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The MYB gene is a master regulator of hematopoiesis and contributes to leukemogenesis in several species including humans. Although it is clear that MYB can promote proliferation, suppress apoptosis and block differentiation, the identities of the MYB target genes that mediate these effects have only been partially elucidated. Several studies, including our own, have collectively identified substantial numbers of MYB target genes, including candidates for each of these activities; however, functional validation, particularly in the case of differentiation suppression, has lagged well behind. Here we show that GFI1, which encodes an important regulator of hematopoietic stem cell (HSC) function and granulocytic differentiation, is a direct target of MYB in myeloid leukemia cells. Chromatin immunoprecipitation and reporter studies identified a functional MYB-binding site in the promoter region of GFI, whereas ectopic expression and small hairpin RNA-mediated knockdown of MYB resulted in concomitant increases and decreases, respectively, in GFI1 expression. We also demonstrate that GFI1, like MYB, can block the induced monocytic differentiation of a human acute myeloid leukemia cell line, and most importantly, that GFI1 is essential for MYB's ability to block monocytic differentiation. Thus, we have identified a target of MYB that is a likely mediator of its myeloid differentiation-blocking activity, and which may also be involved in MYB's activities in regulating normal HSC function and myeloid differentiation. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the influence of coping heights on the strain around the abutment teeth and at the middle part of mandibular overdentures, using strain gauges. A mandibular edentulous model with a silicone artificial mucosa of thickness 2 mm was made. Two artificial roots were embedded on both sides in the canine position. The coping had a dome-shaped upper surface at a height of 0, 2, 4 and 6 mm. On the lingual polished surface of the overdenture, three strain gauges were attached in the left canine position at the vertical level corresponding to the top of the 6, 4 and 2 mm copings and two strain gauges were attached in the middle section (upper and lower). A vertical loading of 49 N was applied on the occlusal surface of first premolar, first molar and second molar. When loading on the first premolar adjacent to an abutment, the largest tensile strain was observed on the overdenture surface close to the top of each coping, independent of coping heights. When loading on the first premolar on the opposite side, the tensile strains around the coping were remarkably smaller. In the middle part of the overdenture, the compressive strains became larger by reducing the coping height or loading on distal point. The largest tensile strain was observed on the overdenture surface close to the top of copings, independent of coping heights. [ABSTRACT FROM AUTHOR]

CXC ligand (L)12 is a chemokine implicated in the migration, invasion and metastasis of cancer cells via interaction with its receptors CXC chemokine receptor (CXCR)4 and CXCR7. In the present study, CXCL12-mediated Ca2+ signalling was compared with two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which demonstrate distinct metastatic potential. CXCL12 treatment induced Ca2+ responses in the more metastatic MDA-MB-231 cells but not in the less metastatic MDA-MB-468 cells. Assessment of mRNA levels of CXCL12 receptors and their potential modulators in both cell lines revealed that CXCR4 and CXCR7 levels were increased in MDA-MB-231 cells compared with MDA-MB-468 cells. Cluster of differentiation (CD)24, the negative regulator of CXCL12 responses, demonstrated increased expression in MDA-MB-468 cells compared with MDA-MB-231 cells, and the two cell lines expressed comparable levels of hypoxia-inducible factor (HIF)2α, a CXCR4 regulator. Induction of epithelialmesenchymal transition (EMT) by epidermal growth factor exhibited opposite effects on CXCR4 mRNA levels compared with hypoxia-induced EMT. Neither EMT inducer exhibited an effect on CXCR7 expression, however hypoxia increased HIF2α expression levels in MDA-MB-468 cells. Analysis of the gene expression profiles of breast tumours revealed that the highest expression levels of CXCR4 and CXCR7 were in the Claudin-Low molecular subtype, which is markedly associated with EMT features. [ABSTRACT FROM AUTHOR]

c-Myb is an essential hematopoietic transcription factor that controls proliferation and differentiation of progenitors during blood cell development. Whereas sumoylation of the C-terminal regulatory domain (CRD) is known to have a major impact on the activity of c-Myb, no role for noncovalent binding of small ubiquitin-like modifier (SUMO) to c-Myb has been described. Based on the consensus SUMO-interacting motif (SIM), we identified and examined putative SIMs in human c-Myb. Interaction and reporter assays showed that the SIM in the in the transactivation domain of c-Myb (V267NIV) is functional. This motif is necessary for c-Myb to be able to interact noncovalently with SUMO, preferentially SUMO2/3. Destroying the SUMO-binding properties by mutation resulted in a large increase in the transactivation potential of c-Myb. Mutational analysis and overexpression of conjugation-defective SUMO argued against intramolecular repression caused by sumoylated CRD and in favor of SUMO-dependent repression in trans. Using both a myeloid cell line-based assay and a primary hematopoietic cell assay, we addressed the transforming abilities of SUMO binding and conjugation mutants. Interestingly, only loss of SUMO binding, and not SUMO conjugation, enhanced the myeloid transformational potential of c-Myb. c-Myb with the SIM mutated conferred a higher proliferative ability than the wild-type and caused an effective differentiation block. This establishes SUMO binding as a mechanism involved in modulating the transactivation activity of c-Myb, and responsible for keeping the transforming potential of the oncoprotein in check. [ABSTRACT FROM AUTHOR]

