities seems to influence the diagnostic accuracy against a pathology reference standard. Further studies are needed to establish evidence-based guidelines for the strategy of using previous imaging and reports to improve diagnostic accuracy.

Use of 18F-NaF PET in the staging of skeletal metastases of newly diagnosed, high-risk prostate cancer patients: a nationwide cohort study.

OBJECTIVE: To determine whether preoperative staging of high-risk prostate cancer with 18F-sodium-fluoride (18F-NaF) positron emission tomography (PET) reduces the risk of skeletal metastases. DESIGN: Nationwide, population-based cohort study using real-world data. SETTING: The study used national health registries, including all sites in Denmark from 2011 to 2018. PARTICIPANTS: Newly diagnosed high-risk prostate cancer patients who underwent radical prostatectomy from 2011 to 2018. Patients were stratified into two groups according to the preoperative imaging modality of either 18F-NaF PET or bone scintigraphy. MAIN OUTCOME MEASURES: The risk of skeletal-related events (SREs) as a proxy for skeletal metastases following radical prostatectomy. The secondary endpoint was overall survival. RESULTS: Between 1 January 2011 and 31 December 2018, 4183 high-risk patients underwent radical prostatectomy. Of these patients, 807 (19.3%) underwent 18F-NaF PET and 2161 (51.7%) underwent bone scintigraphy. The remaining 30% were examined by a different imaging method or did not undergo imaging. Using the inverse probability of treatment weighting to control potential confounding, the HR of experiencing an SRE for patients in the 18F-NaF PET group versus the bone scintigraphy group was 1.15 (95% CI 0.86 to 1.54). The 3-year survival rates were 97.4% (95% CI 96.1 to 98.7) and 97.1% (95% CI 96.4 to 97.9) for patients receiving 18F-NaF PET and bone scintigraphy, respectively. CONCLUSION: Patients with high-risk prostate cancer undergoing preoperative staging with 18F-NaF PET did not display a lower risk of developing SREs after prostatectomy compared with patients undergoing bone scintigraphy. The survival rates were similar between the two groups.

The predictive value of self-compassion for psychological adjustment in left ventricular assist device patients: an observational study.

AIMS: Implantation of a left ventricular assist device (LVAD) is an established treatment option for patients with advanced heart failure. However, apart from its challenging medical management, it comes with serious psychological implications. Empirical evidence suggests that self-compassion, a self-regulation strategy for countering negative self-directed emotions, might be a promising approach in facilitating psychological adjustment also in LVAD patients. The aims of the present study were to investigate self-compassion as a protective factor for anxiety and depressive symptoms, to test whether taking a decentred perspective mediates these effects, and to explore whether self-compassion predicts the clinically rated functional health status. METHOD AND RESULTS: A sample of N = 45 patients (36 male) with a mean age of 60.5 years (SD = 10.8) from the outpatient department for terminal heart failure at the University Medical Center in Kiel, Germany, participated in the study. Patients completed self-report measures for psychological adjustment (HADS), self-compassion (SCS), and decentring (EQ). Functional health status was determined by the NYHA classification. The more patients were self-compassionate, the less they reported anxiety (r = -0.28) and depressive symptoms (r = -0.34). Decentring mediated both effects. Moreover, self-compassion predicted the functional health status, even when controlling for anxiety (odds ratio [OR] = 0.09) and depressive symptoms (OR = 0.11). CONCLUSIONS: This study provides the first evidence for a significant interrelation between self-compassion and common adverse psychological conditions in LVAD patients. Longitudinal data and the evaluation of interventions to strengthen self-compassion are needed to further validate the beneficial effects of self-compassion in LVAD patients in the future.

Observer experience and accuracy of 18F-sodium-fluoride PET/CT for the diagnosis of bone metastases in prostate cancer.

