Moreover, sperm concentration and motility parameters did not differ between treatments (P > 0.05). Compared to the 38.8 °C control, our in vitro heat shock model significantly increased sperm DNA damage after incubation at 54 and 60 °C (3.0 ± 1.0, 2.9 ± 1.0, 1.2 ± 0.3, 2.5 ± 0.7, 9.0 ± 3.7, 16.2 ± 7.1, 14.2 ± 5.8 and 41.8 ± 18.6% respectively; P ≤ 0.05). However, these temperatures rendered sperm completely immotile or dead, with most motility parameters declining rapidly to zero above 40 or 42 °C. In conclusion, our results suggest that temperature combined with individual factors may contribute to a boar’s overall susceptibility to heat stress. Refinement of these models particularly of the in vitro heat shock model could be further pursued to overcome environmental variability, reduce whole animal experiments and provide a putative diagnostic fertility screening tool to evaluate heat tolerance in the boar.

To evaluate the ability of geldanamycin to modulate two opposing TNFα/TNFR1-triggered signals for inflammation and cell death.

The effects of geldanamycin on TNFα-induced proinflammatory cytokine production, apoptosis, NF-κB activation, caspase activation, and necroptosis in a human rheumatoid synovial cell line (MH7A) were evaluated via ELISA/qPCR, flow cytometry, dual-luciferase reporter assay, and western blotting assay, respectively. In addition, therapeutic effects on murine collagen-induced arthritis (CIA) were also evaluated.

Geldanamycin disrupted RIPK1 in MH7A, thereby inhibiting TNFα-induced proinflammatory cytokine production and enhancing apoptosis. TNFα-induced NF-κB and MLKL activation was inhibited, whereas caspase 8 activation was enhanced. Recombinant RIPK1 restored the geldanamycin-mediated inhibition of TNFα-induced NF-κB activation. In addition, GM showed more clinical effectiveness than a conventional biologic TNF inhibitor, etanercept, in murine CIA and significantly attenuated synell line, MH7A. • GM showed more clinical effectiveness than a conventional biologic TNF-inhibitor, etanercept, in murine collagen-induced arthritis (CIA), and significantly attenuated synovial hyperplasia, a histopathological hallmark of RA. • Therapeutic targeting RIPK1 may be a novel concept which involves TNF inhibitor acting as a TNFR1-signal modulator and have great potential for a more fundamental, effective, and safer TNF-inhibitor.

We aimed in this study to determine the level of serum fetuin-A level in systemic lupus erythematosus patients, assess the correlation between serum fetuin-A level and the activity of disease and the frequency of musculoskeletal manifestations, and detect the frequency of atherosclerosis among these patients by using carotid ultrasonography.

This case-control study was carried out on 31 SLE patients attending the inpatient and outpatient clinics of Rheumatology and Rehabilitation Department, Faculty of Medicine, Zagazig university hospitals and 31 apparently healthy age- and sex-matched controls between January 1,2017, and December 31, 2018.

There is a highly significant difference between the two studied groups as regard fetuin-A and carotid intima-media thickness. There is a strong positive significant correlation between fetuin-A with C3 and a negative significant correlation between fetuin-A with Anti-dsDNA, SLEDAI, and carotid intima-media thickness in case group.

Fetuin-A levels were decreased in SLE patients, and these levels were inversely correlated with carotid intima-media thickness. Key Points • Fetuin-A level is a biomarker of atherosclerosis and asses disease activity in SLE patients.

Fetuin-A levels were decreased in SLE patients, and these levels were inversely correlated with carotid intima-media thickness. Key Points • Fetuin-A level is a biomarker of atherosclerosis and asses disease activity in SLE patients.In this study, we examine sublingual videomicroscopy and nailfold videocapillaroscopy (NVC) features in systemic sclerosis (SSc) patients presenting for routine care. Consented participants met classification criteria for SSc. Sublingual videomicroscopy testing was performed in each subject, followed by a NVC assessment. Sublingual assessment provided a density measurement, red blood cell fraction (RBC fract), and perfused boundary region (PBR) score. NVC evaluator defined nailfold findings as normal; specific changes for „early,” „active,” and „late” scleroderma pattern; or „non-specific” changes. Microangiopathy evolution score was calculated for each participant. Statistical evaluation was performed by non-parametric tests to assess the correlation of the two tools. Thirty-nine SSc patients with limited cutaneous disease participated in this study. Most participants had late pattern NVC. There was a highly significant association between the total sublingual microvascular density and number of capillaries sublingual microscopy can identify a loss of capillary density in SSc patients.We aim to explore real-world biological survival stratified for discontinuation reason and determine its influenceability in rheumatoid arthritis (RA) patients. Data from the local pharmacy database and patient records of a university hospital in the Netherlands were used. RA patients who started a biological between 2000 and 2020 were included. Data on age, anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) status, presence of erosions, gender, body mass index, time to first biological, biological survival time, use of csDMARDs, and discontinuation reasons were collected. Of the included 318 patients, 12% started their first biological within 6 months after diagnosis. The median time to first biological was 3.6 years (95% CI, 1.0-7.2). The median survival of the first- and second-line biological was respectively 1.7 years (95% CI, 1.3-2.2) and 0.8 years (95% CI, 0.5-1.0) (p = 0.0001). Discontinuation reasons for the first-line biological were ineffectiveness (47%), adverse events (17%), re Points • Prolonged biological survival is a surrogate for treatment effectiveness; however, an increasing amount of patients will taper treatment due to remission, and factors influencing biological survival based on separate reasons for discontinuation have not been explored. • We found that combining a biological DMARD with a conventional synthetic DMARD increases biological DMARD survival. Rheumatoid factor is negatively associated with biological survival. Anti-citrullinated protein antibody is negatively associated with the inability to discontinue the biological when remission was reached. • The first step towards personalized medicine might be tailoring of treatment based upon autoantibody status.

