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Sequence variants in Eyes Shut Homolog (EYS) gene are one of the most frequent causes of autosomal recessive retinitis pigmentosa (RP). Herein, we describe an Italian RP family characterized by EYS-related pseudodominant inheritance. The female proband, her brother, and both her sons showed typical RP, with diminished or non-recordable full-field electroretinogram, narrowing of visual field, and variable losses of central vision. To investigate this apparently autosomal dominant pedigree, next generation sequencing (NGS) of a custom panel of RP-related genes was performed, further enhanced by bioinformatic detection of copy-number variations (CNVs). Unexpectedly, all patients had a compound heterozygosity involving two known pathogenic EYS variants i.e., the exon 33 frameshift mutation c.6714delT and the exon 29 deletion c.(5927þ1_5928-1)_(6078þ1_6079-1)del, with the exception of the youngest son who was homozygous for the above-detailed frameshift mutation. No pathologic eye conditions were instead observed in the proband’s husband, who was a heterozygous healthy carrier of the same c.6714delT variant in exon 33 of EYS gene. These findings provide evidence that pseudodominant pattern of inheritance can hide an autosomal recessive RP partially or totally due to CNVs, recommending CNVs study in those pedigrees which remain genetically unsolved after the completion of NGS or whole exome sequencing analysis. [ABSTRACT FROM AUTHOR]

Introduction: X-linked retinitis pigmentosa (XLRP) is a rare, incurable, vision-threatening, genetic disease. In this study, we aimed to reveal the real-world burden of this disease from the viewpoint of retina specialists and geneticists involved directly in XLRP care and to identify unique insights that may not otherwise be available through typical clinical studies or health economic research. Methods: In this exploratory, cross-sectional study (EXPLORE XLRP-1), retina specialists (n = 20) and geneticists (n = 5) in France, Germany, Italy, Spain, and the UK provided anonymized insights on their experiences managing patients with XLRP (n = 80) via an online survey and 60-min telephone interview. Results: Survey respondents reported that patient independence decreased over time, where 37% of patients were considered "completely autonomous" at diagnosis versus 23% at the last consultation. At their last visit, 45% of patients were active in the workforce; 67% (12/18) of "completely autonomous" patients had active working status compared with 13% (1/8) of "completely dependent" patients. The average time from onset of symptoms to diagnosis was 4 years and varied among countries. In 78% of patients, XLRP was confirmed by genetic testing, the rate of which varied among countries (range, 50–94%), taking up to 6 months to receive results. Specialists identified unmet needs in XLRP management including more standardized assessments of quality of life (QoL) as well as easier and earlier access to specialists, genetic testing, patient support programs, and effective treatment options. Conclusions: The diagnosis, genetic testing, and management pathways among patients with XLRP can vary considerably. There is a need for more standardized diagnosis and management pathways, and QoL assessments, due to the major impact that XLRP has on patients' lives. [ABSTRACT FROM AUTHOR]

A study conducted in Italy evaluated the feasibility of expanding the services offered by local pharmacies to include screening for dry eye disease (DED). The study collected data from over 8,000 individuals who participated in a nationwide screening initiative. The results showed that a significant number of patients with dry eye symptoms were dispensed with tear substitutes for symptomatic treatment. Female sex, Asian ethnicity, and the degree of meibomian gland loss were found to be associated with dry eye symptoms. The study suggests that pharmacy-based screening programs could improve access to rapid diagnostic testing and optimize therapy for DED. However, further research is needed to evaluate the efficacy and cost-effectiveness of these programs. [Extracted from the article]

Localized prostate cancer is a very heterogeneous disease, from both a clinical and a biological/biochemical point of view, which makes the task of producing stratifications of patients into risk classes remarkably challenging. In particular, it is important an early detection and discrimination of the indolent forms of the disease, from the aggressive ones, requiring post-surgery closer surveillance and timely treatment decisions. This work extends a recently developed supervised machine learning (ML) technique, called coherent voting networks (CVN) by incorporating a novel model-selection technique to counter the danger of model overfitting. For the challenging problem of discriminating between indolent and aggressive types of localized prostate cancer, accurate prognostic prediction of post-surgery progression-free survival with a granularity within a year is attained, improving accuracy with respect to the current state of the art. The development of novel ML techniques tailored to the problem of combining multi-omics and clinical prognostic biomarkers is a promising new line of attack for sharpening the capability to diversify and personalize cancer patient treatments. The proposed approach allows a finer post-surgery stratification of patients within the clinical high-risk category, with a potential impact on the surveillance regime and the timing of treatment decisions, complementing existing prognostic methods. [ABSTRACT FROM AUTHOR]

