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Purpose: To evaluate the visual outcomes and efficacy of astigmatism correction using a new hydrophobic trifocal toric intraocular lens (IOL). Methods: This study involved 62 eyes implanted with the FineVision HP Toric IOL. The visual and refractive outcomes were assessed preoperatively and 6 weeks after the surgery. Specifically, monocular uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity (UIVA) at 80 and 60 cm and uncorrected near visual acuity at (UNVA) at 40 cm were evaluated. The rotational stability of the lens was also assessed. Results: Sixty-one eyes (98.39%) were within ± 1.00D and 55 eyes (88.71%) were within ± 0.50 D of spherical equivalent, with a mean value of 0.09± 0.39 D. 51 (82.26%) and 61 (98.39%) eyes had a UDVA of ≥ 20/20 and ≥ 20/25, respectively, and for CDVA these values were as follows: 59 (95.16%) and 62 eyes (100%), respectively. The mean UDVA and CDVA were 0.01± 0.06 and − 0.01± 0.04logMAR, respectively. Greater than or equal to unaided 20/20 vision was achieved at 40 cm in 42 (67.74%), UIVA at 60 cm in 42 (67.74%) and 50 eyes (80.65%) at 80 cm. Those achieving ≥ 20/25 were 56 (90.32%, 40 cm), 59 (95.16%, 60 cm), and 62 eyes (100%, 80 cm). Postoperative mean values were 0.04± 0.07, 0.03± 0.07, and 0.00± 0.07logMAR for UCNVA, UIVA at 60 cm, and UIVA at 80 cm, respectively. The mean rotation of the IOL was 5.8 degrees. Conclusion: This hydrophobic trifocal toric IOL provides good refractive outcomes with excellent visual acuity across multiple distances, providing a full range of focus. [ABSTRACT FROM AUTHOR]

Background: this study aims to investigate the accuracy and completeness of ChatGPT in answering questions and solving clinical scenarios of interceptive orthodontics. Materials and Methods: ten specialized orthodontists from ten Italian postgraduate orthodontics schools developed 21 clinical open-ended questions encompassing all of the subspecialities of interceptive orthodontics and 7 comprehensive clinical cases. Questions and scenarios were inputted into ChatGPT4, and the resulting answers were evaluated by the researchers using predefined accuracy (range 1–6) and completeness (range 1–3) Likert scales. Results: For the open-ended questions, the overall median score was 4.9/6 for the accuracy and 2.4/3 for completeness. In addition, the reviewers rated the accuracy of open-ended answers as entirely correct (score 6 on Likert scale) in 40.5% of cases and completeness as entirely correct (score 3 n Likert scale) in 50.5% of cases. As for the clinical cases, the overall median score was 4.9/6 for accuracy and 2.5/3 for completeness. Overall, the reviewers rated the accuracy of clinical case answers as entirely correct in 46% of cases and the completeness of clinical case answers as entirely correct in 54.3% of cases. Conclusions: The results showed a high level of accuracy and completeness in AI responses and a great ability to solve difficult clinical cases, but the answers were not 100% accurate and complete. ChatGPT is not yet sophisticated enough to replace the intellectual work of human beings. [ABSTRACT FROM AUTHOR]

Background: The role of hormonal replacement therapy in menopause is under debate. The premature closure of the Women's Health Initiative (WHI) study in 2002 is still a source of concern among treating physicians. Objectives: The interest in alternatives to conventional hormone therapy has significantly increased. The adoption of personalized steroid hormone galenic preparations, formulated by compounding pharmacies, has recently spread. Methods: In June 2023, an extensive literature search was conducted by different authors to identify relevant studies in various databases (MEDLINE, Embase, PubMed, and Cochrane). The studies that met the inclusion and exclusion criteria were further analyzed, and relevant data were extracted and analyzed for each paper. Any discrepancies between the investigators were resolved through a consensus approach. Outcomes: The primary outcomes observed included the clinical utility of CBHT. This study reviewed the current evidence on the utility of compounded bioidentical hormones, concluding that improving knowledge and awareness of bioidentical hormones is necessary to consider their use in clinical practice. Conclusion and Outlook: These formulations might provide effective options to best tailor therapies to each patient. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease with high mortality. Liver involvement is common (based on elevated liver function tests) with most patients demonstrating acute hepatitis. Liver biopsies are frequently obtained in the setting of suspected HLH for the purpose of identification of erythrophagocytosis, and if present, this finding is thought to suggest or support the diagnosis of HLH. However, there are problems with this approach; in particular, we do not know whether this finding is reproducible or whether it is specific to HLH. Therefore, we conducted a multi-institutional study in which experienced liver pathologists reviewed images taken from liver biopsies from patients with normal liver, acute hepatitis, possible HLH, and clinical HLH to determine if there was agreement about the presence or absence of erythrophagocytosis, and to ascertain whether the finding corresponds to a clinical diagnosis of HLH. Twelve liver pathologists reviewed 141 images in isolation (i.e., no clinical information or diagnosis provided). These came from 32 patients (five normal, 17 acute hepatitis, six HLH, four possible HLH). The pathologists classified each image as negative, equivocal, or positive for erythrophagocytosis. Kappa was.08 (no agreement) for case-level and 0.1 for image-level (1.4% agreement, based on two images which were universally considered negative). There was no difference in the proportion of pathologists who diagnosed erythrophagocytosis among those with different diagnoses at case or image-level (p = 0.82 and p = 0.82, respectively). Thus, erythrophagocytosis is an entirely unreliable histologic parameter in liver, as it is irreproducible and not demonstrably associated with a clinical disease (namely, HLH). Unless and until more reliable guidelines can be established, pathologists should refrain from commenting on the presence or absence of erythrophagocytosis in liver biopsy. [ABSTRACT FROM AUTHOR]