The structural design of removable partial dentures (RPDs) is critical for preventing distortion of the prosthesis, protecting abutment teeth and residual ridges as well as for high masticatory performance. The aim of this study was to clarify the feasibility and utility of a computer-aided designing (CAD) system with finite element analysis (FEA) for molar teeth arrangement in unilateral distal extension base RPDs. The shapes of artificial teeth and residual ridge were measured and converted into point group data. Solid models were created from surface-modelled point group data in a 3D surface CAD format. An occlusal rim was created on the residual ridge mucosa and the occlusal rim - residual ridge mucosa model with FEA function was created. Stress distribution on the residual ridge mucosa was compared by changing the loading point. The artificial teeth were then arranged in locations with the lowest amount of stress. After building an artificial teeth – saddle – residual ridge mucosa model, stress distribution in the residual ridge mucosa was re-evaluated by simulating occlusal force. On the occlusal rim - residual ridge mucosa model, stress was reduced when the loading point was located around the buccal shelf where functional cusps of artificial teeth were charted. It was confirmed that stress distribution in the residual ridge mucosa was equalized on the artificial teeth – saddle – residual ridge mucosa model. This system might be clinically useful tool for designing RPDs if FEA-guided designing of retainers and connectors can be added. [ABSTRACT FROM AUTHOR]

The tumor suppressor Gadd45α was earlier shown to be a repressed target of sustained receptor-mediated ERK1/2 signaling. We have identified Gadd45α as a downregulated gene in response to constitutive signaling from two FLT3 mutants (FLT3-ITD and FLT3-TKD) commonly found in AML, and a leukemogenic GM-CSF receptor trans-membrane mutant (GMR-V449E). GADD45A mRNA downregulation is also associated with FLT3-ITD+ AML. Sustained ERK1/2 signaling contributes significantly to receptor-mediated downregulation of Gadd45α mRNA in FDB1 cells expressing activated receptor mutants, and in the FLT3-ITD+ cell line MV4;11. Knockdown of Gadd45α with shRNA led to increased growth and survival of FDB1 cells and enforced expression of Gadd45α in FDB1 cells expressing FLT3-ITD or GMR-V449E resulted in reduced growth and viability. Gadd45α overexpression in FLT3-ITD+ AML cell lines also resulted in reduced growth associated with increased apoptosis and G1/S cell cycle arrest. Overexpression of Gadd45α in FDB1 cells expressing GMR-V449E was sufficient to induce changes associated with myeloid differentiation suggesting Gadd45α downregulation contributes to the maintenance of receptor-induced myeloid differentiation block. Thus, we show that ERK1/2-mediated downregulation of Gadd45α by sustained receptor signaling contributes to growth, survival and arrested differentiation in AML.Leukemia (2009) 23, 729–738; doi:10.1038/leu.2008.349; published online 8 January 2009 [ABSTRACT FROM AUTHOR]

This study investigated associations between temporomandibular joint (TMJ) sounds and occlusal force or masticatory performance stratified by posterior occlusal supports in older Japanese adults. The subjects consisted of 1646 independently living people over 60 years. Masticatory performance, occlusal force, TMJ sounds and maximal mouth opening were examined. Posterior occlusal supports were classified by the Eichner Index. The prevalence of TMJ sounds was 27·7%, limitation of mouth opening (<40 mm) was 7·9% and TMJ pain was only 1·5%. In the Eichner C group, TMJ sounds were significantly associated with lower occlusal force (OR = 3·20, P = 0·046) and lower masticatory performance (OR = 3·18, P = 0·041) after controlling for gender and age. These associations were not found in the Eichner A and B groups. Within the limitations of this study, the presence of TMJ sounds, even if they were symptomless, was associated with impairment of masticatory function in older adults with reduced occlusal support. [ABSTRACT FROM AUTHOR]

Purpose Gastrointestinal bleeding (GIB) is a common complication of LVAD therapy. Previously, we retrospectively reviewed endoscopic evaluation and outcomes of GIB in LVAD recipients in our center and proposed an endoscopic management algorithm (Figure) to eliminate low yield procedures. Herein, we aimed to prospectively validate this algorithm. Methods We prospectively tested the algorithm in LVAD recipients who presented with GIB between June 2017 and August 2018. We compared the diagnostic and therapeutic yield of endoscopy and healthcare costs between conventional GIB management to the algorithm. Results 33 LVAD pts with GIB were identified. Presentation was consistent with upper GIB in 20 (61%), lower GIB in 5 (15%), and occult GIB in 8 (24%) pts. In total, 41 endoscopies localized a source in 23 (56%) resulting in 14 (36%) interventions at a median length-of-stay (LOS) of 8 d. Of 18 lesions identified, angiodysplasias were the most common (9, 50%) and the small bowel was the most common location (11, 48%). Despite non-adherence to the algorithm in 7 of 33 pts (21%), algorithm implementation increased the diagnostic yield by 70% (p=0.008) and therapeutic yield by 125% (p=0.01), reduced the number of procedures per pt by24% (p<0.01), LOS by 33% (p<0.01), and estimated costs by 18% (p<0.01) in comparison to our retrospective cohort (Table). Conclusion Our endoscopic management algorithm of GIB in LVAD pts is effective in reducing low yield procedures, improving the diagnostic and therapeutic yield of endoscopy, and decreasing healthcare resource utilization. [ABSTRACT FROM AUTHOR]