Introduction: To analyze outcomes on objective ocular surface parameters and subjective symptoms of serial weekly sessions using the Activa mask in patients with meibomian gland dysfunction (MGD). Methods: This is a prospective study including patients with symptomatic MGD who were treated with four weekly sessions using the Activa mask (SBM Sistemi, Turin, Italy). Noninvasive ocular surface examination was carried out before (T0) and 2 weeks after the last mask session (T1) using Idra (SBM Sistemi, Turin, Italy) for the measurement of: (1) noninvasive break-up time (NIBUT); (2) lipid layer thickness (LLT); (3) tear meniscus height (TMH); (4) meibomian gland loss (MGL) of upper and lower eyelids. The I-Pen tear osmolarity system (I-Med Pharma Inc, Dollard-des Ormeaux, Quebec, Canada) was used to measure tear osmolarity values. Ocular discomfort symptoms were ascertained by means of the ocular surface disease index (OSDI) questionnaire. Results: All 25 patients (11 males, 14 females; mean age 57.1 ± 11.9 years) regularly completed the cycle of four mask sessions. No patients used prohibited medications, and no device-related adverse events were noted. At T1, mean values of NIBUT and LLT increased significantly compared to T0 (respectively from 6.0 ± 1.4 to 6.6 ± 1.2 s, P = 0.043, and from 53.2 ± 17.4 to 65.3 ± 16.3 nm, P < 0.001), while mean values of MGL and tear osmolarity decreased significantly (respectively from 17.1 ± 9.3 to 15.1 ± 8.0%, P = 0.014, and from 307.3 ± 12.2 to 301.5 ± 6.8 mOsm/l, P = 0.005). In parallel, OSDI score reduced significantly from 62.4 ± 11.7 at T0 to 34.5 ± 11.2 at T1 (P < 0.001). Conclusion: Weekly serial sessions using the Activa mask significantly improved objective parameters of the ocular surface as well as subjective ocular discomfort symptoms in patients with recalcitrant MGD. As a further benefit from the treatment, patients were able to avoid the use of concomitant medications, apart from tear substitutes, throughout the study. [ABSTRACT FROM AUTHOR]

Purpose: The paper aims to show the monitoring results of an innovative technology, the ejectors plant, tested in the MARINAPLAN PLUS LIFE project framework for sustainable sediment management in harbours. Materials and methods: A monitoring plan has been designed to evaluate the technical, economic and environmental impact of the ejectors plant demonstrator for 15 months, located in Cervia (Italy). In particular, the demonstrator's effectiveness and efficiency have been assessed to determine the yearly operation and maintenance costs. Results and discussion: The techno-economic analysis shows promising results in terms of efficacy and efficiency of the ejectors plant. The ejectors plant guaranteed navigability for the whole period of operation with a yearly cost reduction compared with traditional dredging. Conclusions: The innovative technology promoted by the MARINAPLAN PLUS LIFE project is a promising solution to manage sedimentation in harbours through a cost-effective and a low environmental impact technology. The monitoring actions validated the technology fully and demonstrated its efficacy and sustainability, highlighting the further improvements needed. [ABSTRACT FROM AUTHOR]

To investigate whether diurnal changes in noninvasive ocular surface parameters and subjective symptoms occur in healthy subjects wearing face mask who were analyzed before and after 8 h of continuous use. In this prospective cross-sectional study, healthy volunteers attending the same workplace environment underwent a noninvasive ocular surface workup by means of Keratograph 5 M (Oculus, Wetzlar, Germany) in the same day at 2 different time points: (i) in the early morning before wearing face mask (T0); (ii) after 8 h of continuous face mask use (T1). Noninvasive break-up time (NIBUT), tear meniscus height (TMH), ocular redness and meibomian gland dropout were measured. All subjects were asked to complete the Ocular Surface Disease Index (OSDI) questionnaire before and after 8 h of face mask wearing. Data from 20 healthy subjects (10 males and 10 females, mean age 25.1 ± 3.9 years) were included. Mean value of TMH decreased significantly from 0.29 ± 0.07 at T0 to 0.23 ± 0.07 mm at T1 (P < 0.001); conversely, mean values of NIBUT, redness score and meibomian gland dropout did not change significantly after continuous face mask wearing (always P > 0.532). Concerning ocular discomfort symptoms, mean value of OSDI score worsened significantly at T1 compared to T0 (from 12.9 ± 12.6 to 19.4 ± 12.0; P = 0.017). Continuous face mask wearing for 8 h led to decreased TMH associated with the onset of ocular discomfort symptoms in young healthy subjects. [ABSTRACT FROM AUTHOR]

Computational drug repositioning aims at ranking and selecting existing drugs for novel diseases or novel use in old diseases. In silico drug screening has the potential for speeding up considerably the shortlisting of promising candidates in response to outbreaks of diseases such as COVID-19 for which no satisfactory cure has yet been found. We describe DrugMerge as a methodology for preclinical computational drug repositioning based on merging multiple drug rankings obtained with an ensemble of disease active subnetworks. DrugMerge uses differential transcriptomic data on drugs and diseases in the context of a large gene co-expression network. Experiments with four benchmark diseases demonstrate that our method detects in first position drugs in clinical use for the specified disease, in all four cases. Application of DrugMerge to COVID-19 found rankings with many drugs currently in clinical trials for COVID-19 in top positions, thus showing that DrugMerge can mimic human expert judgment. [ABSTRACT FROM AUTHOR]