Recent data shows a significantly increased risk of diverticulosis among smokers. There is limited data on the association between tobacco smoking and diverticulitis. We aim to determine in-hospital outcomes, length of hospital stay, and resource utilization in a contemporary cohort of diverticulitis patients based on tobacco smoking status.

A retrospective analysis was performed by utilizing the National Inpatient Sample database (2016 and 2017) and the International Classification of Diseases, Tenth Revision codes to identify the patients with the principal diagnosis of diverticulitis and smoking. We assessed all-cause in-hospital mortality, morbidity, length of hospital stay (LOS), and total costs between propensity-matched groups of tobacco smokers vs. nonsmokers with diverticulitis.

We identified 442,273 diverticulitis patients, of whom 96,864 were tobacco smokers, and 345,409 were nonsmokers. Between the two groups, in-hospital mortality was not significant (OR 1.09, 95% CI 0.38-2.6; P = 0.98). Toere was no difference in in-hospital mortality between tobacco smokers vs. nonsmokers with diverticulitis. Smoking has been associated with an increased incidence of complications in diverticulitis with a higher length of hospital stay and resource utilization.

Colorectal neuroendocrine carcinomas (CRC-NECs) are rare, comprising < 1% of colorectal cancers. This study aimed to assess the incidence, clinicopathologic characteristics, prognostic factors, and treatment outcomes of CRC-NEC.

We analysed the Surveillance, Epidemiology, and End Results (SEER) database to identify patients from 20 to 74years old diagnosed with CRC-NEC or common CRC (non-NEC) during 2004-2013. Log-rank testing was conducted to assess survival differences. A competing-risks regression model was used to adjust for covariate effects in the propensity score-matched (PSM) cohort, and adjusted hazard ratios (HRs) were calculated for the raw and PSM cohorts.

We identified 67,484 patients (344 CRC-NEC and 67,140 non-NEC). Lymph node metastasis (LNM) was more common in CRC-NEC (75.29%, n = 259) than in non-NEC (51.53%, n = 34,600) (P < 0.001); 56.40% (n = 194) of CRC-NECs were located on the right side, while 18.31% (n = 63) were located on the left side, with a statistically significant difference in distribution (P < 0.001) compared to that in non-NEC CRC. Multivariate analysis indicated that a left-side location was an independent adverse prognostic factor for CRC-NEC (P = 0.043). CRC-NEC had the poorest cancer-specific survival (median CSS, 9.0months) among assessed cancers, even poorer than that of signet ring cell cancer (median CSS, 24.0months). However, both radical operation (P = 0.007) and chemotherapy (P = 0.008) were beneficial for CSS.

NEC is a rare and extremely aggressive tumour with a poor prognosis. Right-side NEC has a better prognosis than left-side NEC. Early diagnosis, radical surgery, and chemotherapy are imperative for improving survival.

NEC is a rare and extremely aggressive tumour with a poor prognosis. Right-side NEC has a better prognosis than left-side NEC. Early diagnosis, radical surgery, and chemotherapy are imperative for improving survival.

Traditional management of traumatic hemothorax/hemopneumothorax (HTX/HPTX) has been insertion of large-bore 32-40 French (Fr) chest tubes (CTs). Retrospective studies have shown 14Fr percutaneous pigtail catheters (PCs) are equally effective as CTs. Our aim was to compare effectiveness between PCs and CTs by performing the first randomized controlled trial (RCT). We hypothesize PCs work equally as well as CTs in management of traumatic HTX/HPTX.

Prospective RCT comparing 14Fr PCs to 28-32Fr CTs for management of traumatic HTX/HPTX from 07/2015 to 01/2018. We excluded patients requiring emergency tube placement or who refused. Primary outcome was failure rate defined as retained HTX or recurrent PTX requiring additional intervention. Secondary outcomes included initial output (IO), tube days and insertion perception experience (IPE) score on a scale of 1-5 (1 = tolerable experience, 5 = worst experience). Unpaired Student’s t-test, chi-square and Wilcoxon rank-sum test were utilized with significance set aT02553434.