Analysis of efforts to develop peace in Northern Ireland often attributes the foundation of the peace process to the dialogue between the then Sinn Fein president, Gerry Adams, and the Social Democratic and Labour Party's (SDLP) former leader, John Hume, in the late 1980s. However, it has been recognized that attempts to forge peace have a longer timeline, involving the interplay of several national and international historical contexts in which the European Community (EC) / European Union (EU) dimension and the role of the EU institutions in restoring peace and reconciliation has been generally neglected. The objective of this article is therefore to examine the European dimension of the Northern Ireland talks process, addressing the whole range of relationships affecting the political stalemate in the years preceding the signing of Belfast/Good Friday Agreement (GFA). Drawing on never-before-seen United Kingdom (UK) government and EC/EU archival documents and semi-structured élite interviews, this article highlights how the original dialogue on power-sharing and devolution in Northern Ireland included a much stronger EU dimension that it is publicly acknowledged. This article constitutes an emblematic case-study on the 'Europeanisation' of British politics in Northern Ireland, with findings uncovering a new and subtle dimension of the EC/EU role in the Northern Ireland peace process. [ABSTRACT FROM AUTHOR]

The NF-κB family of transcription factors and the Ras family of small GTPases are important mediators of proproliferative signaling that drives tumorigenesis and carcinogenesis. The κB-Ras proteins were previously shown to inhibit both NF-κB and Ras activation through independent mechanisms, implicating them as tumor suppressors with potentially broad relevance to human cancers. In this study, we have used two mouse models to establish the relevance of the κB-Ras proteins for tumorigenesis. Additionally, we have utilized a pan-cancer bioinformatics analysis to explore the role of the κB-Ras proteins in human cancers. Surprisingly, we find that the genes encoding κB-Ras 1 (NKIRAS1) and κB-Ras 2 (NKIRAS2) are rarely down-regulated in tumor samples with oncogenic Ras mutations. Reduced expression of human NKIRAS1 alone is associated with worse prognosis in at least four cancer types and linked to a network of genes implicated in tumorigenesis. Our findings provide direct evidence that loss of NKIRAS1 in human tumors that do not carry oncogenic RAS mutations is associated with worse clinical outcomes. [ABSTRACT FROM AUTHOR]

Paneth cells (PCs), a specialized secretory cell type in the small intestine, are increasingly recognized as having an essential role in host responses to microbiome and environmental stresses. Whether and how commensal and pathogenic microbes modify PC composition to modulate inflammation remain unclear. Using newly developed PC‐reporter mice under conventional and gnotobiotic conditions, we determined PC transcriptomic heterogeneity in response to commensal and invasive microbes at single cell level. Infection expands the pool of CD74+ PCs, whose number correlates with auto or allogeneic inflammatory disease progressions in mice. Similar correlation was found in human inflammatory disease tissues. Infection‐stimulated cytokines increase production of reactive oxygen species (ROS) and expression of a PC‐specific mucosal pentraxin (Mptx2) in activated PCs. A PC‐specific ablation of MyD88 reduced CD74+ PC population, thus ameliorating pathogen‐induced systemic disease. A similar phenotype was also observed in mice lacking Mptx2. Thus, infection stimulates expansion of a PC subset that influences disease progression. Synopsis: Changes in Paneth cell (PC) gene expression and function have been linked to various inflammatory intestinal diseases, such as Crohn's disease. Here, a single‐cell transcriptomic analysis of PC heterogeneity in mice identifies a CD74+ PC subset that is expanded upon inflammation or infection to secrete innate immune response molecules. Single‐cell transcriptome analysis reveals that PC heterogeneity can be modified by microbiota colonization in germ‐free mice.A CD74+ PC subset is expanded upon mouse infection with invasive pathogens, in mouse models of ileitis, and in inflammatory bowel disease–patient biopsies.Paneth cell‐specific ablation of MyD88 pathway dampens the expansion and secretory function of CD74+ PCs upon infection.Deletion of Mptx2, a mucosal pentraxin that is enriched in CD74+ PCs, reduces complement activation and inflammation upon infection. [ABSTRACT FROM AUTHOR]

