Comprehensive assessment of protein loop modeling programs on large-scale datasets: prediction accuracy and efficiency.

Protein loops play a critical role in the dynamics of proteins and are essential for numerous biological functions, and various computational approaches to loop modeling have been proposed over the past decades. However, a comprehensive understanding of the strengths and weaknesses of each method is lacking. In this work, we constructed two high-quality datasets (i.e. the General dataset and the CASP dataset) and systematically evaluated the accuracy and efficiency of 13 commonly used loop modeling approaches from the perspective of loop lengths, protein classes and residue types. The results indicate that the knowledge-based method FREAD generally outperforms the other tested programs in most cases, but encountered challenges when predicting loops longer than 15 and 30 residues on the CASP and General datasets, respectively. The ab initio method Rosetta NGK demonstrated exceptional modeling accuracy for short loops with four to eight residues and achieved the highest success rate on the CASP dataset. The well-known AlphaFold2 and RoseTTAFold require more resources for better performance, but they exhibit promise for predicting loops longer than 16 and 30 residues in the CASP and General datasets. These observations can provide valuable insights for selecting suitable methods for specific loop modeling tasks and contribute to future advancements in the field.

Freeprotmap: waiting-free prediction method for protein distance map.

BACKGROUND: Protein residue-residue distance maps are used for remote homology detection, protein information estimation, and protein structure research. However, existing prediction approaches are time-consuming, and hundreds of millions of proteins are discovered each year, necessitating the development of a rapid and reliable prediction method for protein residue-residue distances. Moreover, because many proteins lack known homologous sequences, a waiting-free and alignment-free deep learning method is needed. RESULT: In this study, we propose a learning framework named FreeProtMap. In terms of protein representation processing, the proposed group pooling in FreeProtMap effectively mitigates issues arising from high-dimensional sparseness in protein representation. In terms of model structure, we have made several careful designs. Firstly, it is designed based on the locality of protein structures and triangular inequality distance constraints to improve prediction accuracy. Secondly, inference speed is improved by using additive attention and lightweight design. Besides, the generalization ability is improved by using bottlenecks and a neural network block named local microformer. As a result, FreeProtMap can predict protein residue-residue distances in tens of milliseconds and has higher precision than the best structure prediction method. CONCLUSION: Several groups of comparative experiments and ablation experiments verify the effectiveness of the designs. The results demonstrate that FreeProtMap significantly outperforms other state-of-the-art methods in accurate protein residue-residue distance prediction, which is beneficial for lots of protein research works. It is worth mentioning that we could scan all proteins discovered each year based on FreeProtMap to find structurally similar proteins in a short time because the fact that the structure similarity calculation method based on distance maps is much less time-consuming than algorithms based on 3D structures.

Clinicopathological and molecular genetic analysis of 13 cases of primary retroperitoneal Ewing sarcoma.

Retroperitoneal Ewing sarcomas (RES) are very rare and mostly described in case reports. The purpose of this study was to retrospectively analyze the clinicopathology, molecular characteristics, biological behavior, and therapeutic information of 13 cases of primary RES with immunohistochemical staining, fluorescence in situ hybridization, RT-PCR and NGS sequencing detection techniques. The thirteen patients included eight males and five females with a mean age of 34 years. Morphologically, the tumors were comprised of small round or epithelial-like cells with vacuolated cytoplasm (6/13,46 %) arranged in diffuse, nested (8/13,62 %) and perivascular (7/13,54 %) patterns. Unusual morphologic patterns, such as meningioma-like swirling structures and sieve-like structures were relatively novel findings. Immunohistochemical studies showed CD99 (12/13; 92 %), CD56 (11/13; 85 %), NKX2.2 (9/13; 69 %), PAX7 (10/11;91 %) and CD117(6/9;67 %) to be positive.12 cases (92 %) demonstrated EWSR1 rearrangement and 3 cases displayed EWSR1::FLI1 fusion by FISH. ERCC4 splice-site variant, a novel pathogenic variant, was discovered for the first time via RNA sequencing. With a median follow-up duration of 14 months (6 to 79 months), 8/13 (62 %) patients died, while 5/13(38 %) survived. Three cases recurred, and five patients developed metastasis to the liver (2 cases), lung (2 cases) and bone (1 case). RES is an aggressive, high-grade tumor, prone to multiple recurrences and metastases, with distinctive morphologic, immunohistochemical, and molecular genetic features. ERCC4 splicing mutation, which is a novel pathogenic variant discovered for the first time, with possible significance for understanding the disease, as well as the development of targeted drugs.