While most patients with early-stage mycosis fungoides (MF) follow an indolent course, patients with advanced-stage MF/Sézary syndrome (SS) have a poor prognosis with a median survival of less than 5years. Although there are a number of treatments currently available, achieving and maintaining a durable response remain challenging, especially in advanced-stage MF/SS. The choice of frontline therapy is dependent on the stage of disease. For early-stage MF, the treatment concept is to control skin lesions mainly by skin-directed therapies, such as topical therapies, phototherapies, and radiotherapies. For advanced-stage MF/SS, systemic treatments by biological or targeted therapies including bexarotene and interferon either alone or in combination are tried first, with more immunosuppressive chemotherapies being reserved for refractory or rapidly progressive disease. Recent improvements in biological or targeted therapies include brentuximab vedotin and mogamulizumab. When biopsy samples have 10% or more CD30vement, mogamulizumab, an antibody binding to C-C chemokine receptor 4, is effective with high response rates. In the refractory setting, alemtuzumab, histone deacetylase inhibitors, pralatrexate, gemcitabine, and doxorubicin are considered as the treatment option. Because only allogeneic hematopoietic stem cell transplantation can offer a chance of cure with durable complete remission, advanced-stage patients with a markedly short life expectancy should be evaluated for eligibility. Given that there are few randomized controlled studies in the literature, it is necessary to investigate which therapy is preferable for each patient with MF/SS by comparative prospective trials.Carcinoma showing thymus-like differentiation (CASTLE) is a rare tumor, especially in the parotid gland. We encountered a CASTLE of the parotid gland and analyzed its clinicopathological features, as well as the genotype using whole exome sequencing (WES). Moreover, we successfully established an organoid culture cell line from the primary tumor tissue. The patient was a 23-year-old woman who underwent superficial parotidectomy with peripheral neck dissection, followed by radiotherapy. Pathologically, the resected specimen showed atypical epithelioid nests and trabeculae with squamous differentiation, separated by thick fibrous septa, accompanied by dense lymphocytes and plasma cell infiltration. Immunohistochemistry revealed that the tumor cells were positive for AE1/AE3, p40, p63, p16, CK5/6, and CD5, and the background lymphocytes were positive for CD5 and CD99. Based on these findings, the tumor was diagnosed as CASTLE. WES uncovered five nonsynonymous and splicing somatic mutations, namely, FREM2 p.Val861Phe, CLK3 p.Phe376Leu, DLGAP1 p.Lys294Asn, NOX1 p.Val165Met, and PSG9 c.430 + 4A > T. Organoid culture cells preserved the histopathological characteristics of the epithelioid component of CASTLE and harbored all five somatic mutations detected in the primary tumor. In conclusion, for the first time to the best of our knowledge, we successfully analyzed a comprehensive genotype and established an organoid culture cell line of a parotid gland CASTLE, which should serve for analyzing the nature of this rare tumor.Medical image data plays a critical role in health care today. Whatever the context of image processing (research and educational activities, diagnostic or forensic purposes, etc.), they are supposed to be treated as highly sensitive. Unfortunately, currently available image-processing tools also enable very sophisticated malicious modification of their content.This paper is focused on the assessment of the effectiveness of selected so-called zero watermarking methods (ones that do not cause any modification of an image sample), in the protection of the integrity, and proving authorship, of these medical image studies. We have studied many zero watermarking methods and selected one representative from each type of known algorithms for comparison.We have conducted a series of simulations over a huge research database of anonymized medical image studies (patient examinations).Melanoma is the most fatal type of skin cancer. Detection of melanoma from dermoscopic images in an early stage is critical for improving survival rates. Numerous image processing methods have been devised to discriminate between melanoma and benign skin lesions. Previous studies show that the detection performance depends significantly on the skin lesion image representations and features. In this work, we propose a melanoma detection approach that combines graph-theoretic representations with conventional dermoscopic image features to enhance the detection performance. Instead of using individual pixels of skin lesion images as nodes for complex graph representations, superpixels are generated from the skin lesion images and are then used as graph nodes in a superpixel graph. An edge of such a graph connects two adjacent superpixels where the edge weight is a function of the distance between feature descriptors of these superpixels. A graph signal can be defined by assigning to each graph node the output of some single-valued function of the associated superpixel descriptor. Features are extracted from weighted and unweighted graph models in the vertex domain at both local and global scales and in the spectral domain using the graph Fourier transform (GFT). Other features based on color, geometry and texture are extracted from the skin lesion images. Several conventional and ensemble classifiers have been trained and tested on different combinations from those features using two datasets of dermoscopic images from the International Skin Imaging Collaboration (ISIC) archive. The proposed system achieved an AUC of [Formula see text], an accuracy of [Formula see text], a specificity of [Formula see text] and a sensitivity of [Formula see text].Chicken is a homeothermic animal; consequently, regardless of fluctuation in weather conditions, it maintains constant body temperature. However, in hot regions and seasons, chickens suffer from heat stress. To dissipate excess heat, besides modifying the environment, which is costly, however, chickens with efficient heat dissipation capacity might be utilized. Naked neck chickens have a higher capacity for heat loss attributable to reduced feather mass. The naked neck mutation (Na) was originated from a large insertion (~ 180 bp) integrated ~ 260-kb downstream of a protein-coding gene-GDF7 (Growth Differentiation Factor 7). Na possesses a cis-regulatory function and upregulates the expression of GDF7-a gene that exhibits a tissue-specific effect by the sensitizing action of retinoic acid. Na suppresses the development of feathers in the neck and vent. Na shows autosomal incomplete dominance and regulates several developmental processes. Na usually segregates at low frequency, which might be attributed to limcken.The microbial H2-producing (hydrogenogenic) carbon monoxide (CO)-oxidizing activity by the membrane-associated CO dehydrogenase (CODH)/energy-converting hydrogenase (ECH) complex is an important metabolic process in the microbial community. However, the studies on hydrogenogenic carboxydotrophs had to rely on inherently cultivation and isolation methods due to their rare abundance, which was a bottleneck in ecological study. Here, we provided gene-targeted sequencing method for the diversity estimation of thermophilic hydrogenogenic carboxydotrophs. We designed six new degenerate primer pairs which effectively amplified the coding regions of CODH genes forming gene clusters with ECH genes (CODHech genes) in Firmicutes which includes major thermophilic hydrogenogenic carboxydotrophs in terrestrial thermal habitats. Amplicon sequencing by these primers using DNAs from terrestrial hydrothermal sediments and CO-gas-incubated samples specifically detected multiple CODH genes which were identical or phylogenetically related to the CODHech genes in Firmictes. Furthermore, we found that phylogenetically distinct CODHech genes were enriched in CO-gas-incubated samples, suggesting that our primers detected uncultured hydrogenogenic carboxydotrophs as well. The new CODH-targeted primers provided us with a fine-grained (~ 97.9% in nucleotide sequence identity) diversity analysis of thermophilic hydrogenogenic carboxydotrophs by amplicon sequencing and will bolster the ecological study of these microorganisms.

