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PURPOSE: The absorbed dose estimation from Voxel-S-Value (VSV) method in heterogeneous media is suboptimal as VSVs are calculated in homogeneous media. The aim of this study is to develop and evaluate new VSV methods in order to enhance the accuracy of Y-90 microspheres absorbed dose estimation in liver, lungs, tumors and lung-liver interface regions. METHODS: Ten patients with Y-90 microspheres SPECT/CT and PET/CT data, six of whom had additional Tc-99m-macroaggregated albumin SPECT/CT data, were analyzed from the Deep Blue Data Repository. Seven existing VSV methods along with three newly proposed VSV methods were evaluated: liver and lung kernel with center voxel scaling (LiLuCK), liver kernel with density correction and lung kernel with center voxel scaling (LiKDLuCK), liver kernel with center voxel scaling and lung kernel with density correction (LiCKLuKD). Monte Carlo (MC) results were regarded as the gold standard. Absolute absorbed dose errors (%AADE) of these methods for the liver, lungs, tumors, upper liver, and lower lungs were assessed. RESULTS: Liver and tumor’s median %AADE of all methods were

In radionuclide therapy, activity kinetics in tissues determine the absorbed doses administered and thus efficacy and side effects of treatment. The objective of this work was to derive expressions for the parameters affecting the absorbed dose to a target tissue for first-order activity kinetics. The activity uptake results from contributions from the first-pass activity flow through the target tissue preceding systemic equilibration and uptake after distribution of the administered compound in the body. The absorbed dose from uptake after equilibration is the product of the mean energy deposited per decay in the target tissue, the time integral of the plasma activity concentration, the plasma volume flow per unit target tissue mass, the probability of activity removal during passage, and the mean lifetime of activity in the target tissue. Quantitative analysis of the determinants of absorbed dose exemplarily for radioiodine therapy indicates that the high uptake often observed in Graves’ disease must be associated with high tissue perfusion and removal probability and that administration of stable iodine increases mean lifetime. For therapies with long residence times of the active compound in the blood, such as radioiodine therapy, the contribution of the first-pass is small compared with uptake after equilibration. The relative first-pass contribution is higher for agents that are rapidly eliminated from the blood pool, such as radiolabelled somatostatin analogues, and may dominate after arterial application. Understanding the determining parameters in radionuclide therapy reveals dose-limiting factors and opens up opportunities to optimise and individualize therapy, potentially improving treatment success rates.

Petunia vein clearing virus (PVCV) is a type member of the genus Petuvirus within the Caulimoviridae family and is defined as one viral unit consisting of a single open reading frame (ORF) encoding a viral polyprotein and one quasi-long terminal repeat (QTR) sequence. Since some full-length PVCV sequences are found in the petunia genome and a vector for horizontal transmission of PVCV has not been identified yet, PVCV is referred to as an endogenous pararetrovirus. Molecular mechanisms of replication, gene expression and horizontal transmission of endogenous pararetroviruses in plants are elusive. In this study, agroinfiltration experiments using various PVCV infectious clones indicated that the replication (episomal DNA synthesis) and gene expression of PVCV were efficient when the QTR sequences are present on both sides of the ORF. Whereas replacement of the QTR with another promoter and/or terminator is possible for gene expression, it is essential for QTR sequences to be on both sides for viral replication. Although horizontal transmission of PVCV by grafting and biolistic inoculation was previously reported, agroinfiltration is a useful and convenient method for studying its replication and gene expression.

This article offers a novel understanding of China's changing engagement in global climate governance over the past decade. This article argues that China has embedded the construction of its international identity, which has been transforming towards what this article conceptualizes to be a 'Yinling leading power', in promoting and leading global climate governance. China's transforming identity construction has contributed to changing its construction of climate justice and led China to proactively undertake more responsibilities, provide international public goods and promote international climate cooperation. Global climate governance has become one of China's prototypical discursive frames in constructing its new international identity, an important platform where China seeks to share leadership with other major powers and the climate leadership in turn constitutes China's new identity. However, China's inadequate response to international expectations and lack of self-reflection in its climate policy have influenced international recognition on its climate leadership and new identity. In general, China's transforming identity construction and its reconstruction of climate justice have far-reaching implications for China and Europe to cooperate and coordinate in strengthening global climate justice and promoting global climate governance.

The dynamic general nesting spatial econometric model for spatial panels with common factors is the most advanced model currently available. It accounts for local spatial dependence by means of an endogenous spatial lag, exogenous spatial lags, and a spatial lag in the error term. It accounts for dynamic effects by means of the dependent variable lagged in time, and the dependent variable lagged in both space and time. Finally, it accounts for global cross-sectional dependence by means of cross-sectional averages or principal components with heterogeneous coefficients, which generalizes the traditional controls for time-invariant and spatial-invariant variables by unit-specific and time-specific effects. This paper provides an overview of the main arguments in favor of each of these model components, as well as some potential pitfalls.

