Epithelioid hemangioendothelioma is a malignant, often indolent vascular tumor which occurs at various anatomic sites. Based on a reciprocal translocation t (1;3)(p36;q25), a consistent WWTR1-CAMTA1 ...fusion gene has been found. An alternate YAP1-TFE3 fusion has been detected in a small and distinct subset of cases.
Thirty-nine tumors, from 24 females and 15 males with an age range 9-85 years, were located in soft tissue (head and neck 8, trunk 5, upper extremities 3, lower extremities 2, mediastinal 1, and paratesticular 1), lymph node (1), breast (1), skin (2), bone (6), lung (7), and liver (2). The cases were investigated using a panel of immunohistochemical markers. The aforementioned fusion-genes were examined using RT-PCR and/or FISH in order to validate their diagnostic value.
Follow-up available for 17 patients ranged from 3 months to 7 years (median interval 1.5 years). Eleven patients were alive without disease, 2 patients were alive with disease after 1.5 and 2 years, respectively. Four patients died of disease after 4 months (n = 1), 5 months (n = 2), and 1.5 years (n = 1).The size, known for 30 lesions, was >3 cm in 9 of them. Histologically, all lesions had classical features, at least focally. Four tumors counted >3 mitoses/50 HPF. Immunohistochemically, all cases tested stained positive for ERG (21), FLI1 (5) and CD31 (39). CD34 and D2-40 positivity was seen in 81% and 71% of the examined cases, respectively. 11/35 cases expressed pan-keratin and 6/20 cases CK8.18. TFE3 showed a nuclear reaction in 21/24 cases, irrespective of TFE3 rearrangement.Molecular genetically, 35/35 cases revealed one of the fusion genes by FISH and/or RT-PCR with WWTR1-CAMTA1 in 33 cases and YAP1-TFE3 in 2 cases.
These results demonstrate the high diagnostic value of FISH and RT-PCR in detecting the fusion genes of EHE. The immunohistochemical utility of TFE3 appears questionable in this study.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4010279141259481.
General large language models (LLMs), such as ChatGPT (GPT-3.5), have demonstrated the capability to pass multiple-choice medical board examinations. However, comparative accuracy of different LLMs ...and LLM performance on assessments of predominantly higher-order management questions is poorly understood. We aimed to assess the performance of 3 LLMs (GPT-3.5, GPT-4, and Google Bard) on a question bank designed specifically for neurosurgery oral boards examination preparation.
The 149-question Self-Assessment Neurosurgery Examination Indications Examination was used to query LLM accuracy. Questions were inputted in a single best answer, multiple-choice format. χ 2 , Fisher exact, and univariable logistic regression tests assessed differences in performance by question characteristics.
On a question bank with predominantly higher-order questions (85.2%), ChatGPT (GPT-3.5) and GPT-4 answered 62.4% (95% CI: 54.1%-70.1%) and 82.6% (95% CI: 75.2%-88.1%) of questions correctly, respectively. By contrast, Bard scored 44.2% (66/149, 95% CI: 36.2%-52.6%). GPT-3.5 and GPT-4 demonstrated significantly higher scores than Bard (both P < .01), and GPT-4 outperformed GPT-3.5 ( P = .023). Among 6 subspecialties, GPT-4 had significantly higher accuracy in the Spine category relative to GPT-3.5 and in 4 categories relative to Bard (all P < .01). Incorporation of higher-order problem solving was associated with lower question accuracy for GPT-3.5 (odds ratio OR = 0.80, P = .042) and Bard (OR = 0.76, P = .014), but not GPT-4 (OR = 0.86, P = .085). GPT-4's performance on imaging-related questions surpassed GPT-3.5's (68.6% vs 47.1%, P = .044) and was comparable with Bard's (68.6% vs 66.7%, P = 1.000). However, GPT-4 demonstrated significantly lower rates of "hallucination" on imaging-related questions than both GPT-3.5 (2.3% vs 57.1%, P < .001) and Bard (2.3% vs 27.3%, P = .002). Lack of question text description for questions predicted significantly higher odds of hallucination for GPT-3.5 (OR = 1.45, P = .012) and Bard (OR = 2.09, P < .001).
On a question bank of predominantly higher-order management case scenarios for neurosurgery oral boards preparation, GPT-4 achieved a score of 82.6%, outperforming ChatGPT and Google Bard.