OBJECTIVE: To evaluate the diagnostic accuracy of observers with different levels of experience in reading 18F-sodium fluoride (NaF) PET/CT images for the diagnosis of bone metastases in prostate cancer (PCa) patients. METHODS: Nine observers with varying NaF PET/CT experience, ranging from no experience to 2000+ examinations, evaluated 211 NaF PET/CT scans from PCa patients participating in one of four prospective trials. Each observer evaluated each NaF PET/CT on a patient level using a trichotomous scale: M0 (no bone metastases), Me (equivocal for bone metastases) and M1 (bone metastases). Subsequently, a dichotomous evaluation was conducted (M0/M1). The final diagnosis was retrieved from the original study. For each observer, ROC curves and the diagnostic accuracy were calculated based on dichotomous and trichotomous scales; in the latter case, Me was first regarded as M1 and then M0. RESULTS: Across all experience levels, the sensitivity, specificity and accuracy using the dichotomous scale ranged from 0.81 to 0.89, 0.93 to 1.00 and 0.91 to 0.94, respectively. Employing the trichotomous scale, novice and experienced observers chose Me in up to 20 vs. 10% of cases, respectively. Considering Me as M0, the sensitivity, specificity and accuracy ranged from 0.78 to 0.89, 0.95 to 1.00 and 0.91 to 0.95, respectively. Considering Me as M1, the sensitivity, specificity and accuracy ranged from 0.86 to 0.92, 0.71 to 0.96 and 0.77 to 0.94, respectively. CONCLUSION: Novice observers used the equivocal option more frequently than observers with NaF PET/CT experience. However, on the dichotomous scale, all observers exhibited high and satisfactory accuracy for the detection of bone metastases, making NaF PET/CT an effective imaging modality even in unexperienced hands.

Characterization of an Insoluble and Soluble Form of Melanin Produced by Streptomyces cavourensis SV 21, a Sea Cucumber Associated Bacterium.

Melanin is a widely distributed and striking dark-colored pigment produced by countless living organisms. Although a wide range of bioactivities have been recognized, there are still major constraints in using melanin for biotechnological applications such as its fragmentary known chemical structure and its insolubility in inorganic and organic solvents. In this study, a bacterial culture of Streptomyces cavourensis SV 21 produced two distinct forms of melanin: (1) a particulate, insoluble form as well as (2) a rarely observed water-soluble form. The here presented novel, acid-free purification protocol of purified particulate melanin (PPM) and purified dissolved melanin (PDM) represents the basis for an in-depth comparison of their physicochemical and biological properties, which were compared to the traditional acid-based precipitation of melanin (AM) and to a synthetic melanin standard (SM). Our data show that the differences in solubility between PDM and PPM in aqueous solutions may be a result of different adjoining cation species, since the soluble PDM polymer is largely composed of Mg2+ ions and the insoluble PPM is dominated by Ca2+ ions. Furthermore, AM shared most properties with SM, which is likely attributed to a similar, acid-based production protocol. The here presented gentler approach of purifying melanin facilitates a new perspective of an intact form of soluble and insoluble melanin that is less chemical altered and thus closer to its original biological form.

Accuracy of hepatobiliary scintigraphy and added value of SPECT/CT versus planar imaging for diagnosing biliary atresia.

OBJECTIVE: Hepatobiliary scintigraphy (HBS) is an important tool in diagnosing biliary atresia in infants. There is limited evidence on the use of single photon emission computed tomography/computed tomography (SPECT/CT) as an additional imaging method to planar imaging. We evaluated the value of SPECT/CT in unclear cases of planar HBS. SUBJECTS AND METHODS: Consecutive patients with suspected biliary atresia who underwent guideline-compliant HBS from January 2010 until March 2020 were reviewed, and cases with SPECT/CT were identified. Each step within the imaging procedure (dynamic, static [early and late], and SPECT/CT) was blindly reread in consensus by two observers and categorized based on a 5-point scale: 0, definitely no bowel excretion (i.e., atresia confirmed); 1, probably positive; 2,equivocal; 3, probably negative; and 4, definite negative (i.e., atresia not confirmed). In this analysis, categories were dichotomized as negative for biliary atresia (scores 3-4) or positive (scores 0-2, including equivocal scans). Available follow-up information constituted the standard of truth (SoT). RESULTS: Twenty-three infants had HBS, among which ten (4 boys and 6 girls; mean age 36 days; range 8-108) underwent SPECT/CT. Single photon emission computed tomography SPECT/CT was performed as early examination (<8h) in 3 subjects and late (8 to 24 h) in 7 infants. Reread SPECT/CT was categorized as positive for atresia in three infants and negative in seven infants. The SoT showed biliary atresia in one of ten patients. Single photon emission computed tomography/CT was true positive in one case, false positive in two, and true negative in seven. No false negative cases were noted. The diagnostic performance of SPECT/CT showed a sensitivity of 100%, specificity of 78%, positive predictive value (PPV) of 33%, negative predictive value (NPV) of 100%, and accuracy of 90%. For comparison, the diagnostic performance of planar HBS showed a sensitivity of 100%, specificity of 67%, PPV of 25%, NPV of 100%, and accuracy of 70%. In summary, the addition of SPECT/CT to planar HBS improved specificity andaccuracyand marginally improved PPV. Single photon emission computed tomography/CT provided more confidence in the final conclusion in 8/10 patients. In the remaining two cases, SPECT/CT did not improve the level of confidence (one remained equivocal, and one changed from probably no excretion to equivocal). CONCLUSION: These preliminary data demonstrated increased accuracy of add-on SPECT to planar HBS predominantly due to improved specificity. This finding is consistent with the existing but limited literature and supports the recommendation of routine use of SPECT/CT or SPECT.