Here we make an original, empirical contribution to debates on welfare pluralism, the mixed economies of welfare and territorial rescaling by comparing civil society approaches to tackling youth unemployment in England, Scotland and Wales. Our core finding is that academic and policy literature's frequent characterisation of the UK as a single Liberal welfare regime is based on methodological nationalism privileging state‐wide analyses. In short, a scalar fallacy pervasive in international welfare studies. In the context of the global rise of meso‐government and so‐called 'stateless nations' pressing for greater autonomy, our case‐study challenges the dominant paradigm. Our analysis shows the liberal characteristics of work‐first policy orientation and marketised civil society are concentrated in England then tempered by devolved (social) policy. Based on contrasting, left‐of‐centre and civic nationalist governing traditions, grounded in multi‐level electoral politics, we show the devolved nations taking a different approach to Westminster, partially eschewing the market and incorporating collectivism and co‐production. [ABSTRACT FROM AUTHOR]

Endocrine disorders negatively influence the ovarian function, and increasing incidence of endocrine diseases with age may have further negative effects on pregnancy rate. Prospective cohort study of 231 consecutively enrolled patients underwent IVF treatment. In patients with known endocrine disorders, the laboratory parameters were corrected before IVF treatment. One hundred sixty one patients (69.7%) had at least one known and treated endocrine disorder (study group), and 70 patients were endocrine negative (control group). Endocrine disorders diagnosed were thyroid disorders (32.5%), diminished ovarian reserve (23.8%), insulin resistance (22.5%), PCOS (15.2%), hyperprolactinaemia (13.4%), obesity (12.1%), hypogonadotropic hypogonadism (0.8%) and congenital adrenal hyperplasia (0.2%). Before the IVF treatment, systematic endocrine laboratory examinations were performed in all patients. Higher age, BMI and FSH were found in the study group, while AMH level was lower. There were no differences in LH, E2, prolactin, TSH, FT3, FT4, TT, DHEAS, androstendione, 17-OHP and SHBG level between the study and control groups. The study group had higher baseline glucose, baseline insulin, 120-min glucose and 120-min insulin level after oral glucose tolerance test. With no difference in the IVF cycles performed, pregnancy rate was lower in the study group (61.43% vs. 34.16%; p = 0.003), and this difference (p = 0.0151) remained in age-corrected rates, as well. The analyses were also performed in individual endocrinology groups. The prevalence of endocrine disorders is high in females participating in IVF programs, and they are often accompanying each other. Even after proper correction, the presence of the endocrine disorder negatively influences the pregnancy rate in IVF treatment. [ABSTRACT FROM AUTHOR]

Flame-generated soot particles from two different fuels, benzene (B) and ethylene (E), at different ageing conditions, were analysed to assess their morphological and structural features. Samples were collected at 6, 10 and 14 mm from the nozzle location. Traditional 2D transmission electron microscopy (TEM) and a novel 3D TEM were used to investigate morphology variations. High-resolution TEM (HRTEM) was used to capture structural characteristics. Samples were then placed on lacey carbon microgrids. A field emission gun TEM was used to capture images of the agglomerates. Tilt series of ±60 degrees were acquired at 1-degree steps to perform the 3D reconstruction. IMOD software and backwards projection were used to reconstruct the tomogram from the tilt series. The 2D analysis revealed that soot particles' agglomerations for both fuels change from a bundle to a chain-like structure as they "age", i.e., extracted at a higher "flame height". In B, the primary particle diameter increases as they get "older," whereas in E, the opposite happens, and overall, E particles are bigger than B ones. The nanostructure presents ordered regions with parallel-stacked layers of carbon lamellae. This is more evident in the aged soot samples, with the difference that in E a thick amorphous layer is present at the edge of the particles, which is not observable for B. A nanostructure analysis suggests a trend of increasing fringes length as the soot ages, going from 1.04 nm of B6 to 1.22 nm of B10 to 1.05 nm of B14 and from 1.139 nm of E6 to 1.20 nm of E14 (±0.02 nm). The tortuosity does not vary greatly across all the samples, ranging between 1.132 and 1.149 (±0.004). Separation is also quite similar everywhere, with 0.404 nm of B6, 0.392 nm of B10, 0.399 nm of B14, 0.397 nm of E6 and 0.396 nm of E14 (±0.002 nm). Ring structures and particle overlaps, two examples of geometrical characteristics concealed in 2D, can be seen in the 3D reconstructions. Furthermore, the comparison between 3D and 2D volume and surface area raises questions about the reliability of those parameters as derived from 2D measurements. This study advances knowledge of how soot structure can be affected by the fuel type and emphasises the significance of how soot is investigated. [ABSTRACT FROM AUTHOR]

