bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated microsatellite instability at selected tetranucleotide (EMAST) repeats in gastric cancer: a distinct microsatellite instability type with potential clinical impact?
Authors: Herz Anna‐Lina , Wisser Sarah , Kohlruss Meike , Slotta‐Huspenina Julia , Jesinghaus Moritz , Grosser Bianca , Steiger Katja , Novotny Alexander , Hapfelmeier Alexander , Schmidt Thomas , Gaida Matthias M , Weichert Wilko , Keller Gisela 
Published: January 2022

AbstractWe investigated the clinical impact of elevated microsatellite instability at selected tetranucleotide (EMAST) repeats in the context of neoadjuvant chemotherapy (CTx) in gastric/gastro‐oesophageal adenocarcinomas. We analysed 583 resected tumours (272 without and 311 after CTx) and 142 tumour biopsies before CTx. If at least two or three of the five tetranucleotide repeat markers tested showed instability, the tumours were defined as EMAST (2+) or EMAST (3+), respectively. Expression of mismatch repair proteins including MSH3 was analysed using immunohistochemistry. Microsatellite instability (MSI) and Epstein–Barr virus (EBV) positivity were determined using standard assays. EMAST (2+) and (3+) were detected in 17.8 and 11.5% of the tumours, respectively. The frequency of EMAST (2+) or (3+) in MSI‐high (MSI‐H) tumours was 96.2 or 92.5%, respectively, demonstrating a high overlap with this molecular subtype, and the association of EMAST and MSI status was significant (each overall p < 0.001). EMAST (2+ or 3+) alone in MSI‐H and EBV‐negative tumours demonstrated only a statistically significant association of EMAST (2+) positivity and negative lymph node status (42.3% in EMAST (2+) and 28.8% in EMAST negative, p = 0.045). EMAST alone by neither definition was significantly associated with overall survival (OS) of the patients. The median OS for EMAST (2+) patients was 40.0 months (95% confidence interval [CI] 16.4–63.6) compared with 38.7 months (95% CI 26.3–51.1) for the EMAST‐negative group (p = 0.880). The median OS for EMAST (3+) patients was 46.7 months (95% CI 18.2–75.2) and 38.7 months (95% CI 26.2–51.2) for the negative group (p = 0.879). No statistically significant association with response to neoadjuvant CTx was observed (p = 0.992 and p = 0.433 for EMAST (2+) and (3+), respectively). In conclusion, our results demonstrate a nearly complete intersection between MSI‐H and EMAST and they indicate that EMAST alone is not a distinct instability type associated with noticeable clinico‐pathological characteristics of gastric carcinoma patients.
C(sp3)−H Arylation Promoted by a Heterogeneous Palladium‐N‐Heterocyclic Carbene Complex in Batch and Continuous Flow
Authors: Ferlin Francesco , Anastasiou Ioannis , Salameh Nihad , Miyakoshi Takeru , Baudoin Olivier , Vaccaro Luigi 
Published: January 2022

AbstractA heterogeneous reusable palladium(II)‐bis(N‐heterocyclic carbene) catalyst was prepared and shown to catalyze the intramolecular C(sp3)−H activation/cyclization of N‐alkyl‐2‐bromoanilines furnishing indolines. This new catalytic system was based on a bis‐imidazolium ligand immobilized on a spaced cross‐linked polystyrene support. The iodide ligands on the catalyst played a central role in the efficiency of the process occurring through a “release and catch” mechanism. The heterogeneous nature of the catalyst was further exploited in the design of a continuous‐flow protocol that allowed a more efficient recovery and reuse of the catalyst, as well as a very fast and safe procedure.
Pulmonary epithelial‐myoepithelial carcinoma (P‐EMC) with focal high grade transformation: Molecular and cytologic findings
Authors: Charles River , Murray Sarah , Gray Eric , Hu Jingjing 
Published: January 2022