For a patient affected by breast cancer, after tumor removal, it is necessary to decide which adjuvant therapy is able to prevent tumor relapse and formation of metastases. A prediction of the outcome of adjuvant therapy tailored for the patient is hard, due to the heterogeneous nature of the disease. We devised a methodology for predicting 5-years survival based on the new machine learning paradigm of coherent voting networks, with improved accuracy over state-of-the-art prediction methods. The 'coherent voting communities' metaphor provides a certificate justifying the survival prediction for an individual patient, thus facilitating its acceptability in practice, in the vein of explainable Artificial Intelligence. The method we propose is quite flexible and applicable to other types of cancer. [ABSTRACT FROM AUTHOR]

Ultrasound cyclo plasty (UCP) is a recently developed surgical technique for glaucoma allowing a selective and controlled coagulation of the ciliary body. We herein investigated the long-term efficacy and safety of UCP for the treatment of glaucoma. This prospective study included patients with primary and secondary glaucoma. All surgeries were performed using the EyeOP1 device (Eye Tech Care, Rillieux-la-Pape, France). Sixty-six patients were included, and 60 completed regularly the 2-year follow-up. Preoperative IOP was 28.5 ± 9.6 mmHg and significantly decreased to 17.0 ± 5.4 at 2 years (p < 0.001). The daily number of both hypotensive eye drops and acetazolamide tablets decreased significantly (respectively, from 2.6 ± 1.1 to 1.7 ± 1.2 and from 0.7 ± 0.8 to 0.2 ± 0.5; both p < 0.001). At 2 years, 68.1% of patients met the definition of qualified success (IOP < 21 mmHg regardless of glaucoma medications) and 10.3% of patients met the definition of complete success (IOP < 21 mmHg without glaucoma medications). No major intra- or postoperative complications occurred; however, 15 eyes required additional glaucoma surgery. These results suggest that UCP is an effective and safe procedure to reduce IOP in glaucoma patients through a 2-year follow-up period. [ABSTRACT FROM AUTHOR]

Summary: The recircumscription and updated synopsis of Thyrsanthemum, together with a synopsis of Weldenia, are presented, with three new combinations, four new lectotypes, an identification key, and comments, distribution maps, and illustrations for all accepted species. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to evaluate choroidal vascular changes in patients with neovascular age-related macular degeneration (nAMD) treated with aflibercept injection over a 3-month period. Methods: Enhanced depth imaging optical coherence tomography scans of 60 eyes with treatment-naïve nAMD and 60 unaffected fellow eyes were retrospectively analyzed. Data was collected at baseline and after 3 monthly intravitreal injections of aflibercept. The ImageJ software was used to binarize OCT scans and measure total choroid area (TCA), luminal area (LA), and stromal area (SA). Choroidal vascularity index (CVI) was defined as the ratio of LA to TCA. Results: After treatment, subfoveal choroidal thickness (CT) in nAMD eyes significantly decreased from 210. 6 ± 61.6 to 194.6 ± 58.7 μm (P < 0.001), TCA from 1.620 ± 0.502 to 1.500 ± 0.451 mm2 (P < 0.001), LA from 1.075 ± 0.335 to 0.985 ± 0.307 mm2 (P < 0.001), SA from 0.545 ± 0.176 to 0.516 ± 0.153 mm2 (P = 0.005), and CVI from 66.36 ± 2.89 to 65.46 ± 2.87% (P = 0.009). The decrease of CVI after treatment was significantly correlated with baseline CVI (Rs = 0.466, P < 0.001), but not with the change in BCVA and presence of dry macula after treatment (always P > 0.05). Conclusion: Choroidal thickness and vascularity significantly decreased after treatment with aflibercept in nAMD eyes. Besides the pharmacologic effect on the neovascular lesion, aflibercept may induce vascular changes also on the underlying choroid. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the correlation between postoperative corneal astigmatism (PCA) and values of intraoperative keratoscopy analyzed with a newly developed automated technique in patients undergoing big-bubble (BB) deep anterior lamellar keratoplasty (DALK). Methods: Photographs of keratoscope rings taken at the end of BB-DALK were analyzed using ImageJ for the calculation of "roundness" (R): values = 1 indicate a perfect circle. Pearson's correlation was used to evaluate the relationship between R and PCA that measured 1 week (V1), 3 months (V2), and 18 months (V3), postoperatively. The area under the curve (AUC) of receiver operating characteristic (ROC) curve was used to evaluate the accuracy of R for identifying patients with PCA < 3 diopters (D). The point on the ROC curve nearest to the coordinate (0,100) was used as a cutoff to determine sensitivity and specificity. Results: Data from 121 patients were included. The mean value of R*was 0.93 ± 0.04 (range 0.76–0.99). R showed a significant correlation with PA at V3 (R = − 0.42, P < 0.01). The ROC curve had an AUC of 0.69 (95% CI 0.59–0.79). A cutoff value of R = 0.93 had a sensitivity of 70.3% and specificity of 61.0% for identifying patients with PA < 3D at V3. Conclusions: This new digital analysis of keratoscope rings allows to identify with reasonably good diagnostic accuracy patients with low values of post-DALK astigmatism correctable with spectacles. [ABSTRACT FROM AUTHOR]