The aim of this study is to utilize the Manchester scar scale (MSS) and ultrasound in investigating the association between uterine wall defects and cutaneous scar characteristics after cesarean section (CS).

This is a prospective cohort study. The degree of myometrial loss was quantified by calculating a residual myometrial thickness (RMT) ratio as a percentage of RMT to the pre-cesarean anterior uterine wall thickness. Cutaneous scar assessment was performed according to the MSS. Spearman’s correlation and the Kruskal-Wallis test with a cut-off value of p < 0.05 were used for statistical analysis.

Twohundred forty seven women, of which 2.4% had an Asian, 3.6% an Afro-American, 82% a Caucasian and 12% a Mediterranean background, were recruited. The RMT ratio ranged between 11.9 and 100% with a median of 55.8% and an average of 56%. MSS scores ranged from 4 to 13 with a median of 5 and an average of 6. Spearman’s correlation between MSS and RMT ratio show a rho of -0.01 with a p value of 0.8. The correlation between MSS and RMT ratio within the four ethnical groups showed a p value between 0.3 and 0.8 and a rho between 0.8 and -0.8. The Kruskal-Wallis test showed an eta

of 0.13 and a p value of 0.0002 for the effect of ethnicity on MSS and an eta

of 0.009 and a p value of 0.68 for the effect of ethnicity on the RMT ratio.

CS laparotomy scars heal differently between ethnical groups, but generally with satisfying results. Ethnicity does not affect myometrial healing and scar appearance does not reflect myometrial healing after CS. Thus, separate uterine sonographic assessment is recommended.

CS laparotomy scars heal differently between ethnical groups, but generally with satisfying results. Ethnicity does not affect myometrial healing and scar appearance does not reflect myometrial healing after CS. Thus, separate uterine sonographic assessment is recommended.

To evaluate COX-2 and Nrf2/GPx3 expressions in the lamina propria of the anterior vaginal wall tissues of women with and without pelvic organ prolapse (POP).

Tissue samples of anterior vaginal wall were examined using HE staining, immuohistochemical staining and Western blot for the expressions of COX-2/PGE2, Nrf2/GPx3, MMP2, TIMP1, collagen I and collagen III (n = 35, per group).

Compared with control group, collagen fibers of the anterior vaginal wall were disorganized and discontinuous. Expressions of Nrf2, GPx3, TIMP1, collagen I and collagen III were found significantly lower in POP group (P < 0.05); while, expressions of COX-2, PGE2, and MMP2 were found significantly higher in POP group (P < 0.05). Statistically significant correlations of COX-2 and Nrf2/GPx3 were showed (P < 0.01).

We found that the interaction between inflammation and oxidative stress was closely related to the development of POP. This study demonstrates that COX-2 and Nrf2 pathways may be involved in pathogenesis of POP, as promising potential therapeutic targets and agents.

We found that the interaction between inflammation and oxidative stress was closely related to the development of POP. This study demonstrates that COX-2 and Nrf2 pathways may be involved in pathogenesis of POP, as promising potential therapeutic targets and agents.

To compare the image quality between the vendor-agnostic and vendor-specific algorithms on ultralow-dose chest CT.

Vendor-agnostic deep learning post-processing model (DLM), vendor-specific deep learning image reconstruction (DLIR, high level), and adaptive statistical iterative reconstruction (ASiR, 70%) algorithms were employed. One hundred consecutive ultralow-dose noncontrast CT scans (CTDI

; mean, 0.33 ± 0.056 mGy) were reconstructed with five algorithms DLM-stnd (standard kernel), DLM-shrp (sharp kernel), DLIR, ASiR-stnd, and ASiR-shrp. Three thoracic radiologists blinded to the reconstruction algorithms reviewed five sets of 100 images and assessed subjective noise, spatial resolution, distortion artifact, and overall image quality. They selected the most preferred algorithm among five image sets for each case. Image noise and signal-to-noise ratio were measured. Edge-rise-distance was measured at a pulmonary vessel, i.e., the distance between two points where attenuation was 10% and 90% of maximaattenuation compared to a vendor-agnostic algorithm.In the process of diagnosis and disease monitoring, it is important to quickly and easily detect protein biomarkers. The strategy reported here is an attempt to prepare Bi2MoO6 nanomaterial with new three-dimensional holes morphology surrounded by rod and sheet to construct a simple and sensitive sensing platform, where Bi2MoO6/ionic liquid (IL) composite was modified on the carbon paste electrode (CPE). In order to monitor the assembly process of human IgG immunosensors, a plurality of electrochemical tests such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) was executed. The obtained BSA/anti-IgG/GA/Bi2MoO6/IL-CPE displayed prominent conductivity and high sensitivity in detecting human immunoglobulin G (human IgG). Under the optimal experimental conditions, the results by differential pulse voltammetry (DPV) showed that the constructed label-free IgG immunosensor can detect IgG in the range of 0.01 to 1000 ng mL-1, and limit of detection (LOD) was 4 pg mL-1. The immunosensor displayed good performances including selectivity, reproducibility, and stability. Based on preliminary experiments, Bi2MoO6 and its composite materials are very promising for the construction of a variety biosensors for the analysis of other biological substances. Graphical abstract.During the last years, microplastics in the environment came to the fore in environmental science research. For an appropriate risk assessment, it is essential to know the levels of microplastic contamination in the environment. In the field of microplastic detection, extensive research has been carried out in recent years. While common methods such as Raman spectroscopy and pyrolysis GC-MS are time-consuming and require trained staff and expensive equipment, there is the need for a cheap and easily applicable method. Staining microplastics with the fluorescent dye Nile red (NR) has a high potential to fulfill these criteria. In our work, we tested Nile red and newly developed derivatives, with the aim of achieving greater selectivity for plastic particles and more intense fluorescence. In addition, the influence of using different solvents and water at different pH values in the dyeing process was investigated by analyzing solid sample fluorescence spectra of dyed microplastics and natural particles. Finally, the method developed from the acquired knowledge was tested for sea salt. Graphical abstract.

