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IntroductionDetection of PIK3CA mutations in primary tumors and liquid biopsy samples is of increasing importance for treatment decisions and therapy resistance in many types of cancer. The aim of the present study was to directly compare the efficacy of a relatively inexpensive ultrasensitive real-time PCR with the well-established and highly sensitive technology of ddPCR for the detection of the three most common hotspot mutations of PIK3CA, in exons 9 and 20, that are all of clinical importance in various types of cancer.Patients and methodsWe analyzed 42 gDNAs from primary tumors (FFPEs), 29 plasma-cfDNA samples, and 29 paired CTC-derived gDNAs, all from patients with ER+ metastatic breast cancer, and plasma from 10 healthy donors. The same blood draws were used for CTC isolation using EpCAM beads for positive immunomagnetic enrichment. All FFPEs and plasma-cfDNA samples were analyzed in parallel for PIK3CA mutations by ultrasensitive real-time PCR assay and droplet digital PCR.ResultsIn gDNAs from FFPEs, using ultrasensitive real-time PCR, the p.E545K mutation was detected in 22/42(52.4%), and the p.E542K and p.H1047R mutations were detected in 14/42(33.3%) and 16/42(38.1%), respectively. Using ddPCR, the p.E545K mutation was detected in 22/42(52.4%), p.E542K in 17/42(40.5%), and p.H1047R in 19/42(45.2%) samples, revealing a concordance between the two methodologies of 81%, 78.6% and 78.6% for each mutation respectively. In plasma-cfDNA, using ultrasensitive real-time PCR, the p.E545K mutation was detected in 11/29(38%) and both p.E542K and p.H1047R mutations in 2/29(6.9%).In the same plasma-cfDNA samples using ddPCR, p.E545K was detected in 1/29(3.5%), p.E542K in 2/29(6.9%), and p.H1047R in 3/29(10.5%) samples, revealing a concordance of 65.5%,100% and 93.1% for each mutation respectively. In paired CTC-derived gDNAs p.E545K was detected in 11/29(38%), p.E542K in 3/29(10.3%), and p.H1047R in 7/29(24.1%) samples.ConclusionsThis low-cost, high-throughput and ultrasensitive real-time PCR assay provides accurate and specific detection of PIK3CA hotspot mutations in liquid biopsy samples and gives similar results to ddPCR. This assay can be performed in labs where digital PCR instrumentation is not available. In CTC-derived gDNA and paired plasma-cfDNA, PIK3CA mutations detected were not identical, revealing that CTC and plasma-cfDNA give complementary information.

Determination of microsatellite instability (MSI)/mismatch repair (MMR) status in cancer has several clinical implications. Our aim was to integrate MSI/MMR status from patients tested in Greece to assess the prevalence of MSI-high (MSI-H)/deficient MMR (dMMR) per tumor type, testing patterns over time and concordance between MSI and MMR status. We retrospectively recorded MSI/MMR testing data of patients with diverse tumor types performed in pathology and molecular diagnostics laboratories across Greece. Overall, 18 of 22 pathology and/or molecular diagnostics laboratories accepted our invitation to participate. In the 18 laboratories located across the country, 7916 tumor samples were evaluated for MSI/MMR status. MSI/MMR testing significantly increased in patients with colorectal cancer (CRC) and other tumor types overtime (p < 0.05). The highest prevalence was reported in endometrial cancer (47 of 225 patients, 20.9%). MSI-H/dMMR was observed in most tumor types, even in low proportions. Among 904 tumors assessed both for MSI and MMR status, 21 had discordant results (overall discordance rate, 2.3%). We reported MSI-H/dMMR prevalence rates in patients with diverse cancers, while demonstrating increasing referral patterns from medical oncologists in the country overtime. The anticipated high rate of concordance between MSI and MMR status in paired analysis was confirmed.

We consider a version of the Hospitals/Residents problem which was first defined in 1962 by Gale and Shapley [9] under the name "College Admissions Problem". In particular, we consider the Firms/Candidates problem, where each Firm wishes to hire at least one Candidate and each Candidate can be finally assigned to a single Firm. We present an efficient implementation of the Gale and Shapley "propose-and-reject" algorithm when applied to the case of the Firms/Candidates problem.

Background and Aim. Degenerative Aortic Stenosis (DAS) is a common disease that causes substantial morbidity and mortality worldwide, especially in the older population. Our aim was to further investigate novel serum and tissue biomarkers to elucidate biological processes involved in this entity. Material and Methods. We evaluated the expression of six biomarkers significantly involved in cardiovascular pathology, i.e., irisin, periostin, osteoglycin, interleukin 18, high mobility group box 1 and proprotein convertase subtilisin/kexin type 9 in the serum at the protein level, and in the tissue at both the protein and mRNA levels of patients with AS (N = 60). Five normal valves obtained after transplantation from hearts of patients with idiopathic dilated cardiomyopathy were also studied. Serum measurements were also performed in 22 individuals without valvular disease who served as controls (C). Results. Higher levels of all factors were found in DAS patients’ serum than in normal C. IHC and PCR mRNA tissue analysis showed the presence of all biomarkers in the aortic valve cusps with DAS, but no trace of PCR mRNA was found in the five transplantation valves. Moreover, periostin serum levels correlated significantly with IHC and mRNA tissue levels in AS patients. Conclusion. We showed that six widely prevalent biomarkers affecting the atherosclerotic process were also involved in DAS, suggesting a strong osteogenic and pro-inflammatory profile, indicating that aortic valve calcification is a multifactorial biological process.