Purpose: To translate, adapt and validate the Endometriosis Health Profile-5 (EHP-5) in Croatian population. Methods: This validation study is a part of a prospective, observational study (EHP-5 CRO) with aim of implementation of EHP-5 and to provide better insight in quality of life consideration of women with endometriosis in Croatian clinical practice. A 150 consecutive patients with surgically proven endometriosis were enrolled. The translation to Croatian followed standardized procedure. Cronbach's Alpha was calculated to calculate internal consistency reliability of EHP-5. The test–retest reliability was calculated using intraclass correlation coefficient (ICC). The t test for independent samples was used to assess known-groups validity. Results: Both EHP-5 core and EHP-5 modular parts of the questionnaire had good internal consistency, assessed by the Cronbach's Alpha coefficient (α = 0.793 and α = 0.842, respectively). Obtained results indicate very good reliability for core as well as for modular part of EHP-5 questionnaire (ICC = 0.896 and 0.936, respectively). The independent t test showed that women who reported their pain with VAS scale 7 or more had significantly higher results (p < 0.001) on EHP-5 (M = 50.63) compared with women who reported their pain 6 or less (M = 26.91). Furthermore, we found statistically significant difference between women who are infertile with women who are fertile (p < 0.001), whereby infertile women had higher average result on EHP-5 (M = 49.55) compared with fertile women (M = 34.36). Conclusions: The Croatian version of the EHP-5 have very good psychometric characteristics and can be used as a reliable tool for assessing patients with endometriosis in everyday clinical practice. [ABSTRACT FROM AUTHOR]

Aims: Olmesartan, an angiotensin receptor blocker (ARB) used for hypertension management, is known to cause a sprue-like enteropathy in a subset of patients. Rare cases of gastritis occurring with ARB use have also been reported, but the histological features of ARB-induced gastritis and the response to drug cessation have not been examined in a dedicated case-series. Methods and results: Cases of suspected ARB-induced gastritis were identified from the pathology archives of four institutions. Haematoxylin and eosin (H&E) slides from gastric biopsies were reviewed. Fifteen patients (14 female, one male) were identified. The most common presenting symptoms were diarrhoea (10) and weight loss (six). Gastric biopsies commonly showed a full-thickness active chronic gastritis with surface epithelial injury involving the antrum and body. Glandular atrophy, intra-epithelial lymphocytosis and/or subepithelial collagen thickening were also present in some cases. Duodenal involvement, including villous atrophy, intra-epithelial lymphocytosis and/or collagenous sprue, was identified in 11 of 13 cases with concurrent duodenal biopsies. Following drug cessation, symptomatic improvement occurred in all 11 cases for which follow-up data were available. Histological resolution occurred in five of eight cases with follow-up gastric biopsies, with improvement seen in the remaining three biopsies. Conclusion: ARB-induced gastritis typically presents as active chronic gastritis, frequently with associated surface epithelial injury. Glandular atrophy, intraepithelial lymphocytosis and/or subepithelial collagen thickening may also be present. These gastric changes can be seen without associated duodenal injury in rare cases, and they should alert the pathologist to the possibility of ARB-induced injury. Drug cessation results in marked symptomatic and histological improvement. [ABSTRACT FROM AUTHOR]

Philadelphia has increasingly adopted Harm Reduction (HR) strategies which, despite reducing morbidity and mortality, remain controversial. This study examines attitudes toward HR among substance use treatment professionals. 117 treatment professionals completed an anonymous online survey assessing their attitudes about four specific HR interventions: medication assisted treatment (MAT), naloxone, needle and syringe exchange programs (NSPs), and overdose prevention sites (OPSs). Findings indicate that treatment professionals generally had a positive perception of HR interventions as more than 90% agreed that MAT and naloxone should be discussed with clients and more than 80% agreed that NSPs and OPSs should be discussed. However, treatment professionals also endorsed concern about how certain interventions impact communities as only 28–30% indicated being comfortable if an NSP or OPS were to open on their block. Moreover, only 50% of respondents agreed that NSPs help users to seek treatment while 16% believed that OPSs would lead to increased substance use. Of note, professionals with more experience and knowledge about HR tended to have more positive attitudes, whereas professionals who supported abstinence and 12-step programs had more negative views of HR. Implications for education to facilitate improved attitudes toward and implementation of HR interventions are discussed. [ABSTRACT FROM AUTHOR]

Purpose: Spinal cord gray‐matter imaging is valuable for a number of applications, but remains challenging. The purpose of this work was to compare various MRI protocols at 1.5 T, 3 T, and 7 T for visualizing the gray matter. Methods: In vivo data of the cervical spinal cord were collected from nine different imaging centers. Data processing consisted of automatically segmenting the spinal cord and its gray matter and co‐registering back‐to‐back scans. We computed the SNR using two methods (SNR_single using a single scan and SNR_diff using the difference between back‐to‐back scans) and the white/gray matter contrast‐to‐noise ratio per unit time. Synthetic phantom data were generated to evaluate the metrics performance. Experienced radiologists qualitatively scored the images. We ran the same processing on an open‐access multicenter data set of the spinal cord MRI (N = 267 participants). Results: Qualitative assessments indicated comparable image quality for 3T and 7T scans. Spatial resolution was higher at higher field strength, and image quality at 1.5 T was found to be moderate to low. The proposed quantitative metrics were found to be robust to underlying changes to the SNR and contrast; however, the SNR_single method lacked accuracy when there were excessive partial‐volume effects. Conclusion: We propose quality assessment criteria and metrics for gray‐matter visualization and apply them to different protocols. The proposed criteria and metrics, the analyzed protocols, and our open‐source code can serve as a benchmark for future optimization of spinal cord gray‐matter imaging protocols. [ABSTRACT FROM AUTHOR]