Hyperbolic relational graph convolution networks plus: a simple but highly efficient QSAR-modeling method.

Accurate predictions of druggability and bioactivities of compounds are desirable to reduce the high cost and time of drug discovery. After more than five decades of continuing developments, quantitative structure-activity relationship (QSAR) methods have been established as indispensable tools that facilitate fast, reliable and affordable assessments of physicochemical and biological properties of compounds in drug-discovery programs. Currently, there are mainly two types of QSAR methods, descriptor-based methods and graph-based methods. The former is developed based on predefined molecular descriptors, whereas the latter is developed based on simple atomic and bond information. In this study, we presented a simple but highly efficient modeling method by combining molecular graphs and molecular descriptors as the input of a modified graph neural network, called hyperbolic relational graph convolution network plus (HRGCN+). The evaluation results show that HRGCN+ achieves state-of-the-art performance on 11 drug-discovery-related datasets. We also explored the impact of the addition of traditional molecular descriptors on the predictions of graph-based methods, and found that the addition of molecular descriptors can indeed boost the predictive power of graph-based methods. The results also highlight the strong anti-noise capability of our method. In addition, our method provides a way to interpret models at both the atom and descriptor levels, which can help medicinal chemists extract hidden information from complex datasets. We also offer an HRGCN+'s online prediction service at https://quantum.tencent.com/hrgcn/.

Data transmission with up to 100 orbital angular momentum modes via commercial multi-mode fiber and parallel neural networks.

This work presents an artificial intelligence enhanced orbital angular momentum (OAM) data transmission system. This system enables encoded data retrieval from speckle patterns generated by an incident beam carrying different topological charges (TCs) at the distal end of a multi-mode fiber. An appropriately trained network is shown to support up to 100 different fractional TCs in parallel with TC intervals as small as 0.01, thus overcoming the problems with previous methods that only supported a few modes and could not use small TC intervals. Additionally, an approach using multiple parallel neural networks is proposed that can increase the system's channel capacity without increasing individual network complexity. When compared with a single network, multiple parallel networks can achieve the better performance with reduced training data requirements, which is beneficial in saving computational capacity while also expanding the network bandwidth. Finally, we demonstrate high-fidelity image transmission using a 16-bit system and four parallel 14-bit systems via OAM mode multiplexing through a 1-km-long commercial multi-mode fiber (MMF).

Rationale and design of a prospective, multicenter, phase II clinical trial of safety and efficacy evaluation of long course neoadjuvant chemoradiotherapy plus tislelizumab followed by total mesorectal excision for locally advanced rectal cancer (NCRT-PD1-LARC trial).

BACKGROUND: Long course radiotherapy plus neoadjuvant chemotherapy followed by resection (total mesorectal excision, TME) has accepted widespread recognized in the treatment of locally advanced rectal cancer (LARC). Tislelizumab, an anti-PD1 humanized IgG4 monoclonal antibody, has been demonstrated with clinical activity and is approved for treating recurrent/refractory classical Hodgkin lymphoma and locally advanced/metastatic urothelial carcinoma in China. However, the safety and efficacy of long course (neoadjuvant chemoradiotherapy, NCRT) plus tislelizumab followed by TME for LARC is still uncertain. METHODS: This NCRT-PD1-LARC trial will be a prospective, multicenter and phase II clinical trial designed to evaluate the safety and efficacy of LARC patients treated with long course NCRT plus tislelizumab followed by TME. This trial will consecutively enroll 50 stage II/III LARC patients (cT3N0M0 and cT1-3N1-2M0) with the tumor distal location ≤ 7 cm from anal verge at 7 centers in China. The enrolled patients will receive long course radiotherapy (50 Gy/25 f, 2 Gy/f, 5 days/week) and three 21-day cycles capecitabine (1000 mg/m2, bid, po, day1-14) plus three 21-day cycles tislelizumab (200 mg, iv.gtt, day8), followed by TME 6-8 weeks after the end of radiotherapy. The primary efficacy endpoint will be the pathological complete response (pCR) rate, which is defined as absence of viable tumor cells in the primary tumor and lymph nodes. DISCUSSION: To our knowledge, this trial is the first multicenter clinical trial in China to assess the safety and efficacy of NCRT plus anti-PD1 therapy followed by TME to treat patients with LARC. NCRT followed by TME was recognized as the most recommended treatment against LARC while could not be completely satisfied in clinic. This study expects to provide a solid basis and encouraging outcomes for this promising combination of radiotherapy, chemotherapy and immunotherapy in LARC. TRIAL REGISTRATION: Name of the registry: ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT04911517. Date of registration: 23 May 2021. URL of trial registry record: https://www. CLINICALTRIALS: gov/ct2/show/NCT04911517?id=BFH-NCRTPD&draw=2&rank=1 .