The secondary cell wall, which is mainly composed of cellulose, hemicellulose, and lignin, constitutes woody tissues and gives physical strength and hydrophobic properties for resistance against environmental stresses. We cloned and functionally analyzed the homologous transcription factor (TF) genes of SECONDARY WALL NAC (SWN) proteins from Hachiku bamboo (Phyllostachys nigra; PnSWNs). An RT-PCR analysis showed that PnSWNs are expressed in young tissues in bamboo. Their transcriptional activation activities were higher than that of the Arabidopsis NAC SECONDARY WALL THICKENING PROMOTING FACTOR 3 (NST3) TF, which was equivalent to SWN TFs in monocot. PnSWNs preferred to activate the genes related to secondary cell wall formation but not the genes related to programmed cell death. When PnSWNs were expressed in Arabidopsis, they highly induced secondary cell wall formation, like previously-shown rice SWN1. Dissection analysis revealed that this high activity largely depends on C-terminal domain. These results demonstrate that the cloned bamboo SWNs function as regulators of secondary cell wall formation with strong activation ability derived from C-terminal domain, and could be served as new genetic tools for secondary cell wall manipulation.

Introduction: Endometriosis is defined by the presence of endometrial tissue outside the uterus, therefore leading to a chronic inflammatory reaction, adhesions development, scar tissue and a distorted pelvic female anatomy, most of the times leading to female infertility. Kisspeptin represents a neuropeptide thought to have an essential role in the reproductive functions of both female and male patients. Recently, positive correlations with kisspeptins were noticed in patients diagnosed with endometriosis. Materials and methods: Our study was performed between January 2021-March 2022 in “Elena Doamna” Clinical Hospital of Obstetrics and Gynecology Iasi, Romania. It was a prospective case-control study and included two groups of patients. Both groups consisted in female patients aged between 18 and 45 years, with a body mass index (BMI) between 18,5-30 kg/m2 and similar medical data. Patients in the study group had primary or secondary infertility and endometriosis, while the control group consisted of women with no reproductive issues who had healthy regular menstruations and at least one child. All patients agreed to participate in our study and signed the consent form. Clinical examination, pelvic ultrasound and hormonal dosages were performed. We tested the levels of LH, FSH, kisspeptin, estradiol, prolactin, testosterone, insulin and the glycemic levels in both groups during the follicular phase of their menstrual cycle. Results: We managed to enroll eight patients with endometriosis in the study group and an equal number of patients in the control group. There were significant differences between serum kisspeptin levels, but not also between other hormonal dosages. All patients in the study group had medical evidences of endometriomas but none of them had been subjected to laparoscopy. Conclusions: When considering our study, we regarded the first attribution given to kisspeptin, the one of a metastasis suppressor, and concluded that the high serum values of kisspeptin in patients with endometriosis represented a compensatory-adaptive mechanism needed to constrain future spread of endometriomas in early stages of this pathology.

Objective Osteoarthritis is the most common joint disease with treatment involving a multidisciplinary approach with pharmacological, physical therapies and surgery as options. Qualitative research can help us to understand the complexity of managing health conditions and this understanding plays a role in good clinical practice. We aimed to systematically search for, identify, and synthesise qualitative research exploring the experience of living with osteoarthritis, including decision making about joint replacement. Methods We comprehensively searched 4 bibliographic databases and used the methods of meta-ethnography to synthesise qualitative research findings. We screened 10 ​123 titles, 548 abstracts, and 139 full texts. We included findings from 118 reports (105 unique samples) of at least 2534 adults living with osteoarthritis around the world. Results We developed 7 themes: Becoming your own expert can be hard work; Living has become a careful balancing act; Medication is a double-edged sword; I have other things in my life to consider; You have to weigh up the odds of surgery; Surgery is the only effective option; and Surgery will give me a chance to live now. These findings have been drawn into a conceptual model reflecting a complex balancing act with tensions underpinning treatment decision making. Conclusions Osteoarthritis is framed as a world where patients become their own expert about their management and healthcare choices. Our conceptual model highlights key tensions underpinning treatment decision-making. These findings provide clinicians with insight of the complex nature of these decisions and how they can help patients through shared decision making.

We show that a A-linear map of Hilbert A-modules is induced by a unitary Hilbert module operator if and only if it extends to an ordinary unitary on appropriately defined enveloping Hilbert spaces. Applications to the theory of multiplicative unitaries let us to compute the equivalence classes of Hilbert modules over a class of C*-algebraic quantum groups. We, thus, develop a theory that, for example, could be used to show non-existence of certain co-actions. In particular, we show that the Cuntz semigroup functor takes a co-action to a multiplicative action.