Introduction: Endoscopic ultrasound (EUS) allows for characterization and biopsy of pancreatic lesions. Pancreatic cystic neoplasms (PCN) include mucinous (M-PCN) and nonmucinous lesions (NM-PCN). Pancreatic ductal adenocarcinoma (P-DAC) is the commonest pancreatic solid lesion (PSL), followed by pancreatic neuroendocrine tumor (P-NET). Although EUS is preferred for pancreatic lesion evaluation, its diagnostic accuracy is suboptimal. This multicentric study aims to develop a convolutional neural network (CNN) for detecting and distinguishing PCN (namely M-PCN and NM-PCN) and PSL (particularly P-DAC and P-NET)., Methods: A CNN was developed with 378 EUS examinations from 4 international reference centers (Centro Hospitalar Universitário São João, Hospital Universitario Puerta de Hierro Majadahonda, New York University Hospitals, Hospital das Clínicas Faculdade de Medicina da Universidade de São Paulo). About 126.000 images were obtained-19.528 M-PCN, 8.175 NM-PCN, 64.286 P-DAC, 29.153 P-NET, and 4.858 normal pancreas images. A trinary CNN differentiated normal pancreas tissue from M-PCN and NM-PCN. A binary CNN distinguished P-DAC from P-NET. The total data set was divided into a training and testing data set (used for model's evaluation) in a 90/10% ratio. The model was evaluated through its sensitivity, specificity, positive and negative predictive values, and accuracy., Results: The CNN had 99.1% accuracy for identifying normal pancreatic tissue, 99.0% and 99.8% for M-PCN and NM-PCN, respectively. P-DAC and P-NET were distinguished with 94.0% accuracy., Discussion: Our group developed the first worldwide CNN capable of detecting and differentiating the commonest PCN and PSL in EUS images, using examinations from 4 centers in 2 continents, minimizing the impact of the demographic bias. Larger multicentric studies are needed for technology implementation., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Our research group previously identified graviquinone (1) as a promising antitumor metabolite that is formed in situ when the antioxidant methyl caffeate scavenges free radicals. Furthermore, it exerted a DNA damaging effect on cancer cells and a DNA protective effect on normal keratinocytes. To expand and explore chemical space around qraviquinone, in the current work we synthesized 9 new alkyl-substituted derivatives and tested their in vitro antitumor potential. All new compounds bypassed ABCB1-mediated multidrug resistance and showed highly different cell line specificity compared with 1. All compounds were more potent in MDA-MB-231 than on MCF-7 cells. The n-butyl-substituted derivatives 2 and 8 modulated the cell cycle and inhibited the ATR-mediated phosphorylation of checkpoint kinase-1 in MCF-7 cells. As a significant expansion of our previous findings, our results highlight the potential antitumor value of alkyl-substituted graviquinone derivatives., (© 2024 The Author(s). ChemMedChem published by Wiley-VCH GmbH.)

Automated volumetric segmentation of the pancreas on cross-sectional imaging is needed for diagnosis and follow-up of pancreatic diseases. While CT-based pancreatic segmentation is more established, MRI-based segmentation methods are understudied, largely due to a lack of publicly available datasets, benchmarking research efforts, and domain-specific deep learning methods. In this retrospective study, we collected a large dataset (767 scans from 499 participants) of T1-weighted (T1 W) and T2-weighted (T2 W) abdominal MRI series from five centers between March 2004 and November 2022. We also collected CT scans of 1,350 patients from publicly available sources for benchmarking purposes. We introduced a new pancreas segmentation method, called PanSegNet, combining the strengths of nnUNet and a Transformer network with a new linear attention module enabling volumetric computation. We tested PanSegNet's accuracy in cross-modality (a total of 2,117 scans) and cross-center settings with Dice and Hausdorff distance (HD95) evaluation metrics. We used Cohen's kappa statistics for intra and inter-rater agreement evaluation and paired t-tests for volume and Dice comparisons, respectively. For segmentation accuracy, we achieved Dice coefficients of 88.3% (±7.2%, at case level) with CT, 85.0% (±7.9%) with T1 W MRI, and 86.3% (±6.4%) with T2 W MRI. There was a high correlation for pancreas volume prediction with R 2 of 0.91, 0.84, and 0.85 for CT, T1 W, and T2 W, respectively. We found moderate inter-observer (0.624 and 0.638 for T1 W and T2 W MRI, respectively) and high intra-observer agreement scores. All MRI data is made available at https://osf.io/kysnj/. Our source code is available at https://github.com/NUBagciLab/PaNSegNet., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ulas Bagci reports financial support was provided by National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This paper presents an overview of recent hardware extensions and data analysis developments to the Wendelstein 7-X visible core spectroscopy systems. These include upgrades to prepare the in-vessel components for long-pulse operation, nine additional spectrometers, a new line of sight array for passive spectroscopy, and a coherence imaging charge exchange spectroscopy diagnostic. Progress in data analysis includes ion temperatures and densities from multiple impurity species, a statistical comparison with x-ray crystal spectrometer measurements, neutral density measurements from thermal passive Balmer-alpha emission, and a Bayesian analysis of active hydrogen emission, which is able to infer electron density and main ion temperature profiles., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/).)