We present the results of our survey of 1612-MHz circumstellar OH maser emission from asymptotic giant branch (AGB) stars and red supergiants (RSGs) in the Large Magellanic Cloud (LMC). We have ...discovered four new circumstellar maser sources in the LMC, and increased the number of reliable wind speeds from infrared (IR) stars in the LMC from 5 to 13. Using our new wind speeds, as well as those from Galactic sources, we have derived an updated relation for dust-driven winds: ... We compare the subsolar metallicity LMC OH/IR stars with carefully selected samples of more metal-rich OH/IR stars, also at known distances, in the Galactic Centre and Galactic bulge. We derive pulsation periods for eight of the bulge stars for the first time by using near-IR photometry from the Vista Variables in the Via Lactea survey. We have modelled our LMC OH/IR stars and developed an empirical method of deriving gas-to-dust ratios and mass-loss rates by scaling the models to the results from maser profiles. We have done this also for samples in the Galactic Centre and bulge and derived a new mass-loss prescription which includes luminosity, pulsation period, and gas-to-dust ratio ... The tightest correlation is found between mass-loss rate and luminosity. We find that the gas-to-dust ratio has little effect on the mass-loss of oxygen-rich AGB stars and RSGs within the Galaxy and the LMC. This suggests that the mass-loss of oxygen-rich AGB stars and RSGs is (nearly) independent of metallicity between a half and twice solar. (ProQuest: ... denotes formulae/symbols omitted.)
Myoepithelial carcinoma of soft tissue (MEC) and cellular extraskeletal myxoid chondrosarcoma (cEMC) share striking similarities. In this paper, we compare ten MECs with five cEMCs. MEC patients had ...an equal gender distribution. The age range was 15–76 years (mean, 42 years). Tumours were located on extremities, pelvic girdle, vulva and neck. Follow-up, available for nine patients, ranged from 4 to 85 months (mean, 35 months). Five patients were alive without evidence of disease, two were alive with disease and two died 8 months after the initial diagnosis. cEMCs were from three males and two females with an age range of 37–82 years (mean, 57 years); they presented in extremities, shoulder and paravertebral/cervical. Follow-up, available for four patients, ranged from 6 to 220 months (mean, 61 months). All patients were alive, two with recurrences and/or metastases and two without evidence of disease. Morphologically, the distinction between these two entities was difficult since all cases exhibited features typically seen in myoepithelial tumours. Immunohistochemically, MECs expressed pan-keratin (80 %), epithelial membrane antigen (EMA; 57 %), S100 (50 %), alpha-smooth muscle actin (ASMA; 75 %), calponin (67 %) and p63 (25 %). S100 and EMA were expressed in 40 % of cEMC cases respectively with additional immunoreactivity for p63, ASMA and glial fibrillary acidic protein in one case. Pan-keratin was negative in all neoplasms.
NR4A3
rearrangement was present in four of four cEMCs and in none of the MECs. In contrast, three of nine (33 %) MECs and four of five (80 %) cEMCs showed an
EWSR1
rearrangement. In summary, MECs and cEMCs share clinical, morphological, immunohistochemical and genetic characteristics. The pathognomic rearrangement of
NR4A3
is a useful diagnostic feature in identifying cEMCs.
This paper presents time-series observations and analysis of broadband night sky airglow intensity 4 September 2018 through 30 April 2020. Data were obtained at 5 sites spanning more than 8500 km ...during the historically deep minimum of Solar Cycle 24 into the beginning of Solar Cycle 25. New time-series observations indicate previously unrecognized significant sources of broadband night sky brightness variations, not involving corresponding changes in the Sun's 10.7 cm solar flux, occur during deep solar minimum. New data show; (1) Even during a deep solar minimum the natural night sky is rarely, if ever, constant in brightness. Changes with time-scales of minutes, hours, days, and months are observed. (2) Semi-annual night sky brightness variations are coincident with changes in the orientation of Earth's magnetic field relative to the interplanetary magnetic field. (3) Solar wind plasma streams from solar coronal holes arriving at Earth's bow shock nose are coincident with major night sky brightness increase events. (4) Sites more than 8500 km along the Earth's surface experience nights in common with either very bright or very faint night sky airglow emissions. The reason for this observational fact remains an open question. (5) It is plausible, terrestrial night airglow and geomagnetic indices have similar responses to the solar energy input into Earth's magnetosphere. Our empirical results contribute to a quantitative basis for understanding and predicting broadband night sky brightness variations. They are applicable in astronomical, planetary science, space weather, light pollution, biological, and recreational studies.
