Amyloid-beta pathology-induced nanoscale synaptic disruption:the case of the GABA_B-GIRK assembly

Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.

NLRP3-mediated autophagy dysfunction links gut microbiota dysbiosis to tau pathology in chronic sleep deprivation

Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive decline.However,the underlying mechanisms remain obscure.In the present study,we identified the existence of a microbiota-gut-brain axis in cognitive deficits resulting from chronic SD and revealed a potential pathway by which gut microbiota affects cognitive functioning in chronic SD.Our findings demonstrated that chronic SD in mice not only led to cognitive decline but also induced gut microbiota dysbiosis,elevated NLRP3 inflammasome expression,GSK-3βactivation,autophagy dysfunction,and tau hyperphosphorylation in the hippocampus.Colonization with the“SD microbiota”replicated the pathological and behavioral abnormalities observed in chronic sleep-deprived mice.Remarkably,both the deletion of NLRP3 in NLRP3-/-mice and specific knockdown of NLRP3 in the hippocampus restored autophagic flux,suppressed tau hyperphosphorylation,and ameliorated cognitive deficits induced by chronic SD,while GSK-3βactivity was not regulated by the NLRP3 inflammasome in chronic SD.Notably,deletion of NLRP3 reversed NLRP3 inflammasome activation,autophagy deficits,and tau hyperphosphorylation induced by GSK-3βactivation in primary hippocampal neurons,suggesting that GSK-3β,as a regulator of NLRP3-mediated autophagy dysfunction,plays a significant role in promoting tau hyperphosphorylation.Thus,gut microbiota dysbiosis was identified as a contributor to chronic SD-induced tau pathology via NLRP3-mediated autophagy dysfunction,ultimately leading to cognitive deficits.Overall,these findings highlight GSK-3βas a regulator of NLRP3-mediated autophagy dysfunction,playing a critical role in promoting tau hyperphosphorylation.

Digital pathology-based artificial intelligence models for differential diagnosis and prognosis of sporadic odontogenic keratocysts

Odontogenic keratocyst(OKC)is a common jaw cyst with a high recurrence rate.OKC combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin syndrome.Moreover,OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw cysts.Because of the different prognosis,differential diagnosis of several cysts can contribute to clinical management.We collected 519 cases,comprising a total of 2157 hematoxylin and eosinstained images,to develop digital pathology-based artificial intelligence(AI)models for the diagnosis and prognosis of OKC.The Inception_v3 neural network was utilized to train and test models developed from patch-level images.Finally,whole slide imagelevel AI models were developed by integrating deep learning-generated pathology features with several machine learning algorithms.The AI models showed great performance in the diagnosis(AUC=0.935,95%CI:0.898–0.973)and prognosis(AUC=0.840,95%CI:0.751–0.930)of OKC.The advantages of multiple slides model for integrating of histopathological information are demonstrated through a comparison with the single slide model.Furthermore,the study investigates the correlation between AI features generated by deep learning and pathological findings,highlighting the interpretative potential of AI models in the pathology.Here,we have developed the robust diagnostic and prognostic models for OKC.The AI model that is based on digital pathology shows promise potential for applications in odontogenic diseases of the jaw.

Going straight for the gut:gut-brain axis pathology and treatment of Parkinson's disease

This perspective focuses on the recent literature regarding the role of the gut-brain axis(GBA) in fecal microbiota transplantation(FMT) and stem cell therapy(SCT) in Parkinson's disease(PD).PD is the second most common neurodegenerative disease in the United States,yet therapies remain limited.Current research suggests that the GBA may play a role in the pathogenesis of PD.GBAbased FMT as well as SCT offer promising new avenues for PD treatment.Pro bing the interactions between FMT and SCT with the GBA may reveal novel therapeutics for PD.

