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Background: Nonsurgical management of congenital ear anomalies using molding devices shows efficacy but lacks standardization of treatment protocols and outcome measures. Learning Objective: To compare ear molding techniques and identify factors related to treatment outcomes. Design Type: Systematic review of the literature (1990-2021). Methods: Studies reporting molding for congenital ear anomalies were assessed. PRISMA guidelines were used. Data extracted included: age at treatment initiation, treatment duration, correction rates, and complications. Data analysis included descriptive statistics and outcomes were compared using the Student t-test. Results: In total, 37 studies with 3,341 patients (mean patients per study, 95; range, 5-488) were included. Infants in whom treatment was initiated at 4.8 weeks (median, 3.7; range, 0.9-8.8 weeks) were treated for 5.1 weeks (median 4.7, range 2.6-7.6 weeks) with 11.0 months follow-up (median 11.4, range 1.4-21.0 months). Individualized devices (physician-customized) were used more (62.2% of studies) than commercial devices. No difference in correction (p = 0.44) or complication rates (p = 0.19) was identified between devices. Totally, 70.3% of studies reported complications and 40.5% of studies included long-term follow-up data. Conclusions: The available evidence supports initiating ear molding in the first weeks of life to be most effective, yet outcome data should be standardized in future studies to improve evidence quality.
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Porphyromonas gingivalis is the primary microbe in the "periodontal red complex" bacteria (PRCB) along with Tannerella forsythia and Treponema denticola, which are linked to periodontal disease (PD). These pathogens are also implicated in various systemic disorders, but their association with the incidence of gastrointestinal (GI) cancer is less explored. A systematic review followed by a meta-analysis was conducted as per standard guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2022) to find this association between GI cancers and PRCB after a literature search for full-text papers in the English language (between 2010 and 2023) in databases (Cochrane Library, PubMed, and Web of Science) with suitable keywords using the Boolean search strategy. Data extraction involved titles, abstracts, and full texts retrieved and scored by the modified Newcastle-Ottawa Scale. The data were analyzed by the Review Manager (RevMan 5.2, Cochrane Collaboration, Denmark). Standard Cochran Q test and I2 statistics (for heterogeneity) and a random effects model (pooled OR with 95% CI) were applied to report results. P. gingivalis among the PRCB was linked to GI cancers (OR: 2.16; 95% CI: 1.34-3.47). T. forsythia and T. denticola did not show meaningful associations as per existing evidence for GI cancers.
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Lanthanide metal clusters excel in combining molecular and material chemistry properties. Here, we report an efficient cooperative sensitization UC phenomenon of a Eu3+/Yb3+ nonanuclear lanthanide cluster in CD3OD. The synthesis and characterization of the heteronuclear cluster in the solid state and solution are described together with the UC phenomenon showing Eu3+ luminescence in the visible region upon 980 nm NIR excitation of Yb3+ at concentrations as low as 100 nM. Alongside being the Eu/Yb cluster to display UC (with a quantum yield value of 4.88 × 10-8 upon 1.13 W cm-2 excitation at 980 nm), the cluster exhibits downshifted light emission of Yb3+ in the NIR region upon 578 nm visible excitation of Eu3+, which is ascribed to sensitization pathways for Yb through the 5D0 energy levels of Eu3+. Additionally, a faint emission is also observed at ca. 500 nm upon 980 nm excitation, originating from the cooperative luminescence of Yb3+. The [Eu8Yb(BA)16(OH)10]Cl cluster (BA = benzoylacetonate) is also a field-induced single-molecular magnet (SMM) under 4K with a modest Ueff/kB of 8.48 K, thereby joining the coveted list of Yb-SMMs and emerging as a prototype system for next-generation devices, combining luminescence with single-molecular magnetism in a molecular cluster.