Three-dimensional (3D) structures of the genome are dynamic, heterogeneous and functionally important. Live cell imaging has become the leading method for chromatin dynamics tracking. However, ...existing CRISPR- and TALE-based genomic labeling techniques have been hampered by laborious protocols and are ineffective in labeling non-repetitive sequences. Here, we report a versatile CRISPR/Casilio-based imaging method that allows for a nonrepetitive genomic locus to be labeled using one guide RNA. We construct Casilio dual-color probes to visualize the dynamic interactions of DNA elements in single live cells in the presence or absence of the cohesin subunit RAD21. Using a three-color palette, we track the dynamic 3D locations of multiple reference points along a chromatin loop. Casilio imaging reveals intercellular heterogeneity and interallelic asynchrony in chromatin interaction dynamics, underscoring the importance of studying genome structures in 4D.
Although the benefits of antithrombotic drugs are indisputable to reduce thrombotic events, they carry a high risk of compromising patient safety. No previous studies investigated the implementation ...and (cost-) effectiveness of a hospital-based multidisciplinary antithrombotic team on bleeding and thrombotic outcomes. The primary aim of this study was to compare the proportion of patients with a composite end point consisting of one or more bleeding episodes or one or more thrombotic event from hospitalization until three months after hospitalization.
A prospective, multicenter before-after intervention study was conducted in two Dutch hospitals. Adult patients hospitalized between October 2015 and December 2017 treated with anticoagulant therapy were included. The primary aim was to estimate the proportion of patients with a composite end point consisting of one or more bleeding episodes or one or more thrombotic event from hospitalization until three months after hospitalization. The intervention was the implementation of a multidisciplinary antithrombotic team focusing on education, medication reviews by pharmacists, implementing of local anticoagulant therapy guidelines based on national guidelines, patient counselling and medication reconciliation at admission and discharge. The primary endpoint was analysed using segmented linear regression. We obtained data for 1,886 patients: 941 patients were included in the usual care period and 945 patients in the intervention period. The S-team study showed that implementation of a multidisciplinary antithrombotic team over time significantly reduced the composite end point consisting of one or more bleeding episodes or one or more thrombotic event from hospitalization until three months after hospitalization in patients using anticoagulant drugs (-1.83% (-2.58% to -1.08%) per 2 month period).
This study shows that implementation of a multidisciplinary antithrombotic team over time significantly reduces the composite end point consisting of one or more bleeding episodes or one or more thrombotic event from hospitalization until three months after hospitalization in patients using anticoagulant drugs.
Trialregister.nl NTR4887.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Poly(ADP‐ribose) polymerase (PARP) inhibitors (PARPi) are effective in cancers with defective homologous recombination DNA repair (HRR), including BRCA1/2‐related cancers. A test to identify ...additional HRR‐deficient tumors will help to extend their use in new indications. We evaluated the activity of the PARPi olaparib in patient‐derived tumor xenografts (PDXs) from breast cancer (BC) patients and investigated mechanisms of sensitivity through exome sequencing, BRCA1 promoter methylation analysis, and immunostaining of HRR proteins, including RAD51 nuclear foci. In an independent BC PDX panel, the predictive capacity of the RAD51 score and the homologous recombination deficiency (HRD) score were compared. To examine the clinical feasibility of the RAD51 assay, we scored archival breast tumor samples, including PALB2‐related hereditary cancers. The RAD51 score was highly discriminative of PARPi sensitivity versus PARPi resistance in BC PDXs and outperformed the genomic test. In clinical samples, all PALB2‐related tumors were classified as HRR‐deficient by the RAD51 score. The functional biomarker RAD51 enables the identification of PARPi‐sensitive BC and broadens the population who may benefit from this therapy beyond BRCA1/2‐related cancers.
Synopsis
Sensitive and highly specific biomarkers usable in archived formalin fixed parafin embedded (FFPE) tumour samples are needed to extend the use of PARP inhibitors beyond BRCA1/2‐related cancers. The RAD51 score may satisfy this clinical unmet need.
The RAD51 score shows complete discriminative capacity in predicting PARP inhibitor response.
The RAD51 score is feasible in routine breast tumor samples without prior exposure to DNA damaging agents.
Carrying a PALB2 mutation is associated with a low RAD51score.
Sensitive and highly specific biomarkers usable in archived formalin fixed parafin embedded (FFPE) tumour samples are needed to extend the use of PARP inhibitors beyond BRCA1/2‐related cancers. The RAD51 score may satisfy this clinical unmet need.
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