Control of Nozzle Flow Using Rectangular Ribs at Sonic and Supersonic Mach Numbers

This study deals with base pressure management in a duct for various values of the Mach number(M),namely,Mach number corresponding to sonic and four supersonic conditions.In addition to the Mach number,the nozzle pressure ratio(NPR),the area ratio,the rib dimension,and the duct length are influential parameters.The following specific values are examined at M=1,1.36,1.64,and 2,and NPRs between 1.5 and 10.The base pressure is determined by positioning ribs of varying heights at predetermined intervals throughout the length of the square duct.When the level of expansion is varied,it is seen that the base pressure initially drops for overexpanded flows and increases for under-expanded flows.When ribs are present,the flow field in the duct and pressure inside the duct fluctuate as the base pressure rises.Under-expanded flows can achieve a base pressure value that is suitably high without experiencing excessive changes in the duct flow in terms of static pressure if a rib height around 10%of the duct height close to the nozzle exit is considered.Rectangular rib passive control does not negatively affect the duct’s flow field.

Bilateral Cervical Ribs Fusing or Naffziger Syndrome: About an Observation in Guinea and Literature Review

Thoraco-brachial outlet syndrome (TDSD) or cervical rib brings together all the clinical symptoms (arterial, neurological and/or venous) due to extrinsic, intermittent or permanent compression of the vascular-nervous elements of the root of the upper limb during cervico-thoraco-brachial crossing syndrome. This pathology is relatively common but often overlooked;it affects women more often (between 4/1 and 2/1) and is rare in children. We report the case of a 59-year-old female patient seen in the department for paresthesia and muscular weakness of the upper limbs rated 3/5 on the right and 4/5 on the left progressively evolving over 39 years, electromyography (EMG) showed indicated compression of the brachial plexus and the CT scan confirmed the presence of bilateral cervical ribs fused with the first on the left. She benefited from physiotherapy while awaiting her surgery, and unfortunately, she died of a stroke in the traumatology department. This pathology is the first in our department to be supported by a review of the literature.

Hysterectomies for Gynaecological Pathology: 56 Cases at the Segou Regional Hospital in Mali

Introduction: Hysterectomy is a surgical procedure involving partial or total removal of the uterus. It is the most common gynaecological surgery in the world. Objective: To describe the epidemio-clinical and prognostic aspects of gynaecological hysterectomies. Patients and methods: This was an 18-month retrospective prospective descriptive study with a six-month follow-up period from 1 December 2020 to 31 May 2022 carried out in the gynaecology department of the Segou regional hospital. Results: Fifty-six (56) hysterectomies were performed out of 118 gynaecological surgical procedures (47.45%). The mean age was 47 ± 11.77 years. Large multiparous women were the most common (50%), with an average parity of 4.58. The main indications were uterine fibroids (30.4%), precancerous lesions of the cervix (17.85%) and uterine prolapse (17.85%). The abdominal route was the most commonly used surgical route (82.14%). Hysterectomy was total in 100% of cases and associated with bilateral adnexectomy in 48.2% of cases. The intra- and post-operative prognosis was satisfactory in 94.6% of cases. No deaths were recorded. The average length of stay was 3.28 days, irrespective of the surgical approach. Three cases of dyspareunia were noted among those who had resumed sexual activity.

Using MsfNet to Predict the ISUP Grade of Renal Clear Cell Carcinoma in Digital Pathology Images

Clear cell renal cell carcinoma(ccRCC)represents the most frequent form of renal cell carcinoma(RCC),and accurate International Society of Urological Pathology(ISUP)grading is crucial for prognosis and treatment selection.This study presents a new deep network called Multi-scale Fusion Network(MsfNet),which aims to enhance the automatic ISUP grade of ccRCC with digital histopathology pathology images.The MsfNet overcomes the limitations of traditional ResNet50 by multi-scale information fusion and dynamic allocation of channel quantity.The model was trained and tested using 90 Hematoxylin and Eosin(H&E)stained whole slide images(WSIs),which were all cropped into 320×320-pixel patches at 40×magnification.MsfNet achieved a micro-averaged area under the curve(AUC)of 0.9807,a macro-averaged AUC of 0.9778 on the test dataset.The Gradient-weighted Class Activation Mapping(Grad-CAM)visually demonstrated MsfNet’s ability to distinguish and highlight abnormal areas more effectively than ResNet50.The t-Distributed Stochastic Neighbor Embedding(t-SNE)plot indicates our model can efficiently extract critical features from images,reducing the impact of noise and redundant information.The results suggest that MsfNet offers an accurate ISUP grade of ccRCC in digital images,emphasizing the potential of AI-assisted histopathological systems in clinical practice.