A total of 11 bacterial strains capable of completely degrading 2-butoxyethanol (2-BE) were isolated from forest soil, a biotrickling filter, a bioscrubber, and activated sludge, and identified by 16S rRNA gene sequence analysis. Eight of these strains belong to the genus Pseudomonas; the remaining three strains are Hydrogenophaga pseudoflava BOE3, Gordonia terrae BOE5, and Cupriavidus oxalaticus BOE300. In addition to 2-BE, all isolated strains were able to grow on 2-ethoxyethanol and 2-propoxyethanol, ethanol, n-hexanol, ethyl acetate, 2-butoxyacetic acid (2-BAA), glyoxylic acid, and n-butanol. Apart from the only gram-positive strain isolated, BOE5, none of the strains were able to grow on the nonpolar ethers diethyl ether, di-n-butyl ether, n-butyl vinyl ether, and dibenzyl ether, as well as on 1-butoxy-2-propanol. Strains H. pseudoflava BOE3 and two of the isolated pseudomonads, Pseudomonas putida BOE100 and P. vancouverensis BOE200, were studied in more detail. The maximum growth rates of strains BOE3, BOE100, and BOE200 at 30 °C were 0.204 h-1 at 4 mM, 0.645 h-1 at 5 mM, and 0.395 h-1 at 6 mM 2-BE, respectively. 2-BAA, n-butanol, and butanoic acid were detected as potential metabolites during the degradation of 2-BE. These findings indicate that the degradation of 2-BE by the isolated gram-negative strains proceeds via oxidation to 2-BAA with subsequent cleavage of the ether bond yielding glyoxylate and n-butanol. Since Gordonia terrae BOE5 was the only strain able to degrade nonpolar ethers like diethyl ether, the degradation pathway of 2-BE may be different for this strain., Projekt DEAL, Landesgraduiertenförderung der Universität Stuttgart

Objectives Understanding if police malfeasance might be “contagious” is vital to identifying efficacious paths to police reform. Accordingly, we investigate whether an officer’s propensity to engage in misconduct is associated with her direct, routine interaction with colleagues who have themselves engaged in misbehavior in the past. Methods Recognizing the importance of analyzing the actual social networks spanning a police force, we use data on collaborative responses to 1,165,136 “911” calls for service by 3475 Dallas Police Department (DPD) officers across 2013 and 2014 to construct daily networks of front-line interaction. And we relate these cooperative networks to reported and formally sanctioned misconduct on the part of the DPD officers during the same time period using repeated-events survival models. Results Estimates indicate that the risk of a DPD officer engaging in misconduct is not associated with the disciplined misbehavior of her ad hoc, on-the-scene partners. Rather, a greater risk of misconduct is associated with past misbehavior, officer-specific proneness, the neighborhood context of patrol, and, in some cases, officer race, while departmental tenure is a mitigating factor. Conclusions Our observational findings—based on data from one large police department in the United States—ultimately suggest that actor-based and ecological explanations of police deviance should not be summarily dismissed in favor of accounts emphasizing negative socialization, where our study design also raises the possibility that results are partly driven by unobserved trait-based variation in the situations that officers find themselves in. All in all, interventions focused on individual officers, including the termination of deviant police, may be fruitful for curtailing police misconduct—where early interventions focused on new offenders may be key to avoiding the escalation of deviance.

Aims Heart disease is associated with an increased risk for ischaemic stroke. However, the predictive value of reduced left ventricular ejection fraction (LVEF) for stroke is controversial and only observed in patients with severe reduction. LV global longitudinal strain (LV GLS) can detect subclinical LV systolic impairment when LVEF is normal. We investigated the prognostic role of LV GLS for incident stroke in a predominantly elderly cohort. Methods and results Two-dimensional echocardiography with speckle tracking was performed in the Cardiac Abnormalities and Brain Lesions (CABL) study. Among 708 stroke-free participants (mean age 71.4 ± 9.4 years, 60.9% women), abnormal LV GLS (>−14.7%: 95% percentile of the subgroup without risk factors) was detected in 133 (18.8%). During a mean follow-up of 10.8 ± 3.9 years, 47 participants (6.6%) experienced an ischaemic stroke (26 cardioembolic or cryptogenic, 21 other subtypes). The cumulative incidence of ischaemic stroke was significantly higher in participants with abnormal LV GLS than with normal LV GLS (P < 0.001). In multivariate stepwise logistic regression analysis, abnormal LV GLS was associated with ischaemic stroke independently of cardiovascular risk factors including LVEF, LV mass, left atrial volume, subclinical cerebrovascular disease at baseline, and incident atrial fibrillation [hazard ratio (HR): 2.69, 95% confidence interval (CI): 1.47–4.92; P = 0.001]. Abnormal LV GLS independently predicted cardioembolic or cryptogenic stroke (adjusted HR: 3.57, 95% CI: 1.51–8.43; P = 0.004) but not other subtypes. Conclusion LV GLS was a strong independent predictor of ischaemic stroke in a predominantly elderly stroke-free cohort. Our findings provide insights into the brain–heart interaction and may help improve stroke primary prevention strategies.