To evaluate PET/MR lung nodule detection compared to PET/CT or CT, to determine growth of nodules missed by PET/MR, and to investigate the impact of missed noduleson clinical management in primary abdominal malignancies.

This retrospective IRB-approved study included [18F]-FDGPET/MR in 126 patients. All had standard of care chest imaging (SCI) with diagnostic chest CT or PET/CT within 6weeks of PET/MR that served as standard of reference. Two radiologists assessed lung nodules (size, location, consistency, position, and [18F]-FDGavidity) on SCI and PET/MR. A side-by-side analysis of nodules on SCI and PET/MR was performed. The nodules missed on PET/MR were assessed on follow-up SCI to ascertain their growth (≥ 2mm); their impact on management was alsoinvestigated.

A total of 505 nodules (mean 4mm, range 1-23mm) were detected by SCI in 89/126 patients (66M60F, mean age 60years). PET/MR detected 61 nodules for a sensitivity of 28.1% for patient and 12.1% for nodule, with higher sensitivity for > 7 mm nssible different implications in patients without extra-thoracic spread.

The aim of this study was to explore the role of [

Ga]Ga-DOTA-FAPI-04 positron emission tomography/computed tomography (PET/CT), compared with

F-fluorodeoxyglucose [

F]-FDG PET/CT, for evaluating peritoneal carcinomatosis in patients with various types of cancer.

Patients with suspected peritoneal malignancy, who underwent both [

F]-FDG and [

Ga]Ga-DOTA-FAPI-04 PET/CT between October 2019 and August 2020, were retrospectively analysed. The radiotracer uptake, peritoneal cancer index (PCI) score, and diagnostic performance of [

F]-FDG and [

Ga]Ga-DOTA-FAPI-04 PET/CT were evaluated and compared.

Our cohort consisted of 46 patients, including 16 patients with diffuse-type peritoneal carcinomatosis, 27 with nodular-type peritoneal carcinomatosis, and 3 true-negative patients. A significant difference in standard uptake values (SUV) of lesions between [

F]-FDG and [

Ga]Ga-DOTA-FAPI-04 PET/CT examination was observed (median SUV 3.48 vs. 9.82; P < 0.001), particularly in peritoneal carcinomatosishermore, the uptake of [68Ga]Ga-DOTA-FAPI-04 in peritoneal carcinomatosis was significantly higher than that of [18F]-FDG, demonstrating a larger extent of the lesions and yielding a higher PCI score. This could help enhance the image contrast, improve physicians’ diagnostic confidence, and reduce the proportion of missed diagnoses.

Standardized uptake value ratio (SUVr) used to quantify amyloid-β burden from amyloid-PET scans can be biased by variations in the tracer’s nonspecific (NS) binding caused by the presence of cerebrovascular disease (CeVD). In this work, we propose a novel amyloid-PET quantification approach that harnesses the intermodal image translation capability of convolutional networks to remove this undesirable source of variability.

Paired MR and PET images exhibiting very low specific uptake were selected from a Singaporean amyloid-PET study involving 172 participants with different severities of CeVD. Two convolutional neural networks (CNN), ScaleNet and HighRes3DNet, and one conditional generative adversarial network (cGAN) were trained to map structural MR to NS PET images. NS estimates generated for all subjects using the most promising network were then subtracted from SUVr images to determine specific amyloid load only (SAβ

). Associations of SAβ

with various cognitive and functional test scores were then computed and compared to results using conventional SUVr.

Multimodal ScaleNet outperformed other networks in predicting the NS content in cortical gray matter with a mean relative error below 2%. Compared to SUVr, SAβ

showed increased association with cognitive and functional test scores by up to 67%.

Removing the undesirable NS uptake from the amyloid load measurement is possible using deep learning and substantially improves its accuracy. This novel analysis approach opens a new window of opportunity for improved data modeling in Alzheimer’s disease and for other neurodegenerative diseases that utilize PET imaging.

Removing the undesirable NS uptake from the amyloid load measurement is possible using deep learning and substantially improves its accuracy. This novel analysis approach opens a new window of opportunity for improved data modeling in Alzheimer’s disease and for other neurodegenerative diseases that utilize PET imaging.Digestion of dietary protein in teleosts results in high ammonia levels within the intestinal chyme that may reach concentrations that are many-fold greater than blood plasma levels. We used in vitro gut sac preparations of the ammoniotelic rainbow trout (Oncorhynchus mykiss) to investigate the role of the intestine in producing and transporting ammonia and urea, with specific focus on feeding versus fasting, and on responses to loading of the lumen with 2 mmol L-1 glutamine or 2 mmol L-1 ammonia. Feeding increased not only ammonia production and both mucosal and serosal fluxes, but also increased urea production and serosal fluxes. Elevated urea production was accompanied by an increase in arginase activity but minimal CPS III activity, suggesting that urea may be produced by direct arginolysis. The ammonia production and serosal fluxes increased in fasted preparations with glutamine loading, indicating an ability of the intestinal tissue to deaminate glutamine and perhaps use it as an energy source. However, there was little evidence of urea production or transport resulting from the presence of glutamine. Furthermore, the intestinal tissues did not appear to convert surplus ammonia to urea as a detoxification mechanism, as urea production and serosal flux rates decreased in fed preparations, with minimal changes in fasted preparations. Nevertheless, there was indirect evidence of detoxification by another pathway, as ammonia production rate decreased with ammonia loading in fed preparations. Overall, our study suggests that intestinal tissues of rainbow trout have the ability to produce urea and detoxify ammonia, likely via arginolysis.