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BACKGROUND: Differential responses to neoadjuvant therapy (NAT) exist in pancreatic ductal adenocarcinoma (PDAC); however, contributing factors are poorly understood. Tobacco smoke is a common risk factor for PDAC, with nicotine-induced chemoresistance observed in other cancers. This study aimed to explore the potential association between tobacco use and NAT efficacy in PDAC. METHODS: A single-center, retrospective analysis was conducted that included all consecutive patients with PDAC who underwent surgical resection after NAT with a documented smoking history (N = 208). NAT response was measured as percentage fibrosis in the surgical specimen. Multivariable models controlled for covariates and survival were modeled using the Kaplan-Meier method. RESULTS: Postoperatively, major responses to NAT (>95% fibrosis) were less frequently observed in smokers than in nonsmokers (13.7% vs 30.4%, respectively; P = .021). Pathologic complete responses were similarly less frequent in smokers than in nonsmokers (2.1% vs 9.9%, respectively; P = .023). On multivariate analysis controlling for covariates, smoking history remained independently associated with lower odds of major fibrosis (odds ratio [OR], 0.25; 95% CI, 0.10-0.59; P = .002) and pathologic complete response (OR, 0.21; 95% CI, 0.03-0.84; P = .05). The median overall survival was significantly longer in nonsmokers than in smokers (39.1 vs 26.6 months, respectively; P = .05). CONCLUSION: Tobacco use was associated with diminished pathologic responses to NAT. Future research to understand the biology underlying this observation is warranted and may inform differential NAT approaches or counseling among these populations.
Subject(s)
Carcinoma, Pancreatic Ductal , Neoadjuvant Therapy , Pancreatic Neoplasms , Smoking , Humans , Pancreatic Neoplasms/therapy , Pancreatic Neoplasms/pathology , Male , Female , Retrospective Studies , Middle Aged , Aged , Smoking/adverse effects , Smoking/epidemiology , Carcinoma, Pancreatic Ductal/therapy , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/pathology , Treatment Outcome , Fibrosis , Adenocarcinoma/therapy , Adenocarcinoma/pathology , Risk Factors , Kaplan-Meier EstimateABSTRACT
Aim: The present study was conducted for assessing variability in calretinin expression among odontogenic cysts as well as tumor cases. Materials and Methods: Fifteen cases were included in the present research consisting of cases like - dentigerous cyst, odontogenic keratocyst, apical radicular cyst along with tumors like ameloblastoma, ameloblastic carcinoma, adenomatoid odontogenic tumor. Calretinin antibody was used for immunohistochemical staining. The amount of expression of this calretinin was statistically analyzed with the help of Chi-square test where P < 0.05 was considered noteworthy statistically. Results: Most cases of ameloblastomas were highly positive for calretinin expression as compared to other cysts and tumors. Therefore, the correlation of this variation of expression of calretinin was statistically noteworthy (P = 0.00). Conclusion: In this study, we concluded that for ameloblastomas, calretinin can be a specific marker immunohistochemically and can help in identifying the amount of aggressive spread of various odontogenic tumors.
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Aim: In our study, we evaluated the gender dimorphism among dental measurements of selected people in a South Indian district. Methodology: In our research, 500 participants between 17 and 25 years of age were included after taking their maxillary arch impressions. Utilizing Korkhaus compass and digital caliper, depth of palatal area as well as maxillary arch as a whole was done. T-test was done to initiate the comparative analysis between the palatal arch and complete maxillary arch depths where P < 0.05 was denoted significant statistically. Results: It was recorded that complete maxillary arch depth measurements were increased in case of men as compared to women, whereas the measurements related to depth of the palatal arch were not statistically significant. Conclusion: In our research, we found that complete maxillary arch depth can be utilized for gender segregation accompanied with other auxiliary methods. The mean value for both these measurements can be utilized as a standard measurement for advance research.
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Pseudomembranes in the large and small intestines are common in hospitalized patients that are immunosuppressed or on certain oral antibiotics. Pseudomembranous enterocolitis, histologically characterized by volcanic-like eruption of inflammatory cellular exudate from the mucosal surface, is mainly attributed to Clostridium difficile toxins and often presents with symptomatic diarrhea. Rarely, there are case reports of similar pseudomembranous lesions limited to the stomach in the absence of intestinal involvement. In this paper, we present a case of localized pseudomembranous gastritis in a 76-year-old patient with personal history limited to prior gastrointestinal bleed, liver cirrhosis, alcohol dependence, diabetes mellitus, and hypertension who was referred to the emergency department from his primary care physician's office due to low hemoglobin.