BACKGROUND: Salivary duct carcinoma with rhabdoid features (SDC-RF) is a recently-described salivary gland tumor that bears striking histologic similarity to lobular carcinoma of the breast. While this tumor has an apocrine phenotype that supports classification as a variant of SDC, it infrequently arises in association with conventional SDC. Furthermore, discohesive architecture can be seen in non-apocrine salivary carcinomas, raising the possibility that discohesive growth should define a separate entity. In this study, we aimed to perform comprehensive molecular profiling of SDC-RF to better understand its pathogenesis and classification. METHODS: We documented the clinicopathologic features of 9 cases of SDC-RF and performed immunostains including AR, GCDFP, and e-cadherin on all cases. We also performed targeted next generation sequencing (NGS) panels on 7 cases that had sufficient tissue available. RESULTS: The SDC-RF represented 8 men and 1 woman with a median age of 67 years (range 63–83 years) and included 6 parotid, 2 buccal, and 1 submandibular primary. All tumors were uniformly composed of discohesive cells with abundant eosinophilic cytoplasm; signet-ring cell features were seen in 2 cases. All tumors were also positive for AR (100%) and GCDFP (100%), and 7 tumors (78%) displayed lost or abnormal e-cadherin. NGS highlighted concomitant PIK3CA and HRAS mutations in 4 tumors, with additional cases harboring TP53, PTEN, and AKT1 mutations. Furthermore, CDH1 alterations were seen in 6 cases, including a novel CDH1::CORO7 fusion. Among 5 patients with follow-up available, 3 (60%) developed local recurrence and widespread distant metastasis and died of disease at a median 20 months (range 10–48 months). CONCLUSIONS: Overall, our findings confirm frequent CDH1 mutations and e-cadherin inactivation in SDC-RF, similar to discohesive tumors from other sites. We also highlight an apocrine molecular profile similar to conventional SDC. However, occasional AKT1 mutation and signet-ring features suggest SDC-RF may also be related to mucinous adenocarcinoma. As more salivary tumors with discohesive growth are identified, it may become clearer whether SDC-RF should remain in the SDC family or be recognized as a separate entity.

Endoplasmic reticulum (ER) stress activates unfolded protein responses (UPRs), such as promoting protein folding under the control of specific gene expression. Our previous study showed that ER stress induced by ER stress inducers such as tunicamycin (Tm), an inhibitor of N-linked glycan synthesis, causes ectopic lignin deposition in Arabidopsis roots, but the relationship between UPR and ectopic lignin deposition remains unclear. The receptor-like kinase THESEUS1 (THE1) has been shown to sense cell wall damage (CWD) induced in Arabidopsis by cellulose synthase inhibitors such as isoxaben (ISO) and to activate ectopic lignin deposition. In this study, we assessed the involvement of THE1 in ectopic lignin deposition caused by the ER stress inducer Tm. The loss-of-function mutation of THE1, the1-3, suppressed Tm-induced root growth inhibition and ectopic lignin deposition, revealing that THE1 is involved in root growth defects and ectopic lignin deposition caused by ER stress. Similarly, ISO treatment induced ectopic lignin deposition as well as the expression of the UPR marker genes binding protein 3 (BiP3) and ER-localized DnaJ 3b (ERdj3b). Conversely, in the the1-3 mutant, ISO-induced ectopic lignin deposition and the expression of BiP3 and ERdj3b were suppressed. These results showed that THE1 is involved in not only root growth inhibition and ectopic lignin deposition caused by ER stress but also CWD-induced UPR.

In rice, the lysin motif (LysM) receptor-like kinase OsCERK1, originally identified as the essential molecule for chitin-triggered immunity, plays a key role in arbuscular mycorrhizal (AM) symbiosis. As we previously reported, although AM colonization was largely repressed at 2 weeks after inoculation (WAI), arbuscules were observed at 5 WAI in oscerk1 mutant. Conversely, most mutant plants that defect the common symbiosis signaling pathway exhibited no arbuscule formation. Concerning the reason for this characteristic phenotype of oscerk1, we speculated that OsRLK10, which is a putative paralog of OsCERK1, may have a redundant function in AM symbiosis. The protein sequences of these two genes are highly conserved and it is estimated that the gene duplication occurred 150 million years ago. Here we demonstrated that OsCERK2/OsRLK10 induced AM colonization and chitin-triggered reactive oxygen species production in oscerk1 knockout mutant as similar to OsCERK1. The oscerk2 mutant showed a slight but significant reduction of AM colonization at 5 WAI, indicating the contribution of OsCERK2 for AM symbiosis. However, the oscerk2;oscerk1 double-knockout mutant produced arbuscules at 5 WAI as similar to the oscerk1 mutant, indicating that the redundancy of OsCERK1 and OsCERK2 did not explain the mycorrhizal colonization in oscerk1 at 5 WAI. These results indicated that OsCERK2 has a potential to regulate both chitin-triggered immunity and AM symbiosis and at least partially contributes to AM symbiosis in rice though the contribution of OsCERK2 appears to be weaker than that of OsCERK1.

Texts are not monolithic entities but rather coherent collections of micro illocutionary acts which help to convey a unitary message of content and purpose. Identifying such text segments is challenging because they require a fine-grained level of analysis even within a single sentence. At the same time, accessing them facilitates the analysis of the communicative functions of a text as well as the identification of relevant information. We propose an empirical framework for modelling micro illocutionary acts at clause level, that we call content types, grounded on linguistic theories of text types, in particular on the framework proposed by Werlich in 1976. We make available a newly annotated corpus of 279 documents (for a total of more than 180,000 tokens) belonging to different genres and temporal periods, based on a dedicated annotation scheme. We obtain an average Cohen’s kappa of 0.89 at token level. We achieve an average F1 score of 74.99% on the automatic classification of content types using a bi-LSTM model. Similar results are obtained on contemporary and historical documents, while performances on genres are more varied. This work promotes a discourse-oriented approach to information extraction and cross-fertilisation across disciplines through a computationally-aided linguistic analysis.