The pervasiveness of doping and findings of anti-doping corruption threaten weightlifting’s position at the 2024 Olympic Games. Analysing the practices of doping in weightlifters could identify patterns in doping that assist in future detection.

We analysed publicly available data on sanctioned athletes/support personnel from the International Weightlifting Federation between 2008 and 2019 and announced retrospective Anti-Doping Rule Violations (ADRVs) from the 2008 and 2012 Olympic Games.

There were 565 sanctions between 2008 and 2019 of which 82% related to the detection of exogenous Anabolic Androgenic Steroid (AAS) metabolites and markers indicating endogenous AAS usage. The detection of exogenous AAS metabolites, markers of endogenous AAS usage and other substance metabolites varied by IWF Continental Federation (p ≤ 0.05) with Europe (74%, 11%, 15%) and Asia (70%, 15%, 15%) showing a higher detection of exogenous AAS compared to Pan America (37%, 30%, 33%) and Africa (50%, 17%, 33%). When looking , weightlifting would benefit from the targeted testing of certain regions and continuing investment in long-term sample storage as the sensitivity and specificity of detection continues to improve.The cavovarus foot (CF) is a complex three-dimensional foot deformity. In addition to primary forms, secondary forms can be distinguished. The diagnosis of CF is made clinically; however, anamnestic information, a targeted examination including neurological status and at least radiological imaging using the hindfoot-centered imaging technique are required to determine the treatment. Conservative treatment for CF consists of the provision of insoles up to the adaptation of an orthopedic custom-made shoe, depending on the severity of the deformity. The indications for a surgical procedure are present in the case of increasing complaints, although the timing should be extensively discussed with the patient in order to be able to achieve the best functional results. Surgical treatment is generally complex but a combination of soft tissue interventions and osteotomy/arthrodesis can usually be used to achieve a plantigrade foot position and thereby enable the patient to walk with a functionally improved gait.The introduction of tyrosine kinase inhibitors (TKIs) has improved the overall survival of chronic myeloid leukemia patients in chronic phase (CP-CML) and reduced the rate of disease-related mortality. Conflicting results have been however reported between data emerged from sponsored clinical trials and from population-based registries. Moreover, no data are so far available for patients treated with frontline second-generation TKIs, excluding those from sponsored studies. We analyzed the mortality rate of 2315 CP-CML patients treated with frontline second-generation TKIs through the Italian Medicines Agency (AIFA) registries and compared it with the ISTAT mortality rate of the general population. The estimated differences show that the increased rate of mortality in CP-CML patients is less than 1% for the class 0-29 years, stable around 2% for the intervals 30-44 years and 45-59 years, and 1.4% for the interval 60-74 years; interestingly this rate is reduced for patients aged 75 years and more as compared to the general population (- 0.65%). The difference between potential and estimated deaths is higher among women in the age classes between 30 and 74 years.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective and curative treatment for acute myeloid leukemia (AML). We explored the outcome of haploidentical donor (HID) transplantation for intermediate-risk AML and compared to that of matched sibling donor (MSD) transplants. One hundred twenty-seven consecutive patients with intermediate-risk AML in the first complete remission (CR1) who underwent allo-HSCT between January 1, 2015, and August 1, 2016, were enrolled. Thirty-seven patients received MSD grafts, and 90 received HID grafts. The 2-year leukemia-free survival (LFS) of the HID group was comparable to that of the MSD group 82.0% ± 4.1% versus 82.7% ± 6.4%, P = 0.457. The 2-year cumulative incidences of relapse and transplantation-related mortality (TRM) were comparable between the HID and MSD groups (relapse, 4.5% ± 0.1%, versus 11.5% ± 0.3%, P = 0.550; TRM, 13.4% ± 0.1% vs. 5.8% ± 0.2%, P = 0.154). The HID recipients had a trend of a lower 2-year cumulative incidence of positive posttransplant flow cytometry (FCM+) and relapse than the MSD recipients (5.6% ± 0.1% vs. 19.9% ± 0.5%, P = 0.092). These results suggest that the outcomes of allo-HSCT with HIDs are comparable to those with MSDs in terms of LFS, TRM, and relapse for intermediate-risk AML in CR1. HIDs could be an alternative to MSDs for intermediate-risk AML.Allogeneic hematopoietic stem cell transplantation (HCT) is associated with significant morbidity and mortality. Elevated pre-transplant ferritin level (ferritinPre-HCT) is reported to be associated with increased mortality following HCT. The present study attempted to determine whether post-transplant ferritin level (ferritinPost-HCT) is associated with outcomes post-HCT, especially in the subgroups which developed acute or chronic graft-versus-host disease (GVHD). Out of 229 patients with serum ferritin level measured post-HCT, median ferritinPost-HCT was 2178 ng/mL. Patients were stratified into low- or high-risk groups using recursive partitioning, based on ferritinPost-HCT (≤ 3169 vs > 3169 ng/mL) and ferritinPre-HCT (≤ 669 vs > 669 ng/mL). Compared to the low ferritinPost-HCT group, the high ferritinPost-HCT group had lower 3-year overall survival (OS) (40.0% vs 66.7%, p  less then  0.001) and higher non-relapse mortality (NRM) (48.6% vs 17.8%, p  less then  0.001), but no difference in relapse (10.5% vs 19.7%, p = 0.079). Multivariate analysis confirmed ferritinPost-HCT as an independent prognostic factor for OS (p = 0.001, HR = 2.323) and NRM (p  less then  0.001, HR = 3.905). However, ferritinPre-HCT did not stratify well for OS or NRM. FerritinPost-HCT was also found to be an independent prognostic marker for OS and NRM in the subgroups which developed GVHD. In our cohort, high ferritinPost-HCT levels were significantly associated with decreased OS and increased NRM independent of ferritinPre-HCT or GVHD. Additional studies including larger sample sizes and prospective investigation are warranted to clarify the prognostic significance and pathophysiology of pre- and post-transplant hyperferritinemia.Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2. Primarily an infection of the lower respiratory tract, it is now well known to cause multisystem abnormalities. Hematologic manifestations constitute a significant area of concern. Severe acute respiratory syndrome coronavirus 2 infects monocytes and endothelial cells leading to a complex downstream cascade, cytokine storm, and eventual intravascular thrombosis. Coronavirus disease 2019 causes lymphopenia, neutrophilia, and thrombocytopenia. Prophylactic anticoagulation is vital in patients with coronavirus disease 2019, as its effect on the coagulation system is associated with significant morbidity and mortality. The disease can cause both arterial and venous thromboses, especially pulmonary embolism and pulmonary microthrombi. A high index of suspicion is indispensable in recognizing these complications, and timely institution of therapeutic anticoagulation is vital in treating them. Virus-induced disseminated intravascular coagulation is uncommon but shares some similarities to sepsis-induced disseminated intravascular coagulation. Marked elevations in hematologic biomarkers such as lactate dehydrogenase, D-dimer, ferritin, and C-reactive protein are associated with worse outcomes. Understanding the pathophysiology and recognizing factors associated with poor prognosis are crucial in improving patient outcomes with coronavirus disease 2019.Anthropogenic nitrogen (N) deposition is significantly altering both community structure and ecosystem processes in terrestrial ecosystems across the globe. However, our understanding of the consequences of N deposition in dryland systems remains relatively poor, despite evidence that drylands may be particularly vulnerable to increasing N inputs. In this study, we investigated the influence of 7 years of multiple levels of simulated N deposition (0, 2, 5, and 8 kg N ha-1 year-1) on plant community structure and biological soil crust (biocrust) cover at three semi-arid grassland sites spanning a soil texture gradient. Biocrusts are a surface community of mosses, lichens, cyanobacteria, and/or algae, and have been shown to be sensitive to N inputs. We hypothesized that N additions would decrease plant diversity, increase abundance of the invasive annual grass Bromus tectorum, and decrease biocrust cover. Contrary to our expectations, we found that N additions did not affect plant diversity or B. tectorum abundance. In partial support of our hypotheses, N additions negatively affected biocrust cover in some years, perhaps driven in part by inter-annual differences in precipitation. Soil inorganic N concentrations showed rapid but ephemeral responses to N additions and plant foliar N concentrations showed no response, indicating that the magnitude of plant and biocrust responses to N fertilization may be buffered by endogenous N cycling. More work is needed to determine N critical load thresholds for plant community and biocrust dynamics in semi-arid systems and the factors that determine the fate of N inputs.