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The versatile properties of bipolar organic electrode materials have attracted considerable attention in the field of electrochemical energy storage (EES). However, their practical application is hindered by their inherent limitations including low intrinsic electrical conductivity, low specific capacity, and high solubility. Herein, a bipolar organic molecule combining both porphyrin and ferrocene moieties (CuDEFcP) [5,15-bis(ethynyl)-10,20-di ferrocenyl porphinato]copper(II)) has been developed. It is proposed as a new organic electrode material with multifunctional application for rechargeable organic lithium-based batteries (ROLBs) and dual-ion organic symmetric batteries (SDIBs). Superior performance was delivered as cathode material in lithium based dual-ion batteries (LDIBs), with a high initial discharge capacity of 300â mAh. g-1 at 0.2â A. g-1 and a reversible capacity of 58â mAh. g-1 after 5000â cycles at 1â A. g-1. However, employing it as an anode material in lithium-ion batteries (LIBs), a reversible capacity of 295â mAh. g-1 at 0.2â A. g-1 was delivered. In SDIBs, in which CuDEFcP is used as both anode and cathode, an average discharge voltage of 2.4â V and an energy density of 261â Wh.kg-1 were achieved.
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OBJECTIVE: Hepatic overexpression of the thrombospondin 2 gene (THBS2) and elevated levels of circulating thrombospondin 2 (TSP2) have been observed in patients with chronic liver disease. This study aimed to identify the specific cells expressing THBS2/TSP2 in non-alcoholic fatty liver disease (NAFLD) and investigate the underlying mechanism behind THBS2/TSP2 upregulation. DESIGN: Comprehensive NAFLD liver gene datasets, including single-cell RNA sequencing (scRNA-seq), in-house NAFLD liver tissue, and LX-2 cells derived from human hepatic stellate cells (HSCs), were analysed using a combination of computational biology, genetic, immunological, and pharmacological approaches. RESULTS: Analysis of the genetic dataset revealed the presence of 1433 variable genes in patients with advanced fibrosis NAFLD, with THBS2 ranked among the top 2 genes. Quantitative polymerase chain reaction (qPCR) examination of NAFLD livers showed a significant correlation between THBS2 expression and fibrosis stage (r = .349, p < .001). In support of this, scRNA-seq data and in situ hybridization demonstrated that the THBS2 gene was highly expressed in HSCs of NAFLD patients with advanced fibrosis. Pathway analysis of the gene dataset revealed THBS2 expression to be associated with the transforming growth factor beta (TGFß) pathway and collagen gene activation. Moreover, the activation of LX-2 cells with TGFß increased THBS2/TSP2 and collagen expression independently of the TGFß-SMAD2/3 pathway. THBS2 gene knockdown significantly decreased collagen expression in LX-2 cells. CONCLUSIONS: THBS2/TSP2 is highly expressed in HSCs and plays a role in regulating fibrogenesis in NAFLD patients. THBS2/TSP2 may therefore represent a potential target for anti-fibrotic therapy in NAFLD.
Subject(s)
Non-alcoholic Fatty Liver Disease , Thrombospondins , Humans , Non-alcoholic Fatty Liver Disease/complications , Liver/pathology , Fibrosis , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolism , Hepatic Stellate Cells/metabolism , Collagen/metabolism , Liver Cirrhosis/complicationsABSTRACT
Infection with the dengue virus can present with a variety of clinical manifestations that can range from asymptomatic or mild disease to severe hemorrhagic shock. In this report, we present a 25-year-old female patient with complaints of fever, headache, vomiting, and a reeling sensation for two days. On further examination, the workup for meningitis was negative, and the patient tested positive for dengue IgM antibodies. The MRI brain showed a restricted central lesion involving the splenium of the corpus callosum in favor of a cytotoxic lesion of the corpus callosum and a transient lesion of the splenium. Based on the MRI, a diagnosis of reversible splenial lesion syndrome (RESLES) was confirmed. Supportive treatment was initiated, and the patient made a complete recovery with no neurological deficits. A repeat MRI of the brain was done one month later, and it revealed complete resolution of the splenial lesion. If dengue fever is treated effectively, it frequently has a favorable prognosis with remission of uncommon, distinct radiological associations.