Development and Validation of Web-Based Nomograms for Predicting Cause-Specific Mortality in Surgically Resected Nonmetastatic Invasive Breast Cancer: A Population-Based Study.

BACKGROUND: This study aims to build nomograms to predict overall survival (OS) and breast cancer-specific death (BCSD) in resected nonmetastatic invasive breast cancer. PATIENTS AND METHODS: Patients extracted from surveillance, epidemiology, and end results database between 2010 and 2014 were analyzed. Through multivariate Cox regression and Fine and Gray competing risks regression, independent predictive factors were identified and integrated to build nomograms for predicting OS and BCSD. The models were validated by bootstrap resampling and an independent cohort. Additionally, the models' performance was measured by the Harrell's C-index, calibrate curve, and time-dependent receiver operating characteristic (ROC) curves. RESULTS: In total, 110,180 cases were identified and enrolled in the analysis, with 83,450 in the training cohort and 26,730 in the validation cohort. Several independent predictive factors for OS and BCSD were identified and integrated to construct the nomograms. The C-indexes in the training cohort and validation cohort were 0.759 and 0.772 for predicting OS, and 0.857 and 0.856 for predicting BCSD, respectively. The nomogram models were well calibrated, and the time-dependent ROC curves verified the superiority of our models for clinical usefulness. Significant differences in the OS and BCSD curves were also observed when stratifying patients into several different risk groups. For convenient access, we deployed these proposed nomograms into web-based calculators. CONCLUSIONS: We established and validated novel nomograms for individualized prediction of OS and BCSD in resected nonmetastatic invasive breast cancer. These nomograms perform better than previous models and could be easily accessed easily by clinicians.

Retracted: Aggravation of Cerebral Ischemia/Reperfusion Injury by Peroxisome Proliferator-Activated Receptor-Gamma Deficiency via Endoplasmic Reticulum Stress.

This paper is retracted at the author's request. Reference: Yueping Chen, Shihui Liu, Guangyong Chen: Aggravation of Cerebral Ischemia/Reperfusion Injury by Peroxisome Proliferator-Activated Receptor-Gamma Deficiency via Endoplasmic Reticulum Stress. Med Sci Monit, 2019; 25:7518-7526. DOI: 10.12659/MSM.915914.

MicroRNA-155-3p promotes glioma progression and temozolomide resistance by targeting Six1.

The prognosis of glioma is generally poor and is the cause of primary malignancy in the brain. The role of microRNAs has been implicated in tumour inhibition or activation. In several cancers, the Six1 signalling pathway has been found to be aberrant and also relates to the formation of tumours. We analysed the database for expression profiles and clinical specimens of various grades of glioma to assess microRNA-155-3p (miR-155-3p) expression. The role of miR-155-3p in glioblastoma, cell cycle, proliferation, apoptosis and resistance to temozolomide was assessed in vitro through flow cytometry and cell proliferation assays. Bioinformatics analyses, and assays using luciferase reporter, and immunoblotting revealed that miR-155-3p targets Six1 and that the relationship between glioma and healthy brain tissues was significantly inverse. In rescue experiments, overexpressed Six1 revoked the changes in cell cycle distribution, proliferation and resistance to temozolomide estimated by apoptosis induced by overexpressed miR-155-3p. MiR-155-3p inhibition reduced glioma cell growth and proliferation in the brain of a mouse model and increased the survival of mice with gliomas. Thus, miR-155-3p modulates Six1 expression and facilitates the progression of glioblastoma and resistance to temozolomide and may act as a novel diagnostic biomarker and a target for glioma treatment.