Numerical Simulation Analysis of Welded Joints in Arch Ribs of Large Span Steel Pipe Arch Bridges

In order to study the residual stress distribution law of welded joints of arch ribs of large-span steel pipe concrete arch bridges,numerical simulation of temperature,stress and strain fields based on ABAQUS for welded joints of arch-ribbed steel tubes using 7-,8-and 9-layer welds is carried out and its accuracy is demonstrated.The steel pipe welding temperature changes,residual stress distribution,different processes residual stress changes in the law,the prediction of post-weld residual stress distribution and deformation are studied in this paper.The results show that the temperature field values and test results are more consistent with the accuracy of numerical simulation of welding,the welding process is mainly in the form of heat transfer;Residual high stresses are predominantly distributed in the Fusion zone(FZ)and Heat-affected zone(HAZ),with residual stress levels tending to decrease from the center of the weld along the axial path,the maximum stress appears in the FZ and HAZ junction;The number of welding layers has an effect on the residual stress distribution,the number of welding layers increases,the residual stress tends to decrease,while the FZ and HAZ high stress area range shrinks;Increasing the number of plies will increase the amount of residual distortion.

Study of microstructure evolution of magnesium alloy cylindrical part with longitudinal inner ribs during hot flow forming by coupling ANN-modified CA and FEA

Hot flow forming(HFF)is a promising forming technology to manufacture thin-walled cylindrical part with longitudinal inner ribs(CPLIRs)made of magnesium(Mg)alloys,which has wide applications in the aerospace field.However,due to the thermo-mechanical coupling effect and the existence of stiffened structure,complex microstructure evolution and uneven microstructure occur easily at the cylindrical wall(CW)and inner rib(IR)of Mg alloy thin-walled CPLIRs during the HFF.In this paper,a modified cellular automaton(CA)model of Mg alloy considering the effects of deformation conditions on material parameters was developed using the artificial neural network(ANN)method.It is found that the ANN-modified CA model exhibits better predictability for the microstructure of hot deformation than the conventional CA model.Furthermore,the microstructure evolution of ZK61 alloy CPLIRs during the HFF was analyzed by coupling the modified CA model and finite element analysis(FEA).The results show that compared with the microstructure at the same layer of the IR,more refined grains and less sufficient DRX resulted from larger strain and strain rate occur at that of the CW;various differences of strain and strain rate in the wall-thickness exist between the CW and IR,which leads to the inhomogeneity of microstructure rising firstly and declining from the inside layer to outside layer;the obtained Hall-Petch relationship between the measured microhardness and predicted grain sizes at the CW and the IR indicates the reliability of the coupled FEA-CA simulation results.

Evaluation of autoimmune phenomena in patients with nonalcoholic fatty liver disease on the basis of liver pathology