Comparison of nuclear imaging techniques and volumetric imaging for the prediction of postoperative mortality and liver failure in patients undergoing localized liver-directed treatments: a systematic review.

BACKGROUND/AIMS: Although volumetric imaging by computed tomography (CT) is the gold standard for preoperative assessment of the future liver remnant, nuclear imaging studies have shown promising data. This systematic review summarized the results from trials investigating volumetric and nuclear medicine imaging for the prediction of postoperative mortality and liver failure (LF). METHODS: MEDLINE and Web of Science were searched for papers investigating nuclear imaging methods for the prediction of postoperative clinical outcomes in patients undergoing local, liver-directed treatments. Only papers investigating both preoperative nuclear imaging and CT or magnetic resonance imaging (MR) for the prediction of postoperative mortality and/or LF were included. RESULTS: Twenty-five trials were qualified for this review. All trials but two used technetium-based tracers for the nuclear imaging examination. Four papers used MR imaging and the remaining used CT for the volumetric evaluation. Overall, the studies were heterogeneous both in terms of methodology and imaging technique. Of the thirteen studies reporting on postoperative mortality, most were descriptive without detailed diagnostic data. A few with detailed data found that nuclear imaging had better predictive value than volumetric imaging. Nineteen studies investigated the prediction of postoperative LF of which seven papers investigated the predictive value of both modalities in multivariable regression analysis. Two papers found that only nuclear imaging parameters were predictive of LF, one paper found that the CT parameter was predictive, and four papers found that combined nuclear and CT/MR imaging parameters were predictive of LF. CONCLUSION: Both methodologies were useful in the preoperative assessment of patients scheduled for liver interventions, especially in combination, but nuclear imaging demonstrated better predictive value for postoperative mortality and LF in a few trials. The overall technical and methodological heterogeneity of the included studies complicates the ability to directly compare the clinical utility of the two imaging techniques.

Validity of negative bone biopsy in suspicious bone lesions.

BACKGROUND: The presence of malignant cells in bone biopsies is considered gold standard to verify occurrence of cancer, whereas a negative bone biopsy can represent a false negative, with a risk of increasing patient morbidity and mortality and creating misleading conclusions in cancer research. However, a paucity of literature documents the validity of negative bone biopsy as an exclusion criterion for the presence of skeletal malignancies. PURPOSE: To investigate the validity of a negative bone biopsy in bone lesions suspicious of malignancy. MATERIAL AND METHOD: A retrospective cohort of 215 consecutive targeted non-malignant skeletal biopsies from 207 patients (43% women, 57% men, median age 64, and range 94) representing suspicious focal bone lesions, collected from January 1, 2011, to July 31, 2013, was followed over a 2-year period to examine any additional biopsy, imaging, and clinical follow-up information to categorize the original biopsy as truly benign, malignant, or equivocal. Standard deviations and 95% confidence intervals were calculated. RESULTS: 210 of 215 biopsies (98%; 95% CI 0.94-0.99) showed to be truly benign 2 years after initial biopsy. Two biopsies were false negatives (1%; 95% CI 0.001-0.03), and three were equivocal (lack of imaging description). CONCLUSION: Our study documents negative bone biopsy as a valid criterion for the absence of bone metastasis. Since only 28% had a confirmed diagnosis of prior cancer and not all patients received adequately sensitive imaging, our results might not be applicable to all cancer patients with suspicious bone lesions.