HOTAIR/miR-125 axis-mediated Hexokinase 2 expression promotes chemoresistance in human glioblastoma.

Drug resistance is one of the major obstacles in glioblastoma (GBM) treatments using temozolomide (TMZ) based conventional chemotherapy. Recent studies revealed that Hexokinase 2 (HK2)-mediated glycolysis is one of the sources, as the association of chemoresistance and the expression of HK2 was confirmed in multiple cancers. However, there has been little knowledge of the functional contribution of HK2 to TMZ resistance in GBM. In our study, we found that HK2 expression is crucial for GBM proliferation and chemoresistance. In contrast to the healthy brain, HK2 expression is much higher in human GBM, especially in those patients with GBM recurrence. High HK2 expression is negatively related to the overall survival in GBM patients. HK2 depletion in GBM cells suppressed the GBM cell proliferation and increased sensitivity to TMZ-induced apoptosis. Both HK2-mediated glycolysis and mitochondria permeability transition pore opening (MPTP) were associated with its function in chemoresistance. Furthermore, we also revealed that the abnormal expression of HK2 was modulated by the expression of HOTAIR, a long non-coding RNA (lncRNA). The absence of HOTAIR in GBM cells suppressed the HK2 expression in protein and mRNA level and, therefore, inhibited the cell proliferation and enhanced the cytotoxicity of TMZ both in vivo and in vitro. HOTAIR promoted the expression of HK2 by targeting mir-125, which suppressed the GBM cell proliferation and increased the TMZ-induced apoptosis. These findings shed light on a new therapeutic strategy in modulating HOTAIR/miR-125, which may interfere with the expression of HK2, and enhance the therapeutic sensitivity of GBM to TMZ.

FDPS promotes glioma growth and macrophage recruitment by regulating CCL20 via Wnt/ß-catenin signalling pathway.

Glioma is one of the most lethal tumours and common malignant in the central nervous system (CNS), which exhibits diffuse invasion and aggressive growth. Several studies have reported the association of FDPS to tumour development and progression. However, the role of FDPS in progression of glioma and macrophage recruitment is not well-elucidated. In the current study, a remarkable enhancement in FDPS level was observed in glioma tissues and associated with poor prognosis, contributed to tumour growth. FDPS was correlated with macrophage infiltration in glioma and pharmacological deletion of macrophages largely abrogated the oncogenic functions of FDPS in glioma. Mechanistically, FDPS activated Wnt/ß-catenin signalling pathway and ultimately facilitates macrophage infiltration by inducing CCL20 expression. In conclusion, overexpressed FDPS exhibits an immunomodulatory role in glioma. Therefore, targeting FDPS may be an effective therapeutic strategy for glioma.

Protocol for expanded indications of endoscopic submucosal dissection for early gastric cancer in China: a multicenter, ambispective, observational, open-cohort study.

BACKGROUND: The main treatment methods for early gastric cancer (EGC) include endoscopic submucosal dissection (ESD) and radical gastrectomy. However, appropriate treatment for patients who exceed the absolute indications for ESD remains unestablished. In China, evidence-based medicine for the expanding indications of ESD and accurate diagnostic staging for EGC patients are lacking. Thus, clinical studies involving Chinese patients with EGC are necessary to select appropriate treatment options and promote China's expanded indications for ESD and diagnostic staging scheme. METHODS: This is a multicenter, ambispective, observational, open-cohort study that is expected to enroll 554 patients with EGC. The study was launched in May 2018 and is scheduled to end in March 2022. All enrolled patients should meet the inclusion criteria. Case report forms and electronic data capture systems are used to obtain clinical data, which includes demographic information, results of perioperative blood- and auxiliary examinations, surgical information, results of postoperative pathology, and the outcomes of postoperative recovery and follow-up. Patients are followed up every 6 months after surgery for a minimum of 5 years. The primary endpoint is the rate of lymph node metastasis (LNM), whereas the secondary endpoints include the following: consistency, sensitivity, and specificity of the results of preoperative examinations and postoperative pathology; cut-off values for LNM; logistic regression model of expanded indications for ESD; and incidence of postoperative complications within the 30-day and 5-year relapse-free survival rates. DISCUSSION: This study will explore and evaluate expanded indications for ESD that match the characteristics of the Chinese population in patients with EGC and will introduce a related staging procedure and examination scheme that is appropriate for China. Ethical approval was obtained from all participating centers. The findings are expected to be disseminated through publications or presentations and will facilitate clinical decision-making in EGC. TRIAL REGISTRATION: The name of the registry is ChiCTR. It was registered on May 9, 2018, with the registration number ( ChiCTR1800016084 ). The clinical trial was launched in May 2018 and will end in March 2022, with enrollment to be completed by December 2021. Trial status: Ongoing.