BACKGROUND Autoimmune phenomena can be used in some patients with nonalcoholic fatty liver disease(NAFLD)in the clinic,but these patients are not autoimmune hepatitis patients.AIM To determine whether autoimmunity is present in patients with NAFLD,this study was performed.METHODS A total of 104 patients with NAFLD diagnosed by liver biopsy at Tianjin Second People’s Hospital between 2019 and 2023 were enrolled.The patients were divided into three groups according to their biopsy results:The NAFL(n=36),nonalcoholic steatohepatitis(n=51),and liver cirrhosis groups(n=17).RESULTS The differences in IgA,an immune marker,among the three groups of patients were statistically significant(P=0.025).In all NAFLD patients,antinuclear antibody and anti-smooth muscle antibody were the most common autoantibodies.The antinuclear antibody detection rate was the highest at 48.1%.The cirrhosis group had the highest autoantibody positivity rate(64.7%).Portal enlargement is also common in NAFLD patients.The rates of positivity for portal lymphoplasmacytic infiltration,small bile duct hyperplasia and interfacial hepatitis were highest in the cirrhosis group;the differences between the cirrhosis group and the other two groups were significant(P<0.05).Hepatocellular rosettes were identified only in the cirrhosis group(11.8%).CONCLUSION Autoimmune phenomena occur in NAFLD patients,especially in patients with NAFLD-related cirrhosis,in whom this phenomenon may be more pronounced.

Microvascular structural changes in esophageal squamous cell carcinoma pathology according to intrapapillary capillary loop types under magnifying endoscopy

BACKGROUND The intrapapillary capillary loop(IPCL)characteristics,visualized using magnifying endoscopy,are commonly assessed for preoperative evaluation of the infiltration depth of esophageal squamous cell carcinoma(ESCC).Japan Esophageal Society(JES)classification is the most widely used classification.Microvascular structural changes are evaluated by magnifying endoscopy for the presence or absence of each morphological factor:tortuosity,dilatation,irregular caliber,and different shapes.However,the pathological characteristics of IPCLs have not been thoroughly investigated,especially the microvascular structures corresponding to the deepest parts of the lesions'infiltration.AIM To investigate differences in pathological microvascular structures of ESCC,which correspond to the deepest parts of the lesions'infiltration.METHODS Patients with ESCC and precancerous lesions diagnosed at Peking University Third Hospital were enrolled between January 2019 and April 2023.Patients first underwent magnified endoscopic examination,followed by endoscopic submucosal dissection or surgical treatment.Pathological images were scanned using a threedimensional slice scanner,and the pathological structural differences in different types,according to the JES classification,were analyzed using nonparametric tests and t-tests.RESULTS The 35 lesions were divided into four groups according to the JES classification:A,B1,B2,and B3.Statistical analyses revealed significant differences(aP<0.05)in the short and long calibers,area,location,and density between types A and B.Notably,there were no significant differences in these parameters between types B1 and B2 and between types B2 and B3(P>0.05).However,significant differences in the short calibers,long calibers,and area of IPCL were observed between types B1 and B3(aP<0.05);no significant differences were found in the density or location(P>0.05).CONCLUSION Pathological structures of IPCLs in the deepest infiltrating regions differ among various IPCL types classified by the JES classification under magnifying endoscopy,especially between the types A and B.

A Multi-Task Deep Learning Framework for Simultaneous Detection of Thoracic Pathology through Image Classification

Thoracic diseases pose significant risks to an individual's chest health and are among the most perilous medical diseases. They can impact either one or both lungs, which leads to a severe impairment of a person’s ability to breathe normally. Some notable examples of such diseases encompass pneumonia, lung cancer, coronavirus disease 2019 (COVID-19), tuberculosis, and chronic obstructive pulmonary disease (COPD). Consequently, early and precise detection of these diseases is paramount during the diagnostic process. Traditionally, the primary methods employed for the detection involve the use of X-ray imaging or computed tomography (CT) scans. Nevertheless, due to the scarcity of proficient radiologists and the inherent similarities between these diseases, the accuracy of detection can be compromised, leading to imprecise or erroneous results. To address this challenge, scientists have turned to computer-based solutions, aiming for swift and accurate diagnoses. The primary objective of this study is to develop two machine learning models, utilizing single-task and multi-task learning frameworks, to enhance classification accuracy. Within the multi-task learning architecture, two principal approaches exist soft parameter sharing and hard parameter sharing. Consequently, this research adopts a multi-task deep learning approach that leverages CNNs to achieve improved classification performance for the specified tasks. These tasks, focusing on pneumonia and COVID-19, are processed and learned simultaneously within a multi-task model. To assess the effectiveness of the trained model, it is rigorously validated using three different real-world datasets for training and testing.