AbstractBackgroundPulmonary epithelial‐myoepithelial carcinoma (P‐EMC) is a rare type of salivary gland tumor of the lung. Diagnosis from preoperative biopsies or fine needle aspiration (FNA) cytology specimens is difficult given the rarity of the tumor and overlapping cytomorphology with other entities. These tumors generally have a good prognosis, however prior reports of recurrence and metastasis to lymph nodes have been reported. Further, little is known about the malignant potential of high grade transformation. The molecular characteristics of this entity are unknown, with only a few case reports commenting on molecular findings. Here, we report a case of P‐EMC with focal high grade transformation. We present its diagnostic pitfalls on cytology specimens, surgical pathology, immunohistochemistry, and molecular findings.Case presentationA 72 year old female presented with an incidentally detected lung mass. A chest computed tomography (CT) demonstrated a left hilar mass measuring 4.1 cm with endobronchial extension into the left upper lobe. On the initial endobronchial core needle biopsy and cytology FNA, the tumor was misinterpreted as squamous cell carcinoma. The patient subsequently underwent a left pneumonectomy along with mediastinal lymph node dissection. Final surgical pathology of the resection specimen indicated a P‐EMC with focal high grade transformation. The patient is disease‐free 1 year post‐surgery.ConclusionsDue to the rarity of P‐EMC, insufficient sampling and histologic heterogeneity, diagnosis of P‐EMC on preoperative core needle biopsy or FNA specimen is difficult. Herein, we present a rare case of P‐EMC, with a pre‐operative FNA cytology specimen that consisted of tumor cells with dense cytoplasm and moderate cytologic atypia, strong positive staining pattern of p40, that was misdiagnosed as squamous cell carcinoma. Follow up surgical resection showed P‐EMC with focal high grade transformation. Salivary gland EMCs with high grade transformation have previously been reported to have a worse prognosis, however, little is known about the malignant potential in the lung. Next generation sequencing (NGS) using a 397‐gene solid tumor panel identified variants in DNMT3A, APC, STAT3 in both low and high grade components, while KDM5C was present only in the high grade transformation.
Salt dissolution tectonism and origin of lacustrine carbonate beds: Mn‐Fe‐calcite and Mn‐siderite micro‐spherulite fabrics of the Lower Cretaceous McMurray Formation, Athabasca Oil Sands deposit, western Canada
Authors: Broughton Paul L. 
Published: January 2022

AbstractSeveral lacustrine carbonate beds, each a metre‐thick interval of densely packed Mn‐rich sideritic micro‐spherulites or Mn‐rich ferroan calcite micro‐spherulites, are recorded for the first time within strata of the Lower Cretaceous McMurray Formation of the northern Athabasca Oil Sands deposit, western Canada. A lower McMurray lacustrine carbonate deposit is characterised by a metre‐thick bed fabric of Mn‐rich siderite micro‐spherulites. The middle and upper interval McMurray beds developed fabrics of Mn2+‐rich ferroan calcite micro‐spherulites. These carbonate beds represent saline lacustrine depositional environments that resulted from the lake bottom sediments ingressed from below by Mn2+‐Fe2+‐rich carbonate‐saturated brines. These up‐section migrations of Devonian formation water were sourced from dissolution trends developed in limestone and halite‐anhydrite beds of the underlying Devonian Prairie Evaporite during Cordilleran deformation of the Alberta Basin foreland. These brines ascended to the overlying McMurray Formation sediments along dissolution‐collapse structures such as breccia pipes, sinkholes and margins of differentially subsided Upper Devonian fault blocks. The up‐section migration of a sulphate‐saturated Fe2+ and Mn2+‐rich brine resulted in the ingress of a lower McMurray lacustrine bottom sediment at a site associated with the development of a peat mire terrain. Microbial redox of the lake bottom sediment resulted in a carbonate bed of micro‐spherulitic fabrics of Mn‐rich siderite interwoven with pyrite laminae. Subsequent salt dissolution events and up‐section migrations of Devonian brine during deposition of the middle and upper McMurray intervals resulted in similar carbonate‐saturated but sulphate‐poor chemistry. These saline flows also ingressed lacustrine bottom sediments below, and resulted in limestone beds of densely packed spherulitic fabrics of Mn‐ferroan calcite, not siderite. These deposits provide insight into largely unknown dispositions of voluminous brine resulting from salt dissolution trends below the Athabasca Oil Sands and further our understanding of controversial McMurray depositional processes.
Global koff‐rates of polyclonal T‐cell populations merge subclonal avidities and predict functionality
Authors: Lückemeier Philipp , Molter Katherine L. , Jarosch Sebastian , Huppertz Patrick , Purcarea Anna , Effenberger Manuel J. P. , Nauerth Magdalena , D'Ippolito Elvira , Schober Kilian , Busch Dirk H. 
Published: January 2022