Introduction: We sought to determine the yield of somatic mutational analysis from endoscopic ultrasound (EUS)-guided biopsies of pancreatic adenocarcinoma compared with that of surgical resection and to assess the impact of these results on oncologic treatment., Methods: We determined the yield of EUS sampling and surgical resection. We evaluated the potential impact of mutational analysis by identifying actionable mutations and its direct impact by reviewing actual treatment decisions., Results: Yield of EUS sampling was 89.5%, comparable with the 95.8% yield of surgical resection. More than a quarter in the EUS cohort carried actionable mutations, and of these, more than 1 in 6 had treatment impacted by mutational analysis., Discussion: EUS sampling is nearly always adequate for somatic testing and may have substantial potential and real impact on treatment decisions., (Copyright © 2024 by The American College of Gastroenterology.)

Purpose: The present clinical study aimed to investigate the load exerted on abutment teeth in patients with distal extension edentulism, with and without a removable partial denture (RPD)., Methods: A total of 55 volunteers with distal extension edentulism who were fitted with an RPD participated in the present study. Occlusal force was measured by having the patients bite down on an occlusal force measuring sheet, and the occlusal forces on both the abutment teeth and the entire dentition with and without the RPD were compared using the Wilcoxon signed-rank test (P < 0.05). The occlusal forces on the abutment and non-abutment teeth were also compared., Results: The median total occlusal force with the RPD in place was significantly greater than that without the RPD, while the median occlusal force on the abutment teeth without the RPD in place was significantly greater than that on the abutment teeth with the RPD. The occlusal forces on the abutment teeth were significantly greater than those on the non-abutment teeth., Conclusions: Within the limitations of the present study, we found that the occlusal forces were greater on the abutment than the non-abutment teeth, and that RPDs may reduce the occlusal forces on abutment teeth.

Objectives: This retrospective study aimed to investigate the differences in tooth loss rate between fixed implant-supported prostheses (FISPs) and removable partial dentures (RPDs) in cases of unilateral free-end missing teeth., Materials and Methods: The data of 324 patients who underwent treatment with FISPs or RPDs for unilateral free-end missing teeth and satisfied the applicable criteria, were evaluated (47 in the FISPs group and 277 in the RPDs group). After propensity score (PS) matching, which was used to extract patients with similar background factors related to prosthetic selection at baseline, survival time analyses were performed with tooth loss as the endpoint. The adjusted variables were age, sex, number of restored teeth, periodontal status, and the practicing dentist's experience in years. The remaining teeth were classified into subcategories in relation to the missing molars., Results: Overall, 58 patients (29 in each group) selected by PS matching were evaluated in the final analysis. The total number of lost teeth was 35 (FISPs group: n = 10; RPDs group: n = 25). The mean (±SD) period to tooth loss and the 10-year survival rates in the FISPs and RPDs groups were 51.6 (±30.1) months and 42.3 (±29.7) months, 70.5% and 16.4%, respectively. The log-rank test showed that significantly longer survival time in FISPs compared with RPDs., Conclusions: After adjustments for confounding factors using PS matching, replacing unilateral free-end missing teeth with FISPs may exhibit a lower tooth loss rate in adjacent and contralateral teeth compared to replacing with RPDs., (© 2024 The Authors. Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Background: We assessed and compared the image quality of normal and pathologic structures as well as the image noise in chest computed tomography images using "adaptive statistical iterative reconstruction-V" (ASiR-V) or deep learning reconstruction "TrueFidelity"., Methods: Forty consecutive patients with suspected lung disease were evaluated. The 1.25-mm axial images and 2.0-mm coronal multiplanar images were reconstructed under the following three conditions: (i) ASiR-V, lung kernel with 60% of ASiR-V; (ii) TF-M, standard kernel, image filter (Lung) with TrueFidelity at medium strength; and (iii) TF-H, standard kernel, image filter (Lung) with TrueFidelity at high strength. Two radiologists (readers) independently evaluated the image quality of anatomic structures using a scale ranging from 1 (best) to 5 (worst). In addition, readers ranked their image preference. Objective image noise was measured using a circular region of interest in the lung parenchyma. Subjective image quality scores, total scores for normal and abnormal structures, and lesion detection were compared using Wilcoxon's signed-rank test. Objective image quality was compared using Student's paired t -test and Wilcoxon's signed-rank test. The Bonferroni correction was applied to the P value, and significance was assumed only for values of P < 0.016., Results: Both readers rated TF-M and TF-H images significantly better than ASiR-V images in terms of visualization of the centrilobular region in axial images. The preference score of TF-M and TF-H images for reader 1 were better than that of ASiR-V images, and the preference score of TF-H images for reader 2 were significantly better than that of ASiR-V and TF-M images. TF-M images showed significantly lower objective image noise than ASiR-V or TF-H images., Conclusion: TrueFidelity showed better image quality, especially in the centrilobular region, than ASiR-V in subjective and objective evaluations. In addition, the image texture preference for TrueFidelity was better than that for ASiR-V., Competing Interests: The authors declare no conflict of interest., (©2024 Tottori University Medical Press.)