Esophagogastroduodenoscopy (EGD) is generally a safe procedure, but adverse events often occur. This highlights the necessity of the quality control of EGD. Complete visualization and photo documentation of upper gastrointestinal (UGI) tracts are important measures in quality control of EGD. To evaluate these measures in large scale, we developed an AI-driven quality control system for EGD through convolutional neural networks (CNNs) using archived endoscopic images.

We retrospectively collected and labeled images from 250 EGD procedures, a total of 2599 images from eight locations of the UGI tract, using the European Society of Gastrointestinal Endoscopy (ESGE) photo documentation methods. The label confirmed by five experts was considered the gold standard. We developed a CNN model for multi-class classification of EGD images to one of the eight locations and binary classification of each EGD procedure based on its completeness.

Our CNN model successfully classified the EGD images into one of the eight regions of UGI tracts with 97.58% accuracy, 97.42% sensitivity, 99.66% specificity, 97.50% positive predictive value (PPV), and 99.66% negative predictive value (NPV). Our model classified the completeness of EGD with 89.20% accuracy, 89.20% sensitivity, 100.00% specificity, 100.00% PPV, and 64.94% NPV. We analyzed the credibility of our model using a probability heatmap.

We constructed a CNN model that could be used in the quality control of photo documentation in EGD. Our model needs further validation with a large dataset, and we expect our model to help both endoscopists and patients by improving the quality of EGD procedures.

We constructed a CNN model that could be used in the quality control of photo documentation in EGD. Our model needs further validation with a large dataset, and we expect our model to help both endoscopists and patients by improving the quality of EGD procedures.

Doppler-guided hemorrhoidal laser procedure consists of sutureless closure of terminal branches of the superior hemorrhoidal artery by laser energy. Clinical results of patients treated with this procedure were analyzed at the completion of 2-year follow-up. Primary endpoint was resolution of symptoms and secondary endpoints were recurrence rate, type of recurrences, re-operation rate, and potential predictive factors for failure.

Bleeding was assessed on a score from 0 to 4 (none = 0; < 1/month = 1; 1/week = 2; > 1/week = 3; 3-4/week = 4), frequency of hemorrhoid-related symptoms with a score of 0-3 (2/year = 1; 3-5/year = 2; < 5/year = 3). Constipation and fecal incontinence were assessed by means of validated scores. Quality of life and pain at defecation were assessed using a visual analog scale of 0-10 (0 = worst possible-10 = best possible quality of life and 0 = no pain-10 = worst pain imaginable, respectively). Recurrence rate and need for re-operation were reported. Potential predictive n be considered as 'first-line’ treatment in patients with low-grade hemorrhoids suffering from bleeding, pain and recurrent acute symptoms in whom conservative treatment failed.