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BACKGROUND: Tumor fibrosis after neoadjuvant treatment (NAT) for pancreatic ductal adenocarcinoma (PDAC) correlates with treatment response. Herein we assessed how different NAT strategies influence pathologic responses and survival. METHODS: Patients with surgically resected PDAC who received NAT (1991-2020) were included. Descriptive statistics compared outcomes amongst fibrosis groups (none, minor <50 â%, partial 51%-94 â%, major ≥95 â%) and NAT (chemotherapy alone, chemoradiation, or chemotherapy â+ âchemoradiation (total neoadjuvant therapy, TNT)). RESULTS: Patients with major fibrosis most often received TNT (65.8 â%, p â< â0.001). Major fibrosis was associated with the greatest rate of downstaging (77.8 â%, p â< â0.001), highest R0 margin rate (100 â%, p â< â0.01), and lowest mean positive lymph node ratio (0.80, p â< â0.01). Amongst complete responders, 11/14 (78.6 â%) received TNT. Median overall (66.3 months, p â= â0.003) and disease-free (54.7months, p â= â0.05) survival were highest with major fibrosis. CONCLUSIONS: Major fibrosis and complete pathologic responses after NAT are most frequent with a TNT strategy and are associated with improved outcomes.
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Background The inguinal region is an area of complex anatomy that could contain diverse uncommon contents in routine clinical practice. Although inguinal hernia repair is one of the commonest surgeries done routinely, thorough preoperative imaging has a significant impact on the outcome of the surgery, by revealing the presence of unusual contents in the inguinal region. Aim The aim of this article is to review the differential diagnosis of the uncommon inguinal pathologies, which can simulate an inguinal hernia, to determine, and to simplify the treatment approach. Conclusions A profound understanding of the imaging characteristics of uncommon inguinal pathologies is crucial for both the radiologists (to prevent misdiagnosis) and the treating physicians (to avoid surgical complications) and ensure optimal management.
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Accelerating the development of synthetic biology applications requires reproducible experimental findings. Different standards and repositories exist to exchange experimental data and metadata. However, the associated software tools often do not support a uniform data capture, encoding, and exchange of information. A connection between digital repositories is required to prevent siloing and loss of information. To this end, we developed the Experimental Data Connector (XDC). It captures experimental data and related metadata by encoding it in standard formats and storing the converted data in digital repositories. Experimental data is then uploaded to Flapjack and the metadata to SynBioHub in a consistent manner linking these repositories. This produces complete connected experimental data sets that are exchangeable. The information is captured using a single template Excel Workbook, which can be integrated into existing experimental workflow automation processes and semiautomated capture of results.
Subject(s)
Metadata , Software , Synthetic Biology/methods , Workflow , AutomationABSTRACT
Standards support synthetic biology research by enabling the exchange of component information. However, using formal representations, such as the Synthetic Biology Open Language (SBOL), typically requires either a thorough understanding of these standards or a suite of tools developed in concurrence with the ontologies. Since these tools may be a barrier for use by many practitioners, the Excel-SBOL Converter was developed to facilitate the use of SBOL and integration into existing workflows. The converter consists of two Python libraries: one that converts Excel templates to SBOL and another that converts SBOL to an Excel workbook. Both libraries can be used either directly or via a SynBioHub plugin.
Subject(s)
Programming Languages , Synthetic Biology , Language , Reference Standards , Workflow , SoftwareABSTRACT
Among several secreted glycoproteins belonging to the thrombospondin family, thrombospondin 2 (TSP2) is involved in various functions, including collagen/fibrin formation. Liver/serum TSP2 levels have been correlated to liver fibrosis stage and disease activity in nonalcoholic fatty liver disease. This study investigated whether serum TSP2 was associated with clinicopathological features in hepatitis C virus (HCV)-infected patients as well. A total of 350 patients with HCV who had undergone liver biopsy were retrospectively enrolled and divided into a discovery cohort (n = 270) and a validation cohort (n = 80). In the discovery cohort, serum TSP2 levels were moderately correlated with both liver fibrosis stage (r = 0.426, P < 0.0001) and activity grade (r = 0.435, P < 0.0001). The area under the receiver operating characteristic curve of TSP2 for predicting severe fibrosis (≥ F3) was 0.78 and comparable to or better than those of autotaxin (0.78), FIB-4 index (0.78), and APRI (0.76). The discovery cohort findings were closely replicated in the validation cohort. Moreover, comprehensive liver genetic analysis of HCV-infected patients confirmed that the expression of the THBS2 gene encoding TSP2 was significantly higher in severely fibrotic F4 than in F1 patients. Circulating TSP2 levels may reflect the severity of hepatic fibrosis/inflammation in HCV-infected patients.