Objectives The Kidney Team at Home program is an educational intervention aimed at patients with chronic kidney disease to assist them in their choice for kidney replacement therapy. Previous studies have shown that the intervention results in an increase in knowledge and communication on kidney replacement therapy, and eventually in an increase in the number of living donor kidney transplantations. The study assesses the cost-effectiveness of the intervention compared to standard care. Methods A dynamic probabilistic Markov model was used to estimate the monetary and health benefits of the intervention in The Netherlands over 10 years. Data on costs and health-related quality of life were derived from the literature. Transition probabilities, prevalence, and incidence rates were calculated using a large national database. An optimistic and a pessimistic implementation scenario were compared to a base case scenario with standard care. Results In both the optimistic and pessimistic scenario, the intervention is cost-effective and dominant compared to standard care: savings were €108,681,985 and €51,770,060 and the benefits were 1382 and 695 QALYs, respectively. Conclusions The superior cost-effectiveness of the intervention is caused by the superior health effects and the reduction of costs associated with transplantation, and the relatively small incremental costs of the intervention. The favorable findings of this implementation project resulted in national uptake of the intervention in The Netherlands as of 2021. This is the first time a psychosocial intervention has been implemented as part of standard care in a kidney replacement therapy program worldwide.

Histomorphometry seems to provide more rigid quantitative elements for histological analysis and to bring less subjectivity to the diagnosis of oral lichen planus lesions (OLP). This study aimed to verify the association between white and red lesions and histomorphometric characteristics of OLP lesions. This retrospective cross-sectional study assessed 48 hematoxylin- and eosin-stained histological sections from incisional biopsies obtained from OLP cases. A single previously calibrated evaluator performed the light microscopy analyses to evaluate morphological and morphometric parameters. Analyses of associations among variables were performed using the Fisher’s exact test. Morphometric variables were assessed using the Mann–Whitney non-parametric test. Comparisons among the three groups (age range) were performed using the Kruskal–Wallis test. In this study, 81.2% of the participants were women aged 0.05) or between lesion type and histological (p > 0.05) and morphometric variables (p > 0.05). Furthermore, the morphometric variables analyzed did not differ between white and red lesions (p > 0.05) or in their associations with clinicopathological variables (p > 0.05). The results of this investigation showed no associations between white and red OLP lesions and the histomorphometric characteristics evaluated.

BACKGROUND: Metastases account for 6–25% of parotid tumors, often presenting dilemmas in their diagnosis. METHODS: Parotid metastases diagnosed on histology/cytology were retrieved. MUC2, MUC5AC, androgen receptor immunohistochemistry was performed in select cases. RESULTS: Fifty-one samples were identified from 42 patients, including 14 aspirates, 7 biopsies and 30 parotidectomies. Previous history was available in 17 cases, 13 parotidectomies accompanied excision of the primary, and relevant clinical data was unavailable for 12 patients. Majority (81%) had head and neck primaries; eye and ocular adnexa were the commonest subsite (52.4%), and sebaceous carcinoma the commonest histology (33%). When history was unavailable, most metastases were initially diagnosed as poorly differentiated carcinoma/malignant tumor, or mucoepidermoid carcinoma on cytology. CONCLUSIONS: Intraparotid metastases encompass a wide spectrum, often mimicking primary salivary gland neoplasms, particularly on limited samples. Metastases should be considered when histological/cytological features are unusual; detailed clinical information and ancillary techniques aid in arriving at an accurate diagnosis.

Bangladesh, a Muslim-majority country, has a national organ donation law that was passed in 1999 and revised in 2018. The law allows living-related and brain-dead donor organ transplantation. There are no legal barriers to these two types of organ donations, but there is no legislation providing necessary costs and incentive measures associated with successful organ transplants. However, many governments across the globe provide different types of incentives for motivating living donors and families of deceased donors. This study assesses the merits and demerits of incentive measures already in use around the world and proposes ethical measures that can promote organ donation in Bangladesh. The primary focus of this paper is to present an ethical analysis of the comparison of incentive measures on organ donation between Bangladesh and the Islamic Republic of Iran as two Muslim countries that operate organ donation for transplantation practices according to Islamic principles. In this paper, I mainly argue that providing a fixed bare minimum financial incentive measure to distantly related living donors and families of deceased donors will encourage Bangladeshis to donate organs in a manner that is ethically justifiable, morally permissible, and socio-economically appropriate. The government of Bangladesh should revise the existing biomedical law to include a provision related to incentive measures and set a strict policy to properly regulate these measures as key stewardship that can ethically promote organ donation for transplantation.