Genes are organized in functional modules (or pathways), thus their action and their dysregulation in diseases may be better understood by the identification of the modules most affected by the disease (aka disease modules, or active subnetworks). We describe how an algorithm based on the Core&Peel method is used to detect disease modules in co-expression networks of genes. We first validate Core&Peel for the general task of functional module detection by comparison with 42 methods participating in the Disease Module Identification DREAM challenge. Next, we use four specific disease test cases (colorectal cancer, prostate cancer, asthma, and rheumatoid arthritis), four state-of-the-art algorithms (ModuleDiscoverer, Degas, KeyPathwayMiner, and ClustEx), and several pathway databases to validate the proposed algorithm. Core&Peel is the only method able to find significant associations of the predicted disease module with known validated relevant pathways for all four diseases. Moreover, for the two cancer datasets, Core&Peel detects further eight relevant pathways not discovered by the other methods used in the comparative analysis. Finally, we apply Core&Peel and other methods to explore the transcriptional response of human cells to SARS-CoV-2 infection, finding supporting evidence for drug repositioning efforts at a pre-clinical level. [ABSTRACT FROM AUTHOR]

To dissect the TBX5 regulatory circuit, we focused on microRNAs (miRNAs) that collectively contribute to make TBX5 a pivotal cardiac regulator. We profiled miRNAs in hearts isolated from wild-type, CRE, Tbx5lox/+and Tbx5del/+ mice using a Next Generation Sequencing (NGS) approach. TBX5 deficiency in cardiomyocytes increased the expression of the miR-183 cluster family that is controlled by Kruppel-like factor 4, a transcription factor repressed by TBX5. MiR-182-5p, the most highly expressed miRNA of this family, was functionally analyzed in zebrafish. Transient overexpression of miR-182-5p affected heart morphology, calcium handling and the onset of arrhythmias as detected by ECG tracings. Accordingly, several calcium channel proteins identified as putative miR-182-5p targets were downregulated in miR-182-5p overexpressing hearts. In stable zebrafish transgenic lines, we demonstrated that selective miRNA-182-5p upregulation contributes to arrhythmias. Moreover, cardiac-specific down-regulation of miR-182-5p rescued cardiac defects in a zebrafish model of Holt–Oram syndrome. In conclusion, miR-182-5p exerts an evolutionarily conserved role as a TBX5 effector in the onset of cardiac propensity for arrhythmia, and constitutes a relevant target for mediating the relationship between TBX5, arrhythmia and heart development. [ABSTRACT FROM AUTHOR]

Background: To report the first two cases of sterile corneal perforation secondary to vitamin A deficiency after biliopancreatic diversion with duodenal switch (BPD/SW). Methods: Observational case series. Results: Two patients with a history of BPD/SW presented with corneal perforation associated with conjunctival xerosis and keratopathy. In both cases, serum vitamin A level dosage revealed a marked deficit, and the patients admitted poor compliance with vitamin supplementation. Oral therapy with vitamin A was started immediately, and in one case ocular surgery was performed to preserve the integrity of the globe. Conclusions: Ophthalmologists should carefully examine the ocular surface of patients undergone bariatric surgery in order to promptly recognize the signs of vitamin A deficiency and avoid serious sight-threatening complications. [ABSTRACT FROM AUTHOR]

Purpose: The paper aims to show the preliminary monitoring and field test results of the innovative technology tested in the framework of the MARINAPLAN PLUS LIFE project for sustainable management of sediment in harbour areas. The technology is based on a patented jet pump that will be able to keep the seabed at a certain level over the time through a continuous removal of silting sediments. Materials and methods: Preliminary field tests were performed to optimise the design of the demo plant and a monitoring plan was devised to evaluate the technical, economic and environmental impacts of the technology, in particular in comparison with dredging. Results and discussion: The preliminary tests showed promising results in terms of efficacy and efficiency of the sediment by-passing device. At the maximum sediment removal capacity, the ejector tested in Cervia showed a sediment flow rate of about 2 m3 h−1, with an electric consumption of about 3.5 kW, and an influence diameter of about 5–7 m, after 15 days of working operation. On the basis of the preliminary results, a 10-ejector demonstrator plant has been designed and realised, and it is now in operation. The analysis of sediment and marine flora and fauna in the installation area in comparison with control areas indicates the negative impact of cyclic dredging in the harbour inlet area. Conclusions: The innovative technology promoted by the MARINAPLAN PLUS LIFE project is a promising solution to manage sediment siltation in harbour areas through a cost-effective and low environmental impact technology. The monitoring of the demo plant operation is fundamental to fully validate the technology and to demonstrate its efficacy and sustainability. [ABSTRACT FROM AUTHOR]

Human pluripotent stem cells (hPSCs) have the capacity to give rise to all differentiated cells of the adult. TGF-beta is used routinely for expansion of conventional hPSCs as flat epithelial colonies expressing the transcription factors POU5F1/OCT4, NANOG, SOX2. Here we report a global analysis of the transcriptional programme controlled by TGF-beta followed by an unbiased gain-of-function screening in multiple hPSC lines to identify factors mediating TGF-beta activity. We identify a quartet of transcriptional regulators promoting hPSC self-renewal including ZNF398, a human-specific mediator of pluripotency and epithelial character in hPSCs. Mechanistically, ZNF398 binds active promoters and enhancers together with SMAD3 and the histone acetyltransferase EP300, enabling transcription of TGF-beta targets. In the context of somatic cell reprogramming, inhibition of ZNF398 abolishes activation of pluripotency and epithelial genes and colony formation. Our findings have clear implications for the generation of bona fide hPSCs for regenerative medicine. The downstream pathway regulating how TGF-beta affects pluripotency of human PSCs is unclear. Here, the authors find that transcription factor ZNF398 binds active promoters/enhancers together with the histone acetyltransferase EP300 and SMAD3, enabling expression of pluripotency and epithelial genes. [ABSTRACT FROM AUTHOR]