Usefulness of Imaging Response Assessment after Irreversible Electroporation of Localized Pancreatic Cancer-Results from a Prospective Cohort.

(1) Background: Irreversible electroporation (IRE) is a nonthermal ablation technique that is being studied in nonmetastatic pancreatic cancer (PC). Most published studies use imaging outcomes as an efficacy endpoint, but imaging interpretation can be difficult and has yet to be correlated with survival. The aim of this study was to examine the correlation of imaging endpoints with survival in a cohort of IRE-treated PC patients. (2) Methods: Several imaging endpoints were examined before and after IRE on 18F-fluorodeoxyglucose positron emission tomography (PET) with computed tomography. Separate analyses were performed at the patient and lesion levels. Mortality rate (MR) ratios for imaging endpoints after IRE were estimated. (3) Results: Forty-one patients were included. Patient-level analysis revealed that progressive disease (PD), as defined by RECIST 1.1, is correlated with a higher MR at all time intervals, but PD, as defined by EORTC PET response criteria, is only correlated with the MR in the longest interval. No correlation was found between PD, as defined by RECIST, and the MR in the lesion-level analysis. (4) Conclusions: Patient-level PD, as defined by RECIST, was correlated with poorer survival after IRE ablation, whereas no correlations were observed in the lesion-level analyses. Several promising lesion-level outcomes were identified.

Response evaluation of bone metastasis in prostate cancer: Preliminary comparison of computerized bone scan index versus standardized clinical criteria.

OBJECTIVE: The correlation between the computer-assisted bone scan index (BSI) responses versus clinical response classification if bone metastases in prostate cancer patients are not clear. We compared changes in BSI with Prostate Cancer Working Group-3 (PCWG3) and MD Anderson (MDA) criteria. MATERIALS AND METHODS: Fifty-six consecutive patients with at least two bone scans (BS) within 12 months were included, who had BS before and after treatment with the same anticancer agent. RESULTS: Progressive disease (PD) by PCWG3 criteria was seen in 28% of the cases (median BSI increased by 1.69 units) versus non-PD in 72% (BSI change -0.13). MDAnderson showed PD in 34% (BSI increase 0.49), 45% stable disease (BSI change 0.00), and 20% partial responses (BSI decrease 1.44). Absolute BSI changes differed significantly among response categories by PCWG3 and MDA criteria (both P<0.0001). Response classification using dichotomized BSI data (>0/≤0 and >0.3/≤0.3 BSI units) showed a significant correlation with PCWG3 and MDA criteria (all P<0.001). Absolute BSI changes and dichotomized BSI correlated to prostate-specific antigen responses (both P<0.001) but not to clinical responses. CONCLUSION: Absolute changes in BSI and BSI response classification correlated significantly with standardized clinical response criteria for the assessment of treatment responses of skeletal metastases in prostate cancer.

Screening of DNA-Encoded Small Molecule Libraries inside a Living Cell.

DNA-encoded small molecule libraries (DELs) have facilitated the discovery of novel modulators of many different therapeutic protein targets. We report the first successful screening of a multimillion membered DEL inside a living cell. We demonstrate a novel method using oocytes from the South African clawed frog Xenopus laevis. The large size of the oocytes of 1 µL, or 100 000 times bigger than a normal somatic cell, permits simple injection of DELs, thus resolving the fundamental problem of delivering DELs across cell membranes for in vivo screening. The target protein was expressed in the oocytes fused to a prey protein, to allow specific DNA labeling and hereby discriminate between DEL members binding to the target protein and the endogenous cell proteins. The 194 million member DEL was screened against three pharmaceutically relevant protein targets, p38α, ACSS2, and DOCK5. For all three targets multiple chemical clusters were identified. For p38α, validated hits with single digit nanomolar potencies were obtained. This work demonstrates a powerful new approach to DEL screening, which eliminates the need for highly purified active target protein and which performs the screening under physiological relevant conditions and thus is poised to increase the DEL amenable target space and reduce the attrition rates.