Ossifying fibroma of the craniofacial bones is a fibro-osseous lesion characterized by varied patterns of bone formation in a fibroblastic stroma. Ossifying fibroma is a putatively benign lesion with no reports of malignant transformation or metastasis. Differentiation from other fibro-osseous lesions can be challenging necessitating synthesis of clinical, radiological and pathological findings. The molecular pathogenesis of ossifying fibroma is poorly understood but recent studies have reported MDM2 gene amplification and chromosomal copy number changes in a subset of ossifying fibromas. MDM2 amplification in ossifying fibroma, if true, presents a diagnostic problem because this genetic event, at least among craniofacial fibro-osseous lesions, was previously considered specific for low-grade osteosarcoma. In the present study, we investigated the utility of MDM2 and CDK4 immunohistochemistry, and fluorescence in situ hybridization for MDM2 gene amplification, in the diagnosis of 44 craniofacial bone ossifying fibromas. Focal MDM2 and CDK4 nuclear immunoreactivity was found in 11 and 1 ossifying fibromas, respectively, but none demonstrated MDM2 amplification by fluorescence in situ hybridization. A single tumor displayed MDM2 amplification without nuclear immunoreactivity to either MDM2 or CDK4. Our data suggest that while focal MDM2 and CDK4 nuclear expression may be detected in a minority of ossifying fibromas, this expression does not correlate with MDM2 amplification. In addition, MDM2 amplification is extremely rare in ossifying fibroma so the detection of this genetic abnormality should continue to raise concern for osteosarcoma.

Paragangliomas and pheochromocytomas are rare neuroendocrine tumors, carrying a germ-line mutation in 40% patients. Sclerosis is a rare histological feature in these tumors. We investigated the possible correlations between histological findings, first sclerosis, immunoreactivity for vesicular catecholamine transporters (VMAT1/VMAT2) and patients’ genotype in a consecutive series of 57 tumors (30 paragangliomas and 27 pheochromocytomas) from 55 patients. The M-GAPP grading system, sclerosis (0–3 scale) and VMAT1/VMAT2 (0–6 scale) immunoreactivity scores were assessed. Germ-line mutations of Succinate Dehydrogenase genes, RET proto-oncogene and Von Hippel Lindau tumor suppressor gene were searched. A germ-line mutation was found in 25/55 (45.5%) patients, mainly with paraganglioma (N = 14/30, 46,66%). Significant (score ≥ 2) tumor sclerosis was found in 9 (16.1%) tumors, i.e., 7 paragangliomas and 2 pheochromocytomas, most of them (8/9) from patients with a germ-line mutation. M-GAPP score was higher in the mutation status (in 76% of patients involving the SDHx genes, in 12% the RET gene and in the remaining 12% the VHL gene) and in tumors with sclerosis (p

Motivation The discovery of the genetic features that underly a phenotype is a fundamental task in microbial genomics. With the growing number of microbial genomes that are paired with phenotypic data, new challenges, and opportunities are arising for genotype-phenotype inference. Phylogenetic approaches are frequently used to adjust for the population structure of microbes but scaling them to trees with thousands of leaves representing heterogeneous populations is highly challenging. This greatly hinders the identification of prevalent genetic features that contribute to phenotypes that are observed in a wide diversity of species. Results In this study, Evolink was developed as an approach to rapidly identify genotypes associated with phenotypes in large-scale multispecies microbial datasets. Compared with other similar tools, Evolink was consistently among the top-performing methods in terms of precision and sensitivity when applied to simulated and real-world flagella datasets. In addition, Evolink significantly outperformed all other approaches in terms of computation time. Application of Evolink on flagella and gram-staining datasets revealed findings that are consistent with known markers and supported by the literature. In conclusion, Evolink can rapidly detect phenotype-associated genotypes across multiple species, demonstrating its potential to be broadly utilized to identify gene families associated with traits of interest. Availability and implementation The source code, docker container, and web server for Evolink are freely available at https://github.com/nlm-irp-jianglab/Evolink.

The collection of post-mortem brain tissue has been a core function of the Alzheimer Disease Research Center’s (ADRCs) network located within the United States since its inception. Individual brain banks and centers follow detailed protocols to record, store, and manage complex datasets that include clinical data, demographics, and when post-mortem tissue is available, a detailed neuropathological assessment. Since each institution often has specific research foci, there can be variability in tissue collection and processing workflows. While published guidelines exist for select diseases, such as those put forth by the National Institute on Aging and Alzheimer Association (NIA-AA), it is of importance to denote the current practices across institutions. To this end a survey was developed and sent to United States based brain bank leaders, collecting data on brain region sampling, including anatomic landmarks used, staining (including antibodies used), as well as whole-slide-image scanning hardware. We distributed this survey to 40 brain banks and obtained a response rate of 95% (38 / 40). Most brain banks followed guidelines defined by the NIA-AA, having H&E staining in all recommended regions and targeted region-based amyloid beta, tau, and alpha-synuclein immunohistochemical staining. However, sampling consistency varied related to key anatomic landmarks/locations in select regions, such as the striatum, periventricular white matter, and parietal cortex. This study highlights the diversity and similarities amongst brain banks and discusses considerations when amalgamating data/samples across multiple centers. This survey aids in establishing benchmarks to enhance dialogues on divergent workflows in a feasible way., Free Neuropathology, Bd. 4 (2023)