Purpose: The purpose of this study was to examine the mechanical influence of edentulous mandibular morphology on peri-implant bone in implant prosthetics by finite element analysis., Materials and Methods: Computed tomographic data from 25 patients with edentulous mandibles were selected and the radius of mandibular curvature and the height of the mandible at the midline were measured in order to clarify the morphological characteristics of the mandible. From the measurement, two patients with the smallest and largest radii of the mandible were selected. Two types of three-dimensional finite element models consisting of the edentulous mandible (small and large radius), superstructure (a cantilever bridge), implants, and abutments were created. Four implants were inserted between the right and left mental foramina. The upper surface of the mandibular condyle was constrained, and a vertical load of 100 N was applied on the occlusal surface of the right first molar. Three-dimensional finite element analysis of each model was performed to examine the mechanical influence of the edentulous mandibular morphology on the peri-implant bone., Results: Measurement of mandibular morphology in CT images indicated that the lower the mandibular height was, the larger was the radius of the anterior mandibular curvature. Finite element analysis revealed that a higher equivalent stress was generated in the peri-implant bone of the model with a larger radius of curvature than that of the model with a smaller radius of curvature. The highest equivalent stress in the mandible was generated in the distal margin of the peri-implant bone posterior to the loaded side of the large radius of curvature model., Conclusions: The mandibular morphology had a mechanical influence on the peri-implant bone.

Purpose: To determine the influence of partial edentulous distal extension and the use of removable partial dental prostheses in partially edentulous areas on the force exerted on the anterior teeth., Materials and Methods: A total of 83 volunteer patients participated in this study. The occlusal force was measured using an occlusal force measuring sheet in the patient's mouth. The occlusal forces and ratios were compared using the Wilcoxon signed-rank test (P < .05)., Results: The force exerted on the anterior teeth increased significantly as the number of remaining teeth decreased in an edentulous distal extension. The force exerted on the anterior teeth decreased significantly with the use of a removable partial dental prosthesis., Conclusions: In a clinical setting, when the number of remaining teeth in a partial edentulous distal extension decreases, the burden on the anterior teeth increases. Our findings suggest that, for patients with partial edentulous distal extension, using a removable partial dental prosthesis is effective in preserving the residual anterior teeth by reducing excessive force.

We describe herein the synthesis of eight new ester-coupled hybrid compounds from thymoquinone and protoflavone building blocks, and their bioactivity testing against multiple cancer cell lines. Among the hybrids, compound 14 showed promising activities in all cell lines studied. The highest activities were recorded against breast cancer cell lines with higher selectivity to MDA-MB-231 as compared to MCF-7. Even though the hybrids were found to be completely hydrolysed in 24 h under cell culture conditions, compound 14 demonstrated a ca. three times stronger activity against U-87 glioblastoma cells than a 1:1 mixture of its fragments. Further, compound 14 showed good tumour selectivity: it acted 4.4-times stronger on U-87 cells than on MRC-5 fibroblasts. This selectivity was much lower, only ca. 1.3-times, when the cells were co-treated with a 1:1 mixture of its non-coupled fragments. Protoflavone-thymoquinone hybrids may therefore serve as potential new antitumor leads particularly against glioblastoma., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ahmed et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Abstract: Diffusion-weighted imaging (DWI) is an increasingly valuable sequence in daily clinical practice, providing both functional and morphological information. The use of DWI can help quantify diffusion using the apparent diffusion coefficient, which reflects the physiological features of the tissue and tumor microcirculation. This knowledge is crucial for understanding and interpreting gynecological imaging. This article reviews the clinical utility of DWI for gynecological imaging, highlighting its ability to aid in the detection of endometrial and cervical cancers, as well as tumor extension and metastasis. In addition, DWI can easily detect the solid components of ovarian cancer (including dissemination), assist in the diagnosis of adnexal torsion, and potentially show bone marrow status. Apparent diffusion coefficient measurement is useful for differentiating between endometrial lesions, uterine leiomyomas, and sarcomas, and may provide important information for predicting the prognosis of gynecological cancers., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Intraductal Papillary Mucinous Neoplasm (IPMN) cysts are pre-malignant pancreas lesions, and they can progress into pancreatic cancer. Therefore, detecting and stratifying their risk level is of ultimate importance for effective treatment planning and disease control. However, this is a highly challenging task because of the diverse and irregular shape, texture, and size of the IPMN cysts as well as the pancreas. In this study, we propose a novel computer-aided diagnosis pipeline for IPMN risk classification from multi-contrast MRI scans. Our proposed analysis framework includes an efficient volumetric self-adapting segmentation strategy for pancreas delineation, followed by a newly designed deep learning-based classification scheme with a radiomics-based predictive approach. We test our proposed decision-fusion model in multi-center data sets of 246 multi-contrast MRI scans and obtain superior performance to the state of the art (SOTA) in this field. Our ablation studies demonstrate the significance of both radiomics and deep learning modules for achieving the new SOTA performance compared to international guidelines and published studies (81.9% vs 61.3% in accuracy). Our findings have important implications for clinical decision-making. In a series of rigorous experiments on multi-center data sets (246 MRI scans from five centers), we achieved unprecedented performance (81.9% accuracy). The code is available upon publication.