Ocean Acoustic Waveguide Remote Sensing (OAWRS) enables fish population density distributions to be instantaneously quantified and continuously monitored over wide areas. Returns from seafloor geology can also be received as background or clutter by OAWRS when insufficient fish populations are present in any region. Given the large spatial regions that fish inhabit and roam over, it is important to develop automatic methods for determining whether fish are present at any pixel in an OAWRS image so that their population distributions, migrations and behaviour can be efficiently analyzed and monitored in large data sets. Here, a statistically optimal automated approach for distinguishing fish from seafloor geology in OAWRS imagery is demonstrated with Neyman–Pearson hypothesis testing which provides the highest true-positive classification rate for a given false-positive rate. Multispectral OAWRS images of large herring shoals during spawning migration to Georges Bank are analyzed. Automated Neyman-Pearson hypothesis testing is shown to accurately distinguish fish from seafloor geology through their differing spectral responses at any space and time pixel in OAWRS imagery. These spectral differences are most dramatic in the vicinity of swimbladder resonances of the fish probed by OAWRS. When such significantly different spectral dependencies exist between fish and geologic scattering, the approach presented provides an instantaneous, reliable and statistically optimal means of automatically distinguishing fish from seafloor geology at any spatial pixel in wide-area OAWRS images. Employing Kullback–Leibler divergence or the relative entropy in bits from Information Theory is shown to also enable automatic discrimination of fish from seafloor by their distinct statistical scattering properties across sensing frequency, but without the statistical optimal properties of the Neyman–Pearson approach.

Abstract In differential diagnosis of posterior mediastinal mass should be included the intrathoracic vagus nerve tumor. Surgical excision of intrathoracic vagus nerve schwannoma is associated with a low recurrence rate and excellent long‐term results.

Abstract Background Restrictive cardiomyopathy is a rare cardiac disease, for which several genes including TNNT2, MYPN, FLNC and TNNI3 have been associated with its familial form. Case presentation Here we describe a female proband with a severely manifested restrictive phenotype leading to heart transplantation at the age of 41, who was found homozygous for the novel TNNI3 mutation: NM_000363.4:c.586G > C, p.(Asp196His). Her parents were third-degree cousins originating from a small village and although they were found heterozygous for the same variant they displayed no symptoms of the disease. Her older sister who was also found heterozygous was asymptomatic. Her twin sister and her brother who were homozygous for the same variant displayed a restrictive and a hypertrophic phenotype, respectively. Their children are all carriers of the mutation and remain asymptomatic until the age of 21. Conclusion These observations point to a recessive mode of inheritance reported for the first time for this combination of gene/disease.

Abstract Background Primary cardiac lymphomas (PCL) represent extremely rare cardiac tumors which are accompanied by poor prognosis, unless they are timely diagnosed and treated. Case presentation Herein we present a 28-year-old, immunocompetent man who presented to our hospital due to progressively worsening symptoms and signs of superior vena cava syndrome. Multi-modality imaging demonstrated a large intracardiac tumor, which was proven, by biopsy, to be a PCL. The patient received targeted chemotherapy which led to total remission of his disease, with no relapse over a 15-month follow-up period. Conclusions Although PCLs are rare, they should always be kept in mind in the differential diagnosis of cardiac tumors. Timely diagnosis of PCLs and appropriate chemotherapy, alone or in combination with radiotherapy, seems to provide the best results.

Spectroscopic reflectance is a versatile optical methodology for the characterization of transparent and semi-transparent thin films in terms of thickness and refractive index. The Fresnel equations are used to interpret the measurements, but their accuracy is limited when surface roughness is present. Nanoroughness can be modelled through a discretized multi-slice and effective medium approach, but to date, this offered mostly qualitative and not quantitative accuracy. Here we introduce an adaptive and nonlocal effective medium approach, which considers the relative size and environment of each discretized slice. We develop our model using finite-difference time-domain simulation results and demonstrate its ability to predict nanoroughness size and shape with relative errors < 3% in a variety of test systems. The accuracy of the model is directly compared to the prediction capabilities of the Bruggeman and Maxwell–Garnett models, highlighting its superiority. Our model is fully parametrized and ready to use for exploring the effects of roughness on reflectance without the need for costly 3D simulations and to be integrated into the Fresnel simulator of spectroscopic reflectance tools.

Late-onset Adamantiades-Behçet's disease (ABD) is a rare inflammatory condition that primarily affects males and has similar clinical features to early-onset ABD. This study compared the prevalence and characteristics of late-onset ABD with early-onset ABD through a systematic review and meta-analysis. The findings showed that late-onset ABD is less common and associated with milder symptoms, such as recurrent oral and genital ulcers, ocular lesions, and a positive pathergy test. Late-onset ABD also has lower rates of vessel involvement. Overall, late-onset ABD may occur predominantly in males and have a milder course compared to early-onset ABD. [Extracted from the article]

Behçet’s disease is a chronic, recurrent, inflammatory disorder characterized by orogenital ulcers and skin lesions; serious manifestations also include ocular, large vessel, gastrointestinal and neurological involvement. Genetic and unknown environmental factors modify the wide clinical spectrum of the disease. During the long clinical course of the disease, testicular and epididymal involvement has been reported, with scrotal pain and swelling being the most common symptoms. In this review, we discuss the various aspects of epididymo-orchitis in Behcet’s disease patients, and we evaluate the diagnostic approaches as well as the empirical therapeutic modalities of this entity.

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease, which affects a wide variety of organs including the spleen. Splenic involvement in SLE includes conditions such as splenomegaly, hyposplenism, infarction, and spontaneous rupture. However, only a few cases of splenic calcifications in patients with SLE have been reported. Herein, we present a case of a 24-year-old female diagnosed with SLE, in which we found diffuse splenic calcifications. The unique pattern of splenic calcifications in SLE contributes to the differential diagnosis from other conditions such as infections and other connective tissue diseases, which also cause calcifications in the spleen.