Effects of astragalus and ginseng polysaccharides on growth performance, immune function and intestinal barrier in weaned piglets challenged with lipopolysaccharide.

This experiment was conducted to evaluate the effects of astragalus polysaccharides (Aps) and ginseng polysaccharide (Gps) on growth performance, liver function, immune function, TLR4 signalling pathways and intestinal barrier in weaned piglets challenged with lipopolysaccharide (LPS). In an experiment spanning 28 days, 180 weaned piglets were randomly divided into three treatment groups: basal diet (Con), basal diet supplemented with 800 mg/kg Gps (Gps) and basal diet supplemented with 800 mg/kg Aps (Aps). At the end of the experiment, 12 piglets of each group were selected; half (n = 6) were intraperitoneally injected with LPS and half with normal saline. Dietary supplementation with Aps and Gps significantly increased (p < .05) the average daily gain and feed conversion rate. Lipopolysaccharide challenge increased (p < .05) expression of serum urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin-1ß (IL-1ß) and tumour inflammatory factor-α (TNF-α), but decreased (p < .05) serum superoxide dismutase (SOD) level, total antioxidant capacity (T-AOC) and immunoglobulin A (IgA) expression. Lipopolysaccharide-challenged piglets fed with Aps or Gps had lower (p < .05) BUN, ALT, AST, IL-1ß and TNF-α levels and greater (p < .05) SOD, T-AOC and IgA levels. Lipopolysaccharide challenge increased (p < .05) the expression of TLR4, MyD88 and NF-κB, and LPS-challenged piglets fed diets supplemented with Aps or Gps increased TLR4 and MyD88 and decreased NF-κB expression. Lipopolysaccharide challenge reduced (p < .05) the jejunal villus height, and piglets fed with Aps or Gps had increased (p < .05) jejunal villus height. Supplementation with Aps or Gps enhanced the expression of occludin and claudin in challenged or unchallenged piglets. In conclusion, dietary supplementation with Aps or Gps enhanced piglet growth performance, alleviated liver dysfunction and reduced immunological stress caused by LPS, as well as increased the intestinal barrier function.

Aggravation of Cerebral Ischemia/Reperfusion Injury by Peroxisome Proliferator-Activated Receptor-Gamma Deficiency via Endoplasmic Reticulum Stress.

BACKGROUND Ischemic stroke is a dominant contributor to disability and mortality worldwide and is recognized as an important health concern. As a transcription factor triggered via stress, peroxisome proliferator-activated receptor-gamma (PPAR-γ) has a crucial impact on differentiation, cell death, and cell growth. However, the role of PPAR-γ and its precise mechanism in cerebral ischemia injury (CII) remain unclear. MATERIAL AND METHODS The male C57Bl/6 mice (12 weeks old, n=52) were subjected to middle cerebral artery occlusion (MCAO). Infarct volume was evaluated by 2, 3, 5-Triphenyltetrazolium chloride staining. Cell apoptosis was measured by terminal dUTP nick-end labeling (TUNEL) staining. The expression of apoptotic-related protein was examined by Western blotting. Neuron2A cells were transfected with PPAR-γ-specific siRNA and then were subjected to oxygen-glucose exhaustion and reoxygenation. RESULTS It was observed that PPAR-γ-deficient mice displayed extended infarct trigon in the MCAO stroke model. Neuronal deficiency was more severe in PPAR-γ-deficient models. Additionally, expression of cell death-promoting Bcl-2 associated X and active caspase-3 was reinforced, while that of cell death-counteracting Bcl-2 was repressed in PPAR-γ-deficient mice. This was characterized by reinforced endoplasmic reticulum (ER) stress reactions in in vivo brain specimens as well as in vitro neurons in ischemia/reperfusion (I/R) injury. CONCLUSIONS This research proved that PPAR-γ protected the brain from cerebral I/R injury by repressing ER stress and indicated that PPAR-γ is a potential target in the treatment of ischemia.