Subject(s)
Hepatitis C, Chronic , Hepatitis C , Humans , Hepacivirus/genetics , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/pathology , Retrospective Studies , Severity of Illness Index , Biomarkers , Liver Cirrhosis/pathology , Liver/pathology , Thrombospondins/genetics , Hepatitis C/complications , Aspartate AminotransferasesABSTRACT
BACKGROUND: Patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy. In selected cases, stereotactic body radiotherapy (SBRT) can be added to the regimen. We hypothesized that adding an adjuvant containing a heat-killed mycobacterium (IMM-101) to SBRT may lead to beneficial immuno-modulatory effects, thereby improving survival. This study aims to investigate the safety of adding IMM-101 to SBRT and to investigate the immuno-modulatory effects of the combination treatment in the peripheral blood of LAPC patients. METHODS: LAPC patients were treated with SBRT (40 Gy) and six intradermal vaccinations of one milligram IMM-101. The primary endpoint was an observed toxicity rate of grade 4 or higher. Targeted gene-expression profiling and multicolor flow cytometry were performed for longitudinal immune-monitoring of the peripheral blood. RESULTS: Twenty patients received study treatment. No treatment-related adverse events of grade 4 or higher occurred. SBRT/IMM-101 treatment induced a transient decrease in different lymphocyte subsets and an increase in CD14+CD16-CD11b+HLA-DRlow myeloid-derived suppressor cells. Importantly, treatment significantly increased activated ICOS+, HLA-DR+ and Ki67+PD1+ T and NK cell frequencies. This was not accompanied by increased levels of most inhibitory markers, such as TIM-3 and LAG-3. CONCLUSIONS: Combination therapy with SBRT and a heat-killed mycobacterium vaccine was safe and had an immune-stimulatory effect.
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Investigating and understanding the intrinsic material properties of biogenic materials, which have evolved over millions of years into admirable structures with difficult to mimic hierarchical levels, holds the potential of replacing trial-and-error-based materials optimization in our efforts to make synthetic materials of similarly advanced complexity and properties. An excellent example is biogenic silica which is found in the exoskeleton of unicellular photosynthetic algae termed diatoms. Because of the complex micro- and nanostructures found in their exoskeleton, determining the intrinsic mechanical properties of biosilica in diatoms has only partly been accomplished. Here, a general method is presented in which a combination of in situ deformation tests inside an SEM with a realistic 3D model of the frustule of diatom Craspedostauros sp. (C. sp.) obtained by electron tomography, alongside finite element method (FEM) simulations, enables quantification of the Young's modulus (E = 2.3 ± 0.1 GPa) of this biogenic hierarchical silica. The workflow presented can be readily extended to other diatom species, biominerals, or even synthetic hierarchical materials.
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BACKGROUND: Patients at risk of developing a disease have to be identified at an early stage to enable prevention. One way of early detection is the use of machine learning based prediction models trained on electronic health records. OBJECTIVES: The aim of this project was to develop a software solution to predict cardiovascular and nephrological events using machine learning models. In addition, a risk verification interface for health care professionals was established. METHODS: In order to meet the requirements, different tools were analysed. Based on this, a software architecture was created, which was designed to be as modular as possible. RESULTS: A software was realised that is able to automatically calculate and display risks using machine learning models. Furthermore, predictions can be verified via an interface adapted to the need of health care professionals, which shows data required for prediction. CONCLUSION: Due to the modularised software architecture and the status-based calculation process, different technologies could be applied. This facilitates the installation of the software at multiple health care providers, for which adjustments need to be carried out at one part of the software only.
Subject(s)
Electronic Health Records , Machine Learning , Humans , SoftwareABSTRACT
Obesity is the major driver of the global epidemic in type 2 diabetes (T2D). In individuals with obesity, impaired insulin action leads to increased lipolysis in adipocytes, resulting in elevated plasma free fatty acid (FFA) levels that promote peripheral insulin resistance, a hallmark of T2D. Here we show, by using a combined genetic/biochemical/pharmacologic approach, that increased adipocyte lipolysis can be prevented by selective activation of adipocyte Gq signaling in vitro and in vivo (in mice). Activation of this pathway by a Gq-coupled designer receptor or by an agonist acting on an endogenous adipocyte Gq-coupled receptor (CysLT2 receptor) greatly improved glucose and lipid homeostasis in obese mice or in mice with adipocyte insulin receptor deficiency. Our findings identify adipocyte Gq signaling as an essential regulator of whole-body glucose and lipid homeostasis and should inform the development of novel classes of GPCR-based antidiabetic drugs.