Neuroimaging studies often lack reproducibility, one of the cardinal features of the scientific method. Multisite collaboration initiatives increase sample size and limit methodological flexibility, therefore providing the foundation for increased statistical power and generalizable results. However, multisite collaborative initiatives are inherently limited by hardware, software, and pulse and sequence design heterogeneities of both clinical and preclinical MRI scanners and the lack of benchmark for acquisition protocols, data analysis, and data sharing. We present the overarching vision that yielded to the constitution of RIN-Neuroimaging Network, a national consortium dedicated to identifying disease and subject-specific in-vivo neuroimaging biomarkers of diverse neurological and neuropsychiatric conditions. This ambitious goal needs efforts toward increasing the diagnostic and prognostic power of advanced MRI data. To this aim, 23 Italian Scientific Institutes of Hospitalization and Care (IRCCS), with technological and clinical specialization in the neurological and neuroimaging field, have gathered together. Each IRCCS is equipped with high- or ultra-high field MRI scanners (i.e., ≥3T) for clinical or preclinical research or has established expertise in MRI data analysis and infrastructure. The actions of this Network were defined across several work packages (WP). A clinical work package (WP1) defined the guidelines for a minimum standard clinical qualitative MRI assessment for the main neurological diseases. Two neuroimaging technical work packages (WP2 and WP3, for clinical and preclinical scanners) established Standard Operative Procedures for quality controls on phantoms as well as advanced harmonized quantitative MRI protocols for studying the brain of healthy human participants and wild type mice. Under FAIR principles, a web-based e-infrastructure to store and share data across sites was also implemented (WP4). Finally, the RIN translated all these efforts into a large-scale multimodal data collection in patients and animal models with dementia (i.e., case study). The RIN-Neuroimaging Network can maximize the impact of public investments in research and clinical practice acquiring data across institutes and pathologies with high-quality and highly-consistent acquisition protocols, optimizing the analysis pipeline and data sharing procedures. [ABSTRACT FROM AUTHOR]

Barium ions block potassium leak channels that contribute to the resting membrane potential in most animal cells (Armstrong and Taylor, 1980). Here we examine the impact of barium on the resting membrane potential of crayfish superficial flexor muscles by replacing the calcium chloride in normal crayfish Ringer's solution with barium chloride. Replacement of calcium chloride with barium chloride resulted in an increase in the resting membrane potential of the tail muscles. Increasing the concentration of barium chloride resulted in an increasingly more positive resting membrane potential. To determine that this effect was not caused by the absence of calcium, barium chloride and calcium chloride were replaced with magnesium chloride in the Ringer's solution. There was no significant difference in the resting membrane potential between the control and magnesium solutions. Barium has been linked with toxicity effects in humans leading to hypokalemia, which is a condition of having low potassium levels within the bloodstream. This may lead to cardiac arrhythmias and muscle weakness. This can be explained, in part, by the direct effect of barium on potassium channels. [ABSTRACT FROM AUTHOR]

This article discusses the use of multivisceral transplantation (MVT) as a treatment for mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), a rare genetic disease characterized by neurological and gastrointestinal symptoms. The patient in the case study was a 26-year-old woman with severe gastrointestinal manifestations of MNGIE. MVT was performed with the goal of halting neurodegeneration and restoring enteral independence. The patient experienced improvements in pain, opioid requirements, and functional status after the transplantation, but unfortunately, she later developed septic complications unrelated to MNGIE and passed away. The authors suggest that MVT should be considered as a treatment option for MNGIE before significant neurological deterioration occurs. [Extracted from the article]

MicroRNAs (miRNAs) are regulatory small non-coding RNAs that function as translational repressors. MiRNAs are involved in most cellular processes, and their expression and function are presided by several factors. Amongst, miRNA editing is an epitranscriptional modification that alters the original nucleotide sequence of selected miRNAs, possibly influencing their biogenesis and target-binding ability. A-to-I and C-to-U RNA editing are recognized as the canonical types, with the A-to-I type being the predominant one. Albeit some bioinformatics resources have been implemented to collect RNA editing data, it still lacks a comprehensive resource explicitly dedicated to miRNA editing. Here, we present MiREDiBase, a manually curated catalog of editing events in miRNAs. The current version includes 3,059 unique validated and putative editing sites from 626 pre-miRNAs in humans and three primates. Editing events in mature human miRNAs are supplied with miRNA-target predictions and enrichment analysis, while minimum free energy structures are inferred for edited pre-miRNAs. MiREDiBase represents a valuable tool for cell biology and biomedical research and will be continuously updated and expanded at https://ncrnaome.osumc.edu/miredibase. [ABSTRACT FROM AUTHOR]