Introduction: The development of non-anastomotic biliary strictures (NAS) following orthotopic adult liver transplantation (OLT) is associated with significant morbidity. We performed a systematic review and meta-analysis to identify all prognostic factors for the development of NAS., Methods: A systematic review was conducted following preferred reporting items for systematic reviews and meta-analyses (PRISMA) and the meta-analysis of observational studies in epidemiology (MOOSE) guidelines. We used the Newcastle-Ottawa scale to assess the quality of the included studies. Using the random-effects model, we calculated the weighted pooled odds ratios (OR), mean differences (MD), hazard ratios (HR), and 95% confidence intervals (CI) of the risk factors., Results: Based on 19 international studies that included a total of 8269 adult LT patients, we calculated an 8% overall incidence of NAS. In this study, 7 potential prognostic factors were associated with a statistically significant hazard ratio for NAS in pooled analyses including (1) DCD donors compared to DBD donors (2) PSC as an indication for a liver transplant (3) Roux-en-Y bile duct reconstruction compared to duct-to-duct reconstruction (4) hepatic artery thrombosis (5) longer cold ischemia time (6) longer warm ischemia time (7) and total operative times., Conclusion: In this systematic review and meta-analysis, we identified 7 prognostic factors for the development of NAS following OLT. These findings might lay the groundwork for development of diagnostic algorithms to better risk stratify patients at risk for development of NAS., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The goal of this study is to perform correlation analysis of Computed tomography (CT) and magnetic resonance imaging (MRI) results in posterior ligament complex (PLC) injury and define the morphological traits of thoracolumbar (TL) burst fractures connected to PLC injury. Forty patients with surgically repaired TL burst fractures between January 2013 and December 2020 were retrospectively analyzed. The patients were split into two groups for comparison based on MRI (Group P: patients with a confirmed or suspected PLC injury; Group N: patients with PLC injury denied). The radiographic morphological examination based on CT scans and clinical evaluation was performed and compared between two groups. The thoracolumbar injury classification and severity score (TLICS), the load sharing classification (LSC) scores, and the number of patients with neurological impairments were considerably greater in Group P. Loss of height of the fracture (loss height), local kyphosis of the fracture (local kyphosis), and supraspinous distance were significantly higher in Group P and significantly associated with PLC injuries indicating severe vertebral body destruction and traumatic kyphosis in multivariate logistic analysis [odds ratio: 1.90, 1.06, and 1.13, respectively]. Cutoff value for local kyphosis obtained from the receiver operating characteristic curve was 18.8. If local kyphosis is greater than 18.8 degrees on CT scans, we should take into account the probability of the highly damaged burst fracture associated with PLC injury. In this situation, we should carefully assess MRI to identify the spinal cord injury or spinal cord compression in addition to PLC injury because these instances likely present with neurological abnormalities.

The purpose of this study was to determine the influence of mandibular unilateral and bilateral distal extension partial edentulous situation and the use of removable partial dental prostheses on the force exerted on maxillary anterior teeth. A commercially available jaw model with exchangeable teeth was used. Seven experimental conditions of mandibular distal extension edentulous situation were prepared and a distal extension removable partial dental prosthesis to replace missing posterior teeth was fabricated. The occlusal force was measured by inserting an occlusal force measuring film between the maxillary and mandibular teeth of the model. An occlusal load was applied and the forces and ratios were compared using the Kruskal-Wallis test and the Mann-Whitney U test (p < 0.05). As a result, the force exerted on the maxillary anterior teeth increased significantly as the number of remaining teeth decreased in unilateral and bilateral edentulous situation. The force exerted on the maxillary anterior teeth decreased significantly with use of a removable partial dental prosthesis. It is concluded that when the number of remaining teeth decreases in mandibular unilateral and bilateral distal extension partial edentulous situation, the burden on the maxillary anterior teeth increases. Our findings suggest that for patients with mandibular distal extension partial edentulous situation, using a removable partial dental prosthesis is effective in preserving the remaining teeth by reducing excessive force., (© 2022. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)

Ginger ( Zingiber officinale ) is widely used as a spice and a traditional medicine. Many bioactivities have been reported for its extracts and the isolated compounds, including cardiovascular protective effects. Different pathways were suggested to contribute to these effects, like the inhibition of platelet aggregation. In this study, we synthesised fourteen 6-gingerol derivatives, including eight new compounds, and studied their antiplatelet, COX-1 inhibitor, and antioxidant activities. In silico docking of selected compounds to h -COX-1 enzyme revealed favourable interactions. The investigated 6-gingerol derivatives were also characterised by in silico and experimental physicochemical and blood-brain barrier-related parameters for lead and preclinical candidate selection. 6-Shogaol ( 2 ) was identified as the best overall antiplatelet lead, along with compounds 3 and 11 and the new compound 17 , which require formulation to optimize their water solubility. Compound 5 was identified as the most potent antioxidant that is also promising for use in the central nervous system (CNS).