Centrifugal pumps are widely used in industry and their damage can cause time losses and production and service level reduction. Due to varying operating conditions, preventive maintenance is the typical strategy to avoid unexpected failures of pumps, but it may involve unnecessary interventions and costs. The paper aims to develop and apply a Condition-Based Maintenance (CBM) procedure on centrifugal pumps to assist decision-making in scheduling maintenance. Through the monitoring of pump state, it would be possible to plan an optimal scheduling of maintenance actions in terms of time, costs and spare parts procurement. The proposed procedure is based on vibration monitoring. Instrumentation, measurement locations, acquisition parameters and pump operating conditions were defined, according to ISO 10816-7 (2009). The method was previously developed for submersible well pumps and now is applied to horizontal and vertical surface centrifugal pumps. Several vibration tests were carried on centrifugal pumps in the plants of the Italian utility Company: Publiacqua S.p.A. (Italy). Pumps under study were selected with varying size and operation time to provide the vibration trend with pump characteristics and operating time, that is a novelty in literature and in practical application. Contrary to what expected by ISO 10816-7 (2009), the paper shows that vibration is influenced by several parameters (e.g. power, pump orientation and rotational speed), which make the ISO standard approach not quite appropriate for centrifugal pumps. As in the proposed method, monitoring the vibrational trend and its variations with time could ensure a more effective CBM strategy. [ABSTRACT FROM AUTHOR]

Purpose: Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cells transplantation, occurring in about half of transplanted patients. This condition seems to be the result of a progressive immune-mediated damage that can involve various tissues, including the eyes. The ocular surface system is the ocular structure most frequently impaired, and dry eye disease is considered the hallmark of ocular GVHD. Given the increasing prevalence and the frequent severe involvement of the ocular surface with vision-threatening complications, ocular GVHD represents a current diagnostic and therapeutic challenge. The purpose of this literature review is to describe all the clinical manifestations occurring in the setting of ocular GVHD, and to further report the outcomes of conventional and novel therapies. Methods: A literature search about ocular GVHD was performed in PubMed, Scopus, Medline databases, and ClinicalTrials.gov as well as through the reference lists of identified publications until January 2019. We have included RCTs, prospective observational studies, prospective and retrospective cohort studies, pilot studies, and review articles. Results: Overall, 107 articles, 3 book chapters, and 6 ongoing registered clinical trials were collected and analyzed. Ocular GVHD can affect all the structures of the entire ocular surface system, including lacrimal and meibomian glands, cornea, conjunctiva, eyelids, nasolacrimal duct, and tears. Current medical treatment is mainly focused on lubrication and control of drainage, tear evaporation, and ocular surface inflammation. Surgical treatment may be necessary in severe, recalcitrant, or complicated cases. Amniotic membrane and tectonic keratoplasty can be valid options to restore the integrity of the cornea. Recently, conjunctival and limbal transplantation from the same living-related bone marrow donor has been proposed to manage both dry eye and limbal stem cell deficiency, without any risk of immunologic rejection. Conclusion: This review provides an up-to-date analysis on clinical findings and current and future management of ocular GVHD. A correct and prompt diagnosis along with an appropriate and aggressive treatment are fundamental for avoiding the occurrence of vision-threatening complications. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate in vivo confocal microscopy (IVCM) features of corneal subbasal nerve plexus (SNP) in the setting of dry eye disease (DED) using fully automated software "ACCMetrics," and to further investigate its diagnostic performance in discriminating DED patients.Methods: IVCM exams of SNP in DED patients and matched control subjects were performed using Heidelberg Retina Tomograph with the Rostock Cornea Module. The following parameters were obtained with ACCMetrics: corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), corneal nerve total branch density (CTBD), corneal nerve fiber area (CNFA), corneal nerve fiber width (CNFW), and corneal nerve fractal dimension (CNFrD). The Mann-Whitney U test was used to compare variables. Receiver operating characteristic curves with calculations of the area under the curve (AUC) were used to describe the accuracy of IVCM parameters for discriminating DED patients from controls.Results: Thirty-nine DED patients and 30 control subjects were included. Significantly, lower values of CNFD, CNBD, and CNFL and higher value of CNFW were found in DED patients compared to controls (respectively, 20.5 ± 8.7 vs 25.4 ± 6.7 n/mm2; 25.6 ± 20.1 vs 37.6 ± 21.5 n/mm2; 12.6 ± 4.4 vs 14.5 ± 2.9 mm/mm2; 0.021 ± 0.001 vs 0.019 ± 0.001 mm/mm2; always p < 0.024). CNFW value had the highest diagnostic power in discriminating DED patients (AUC = 0.828). When the diagnosis of DED was made based on either CNFW or CNBD, the sensitivity was 97.4% and the specificity 46.7%.Conclusions: The software ACCMetrics was able to rapidly detect SNP alterations occurring in the setting of DED and showed good diagnostic performance in discriminating DED patients. [ABSTRACT FROM AUTHOR]