AbstractThe avidity of TCRs for peptide‐major histocompatibility complexes (pMHCs) is a governing factor in how T cells respond to antigen. TCR avidity is generally linked to T‐cell functionality and there is growing evidence for distinct roles of low and high avidity T cells in different phases of immune responses. While physiological immune responses and many therapeutic T‐cell products targeting infections or cancers consist of polyclonal T‐cell populations with a wide range of individual avidities, the role of T‐cell avidity is usually investigated only in monoclonal experimental settings. In this report, we induced polyclonal T‐cell responses with a wide range of avidities toward a model epitope by altered peptide ligands, and benchmarked global avidity of physiological polyclonal populations by investigation of TCR‐pMHC koff‐rates. We then investigated how varying sizes and avidities of monoclonal subpopulations translate into global koff‐rates. Global koff‐rates integrate subclonal avidities in a predictably weighted manner and robustly correlate with the functionality of murine polyclonal T‐cell populations in vitro and in vivo. Surveying the full avidity spectrum is essential to accurately assess polyclonal immune responses and inform the design of polyclonal T‐cell therapeutics.
Embryonic Exposure to Thiamethoxam Reduces Survival and Alters Neurobehavior of Fathead Minnows
Authors: Victoria Shayla , Duffy Sara , Harrahy Elisabeth , King-Heiden Tisha 
Published: January 2022

Abstract
Thiamethoxam is a commonly used neonicotinoid insecticide that acts as a nicotinic acetylcholine receptor (nAChR) agonist. Although vertebrates are less sensitive to neonicotinoid insecticides than invertebrates, some neonicotinoids have been shown to cause neurobehavioral changes in larval fishes. In the present study, we examine the neurobehavioral toxicity of acute and chronic exposure to environmentally relevant concentrations of thiamethoxam in fathead minnows at two different life stages. Whereas acute exposure of embryos to thiamethoxam does not appear to stimulate spontaneous contractions within 1 min, chronic exposure of embryos to 1.57 µg or more thiamethoxam/L caused increased mortality as well as a subtle increase in spontaneous contraction frequency (SCF), which was negatively correlated with early hatching success. Chronic exposure of embryos to 155 µg thiamethoxam/L impaired predator escape response, and chronic exposure to 0.02–14.61 µg thiamethoxam/L impaired foraging efficiency of some fish. Fathead minnows exposed to thiamethoxam beginning post hatch did not experience changes to measured health or neurobehavioral indicators. Taken together, our findings indicate that embryonic life stages are more sensitive to thiamethoxam exposure than later larval life stages. Because early exposure to thiamethoxam can cause deficits in predatory escape behaviors and may impair foraging success, further study of the potential direct and nondirect impacts of thiamethoxam on wild fish populations is warranted. Environ Toxicol Chem 2022;41:1276–1285. © 2022 SETAC
Abstract
Thiamethoxam causes neurobehavioral toxicity in fathead minnow larvae.
The vascular risk factors and vascular neuropathology in subjects with autopsy‐confirmed dementia with Lewy bodies
Authors: Chen Zhi‐Chao , Gan Jinghuan , Yang Yaqi , Meng Qingbo , Han Jiuyan , Ji Yong 
Published: January 2022

AbstractBackgroundThe frequency of vascular risk factors (VRFs) and the relationship between vascular pathology and cognitive function in neurodegenerative disease remains incompletely understood.ObjectiveThe purpose of this study was to describe the frequency of VRFs and vascular pathology and explore the relationship between vascular pathology and cognitive function in dementia with Lewy bodies (DLB).MethodsThis study included 363 autopsy‐confirmed DLB and 753 Alzheimer's disease (AD) patients from the National Alzheimer's Coordinating Center (NACC) database. We used chi‐squared test and analysis of variance to compare the VRFs and related factors in DLB and AD. Multinomial logistic regression and Spearman's correlation test were used to examine the relationship between vascular pathology and cognitive function.ResultsNo significant differences of VRFs were identified between DLB and AD. Alzheimer's disease patients had higher rates of microinfarcts (23.5% vs. 16.3%, p = 0.005) and moderate to severe amyloid angiopathy (45.9% vs. 36.1%, p = 0.002). In DLB patients, only cerebral amyloid angiopathy (CAA) pathology was negatively correlated with memory domain (r = −0.263, p < 0.001) and language (r = −0.112,p = 0.034). The rates of APOE ε4 allele carriers (60.0% vs. 44.9%, p = 0.004) and CAA pathology (45.9% vs.23.4%, p < 0.001) were much higher in the group with an intermediate likelihood of DLB than in the group with a high likelihood. There was a negative correlation between CAA pathology and memory (logical memory) in the group with an intermediate likelihood of DLB.ConclusionNo difference of VRFs was identified between autopsy‐confirmed DLB and AD. Cerebral amyloid angiopathy was shown to be an important pathology in DLB, which specifically correlated with memory and language. The groups with high and intermediate likelihood of DLB differed in terms of CAA pathology, and CAA pathology may play an important role in the development of DLB.
Aspirin use and risk of hepatocellular carcinoma in patients with chronic hepatitis B with or without cirrhosis
Authors: Jang Heejoon , Lee Yun Bin , Moon Hyemi , Chung Jong‐Won , Nam Joon Yeul , Cho Eun Ju , Lee Jeong‐Hoon , Yu Su Jong , Kim Yoon Jun , Lee Juneyoung , Yoon Jung‐Hwan 
Published: January 2022