Therapeutic evaluation of a patient with ruptured intracranial aneurysm without subarachnoid hemorrhage by CT imaging: a case report.

BACKGROUND: The majority of ruptured intracranial aneurysms are combined with subarachnoid hemorrhage, but patients with only intracerebral hematoma without any subarachnoid hemorrhage are extremely rare. CASE PRESENTATION: The patient was hospitalized due to sudden dizziness combined with slurred speech. The patient showed considerable decreased physical activity without any nuchal rigidity. Head CT showed hematoma in the left temporal lobe, and the shape of hematoma was extremely irregular. MRI indicated the absence of any vascular malformations. The patient was diagnosed with middle cerebral artery bifurcation aneurysm in the left by head CTA. Intracranial aneurysm clip and removal of hematoma in the left temporal lobe were performed under general anesthesia. The patient did not show any significant neurological dysfunction after the surgery and was followed up for 4 months after discharge with GOS score of 5 points. CONCLUSIONS: Intracranial hematoma with irregular morphology around the lateral fissure of the brain should be considered critical in order to avoid misdiagnosis and any possibility of missed diagnosis of vascular lesions, so as to ensure an exact therapeutic strategy with good prognosis for the patients.

Meningeal carcinomatosis: three case-reports.

BACKGROUND: Meningeal carcinomatosis (MC) is characterized by diffuse infiltration of tumor cells in meninges. There is no tumor mass in the brain and parenchyma of the spinal cord. MC is divided into primary and metastatic types. MC cases were previously diagnosed postoperatively or at autopsy. Recent advances in spinal abbreviation cytology and imaging have led to increase in number of reported cases. In this study, we discuss the manifestations of MC patients based on magnetic resonance imaging (MRI) findings, as well as the correlation between the manifestations and pathology. CASE PRESENTATION: MC was confirmed in all three cases by lumbar puncture and gadopentetate dimeglumine-enhanced magnetic resonance imaging. Due to different primary diseases, the patients had specific imaging manifestations. CONCLUSION: Enhanced MRI examination is extremely sensitive for detecting abnormalities in meninges, which plays a very important role in the diagnosis of MC. Since meninges of some MC patients cannot be enhanced, the enhanced MRI examination cannot be replaced by conventional cerebrospinal abbreviation examination. Attribute to the diversity of MR contrast agents, which could provide higher lesion conspicuity and enhances lesion detection, there may be some more choices to improve the detection rate of MC patients and prolong their survival lifetime.

Efficacy and safety of using premedication with simethicone/Pronase during upper gastrointestinal endoscopy examination with sedation: A single center, prospective, single blinded, randomized controlled trial.

BACKGROUND AND AIM: To investigate the efficacy and safety of premedication with simethicone/Pronase during esophagogastroduodenoscopy (EGD) with sedation. METHODS: Six hundred and ten patients were randomly allocated to two groups based on type of premedication given. Premedication used in the control group was 10 mL lidocaine hydrochloride mucilage (LHM, N = 314) and premedication used in the intervention group was 80 mL simethicone/Pronase solution plus 10 mL lidocaine hydrochloride mucilage (SP/LHM, N = 296). EGD was done under sedation. Visibility scores, number of mucosal areas that needed cleansing, water consumption for cleansing, time taken for examination, diminutive lesions, pathological diagnosis, patients' gag reflex and oxygenation (pulse oximetry) were recorded. RESULTS: SP/LHM has significantly lower total visibility score than LHM (7.978 ± 1.526 vs 6.348 ± 1.097, P < 0.01). During the procedure, number of intragastric areas that needed cleansing and amount of water consumed were significantly less in the SP/LHM than in the LHM group (P < 0.01). In SP/LHM (P = 0.01), endoscopy procedure duration was significantly longer. Although there was no significant difference in rate of detection of diminutive lesions between LHM and SP/LHM, the endoscopist carried out more biopsies in SP/LHM. This led to a higher rate of diagnosis of atrophic gastritis (P = 0.014) and intestinal metaplasia (P = 0.024). There was no significant difference in gag reflex (P = 0.604) and oxygenation during the endoscopy procedure for either group of patients. CONCLUSION: Routine use of premedication with simethicone/Pronase should be recommended during EGD with sedation.