A generalization of the Oberwolfach problem, proposed by Liu (J Comb Des 8:42-49, 2000), asks for a uniform 2-factorization of the complete multipartite graph Km×n. Here we focus our attention on cyclic 2-factorizations, whose 2-factors are disjoint union of cycles all of even length ℓ. In particular, we present a complete solution for the extremal cases ℓ=4 and ℓ=mn. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate functional prognostic factors and neuroretinal changes after anti-vascular endothelial growth factor (VEGF) treatment in patients with naïve, recent myopic neovascularization (mCNV), as assessed by spectral-domain optical coherence tomography (SD-OCT). Methods: Specific changes in tomographic features between baseline and final follow-up were retrospectively evaluated by two examiners independently. Imaging was obtained by a multi-modal imaging system which combines fluorescein angiography and SD-OCT. Results: Twenty-two eyes (male, six; female, 16; mean age, 65 ± 14 years) were considered. Mean follow-up was 21.5 ± 14 months. Best-corrected visual acuity (BCVA) improved from 0.38 ± 0.26 to 0.16 ± 0.20 logMAR ( p < 0.001). The ellipsoid zone and the external limiting membrane (ELM) were disrupted in 21 (95.5%) and 15 (68.2%) eyes at baseline, and in 16 (72.7%) and nine (40.9%) eyes after therapy respectively. The ellipsoid zone and ELM were typically intact at lesion margins in 13 (59.1%) and 19 eyes (86.5%) respectively at baseline. The inner retina was intact in 20 eyes (91%). Six eyes (27.3%) exhibited complete regression without fibrosis. Absence of hemorrhage and integrity of lesion-adjacent ELM and of lesion-adjacent ellipsoid zone at baseline were factors for better final BCVA ( p ≤ 0.05) Conclusion: Vision gain might occur despite ellipsoid zone or ELM restoration. Hemorrhage could be considered a negative prognostic factor, integrity of lesion-adjacent ELM and of lesion-adjacent ellipsoid zone as positive prognostic factors. Myopic CNV can also resolve completely without fibrosis. [ABSTRACT FROM AUTHOR]

Background: To evaluate macular changes in fellow eyes of patients diagnosed with lamellar macular hole (LMH) using spectral-domain optical coherence tomography (SD-OCT) and blue fundus autofluorescence (B-FAF). Methods: Fellow eyes of patients diagnosed with a LMH were retrospectively evaluated on OCT. Best-corrected visual acuity (BCVA) and central foveal thickness (CFT) were recorded. Corresponding B-FAF images, vitreo-macular relations, and type of epiretinal membranes (ERMs) were also examined. Results: Thirty-five patients were included. At baseline, six fellow eyes (17%) showed a normal foveal profile, 26 (74%) had a tractional ERM, and three cases (9%) revealed a bilateral LMH, one of them with a lamellar hole-associated epiretinal proliferation (LHEP). A posterior vitreous detachment (PVD) was present in 29 patients (83%), four (11%) had only a vitreo-papillary adhesion (VPA), and two (6%) had both vitreo-macular adhesion (VMA) and VPA. After a mean follow-up of 4.6 ± 1.9 years, one eye (3%) developed a vitreous detachment from the macula with persistent VPA, and one developed a PVD from a VPA with subsequent ERM formation. BCVA and mean CFT remained stable in 35 eyes (100%). Likewise, no B-FAF signal variations were detected. One patient developed a LMH during the 3rd year of follow-up. Conclusions: Our data suggest that the presence of a LMH in one eye does not increase significantly the risk of developing the same condition in the fellow eye after 4 years. Bilateral condition is uncommon, and an ERM is often detected in the fellow eye. LHEPs were not observed in fellow eyes with foveal integrity, and all LHEPs observed (in main and fellow eyes) were always associated with LMHs; this supports the hypothesis that LHEP is a consequence and not a causative factor for LMHs. The occurrence of a LMH in one fellow eye after 3 years follow-up may suggest that a higher incidence of bilateral disease could develop in a longer time span. [ABSTRACT FROM AUTHOR]

Human epithelial growth factor receptor 2 (HER2) overexpression and/or amplification is of predictive and prognostic value in infiltrating breast carcinoma (IBC). We evaluated the proportion of HER2-positive cases (score 3 overexpression/score 2 plus fluorescence in situ hybridization (FISH) amplification) in a consecutive series of 2163 patients. According to immunohistochemical analysis of HER2 expression, using Herceptest and FDA criteria, 839 cases had score 0, 476 score 1+, 699 score 2+, and 149 score 3+. Of the 699 scoring 2+ cases, 160 (22.88 %) showed Her2 gene amplification by FISH analysis, making a total of 309 (14.28 %) HER2-positive cases. Grade 1 ductal and special type IBC were never HER2 positive, while only three infiltrating lobular carcinomas but a relevant percentage of small IBC were HER2 positive. Of HER2-positive cases, 52.1 % was pT1 and of these, 38.5 % was pT1b or smaller. Logistic regression analysis revealed that estrogen receptor (ER), progesterone receptor (PgR), grade, and pT were significantly associated with HER2 positivity and that HER2 3+ cases were more frequently of higher grade and pT than HER2 2+/Her2 amplified cases. In addition, HER2 3+ cases were more frequently in ER and PgR negative than HER2 2+/Her2 amplified cases. We conclude that the proportion of HER2 positive cases is lower than that reported in older literature and that pathological characteristics differ between HER2 3+ and HER2 2+/Her2 amplified cases. [ABSTRACT FROM AUTHOR]