Expanding role and scope of artificial intelligence in the field of gastrointestinal pathology

Digital pathology(DP)and its subsidiaries including artificial intelligence(AI)are rapidly making inroads into the area of diagnostic anatomic pathology(AP)including gastrointestinal(GI)pathology.It is poised to revolutionize the field of diagnostic AP.Historically,AP has been slow to adopt digital technology,but this is changing rapidly,with many centers worldwide transitioning to DP.Coupled with advanced techniques of AI such as deep learning and machine learning,DP is likely to transform histopathology from a subjective field to an objective,efficient,and transparent discipline.AI is increasingly integrated into GI pathology,offering numerous advancements and improvements in overall diagnostic accuracy,efficiency,and patient care.Specifically,AI in GI pathology enhances diagnostic accuracy,streamlines workflows,provides predictive insights,integrates multimodal data,supports research,and aids in education and training,ultimately improving patient care and outcomes.This review summarized the latest developments in the role and scope of AI in AP with a focus on GI pathology.The main aim was to provide updates and create awareness among the pathology community.

Retrospective analysis of pathological types and imaging features in pancreatic cancer: A comprehensive study

BACKGROUND Pancreatic cancer remains one of the most lethal malignancies worldwide,with a poor prognosis often attributed to late diagnosis.Understanding the correlation between pathological type and imaging features is crucial for early detection and appropriate treatment planning.AIM To retrospectively analyze the relationship between different pathological types of pancreatic cancer and their corresponding imaging features.METHODS We retrospectively analyzed the data of 500 patients diagnosed with pancreatic cancer between January 2010 and December 2020 at our institution.Pathological types were determined by histopathological examination of the surgical spe-cimens or biopsy samples.The imaging features were assessed using computed tomography,magnetic resonance imaging,and endoscopic ultrasound.Statistical analyses were performed to identify significant associations between pathological types and specific imaging characteristics.RESULTS There were 320(64%)cases of pancreatic ductal adenocarcinoma,75(15%)of intraductal papillary mucinous neoplasms,50(10%)of neuroendocrine tumors,and 55(11%)of other rare types.Distinct imaging features were identified in each pathological type.Pancreatic ductal adenocarcinoma typically presents as a hypodense mass with poorly defined borders on computed tomography,whereas intraductal papillary mucinous neoplasms present as characteristic cystic lesions with mural nodules.Neuroendocrine tumors often appear as hypervascular lesions in contrast-enhanced imaging.Statistical analysis revealed significant correlations between specific imaging features and pathological types(P<0.001).CONCLUSION This study demonstrated a strong association between the pathological types of pancreatic cancer and imaging features.These findings can enhance the accuracy of noninvasive diagnosis and guide personalized treatment approaches.

The relationship between the distribution of HBcAg in liver cells and the pathological manifestations of the liver in 429 HBeAg-positive chronic HBV-infected individuals

Background:The natural history of chronic HBV infection is typically characterized by four stages:the immune tolerance period,the immune clearance period,the immune control period,and the immune escape period.These stages are associated with the distribution of HBcAg in liver cells;however,this relationship remains a topic of broad debate within the field of liver disease.To objectively and quantitatively measure the intracellular distribution of HBcAg,this paper aims to design a method referred to as the“layered evaluation method”and to examine its validation.Methods:The distribution of HBcAg in liver cells is assessed using Image Pro Plus image processing software,along with calculations of cytoplasmic and nuclear positive staining rates.Results:The findings indicate that the highest proportion of patients exhibited a positive cytoplasmic expression rate ranging from 0-2.5%.More than 40% of the total sample was categorized within the 0-2.5% positive nuclear expression range.The HBcAg cytoplasmic positive staining rates were classified into five levels:a cytoplasmic HBcAg positive staining rate of less than 0.05% is designated as level 0,indicating negative expression;a staining rate between 0.05% and 5% is classified as level 1;a rate from 5% to less than 10% is classified as level 2;a rate from 10% to less than 20% is classified as level 3;and a nuclear positivity rate exceeding 20% is classified as level 4.Conclusion:The inflammatory activity grade in these patients was positively correlated with the cytoplasmic distribution of HBcAg.Furthermore,the nuclear distribution rate of HBcAg was significantly higher in the G3 group compared to the other groups.