The diagnosis of inflammatory bowel disease (IBD)-associated dysplasia is challenging, and past studies have demonstrated considerable interobserver variability in such diagnoses. This study aimed to assess interobserver agreement in IBD dysplasia diagnoses among subspecialty GI pathologists and to explore the impact of mentorship on diagnostic variability. Twelve GI pathologist mentees and 7 GI pathologist mentors reviewed 163 digitized slides. Participants rendered a diagnosis of negative for dysplasia, indefinite for dysplasia, low-grade dysplasia, or high-grade dysplasia and provided a confidence level for each case. Interobserver agreement and reliability were assessed using Cohen's and Fleiss' kappa (κ) statistics and intraclass correlation coefficient (ICC) analysis. The overall κ coefficient was 0.42 (95% CI: 0.38-0.46). The overall ICC was 0.67 (95% CI: 0.62-0.72). Κ coefficients ranged from 0.31 to 0.49 for mentor/mentee pairs and from 0.34 to 0.55 for pairs of mentees of the same mentor. The combined κ coefficient was 0.44 (95% CI: 0.39-0.48) for all mentees and 0.39 (95% CI: 0.34-0.43) for all mentors. Common features in low agreement cases included mucosal atrophy, areas of stark contrast, serrations, decreased goblet cells, absent surface epithelium, and poor orientation. Participants were confident in most diagnoses, and increased confidence levels generally correlated with higher interobserver agreement. Interobserver agreement among subspecialist GI pathologists in this curated cohort of IBD dysplasia cases was fair to moderate. Mentorship during GI pathology fellowship does not appear to be a significant factor contributing to interobserver variability, but increased experience also does not seem to improve interobserver agreement. [ABSTRACT FROM AUTHOR]

Objectives: Special AT-rich binding protein 2 (SATB2) immunohistochemistry (IHC) has high sensitivity and specificity for colorectal adenocarcinoma (CRC), but data on its expression in specific subsets of pulmonary, gastric, small bowel, and pancreatobiliary adenocarcinomas (ADCAs) are relatively limited or discordant. We assessed SATB2 expression in a large cohort of ADCAs from these sites to determine its reliability in distinguishing CRC from them.Methods: SATB2 IHC was performed on 335 neoplasms, including 40 lung ADCAs, 165 pancreatobiliary neoplasms (34 intraductal papillary mucinous neoplasms [IPMNs], 19 pancreatic ADCAs, 112 cholangiocarcinomas [CCs]), and 35 gastric, 13 small bowel, 36 ampullary (AMP), and 46 CRC ADCAs. The cases were evaluated for positivity (defined as ≥5% nuclear staining), and an H-score was calculated based on the percentage of SATB2+ cells and staining intensity. Analysis was performed to determine the optimal H-score threshold to separate CRC and non-CRC.Results: SATB2 was positive in 3% of lung, 2% of CC, 17% of gastric, 38% of small bowel, and 6% of AMP ADCAs. All pancreatic ADCA/IPMNs were negative, and 87% CRCs were positive.Conclusions: SATB2 is not entirely specific for colorectal origin and can be expressed in a subset of gastrointestinal ADCAs. It is most useful in the differential of CRC vs lung and pancreatobiliary ADCAs. [ABSTRACT FROM AUTHOR]

Objectives: Steatohepatitic hepatocellular carcinoma is a distinct variant of hepatocellular carcinoma strongly associated with underlying nonalcoholic steatohepatitis. The molecular biology of steatohepatitic hepatocellular carcinoma is not fully elucidated, and thus we aimed to investigate the molecular underpinnings of this entity.Methods: Transcriptomic analysis using RNAseq was performed on eight tumor-nonneoplastic pairs of steatohepatitic hepatocellular carcinoma with comparison to conventional hepatocellular carcinoma transcriptomes curated in The Cancer Genome Atlas. Immunohistochemistry was used to validate key RNA-level findings.Results: Steatohepatitic hepatocellular carcinoma demonstrated a distinctive differential gene expression profile compared with The Cancer Genome Atlas curated conventional hepatocellular carcinomas (n = 360 cases), indicating the distinctive steatohepatitic hepatocellular carcinoma morphology is associated with a unique gene expression profile. Pathway analysis comparing tumor-nonneoplastic pairs revealed significant upregulation of the hedgehog pathway based on GLI1 overexpression and significant downregulation of carnitine palmitoyltransferase 2 transcript. Glutamine synthetase transcript was significantly upregulated, and fatty acid binding protein 1 transcript was significantly downregulated and immunohistochemically confirmed, indicating steatohepatitic hepatocellular carcinoma tumor cells display a zone 3 phenotype.Conclusions: Steatohepatitic hepatocellular carcinoma demonstrates a distinctive morphology and gene expression profile, phenotype of zone 3 hepatocytes, and activation of the hedgehog pathway and repression of carnitine palmitoyltransferase 2, which may be important in tumorigenesis. [ABSTRACT FROM AUTHOR]