BACKGROUND: Giant cell myocarditis (GCM) and cardiac sarcoidosis (CS) are, in contrast to acute non-fulminant myocarditis (ANFM), rare inflammatory diseases of the myocardium with poor prognosis. Although echocardiography is the first-line diagnostic tool in these patients, their echocardiographic appearance has so far not been systematically studied. METHODS: We assessed a total of 71 patients with endomyocardial biopsy-proven GCM (n = 21), and CS (n = 25), as well as magnetic resonance-verified ANFM (n = 25). All echocardiographic examinations, performed upon clinical presentation, were reanalysed according to current guidelines including a detailed assessment of right ventricular (RV) dysfunction. RESULTS: In comparison with ANFM, patients with either GCM or CS were older (mean age (±SD) 55 ± 12 or 53 ± 8 vs 25 ± 8 years), more often of female gender (52% or 24% vs 8%), had more severe clinical symptoms and higher natriuretic peptide levels. For both GCM and CS, echocardiography revealed more frequently signs of left ventricular (LV) dysfunction in form of a reduced ejection fraction (p

Acknowledgements: The authors would like to thank their PhD supervisor Béla Bollobás for his valuable comments., Funder: Engineering and Physical Sciences Research Council; doi: http://dx.doi.org/10.13039/501100000266, Funder: Cambridge Commonwealth, European and International Trust; doi: http://dx.doi.org/10.13039/501100003343, Petruševski and Škrekovski recently introduced the notion of an odd colouring of a graph: a proper vertex colouring of a graph G is said to be odd if for each non-isolated vertex $$x \in V(G)$$ x ∈ V ( G ) there exists a colour c appearing an odd number of times in its neighbourhood N(x). Petruševski and Škrekovski proved that for any planar graph G there is an odd colouring using at most 9 colours and, together with Caro, showed that 8 colours are enough for a significant family of planar graphs. We show that 8 colours suffice for all planar graphs.

Objective:The present study was carried out to compare a bilingual (Balouchi & Persian) vocal patient education program and routine education on patient’s self-efficacy in type 2 diabetes patients suffering from visual impairments. Material and methods:This semi-experimental study was conducted on patients with type 2 diabetes mellitus (T2DM) suffering from visual impairments. A total number of 90 participants were divided into two equal groups: 45 patients in the intervention group and 45 controls in the routine care group. A permuted block randomization (AB) using a random number generator by default was implemented to organize the two groups. One of the researchers collected the demographics and self-efficacy data through face to face interviews. The diabetes management self-efficacy scale (DMSES) was used for self-efficacy assessment. Patients in the intervention group received an MP3 Player including 90 minutes of vocal education. Results:There were no significant differences in participants’ demographic characteristics between the two study groups. However, a remarkable rise was observed in the self-efficacy score (P

Background:Oral lichen planus (OLP) is a chronic inflammatory disease that affects the oral mucosa. This disorder has been suggested to be related to an impairment of lipid metabolism and profile. A number of studies indicate a higher incidence of dyslipidemia in OLP patients compared to not-affected individuals. Objectives: The aim of this study was to investigate the correlations between lipid profile alterations and clinical features of oral lichen planus. Patients and methods:A total of 52 patients diagnosed with OLP were enrolled in this study. Data regarding the demography, symptoms, severity of lesions assesed by Thongprasom score and lipid profile status were collected from the medical charts. The study group was divided into two sub-cohorts: Group 1, which included OLP patients with lipid profile within the normal range, and Group 2 comprising OLP patients with alterations of the lipid status. Results:The comparative analysis between the two groups found a statistically significant association between the lipid profile and OLP symptoms. Thus, the most frequent symptom was pain, in OLP patients with normal lipid status (Group 1), and burning, in those with altered lipid status (Group 2) (p=0.050). Moreover, the presence of symptoms was reported by a higher percentage of patients from Group 2 (75%) than Group 1 (68.25%). Patients reporting burning symptomatology showed higher triglyceride levels than those who reported pain (p=0.032). Furthermore, we found that male OLP patients have higher levels of LDL compared with female subjects (p=0.021). Conclusion:Lipid profile changes are not associated with an increased severity of OLP lesions. A statistically significant association was found between burning sensation and higher lipid profile parameters.

Introduction: Invasive carcinoma of the breast is one of the leading causes of death in women. In developing countries, fine needle aspiration cytology (FNAC) of the breast is used for preoperative diagnosis of breast cancer due to low cost. The grading system of breast carcinoma on FNAC is widely accepted. In the era of neoadjuvant therapy, if grading of breast carcinoma is incorporated in FNAC reports for prognostication, it will be of great help especially in patients with locally advanced disease, older patients with accompanying chronic disease and patients who reject surgery. Hence, there is much to be gained by grading a tumor on FNAC. Materials and methods: The present study was conducted on 40 cases of cytologically diagnosed breast carcinomas. Fine needle aspiration cytology smears were graded by Robinson cytological grading system. All surgical specimens were processed and the histological grading of the resulting slides was done by the Nottingham modification of Bloom Richardson score. Then, the cytological grade was compared with the histological grade and statistical analysis was done. Results:Based on Robinson grading method, cases were classified into grade I (15%), grade II (55%) and grade III (30%). Based on the Nottingham modification of Bloom Richardson (SBR) grading method, the cases were classified as grade I (5%) and grade II and III (47.5%) each. A total concordance rate between both the grading systems was seen in 65% of cases. A positive correlation was found and there was a significant association between Robinson cytological grading and SBR histological grading. Conclusions:Grading breast carcinoma on cytology allows its prognostic evaluation along with diagnostic value without any additional morbidity or expense to the patient. Thus, it is recommended to grade breast carcinomas on FNAC. It helps in deciding the proper line of treatment, so that patients can have a better prognosis.