Mariusz Meszka has conjectured that given a prime $$p=2n+1$$ and a list $$L$$ containing $$n$$ positive integers not exceeding $$n$$ there exists a near $$1$$ -factor in $$K_p$$ whose list of edge-lengths is $$L$$ . In this paper we propose a generalization of this problem to the case in which $$p$$ is an odd integer not necessarily prime. In particular, we give a necessary condition for the existence of such a near $$1$$ -factor for any odd integer $$p$$ . We show that this condition is also sufficient for any list $$L$$ whose underlying set $$S$$ has size $$1$$ , $$2$$ , or $$n$$ . Then we prove that the conjecture is true if $$S=\{1,2,t\}$$ for any positive integer $$t$$ not coprime with the order $$p$$ of the complete graph. Also, we give partial results when $$t$$ and $$p$$ are coprime. Finally, we present a complete solution for $$t\le 11$$ . [ABSTRACT FROM AUTHOR]

Objectives: To compare breast density (BD) assessment provided by an automated BD evaluator (ABDE) with that provided by a panel of experienced breast radiologists, on a multivendor dataset.Methods: Twenty-one radiologists assessed 613 screening/diagnostic digital mammograms from nine centers and six different vendors, using the BI-RADS a, b, c, and d density classification. The same mammograms were also evaluated by an ABDE providing the ratio between fibroglandular and total breast area on a continuous scale and, automatically, the BI-RADS score. A panel majority report (PMR) was used as reference standard. Agreement (κ) and accuracy (proportion of cases correctly classified) were calculated for binary (BI-RADS a-b versus c-d) and 4-class classification.Results: While the agreement of individual radiologists with the PMR ranged from κ = 0.483 to κ = 0.885, the ABDE correctly classified 563/613 mammograms (92 %). A substantial agreement for binary classification was found for individual reader pairs (κ = 0.620, standard deviation [SD] = 0.140), individual versus PMR (κ = 0.736, SD = 0.117), and individual versus ABDE (κ = 0.674, SD = 0.095). Agreement between ABDE and PMR was almost perfect (κ = 0.831).Conclusions: The ABDE showed an almost perfect agreement with a 21-radiologist panel in binary BD classification on a multivendor dataset, earning a chance as a reproducible alternative to visual evaluation.Key Points: Individual BD assessment differs from PMR with κ as low as 0.483. An ABDE correctly classified 92 % of mammograms with almost perfect agreement (κ = 0.831). An ABDE can be a valid alternative to subjective BD assessment. [ABSTRACT FROM AUTHOR]

Let G be an adjoint finite group of Lie type. In this paper we classify the irreducible characters of G which appear with multiplicity 1 in any Gelfand-Graev character of G. Except for groups of type A and G, this property identifies the Steinberg character of G (modulo linear characters). [ABSTRACT FROM AUTHOR]

Intravenous loop diuretics are still the cornerstone of therapy in acute decompensated heart failure, however, the optimal dosage and administration strategies remain poorly defined particularly in patients with an associated renal dysfunction. This is a single-center, pilot, randomized trial involving patients with acute HF and renal dysfunction. Patients were assigned to receive continuous furosemide infusion (cIV) or bolus injections of furosemide (iIV). Primary end points were the evaluation of urine output volumes, renal function, and b-type natriuretic peptide (BNP) levels during treatment time. Secondary end point included: weight loss, length of hospitalization, differences in plasma electrolytes, need for additional treatment, and evaluation of cardiac events during follow-up period. 57 patients were included in the study. The cIV group showed an increase in urine output (2,505 ± 796 vs 2140 ± 468 ml/day, p < 0.04) and a more significant decrease of BNP levels in respect to the iIV group (679.6 ± 397 vs 949 ± 548 pg/ml, p < 0.04). We observed a significant increase in creatinine levels (1.78 ± 0.5 vs 1.41 ± 0.3 mg/dl, p < 0.01), and a reduction of the estimated glomerular filtration rate in cIV (44.8 ± 6.1 vs 46.7 ± 6.1 ml/min, p < 0.05). We observed a significant difference in eGFR ( p = 0.01), creatinine ( p = 0.02) and BNP levels ( p = 0.03) from baseline to the end of treatment in both groups. A significant increase of in-hospital additional treatment as well as length of hospitalization was observed in cIV. Finally, cIV revealed a higher rate of adverse events during the follow-up period ( p < 0.03). cIV appears to provide a more efficient diuresis and BNP level reduction during hospitalization, however, it was associated with increased rate of worsening renal function during hospitalization. cIV also appears related to a longer hospitalization and an increased number of adverse events during follow-up. For all of these reasons, a larger multi-center study is required to determine whether high-dose diuretics are responsible for worsening renal function and to define the best modality of administration. [ABSTRACT FROM AUTHOR]