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) is a complex ecosystem that drives tumor progression; however, in-depth single cell characterization of the PDAC TME and its role in response to therapy is lacking. Here, we perform single-cell RNA sequencing on freshly collected human PDAC samples either before or after chemotherapy. Overall, we find a heterogeneous mixture of basal and classical cancer cell subtypes, along with distinct cancer-associated fibroblast and macrophage subpopulations. Strikingly, classical and basal-like cancer cells exhibit similar transcriptional responses to chemotherapy and do not demonstrate a shift towards a basal-like transcriptional program among treated samples. We observe decreased ligand-receptor interactions in treated samples, particularly between TIGIT on CD8 + T cells and its receptor on cancer cells, and identify TIGIT as the major inhibitory checkpoint molecule of CD8 + T cells. Our results suggest that chemotherapy profoundly impacts the PDAC TME and may promote resistance to immunotherapy., (© 2023. The Author(s).)

Aim: To examine the relationship between the number of present and functional teeth at baseline and future incidence of loss of independence., Methods: Participants were community-dwelling older individuals who participated in a comprehensive geriatric health examination conducted in Kusatsu town, Japan, between 2009 and 2015. The primary endpoint was the incidence of loss of independence among participants, defined as the first certification of long-term care insurance in Japan. The numbers of present and functional teeth at baseline were determined via an oral examination. Demographics, clinical variables (e.g., history of chronic diseases and psychosocial factors), blood nutritional markers, physical functions, and perceived masticatory function were assessed., Results: This study included 1121 individuals, and 205 individuals suffered from loss of independence during the follow-up period. Kaplan-Meier estimates of loss of independence for participants with smaller numbers of present and functional teeth were significantly greater than for those with larger numbers of teeth. Cox proportional hazard analyses indicated that a smaller number of present teeth was not a significant risk factor after adjusting for demographic characteristics. However, the number of functional teeth was a significant risk factor after the adjustment (hazard ratio: 1.975 [1.168-3.340]). Additionally, higher hazard ratios were observed in other adjusted models, but they were not statistically significant., Conclusions: The number of functional teeth may be more closely related to the future incidence of loss of independence than the number of present teeth. This novel finding suggests that prosthodontic rehabilitation for tooth loss possibly prevents the future incidence of this life-event. Geriatr Gerontol Int 2022; 22: 1032-1039., (© 2022 The Authors. Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Purpose: To examine the influence of posterior residual ridge resorption (PRRR) and relining on bending strain around implants under an overdenture., Materials and Methods: Maxillary and mandibular edentulous models were made and covered with white silicone. Four strain gauges were placed on four sides of each implant. Two tissue-level implants were placed bilaterally in the part between the lateral incisors and canines of the mandible. A maxillary conventional denture and a mandibular overdenture were fabricated to fit the models. Three levels of bone resorption around the implant were created: 0, 0.8, and 1.5 mm. The surface of the residual ridge was uniformly removed from the area near the distal side of the implant to the retromolar section, and three levels of PRRR were created (0, 1, and 1.5 mm). After the measurement, the experimental denture of the PRRR of 1 mm and 1.5 mm were relined. Locator attachments were used. A 98-N occlusal force was applied, and bending strains around the implant were measured. The Kruskal-Wallis test and Bonferroni correction were employed to analyze the data., Results: Without relining, at each bone resorption level around the implant, the bending strain was smallest with PRRR of 0 mm and largest with PRRR of 1.5 mm. The bending strain after relining was smaller than the bending strain with ridge resorption. Bending strains after relining were smaller than bending strains with no ridge resorption, but there was no significant difference in bending strain between these three groups., Conclusion: As PRRR increased, the bending strain increased without relining. As bone resorption around the implant progressed, PRRR enhanced the increase in the peri-implant bending strain. Bending strain was reduced when relining was performed.