[Discrepancies in pathologic evaluation of dyaplasia/early cancer in 60 gastric endoscopic submucosal dissection specimens].

OBJECTIVE: To study the reasons for the discrepancies in pathologic diagnosis of gastric dysplasia/early cancer in endoscopic submucosal dissection (ESD) specimens, and how to cope with the discrepancies. METHODS: The pathologic diagnoses in 60 cases of ESD specimens according to the three currently used classification systems (namely Western criteria, Japanese criteria and Vienna classification) were compared. The diagnostic discrepancies were analyzed. RESULTS: Fifteen of the 17 cases diagnosed as low-grade intraepithelial neoplasia according to the Western criteria were revised as adenoma by the Japanese criteria. Amongst the 43 cases of gastric intramucosal adenocarcinoma diagnosed according to the Japanese criteria, 23 cases had concordant diagnosis by the Western criteria. While the diagnosis of low-grade intraepithelial neoplasia/adenoma was basically similar irrespective of classification system used, there were significant differences in the interpretation of gastric early cancer. CONCLUSIONS: The diagnostic discrepancies in the gastric dysplasia/early cancer are mainly related to the morphologic criteria applied in different classifications. In order to facilitate clinical and pathologic communication, a consensus using Vienna/WHO classifications, supplemented with Japanese system, is desirable.

High-Grade Appendiceal Mucinous Neoplasm Mimicking Appendiceal Tubulovillous Adenoma: A Case Report and Literature Review.

High-grade appendiceal mucinous neoplasm (HAMN) has been separated from appendiceal adenocarcinoma recently as an independent entity and categorized into appendiceal mucinous neoplasms. These neoplasms demonstrate distinct histological characteristics, including architectures and appendiceal mural changes similar to low-grade appendiceal mucinous neoplasm but with high-grade cytology, and no infiltrative invasion. Overt mucinous feature are not evident in some cases as the high-grade neoplastic epithelium may show intracytoplasmic mucin reduction. Occasionally, the neoplastic epithelial cells show florid proliferation and tubulovillous configuration and may be misdiagnosed as appendiceal tubulovillous adenoma. We report the case of a 67-year-old woman with appendicular dilatation and luminal mucin. She underwent an ileocecoectomy. The appendiceal lesion was found histologically to be a HAMN, which closely resembled appendiceal tubulovillous adenoma. The tumor cells demonstrated wild-type p53 expression and mismatch repair proficiency by immunochemistry. Molecular testing showed 1 KRAS mutation, 2 PIK3CA mutations, and 1 BRCA2, EP300, TGFBR2, CHD4, CREBBP, FANCC, PKHD1 mutation each in the tumor. The patient was followed up for 1 year with no evidence of disease.

Revealing the Dark Side of Non-Local Attention in Single Image Super-Resolution.

Single Image Super-Resolution (SISR) aims to reconstruct a high-resolution image from its corresponding low-resolution input. A common technique to enhance the reconstruction quality is Non-Local Attention (NLA), which leverages self-similar texture patterns in images. However, we have made a novel finding that challenges the prevailing wisdom. Our research reveals that NLA can be detrimental to SISR and even produce severely distorted textures. For example, when dealing with severely degrade textures, NLA may generate unrealistic results due to the inconsistency of non-local texture patterns. This problem is overlooked by existing works, which only measure the average reconstruction quality of the whole image, without considering the potential risks of using NLA. To address this issue, we propose a new perspective for evaluating the reconstruction quality of NLA, by focusing on the sub-pixel level that matches the pixel-wise fusion manner of NLA. From this perspective, we provide the approximate reconstruction performance upper bound of NLA, which guides us to design a concise yet effective Texture-Fidelity Strategy (TFS) to mitigate the degradation caused by NLA. Moreover, the proposed TFS can be conveniently integrated into existing NLA-based SISR models as a general building block. Based on the TFS, we develop a Deep Texture-Fidelity Network (DTFN), which achieves state-of-the-art performance for SISR. Our code and a pre-trained DTFN are available on GitHub for verification.