In this paper we prove that if G is a finite exceptional simple group of Lie type, then G admits a 2-covering if, and only if, it is one of the following groups: $${G_2(2^{a}), F_4(3^{a}), G_2(2)', ^{2}G_2(3)', ^{2}F_4(2)'}$$ G 2 ( 2 a ) , F 4 ( 3 a ) , G 2 ( 2 ) ′ , 2 G 2 ( 3 ) ′ , 2 F 4 ( 2 ) ′ . Furthermore, if G is a finite sporadic simple group, then G admits a 2-covering if, and only if, G = M 11. [ABSTRACT FROM AUTHOR]

We show that every element of PSL(2, q) is a commutator of elements of coprime orders. This is proved by showing first that in PSL(2, q) any two involutions are conjugate by an element of odd order. [ABSTRACT FROM AUTHOR]

There is limited evidence on the role of 3D mammography with tomosynthesis in breast screening, although early studies suggest that it may improve specificity. We prospectively evaluated the effect of integrating 3D mammography as a triage to assessment in 158 consecutive recalls to assessment (recalled in standard 2D-mammographic screening) in asymptomatic subjects. Radiologists provided 3D mammography-based opinion as to whether recall/assessment was warranted or unnecessary, and all subjects proceeded to assessment. 3D triage was positive (confirmed the need for assessment) in all 21 subjects with breast cancer (there were no false negatives), and would have avoided recall in 102 of 137 (74.4%) subjects with a negative/benign final outcome in whom 3D triage did not recommend recall. Proportion of true negative 3D triage (as a proxy for potential reduction in recalls) was slightly higher in dense than non-dense breasts, did not differ across age-groups, but was significantly associated with the type of lesion seen on imaging (being highest for distortions, asymmetric densities, and lesions with ill-defined margins). While the simulation design may have over-estimated the potential for 3D mammography triage to reduce recalls, this study clearly demonstrates its capability to improve breast screening specificity and to reduce recall rates. Future studies of 3D mammography should further assess its role as a recall-reducing strategy in screening practice and should include formal cost-analysis. [ABSTRACT FROM AUTHOR]

In this paper we determine the full character table of a certain split extension $${H_1(q)\rtimes Sp(2, q)}$$ of the Heisenberg group H 1 by the odd-characteristic symplectic group Sp(2, q). [ABSTRACT FROM AUTHOR]

An ambient air study was conducted in the city of Florence, Italy, in the summer 1996. Tropospheric ozone was continuously monitored with automatic analyzers in three stations, two located in the urban area and one in the hilly surroundings (Settignano). A biomonitoring campaign based on the tobacco cv. Bel-W3 plants was performed in the same area. The highest values were constantly recorded in the Settignano station. The highest 1-hour mean recorded was 197 nl/l; the accumulated exposure over a threshold of 40 nl/l (AOT40) was well above the critical levels standards for protection of the vegetation. A consistent temporal variation was observed and July proved to be the month with the highest ozone levels. Cumulative frequency distribution of ozone maximum daily concentrations exhibited a good fitting to log-normality. No `week-end' effect was observed. Biomonitoring data were in good agreement with chemico-physical ones. [ABSTRACT FROM AUTHOR]

The advancement of sodium-cooled fast reactors (generation IV) faces a critical challenge related to core disruptive accidents. A primary issue is the boron carbide (B4C) and stainless steel (SS) eutectic reaction, leading to premature melting and molten pool formation with boron, affecting neutron balance. This study pioneers the use of radiative heating for high-resolution visualisation and quantification of the eutectic melt composition, providing a novel approach to observing the melting and candling phenomena. Experimental investigations were conducted with B4C pellets and powder in SS hollow claddings, replicating control rods, from 1150 to 1372 °C. The eutectic temperature for B4C pellets was found to be higher than that for B4C powder and invariant with the heating rate. Key findings include two distinct failure processes: SS cladding detachment forming molten droplets and fragmentation of B4C pellets, with sintering observed in B4C powder. X-ray diffraction analysis identified boride phases B0.9Cr0.9Fe1.1, (Cr,Fe)2B, γ-Fe, (Cr,Fe)23(B,C)6, and (Cr,Fe)5B3, solidified at 48–50 °C in argon. This novel study elucidates the eutectic behaviour and boride phase formation in severe reactor conditions, providing critical insights for reactor safety. [ABSTRACT FROM AUTHOR]

Let H be a collection of n hyperplanes in ℝ, let A denote the arrangement of H, and let σ be a ( d−1)-dimensional algebraic surface of low degree, or the boundary of a convex set in ℝ. The zone of σ in A is the collection of cells of A crossed by σ. We show that the total number of faces bounding the cells of the zone of σ is O( n log n). More generally, if σ has dimension p, 0≤ p< d, this quantity is O( n) for d− p even and O( n log n) for d− p odd. These bounds are tight within a logarithmic factor. [ABSTRACT FROM AUTHOR]