The literature on the relationship between regions and the European Union (EU) has generated important insights. Firstly, existing scholarship has found that the EU has empowered, as well as disempowered, regions and sub-national governments. Secondly, researchers have convincingly demonstrated how regions have adapted to the EU opportunity structure. Finally, studies exist that have investigated the ways in which regions and sub-national governments have also influenced the EU opportunity structure. These dimensions are rarely brought together to examine the mutual influence and constant interaction of regions and the EU. Accordingly, this article aims to provide a short systematic account of how empowering and disempowering structures and sub-national governments' endeavours in the United Kingdom (UK) interacted with the European level. It will do so through the Strategic-Relational Approach, showing how regional motivations, processes of devolution, differential opportunities and constraints and strategies of adaptation and transformation are interrelated. The last section will discuss some of the disempowering issues Brexit presents for the UK's territorial and constitutional future. [ABSTRACT FROM AUTHOR]

We present a case of a pediatric liver transplant recipient diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection four days after receiving a living donor liver allograft from her mother. The recipient was a 6‐month‐old with end‐stage liver disease due to biliary atresia and failed Kasai. The infant had an uncomplicated implantation, excellent graft function and down‐trending liver enzymes until developing fevers, diarrhea, and moderate respiratory distress requiring non‐invasive respiratory support. SARS‐CoV‐2 testing (nasal swab Polymerase Chain Reaction) was positive on post‐operative day (POD) 4. Liver enzymes peaked ~1000 U/L (5‐fold higher than the previous day) on POD 6. Histology demonstrated a mixed picture of moderate acute hepatitis and classical elements of mild to moderate acute cellular rejection. Her hepatitis and respiratory symptoms improved coincident with completing treatment with hydroxychloroquine, reduced immunosuppression, and intravenous gamma globulin (IVIG). [ABSTRACT FROM AUTHOR]

The article profiles personalities submitted by readers who have made a difference in other people's lives as of November 2020. Topics discussed include quality engineering professor Mohamed Aichouni who taught quality in everything to his children, and quality assurance director Dawn Bontempo who sets up targets and how to achieve them and puts suggestions of others to use. Also noted is retired quality engineer Dolores Casebolt who set an example in her profession for her son to follow.

Background: Malakoplakia is an uncommon, tumor-like inflammatory disease characterized by impaired histiocytes that are unable to completely digest phagocytized bacteria. The genitourinary tract is the most common site of involvement, however, cases have also been described in the gastrointestinal tract, suggesting that it is the second most common site of involvement. This study investigates the clinical and histologic features of malakoplakia in the gastrointestinal tract. Case presentation: For 23 gastrointestinal specimens (biopsies and resections) from patients with a pathologic diagnosis of malakoplakia, we recorded the gender, age, location, primary diagnosis, endoscopic or surgical indication, endoscopic/gross impression and immune status (immunocompromised vs. immunocompetent). Conclusion: Malakoplakia occurred throughout the length of the gastrointestinal tract with most of the cases located in the sigmoid colon and rectum (n = 10); other sites included the transverse and descending colon (n = 4), stomach/gastroesophageal junction (n = 4), appendix (n = 2), cecum (n = 1), small bowel (n = 1), and the peri-anal area (n = 1). Endoscopically, these lesions most commonly appeared as polyps (n = 10) or masses (n = 5), other clinical endoscopic impressions varied from a thickened area/fibrosis to mucosal erythema. Most patients were immunocompromised due to a disease state (e.g. organ transplantation, cancer diagnosis, autoimmune condition) and/or medication effect. Eight patients with malakoplakia were on immunosuppressive medications (8/23, 35%). Common immunosuppressed disease states included cancer (n = 9), autoimmune disease (n = 5), status post organ transplantation (n = 4), diabetes (n = 5), infection/sepsis (n = 3), and HIV/AIDS (n = 1). Some patients had multiple co-morbidities (i.e. diabetes and organ transplant). Twenty-one patients with malakoplakia were in an immunosuppressive state (21/23, 91%). [ABSTRACT FROM AUTHOR]

Background: Several small cross-sectional studies have investigated cerebrospinal fluid (CSF) flow dynamics in multiple sclerosis (MS) patients and have reported mixed results. Currently, there are no longitudinal studies that investigate CSF dynamics in MS patients. Objective: To determine longitudinal changes in CSF dynamics measured at the level of aqueduct of Sylvius (AoS) in MS patients and matched healthy controls (HCs). Materials and methods: Forty (40) MS patients and 20 HCs underwent 3T MRI cine phase contrast imaging with velocity-encoded pulse-gated sequence at baseline and 5-year follow-up. For atrophy determination, MS patients underwent additional high-resolution 3D T1-weighted imaging. Measures of AoS cross-sectional area (CSA), average systolic and diastolic velocity peaks, maximal systolic and diastolic velocity peaks and average CSF flow rates were determined. Brain atrophy and ventricular CSF (vCSF) expansion rates were determined. Cross-sectional and longitudinal changes were derived by analysis of covariance (ANCOVA) and paired repeated tests. Confirmatory general linear models were also performed. False discovery rate (FDR)-corrected p-values lower than 0.05 were considered significant. Results: The MS population demonstrated significant increase in maximal diastolic peak (from 7.23 to 7.86 cm/s, non-adjusted p = 0.037), diastolic peak flow rate (7.76 ml/min to 9.33 ml/min, non-adjusted p = 0.023) and AoS CSA (from 3.12 to 3.69 mm2, adjusted p = 0.001). The only differentiator between MS patients and HCs was the greater AoS CSA (3.58 mm2 vs. 2.57 mm2, age- and sex-adjusted ANCOVA, p = 0.045). The AoS CSA change was associated with vCSF expansion rate (age- and sex-adjusted Spearman's correlation r = 0.496, p = 0.019) and not with baseline nor change in maximal velocity. The expansion rate of the vCSF space explained an additional 23.8% of variance in change of AoS CSA variance when compared to age and sex alone (R2 = 0.273, t = 2.557, standardized β = 0.51, and p = 0.019). Conclusion: MS patients present with significant longitudinal AoS enlargement, potentially due to regional atrophy changes and ex-vacuo expansion of the aqueduct. [ABSTRACT FROM AUTHOR]