A 35-year-old man was admitted to our department for loss of consciousness. CT and MRI revealed diffuse enhancement of the subarachnoid space surrounding the brainstem and the cerebellar sulci, without any parenchymal lesions in the brain or the spinal cord. Furthermore, gadolinium-enhanced MRI revealed a nodular lesion with heterogeneous enhancement in the right prepontine cistern, at the site from which a biopsy was obtained via right lateral suboccipital craniotomy on the day following admission. Histopathological examination of the resected specimen revealed glioblastoma multiforme. Based on the radiological and histopathological findings, the patient was diagnosed with primary leptomeningeal gliomatosis (PLG). The patient received temozolomide chemotherapy with concurrent radiotherapy and showed radiological remission, 12 months after diagnosis. However, he developed local recurrence 6 months later and died 23 months after diagnosis. Autopsy findings showed tumor cell infiltration of the leptomeninges, as well as the brain and spinal parenchyma. PLG should be considered in the differential diagnosis in patients with diffuse leptomeningeal enhancement even without parenchymal lesions on radiological imaging. A surgical biopsy is recommended for prompt and accurate diagnosis in such cases.

Background and Aim: Upper gastrointestinal tumors account for 5% of upper gastrointestinal bleeds. These patients are challenging to treat due to the diffuse nature of the neoplastic bleeding lesions, high rebleeding rates, and significant transfusion requirements. TC-325 (Cook Medical, North Carolina, USA) is a hemostatic powder for gastrointestinal bleeding. The aim of this study was to examine the outcomes of upper gastrointestinal bleeds secondary to tumors treated with Hemospray therapy., Methods: Data were prospectively collected on the use of Hemospray from 17 centers. Hemospray was used during emergency endoscopy for upper gastrointestinal bleeds secondary to tumors at the discretion of the endoscopist as a monotherapy, dual therapy with standard hemostatic techniques, or rescue therapy., Results: One hundred and five patients with upper gastrointestinal bleeds secondary to tumors were recruited. The median Blatchford score at baseline was 10 (interquartile range [IQR], 7-12). The median Rockall score was 8 (IQR, 7-9). Immediate hemostasis was achieved in 102/105 (97%) patients, 15% of patients had a 30-day rebleed, 20% of patients died within 30 days (all-cause mortality). There was a significant improvement in transfusion requirements following treatment (P < 0.001) when comparing the number of units transfused 3 weeks before and after treatment. The mean reduction was one unit per patient., Conclusions: Hemospray achieved high rates of immediate hemostasis, with comparable rebleed rates following treatment of tumor-related upper gastrointestinal bleeds. Hemospray helped in improving transfusion requirements in these patients. This allows for patient stabilization and bridges towards definitive surgery or radiotherapy to treat the underlying tumor., (© 2021 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Purpose This study aimed to determine the influence of mandibular free-end partial edentulism and use of conventional or implant-supported removable dental prostheses in the partially edentulous area on the load exerted on the maxillary anterior teeth.Methods A jaw model with mandibular free-end missing teeth was used, and a distal extension, removable partial dental prosthesis was fabricated to replace the missing posterior teeth. Four experimental conditions were set up: 1) without prosthesis, 2) with a conventional removable partial dental prosthesis, 3) with an implant-supported removable partial dental prosthesis, and 4) with a complete dental arch. Strain gauges were attached to the root surface of the maxillary left central incisor, canine, first premolar, and first molar. The load exerted on them was calculated based on the calibration coefficient. An occlusal load of 49 N was applied, and the forces were compared using a Kruskal-Wallis test (P < 0.05). Results The load exerted on the maxillary anterior teeth increased significantly with no prosthesis, decreased significantly with a conventional removable partial dental prosthesis, and decreased even more significantly with an implant-supported removable partial dental prosthesis. Conclusions The burden on the maxillary anterior teeth decreased with the use of a removable partial dental prosthesis and decreased even further with the use of an implant-supported dental prosthesis. The use of an implant to support a distal extension removable partial dental prosthesis is potentially effective in preserving the remaining teeth and tissues by reducing excessive stress in patients with mandibular free-end partial edentulism.

Purpose To clarify the rate of posterior residual ridge resorption (PRRR) in different denture treatments and the factors that can affect PRRR.Study selection A bibliographical electronic search was conducted on MeSH, Web of Science, and Ovid databases. Hand searching was also conducted. Longitudinal studies recording the average rate of PRRR in the mandible were included. The effect size was calculated based on the mean rate of PRRR with standard deviation and group size. The random-effects analysis was used to perform meta-analyses across qualified studies.Results A total of 2245 eligible studies were collected from the MeSH, Web of Science, and Ovid databases and hand searching. In the end, 19 studies met the inclusion criteria and were extracted. The average rate of PRRR in different mandibular denture treatments was assessed in this systematic review. The mean combined effect size was -1.05 ± 0.5 (95% confidence interval [CI]: -3.18-1.08) between four-implant overdentures and two-implant overdentures. The combined effect size was -0.01 ± 0.22 (95% CI: -0.93-0.82) between complete dentures and two-implant overdentures. Body mass index, number of dentures used, denture wearing habit, impression technique, artificial tooth material, and peri-implant bone resorption showed no significant effect on the rate of PRRR. Gender, denture material, and relining frequency showed a significant effect on the rate of PRRR.Conclusions This review summarized different average rates of PRRR in mandibular denture treatments. Meta-analyses have reported that four-implant overdenture treatments can lower the rate of PRRR compared to two-implant overdenture treatments. However, there was no significant difference in the treatment effect between the complete denture and two-implant overdenture treatments.