Multilevel analysis of the central-peripheral-target organ pathway:contributing to recovery after peripheral nerve injury

Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.

Helicobacter pylori infection as a contributing factor to metabolic dysfunction-associated steatohepatitis: A population-based insight

This letter discusses the research conducted by Abdel-Razeq et al,highlighting a significant association between Helicobacter pylori(H.pylori)infection and me-tabolic dysfunction-associated steatohepatitis(MASH)in individuals with a prior history of H.pylori infection.Using a comprehensive patient database,the study establishes an independent correlation between H.pylori and an elevated risk of MASH,even after adjusting for coexisting conditions such as obesity,type 2 diabetes,and dyslipidemia.Notably,the findings suggest that H.pylori may wo-rsen liver pathology through inflammatory pathways,contributing to hepatic insulin resistance and lipid accumulation.Although the study provides strong evidence for this association,limitations related to diagnostic heterogeneity in-dicate a need for further research to clarify the underlying mechanisms and to explore the potential roles of genetic and microbiome factors in this relationship.

Cavitary Pulmonary Metastases: CT Features and Their Correlation with the Pathology of the Primary Malignancy

Objective: To study CT features of cavitary pulmonary metastases and to investigate the pos- sible relationship between CT features and the pathology of the primary lesions. Methods: CT ?ndings of 131 cavitary metastatic nodules in 40 patients with pathologically-proved pulmonary metastases were retrospectively analyzed. A comparison between CT signs and the pathologic types of the primary tumors was made. Results: Cavitary metastases and multiple solid nodules coexisted in all patients. Cavitary metastases presented as bubble (n=41), irregular (n=33), cystic (n=26) or small circular (n=31) cavities, with even (n=61) or uneven (n=70) thickness of the cavity wall. Of 131 cavitary nodules, diameter less than 15 mm was seen in 44, between 15–25 mm in 66, 25–40 mm in 17 and larger than 40 mm in 4 respectively. And the wall thickness of the cavity below 4 mm, between 4–15 mm and over 15 mm was respectively seen in 69, 44 and 18 metastatic nodules. Cavitary pulmonary metastases mainly occurred in patients whose primary malignancy was squamous cell carcinoma (n=13) or adenocarcinoma (n=22). Both squamous cell carcinoma and adenocarcinoma had its own CT characteristics. The occurrence of cavity bore no relationship to its site in the lung. Conclusion: Cavitary pulmonary metastases carries certain CT features and its occurrence is related to the pathologic type of the primary malignancy.

G^1端点约束的Bézier曲线曲面的Ribs和Fans

为了得到Bézier曲线曲面的更加适用于网络传输的分解和重构算法,研究了带1阶端点(角点)约束的Bézier曲线曲面的Ribs和Fans,并且得到了相应的曲线曲面的光滑部分和细节部分.反过来,给定Bézier曲线的光滑部分和细节部分,给出了重构原曲线的算法.另外,还把Ribs和Fans的概念与算法推广到三角Bézier曲面.1张n次的三角Bézier曲面能够分解为1张n-1次的Rib、1张n-3次的Fan和3条n-4次Bézier曲线(Fans).数值例子表明对曲线曲面的光滑部分和细节部分的分解是更优与更有效的.