A new approach for determining the complex scalar field radiated by a finite-dimensional source starting from its modulus is proposed and assessed. First, by introducing a suitable relaxation, we show that the original problem can be conveniently tackled in terms of a finite number of different convex programing problems. Then, an effective procedure for dealing with a small number of hierarchically ordered optimizations is introduced and discussed. Numerical experiments, including consideration of an actual radiating source and of noisy data, are provided with reference to the canonical case of far-field data and array antennas. [ABSTRACT FROM AUTHOR]

Examines the largest angle generalization of the rotating bond order potential (LAGROBO) functional representation of potential energy. Connection of atom-diatom arrangements from the reactive processes; Extension of the LAGROBO system for electronically excited atom; Use of LAGROBO potential for lithium, fluorine and hydrogen reaction.

Reports on ab initio calculations and dynamical tests of a potential energy surface for the Na+FH reaction. Fitting of the calculated potential energy values using a polynomial in bond order coordinates; Calculation of reactive properties of the system.

Aim of this in vitro study was to analyze structural properties of two different polymeric orthodontic aligners, Exceed30 (EX30) and Smart Track (LD30), before and after use. Forty patterns of aligners were randomly selected: 20 LD30 and 20 EX30, worn intra-orally for 14±3 days, 22 h/day. From each aligner, 10 specimens were prepared from buccal surfaces of the incisor region by the cutting of samples 5×5 mm under a stereomicroscope. All samples were subjected to Fourier transform infrared spectroscopy, micro-Raman spectroscopy, X-ray diffraction, tensile and indentation strength test. LD30 appeared more homogeneous, with a crystalline fraction lower than EX30 and exhibited a higher elastic behavior and a lower tendency to warp after use than EX30. LD30 demonstrated better adaptability to the dental arch and greater consistency of application of orthodontic forces than produced with EX30. However, both materials showed structural modifications that resulted in increased sample hardness and hyper-plasticity. [ABSTRACT FROM AUTHOR]

The Good Friday Agreement of April 1998 led to the creation of a new set of political institutions within Northern Ireland and between Great Britain and the island of Ireland. A central tenet of the agreement was to promote cross-border cooperation on an all Ireland and border region basis and, consequently, the new institutional setting for this cooperation forms the core of this research. The article will first sketch an analytical approach that enables the analysis to address new policy processes, the state authority, and the multitude of actors involved. Secondly, it will proceed to an in-depth description of the genesis of the implementation of EU-sponsored cross-border cooperation in the context of the Irish border region. The examination will encompass a description and analysis of the development of the European specific border region programme ‘INTERREG’ and the limited results achieved by cross-border cooperation in such framework. Finally, the article will interconnect the creation of new political institutions within Northern Ireland and between North and South with experiences of regionalism and peacebuilding in order to analyse how processes of EU integration and association are related to border conflict amelioration on the island of Ireland. [ABSTRACT FROM PUBLISHER]

The clinical complexity of Internal Medicine patients is a daily challenge for clinicians. Although clinical complexity cannot be directly measured, several scores describe the variability of clinical severity and comorbidity. The aim of this study was to analyze staff workload by assessing the nursing and medical complexity of patients admitted to an Internal Medicine ward. We included 40 consecutive inpatients [52.5% females, mean age 71.2 (18.2) years] classified according to the index of clinical complexity (ICC, type A: very high; type B: high; type C: moderate) and the cumulative illness rating scale (CIRS) severity and comorbidity index. Patient outcomes, hospitalization duration, tests performed, number of daily medications and time to perform standard nursing tasks were analysed across groups. Mean duration of hospitalization was 15.6 (10.1) days; in-hospital mortality was 15%. Mean CIRS severity index (SI) was 1.03 (0.31) and median CIRS comorbidity index (CI) was 2 (range 1-5). Significant differences were observed among ICC groups in time spent performing specific tasks [univariate analysis of variance F(2.37)=17.26, P<0.001]. No significant differences were found between the three groups for mean CIRS-SI [F(2.37)=3.033, P=0.060] and median CIRS-CI [Kruskal Wallis test: c²(2)= 1.672, P=0.433]. Clinical complexity and caring complexity were not correlated in our sample of Internal Medicine inpatients. Optimal care of Internal Medicine patients must take into account their complexity in both the medical and nursing aspects. [ABSTRACT FROM AUTHOR]