Abstract

Background and Aims
Studies on differential effect of aspirin therapy on HCC risk across the spectrum of liver diseases are lacking. We investigated the association between aspirin use and risks of HCC, liver‐associated death, and major bleeding in chronic hepatitis B (CHB) patients with or without cirrhosis.

Approach and Results
We identified 329,635 eligible adults with CHB from 2007 through 2017, using the Korean National Health Insurance Service database, including patients who received aspirin for ≥90 consecutive days (n = 20,200) and patients who never received antiplatelet therapy (n = 309,435). Risks of HCC, liver‐associated mortality, and major bleeding were estimated in a propensity‐score–matched cohort (19,003 pairs), accounting for competing risks. With a median follow‐up of 6.7 years, 10‐year cumulative incidence of HCC was 9.5% in the aspirin‐treated group and 11.3% in the untreated group (adjusted subdistribution hazard ratio [aSHR], 0.85; 95% CI, 0.78–0.92). However, among patients with cirrhosis (2479 pairs), an association of aspirin use with HCC risk was not evident (aSHR, 1.00; 95% CI, 0.85–1.18). Cirrhosis status had a significant effect on the association between aspirin use and HCC risk (pinteraction
, n = 0.04). Aspirin use was also associated with lower liver‐associated mortality (aSHR, 0.80; 95% CI, 0.71–0.90). Moreover, aspirin use was not associated with major bleeding risk (aSHR, 1.09; 95% CI, 0.99–1.21).

Conclusions
Aspirin use was associated with reduced risks of HCC and liver‐associated mortality in adults with CHB. Cirrhosis status had a substantial effect on the association between aspirin use and HCC risk.
Improved sparse representation algorithm for optical coherence tomography images
Authors: Miao Hanyuan , Zhou Xiaohong , Wang Wei , Jiang Weiliang , Jin Tao 
Published: January 2022

AbstractAn improved sparse representation algorithm is proposed for reducing speckle noise in optical coherence tomography (OCT) images. To reduce the dictionary training time, the orthogonal matching pursuit algorithm (OMP) is replaced by a piecewise orthogonal matching pursuit algorithm (ST‐OMP), and a threshold standard is set to train multiple atoms simultaneously to improve the tracking efficiency. Normal, diabetic macular edema, and fundus neovascularization membrane retina OCT images were tested using the proposed algorithm and other denoising algorithms. The results show that the proposed algorithm exhibits an excellent denoising ability. The details and edge information in the OCT images were well preserved by the proposed algorithm. Meanwhile, the image processing time was reduced by half with the proposed algorithm compared with the traditional K‐SVD algorithm.
Biocompatible polymeric blend for pH driven delivery of cytarabine: Effect of feed contents on swelling and release kinetics
Authors: Batool Nighat , Sarfraz Rai Muhammad , Mahmood Asif , Zafar Nadiah , Minhas Muhammad Usman , Hussain Zahid , Rehman Umaira 
Published: January 2022