The Doppler-guided hemorrhoidal laser procedure showed efficacy at long-term follow-up. It can be considered as 'first-line’ treatment in patients with low-grade hemorrhoids suffering from bleeding, pain and recurrent acute symptoms in whom conservative treatment failed.

To determine the frequency and predictive factors for alcohol recidivism following transjugular intrahepatic portosystemic shunts (TIPS) placed in patients with alcoholic cirrhosis.

One hundred ninety-nine patients who had a TIPS placed at a single institution for different indications in the setting of alcoholic cirrhosis were reviewed. Length of sobriety prior to TIPS placement and maintained sobriety at 1, 3 and 6-12months after TIPS placement were recorded. Smoking history, substance abuse and psychiatric comorbidities were also recorded as was ascitic response to TIPS at 1, 3 and 6-12months.

At 1month 11/199 (5.5%) patients had experienced a relapse while, 20/199 (10.1%) had at 3months, and 44/199 (22.1%) had at 12months. There was no difference in ascitic response in those who did and did not relapse at 1month (p = 0.57), 3months (p = 1.00) or 1year (p = 0.44). The mean time of sobriety at the time of TIPS placement for those who relapsed by 12months was significantly less than those who did not relapse (5.11 (1.10-7.90) months vs 18.32 (8.63-48.12) months, p < 0.001). Concurrent psychiatric comorbidity (p < 0.001), substance abuse (p < 0.001), age less than 40 (p = 0.004) and smoking history at the time of procedure (p < 0.001) were also associated with alcohol relapse.

Recidivism is a frequent issue for patients following TIPS placement; those who have concurrent psychiatric comorbidity, substance abuse, smoking history are younger than 40 and shorter sobriety duration prior to TIPS may be at increased risk.

Recidivism is a frequent issue for patients following TIPS placement; those who have concurrent psychiatric comorbidity, substance abuse, smoking history are younger than 40 and shorter sobriety duration prior to TIPS may be at increased risk.

To examine physiochemical characteristics and drug release properties of cisplatin powder and lipiodol mixtures formed by a glass membrane emulsification device compared with a 3-way stopcock.

Seven different types of mixtures were evaluated cisplatin powder and lipiodol directly mixed (suspension), complete cisplatin solution and lipiodol mixed by a 3-way stopcock or the device (emulsion), incomplete cisplatin solution and lipiodol mixed by a 3-way stopcock or the device (solid-in-water emulsion), and contrast material and cisplatin suspension mixed by a 3-way stopcock or the device (solid-in-oil emulsion).

The percentages of water-in-oil were 98.08 ± 0.27% in the emulsion formed by the device, while 70.3 ± 4.63% in the emulsion formed by a 3-way stopcock (P = 0.037). Solid-in-water and solid-in-oil emulsions formed by the device showed 98.09 ± 0.38% and 98.70 ± 0.40% of water-in-oil, respectively, whereas both solid-in-water and solid-in-oil emulsions formed by a 3-way stopcock showed 0.00%. Homogenous droplet sizes were shown by using the device. The half release times of cisplatin in the emulsions formed by the device were 197 ± 19, 244 ± 24 and 478 ± 52min, respectively, which were significantly longer than the emulsion formed by a 3-way stopcock of 8 ± 8min (P = 0.046-0.050). Suspension showed the longest release time; however, the viscosity was lowest.

The glass membrane emulsification device formed almost 100% water-in-oil, whereas 3-way stopcock produced 100% oil-in-water when incomplete solution or suspension was mixed. Slower cisplatin release was shown in the emulsions formed by the device.

The glass membrane emulsification device formed almost 100% water-in-oil, whereas 3-way stopcock produced 100% oil-in-water when incomplete solution or suspension was mixed. Slower cisplatin release was shown in the emulsions formed by the device.

This analysis evaluated the relationship between concentrations of quizartinib and its active metabolite AC886 and QT interval corrected using Fridericia’s formula (QTcF) in patients with relapsed/refractory acute myeloid leukemia (AML) treated in the phase 3 QuANTUM-R study (NCT02039726).

The analysis dataset included 226 patients with AML. Quizartinib dihydrochloride was administered as daily doses of 20, 30, and 60mg. Nonlinear mixed-effects modeling was performed using observed quizartinib and AC886 concentrations and time-matched mean electrocardiogram measurements.

Observed QTcF increased with quizartinib and AC886 concentrations; the relationship was best described by a nonlinear maximum effect (E

) model. The predicted mean increase in QTcF at the maximum concentration of quizartinib and AC886 associated with 60mg/day was 21.1ms (90% CI, 18.3-23.6ms). Age, body weight, sex, race, baseline QTcF, QT-prolonging drug use, hypomagnesemia, and hypocalcemia were not significant predictors of QTcF. Hypokalemia (serum potassium < 3.5mmol/L) was a statistically significant covariate affecting baseline QTcF, but no differences in ∆QTcF (change in QTcF from baseline) were predicted between patients with versus without hypokalemia at the same quizartinib concentration. The use of concomitant QT-prolonging drugs did not increase QTcF further.

QTcF increase was dependent on quizartinib and AC886 concentrations, but patient factors, including sex and age, did not affect the concentration-QTcF relationship. Because concomitant strong cytochrome P450 3A (CYP3A) inhibitor use significantly increases quizartinib concentration, these results support the clinical recommendation of quizartinib dose reduction in patients concurrently receiving a strong CYP3A inhibitor.

NCT02039726 (registered January 20, 2014).

NCT02039726 (registered January 20, 2014).