BackgroundEpilepsy is a common and devastating neurological disease. Its treatment, especially when using phenobarbital, causes liver complications, and it is therefore essential to identify a way to reduce liver complications. This study aimed to investigate the protective effect of ursodeoxycholic acid on liver function in pediatric patients with seizure treated with phenobarbital. Materials and methods:Materials and methods: The present study was conducted on 80 patients (40 in the placebo group and 40 in the ursodeoxycholic acid group). To assess the effect of intervention, liver enzyme levels after five weeks of treatment were recorded. Independent t-test and ANOVA repeated measures were used to compare the means. Conclusions:The study results showed that the administration of ursodeoxycholic acid had a relative effect in improving liver function in patients with liver injury caused by phenobarbital.

Objective:The assessment of novel coronavirus disease 2019 (COVID-19) antibodies is essential to understand the transmission dynamics of contagious disease. The proportion of the population who developed antibodies against the COVID-19 disease can be estimated through population-based serosurveys. This population based cross sectional serosurvey was designed to assess the seroprevalence of IgG and IgM antibodies of COVID-19 infection. Material and methods:A population based cross sectional serosurvey included 1031 residents of Itanagar Capital Complex region (ICR), Arunachal Pradesh, India, aged above five years. Anti-SARS-CoV-2 specific IgG and IgM antibody levels were analyzed by chemiluminescence immunoassay based serological tests. Results:The overall seropositivity for SARS-CoV-2 IgG and IgM was 92.24% and 7.7%, respectively. The seropositivity of IgG and IgM was 97.68% and 2.32%, respectively, in subjects fully vaccinated with two doses, 97.22% and 13.88%, respectively, in those vaccinated with the first dose, and 80% and 11.33%, respectively, in non-vaccinated participants. In contrast to indigenous tribal participants (IgG 90.55% and IgM 8.88%), seroprevalence was high in non-tribal subjects (IgG 94.72% and IgM 6.84%). Age, ethnicity, and area showed a positive correlation, while vaccination status exhibited a negative correlation with IgG levels (Pearson's coefficient -0.535). Conclusions:This first monocentric serosurvey following the high rate of infection with Delta variant in ICR found a high seropositivity for IgG. Further state level serosurveys are needed to assess the infection status, immunological response and associated comorbidities of COVID-19 infection. Periodic vaccination campaigns and early administration of booster doses to the general public might be beneficial in preserving immunity and prevent illness.

Background: Minimal hepatic encephalopathy (MHE) consists of subtle cognitive deficits that are not apparent on a standard neurological examination. Minimal hepatic encephalopathy has been reported in up to 80% of cirrhotic patients and is associated with decreased job performance, poor driving performance, impaired quality of life, and poor survival. In parallel, brain magnetic resonance imaging (MRI) abnormalities are known to occur in liver cirrhotic patients in the form of T1 globus pallidus hyperintensities. In recent years, a new psychometric test for diagnosing MHE has been developed as an app for smartphones and tablets (EncephalApp Stroop test). A translated version of the app is available in Romanian language. Aim:To use EncephalApp Stroop test for MHE diagnosis in our cirrhotic patients; to describe the main brain MRI abnormalities encountered in these patients; and to establish if Stroop test results correlate with imaging findings, clinical neurologic findings, and liver function parameters or prognosis. Material and methods:Cross-sectional study over a one-year period, involving 30 adult patients with liver cirrhosis. Subjects were evaluated through a standard neurological examination, psychometric testing using EncephalApp Stroop test, electroencephalogram and brain MRI. In parallel, 40 adult healthy controls were also recruited and evaluated with the EncephalApp Stroop test using the same methodology. Results:Age distribution was similar between the two groups (p=0.6). The mean age of patients was 50±10 years and that of controls 51±12 years. Mean Stroop result was 171±26 seconds for the patient group and 143±20 seconds for the control group (p

There are scarce data regarding foot osteomyelitis (FO) caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB). This study investigates the causative organisms, the diagnostic and therapeutic approach and the outcome of these infections. All patients with FO caused by MDR and/or XDR GNB who received treatment in the Department of osseous infectious diseases of the “Attikon” University Hospital of Athens, Greece, were recorded and evaluated during a six-year-period. Seventeen patients, of which 64.7% females, with a mean age of 54.06 years were studied. There were nine cases with diabetic (DFO), and 76.5% of patients reported previous use of antimicrobials. Pathogens were isolated from soft-tissue biopsies or intra-operative tissue samples (n=12) and/or affected bone samples (n=5). In most cases, E. coli and P. aeruginosa were isolated (each 29.4%), followed by P. mirabilis (11.7%), while polymicrobial infection was detected in nine patients (53%). Most cases were given antimicrobial monotherapy (88.2%) with a mean duration of 90.05 days, while surgery significantly promoted cure of the infection. Foot and DFO cases represent a challenging to treat disease, requiring a multidisciplinary approach. Surgical treatment remains the cornerstone of treatment, while it is of utmost importance to isolate the causative organisms. MDR and XDR GNB represent an emerging threat and more data are needed to better understand these infections.