AbstractPurpose of this study was to prepare chitosan/tamarind crosslinked poly (methacrylic acid) hydrogels for pH responsive delivery of cytarabine by using aqueous free radical polymerization technique. Polymers were chemically cross‐linked with monomer (methacrylic acid) using methylene bisacrylamide as cross‐linking agent and ammonium per sulphate as a reaction initiator in aqueous medium. Developed hydrogels were characterized for morphology, physical existence, drug loading (%), compositional and structural analysis, thermal behavior and stability, drug release analysis (pH 1.2 and pH 7.4), and in vivo release kinetics. pH sensitive behavior was established by observing swelling and release behavior at different pH values (1.2 and 7.4). Biocompatibility of network was evaluated through acute oral toxicity studies in rabbits. Results revealed that cytarabine was efficiently loaded in prepared hydrogels with an entrapment efficiency of 54.67%–108.59%. Highest swelling ratio of 38.67 was noticed at pH 7.4. Maximum pH sensitive behavior was seen at pH 7.4 showing maximum drug release up to 94.51%. All developed formulations followed zero order release as confirmed from regression coefficient (R2 = 0.9912–0.9991). In‐vivo studies confirmed enhanced bioavailability of cytarabine. Histopathological examination and hemocompatibility studies proved that developed hydrogel system was safe, biocompatible, nonhemolytic in nature exhibiting no symptoms of dermal, ocular toxicities, and no changes in biochemical parameters of blood and histology of key organs. So, developed hydrogel system can be employed as an excellent drug delivery device where controlled drug delivery is desired.
Inhibition of focal adhesion turnover prevents osteoblastic differentiation through β‐catenin mediated transduction of pro‐osteogenic substrate
Authors: Juhl Otto J. , Merife Anna‐Blessing , Zhang Yue , Donahue Henry J. 
Published: January 2022

AbstractThe mechanism by which substrate surface characteristics are transduced by osteoblastic cells and their progenitors is not fully known. Data from previous studies by our group suggest the involvement of β‐catenin in the mechanism by which substrate surface characteristics are transduced. This focal adhesion and β‐catenin mediated mechanism functions through the liberation of β‐catenin from focal adhesion complexes in response to pro‐osteogenic substrate (POS) characteristics. After liberation, β‐catenin translocates and facilitates upregulation of genes associated with osteogenesis. It is not known whether the observed correlation between focal adhesion turnover and β‐catenin translocation directly results from focal adhesion turnover. In this study we inhibited focal adhesion turnover using a focal adhesion kinase inhibitor PF‐573228. We found that inhibition of focal adhesion turnover resulted in an abrogation of the more rapid translocation and increased transcriptional activity of β‐catenin induced by POS. In addition, inhibition of focal adhesion turnover mitigated the increase in osteoblastic differentiation induced by a POS as measured by alkaline phosphatase enzymatic activity and osteogenic gene and protein expression. Together, these data, coupled with previous findings, suggest that the observed β‐catenin translocation is a result of focal adhesion turnover, providing evidence for a focal adhesion initiated, β‐catenin mediated mechanism of substrate surface signal transduction.
Effects of a collagen hyaluronic acid silk‐fibroin patch with the electroconductive element polyaniline on left ventricular remodeling in an infarct heart model
Authors: Leite Fernanda Gomes , Marana Juliana Fonzar , de Sá Luiza Fernandes Tavares , Alves de Almeida Thais Francine Ribeiro , do Carmo Helison Rafael Pereira , Chaud Marco Vinícius , Grotto Denise , Silveira‐Filho Lindemberg da Mota 
Published: January 2022

AbstractBiodegradable cardiac patches have been able to induce improvement in left ventricular (LV) remodeling. A novel scaffold patch made with collagen and silk‐fibroin (COL‐SF) was further associated to polyaniline (PANi) to increase conductivity. Thus, this study investigated the safety of the association of PANi to a patch, and the improvement in LV remodeling in a myocardial infarct (MI) rat model. Wistar rats underwent MI induction. MI was confirmed with echocardiographic and after 2 weeks, animals (n = 10/group) were randomized into: (a) COL‐SF hyaluronic acid patch, (b) PANi hyaluronic acid patch, (c) MI Control (just repeat thoracotomy). Healthy animals were also followed. Echocardiography was performed at pre‐treatment, and at 2‐, 4‐, and 8‐weeks post‐treatment. Hearts underwent hemodynamic evaluation on Langendorff apparatus and histology for LV thickness and percent of infarct size. Liver, kidneys, and blood samples were evaluated for biochemical, hematological, oxidative stress, and histology. There was a tendency of lower %infarct size in patched animals. LV thickness was higher in the patched animals than controls. Functional echocardiographic indices %Fractional shortening and %LV ejection fraction decreased in the MI control group, but not in the patched animals. PANi presented higher %LVEF versus MI control. PANi presented higher liver transaminases; no morphological changes were observed in histology. Elevation of antioxidant markers was observed. COL‐SF and PANi patches were able to induce better remodeling features compared to MI controls on %infarct size and LV thickness and have not presented echocardiographic worsening. Polyaniline may present a slight improvement on LV remodeling, despite associated to signs of hepatotoxicity and pro‐oxidant effect.