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Abstract Infectious intestinal diseases (IIDs) pose a significant health and economic burden worldwide. Recent observations at the Tri-Service General Hospital, Taiwan, suggest a potential association between IIDs and neurodegenerative diseases, prompting an investigation into this relationship. This study explored interactions between IIDs and neurodegenerative diseases. We conducted a population-based retrospective cohort analysis using data from the National Health Insurance Research Database (NHIRD) of Taiwan. Patients diagnosed with IIDs between 2000 and 2015 were identified along with a matched control group. Covariates, including demographics, comorbidities, and healthcare utilization were considered. The hazard ratios (HRs) of neurodegenerative diseases were assessed using a Cox proportional regression analysis. This study included 297,438 patients: 99,146 and 198,292 patients in the IID and control groups, respectively. Patients with IIDs showed a significantly higher overall risk of neurodegenerative diseases (adjusted hazard ratio [aHR] = 1.144, P

Abstract Background Abnormal expression of protein tyrosine kinase 6 (PTK6) has been proven to be involved in the development of gynecological tumors. However, its immune-related carcinogenic mechanism in other tumors remains unclear. Objective The aim of this study was to identify PTK6 as a novel prognostic biomarker in pan-cancer, especially in lung adenocarcinoma (LUAD), which is correlated with immune infiltration, and to clarify its clinicopathological and prognostic significance. Methods The prognostic value and immune relevance of PTK6 were investigated by using bio-informatics in this study. PTK6 expression was validated in vitro experiments (lung cancer cell lines PC9, NCI-H1975, and HCC827; human normal lung epithelial cells BEAS-2B). Western blot (WB) revealed the PTK6 protein expression in lung cancer cell lines. PTK6 expression was inhibited by Tilfrinib. Colony formation and the Cell Counting Kit-8 (CCK-8) assay were used to detect cell proliferation. The wound healing and trans-well were performed to analyze the cell migration capacity. Then flow cytometry was conducted to evaluate the cell apoptosis. Eventually, the relationship between PTK6 and immune checkpoints was examined. WB was used to estimate the PD-L1 expression at different Tilfrinib doses. Results PTK6 was an independent predictive factor for LUAD and was substantially expressed in LUAD. Pathological stage was significantly correlated with increased PTK6 expression. In accordance with survival analysis, poor survival rate in LUAD was associated with a high expression level of PTK6. Functional enrichment of the cell cycle and TGF-β signaling pathway was demonstrated by KEGG and GSEA analysis. Moreover, PTK6 expression considerably associated with immune infiltration in LUAD, as determined by immune analysis. Thus, the result of vitro experiments indicated that cell proliferation and migration were inhibited by the elimination of PTK6. Additionally, PTK6 suppression induced cell apoptosis. Obviously, PD-L1 protein expression level up-regulated while PTK6 was suppressed. Conclusion PTK6 has predictive value for LUAD prognosis, and could up regulated PD-L1.

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide, and cancer-associated fibroblasts (CAFs) play a major role in the tumor microenvironment (TME), which facilitates the progression of CRC. It is critical to understand how CAFs promote the progression of CRC for the development of novel therapeutic approaches. The purpose of this study was to understand how CAF-derived stromal-derived factor-1 (SDF-1) and its interactions with the corresponding C-X-C motif chemokine receptor 4 (CXCR4) promote CRC progression. Our study focused on their roles in promoting tumor cell migration and invasion and their effects on the characteristics of cancer stem cells (CSCs), which ultimately impact patient outcomes. Here, using in vivo approaches and clinical histological samples, we analyzed the influence of secreted SDF-1 on CRC progression, especially in terms of tumor cell behavior and stemness. We demonstrated that CAF-secreted SDF-1 significantly enhanced CRC cell migration and invasion through paracrine signaling. In addition, the overexpression of SDF-1 in CRC cell lines HT29 and HCT-116 triggered these cells to generate autocrine SDF-1 signaling, which further enhanced their CSC characteristics, including those of migration, invasion, and spheroid formation. An immunohistochemical study showed a close relationship between SDF-1 and CXCR4 expression in CRC tissue, and this significantly affected patient outcomes. The administration of AMD3100, an inhibitor of CXCR4, reversed the entire phenomenon. Our results strongly suggest that targeting this signaling axis in CRC is a feasible approach to attenuating tumor progression, and it may, therefore, serve as an alternative treatment method to improve the prognosis of patients with CRC, especially those with advanced, recurrent, or metastatic CRC following standard therapy.

Key Clinical Message Anorectal gastrointestinal stromal tumors are extremely rare, constituting less than 0.1% of rectal tumors. Surgical resection using a transanal wide excision followed by adjuvant therapy with tyrosine kinase inhibitors can be a successful treatment combination to remove the mass and prevent recurrence while preserving the integrity of the anal sphincter. Abstract Gastrointestinal stromal tumors (GISTs) are a rare subset of neoplasms, accounting for about 1%–2% of primary gastrointestinal malignancies. The stomach is the most common site for GISTs, with anorectal GISTs being exceptionally rare, representing only 0.1% of all rectal tumors. The standard approach for managing localized GIST involves complete surgical excision to achieve negative microscopic margins (R0) while preserving the tumor capsule and maintaining anal sphincter function. Surgical resection with transanal wide excision followed by adjuvant therapy using tyrosine kinase inhibitors can successfully remove the mass, prevent recurrence, and preserve the anal sphincter's integrity. Adjuvant therapy with imatinib is the recommended treatment for all localized GISTs assessed to have an intermediate or high risk of relapse. Here, we report a case of a 63‐year‐old male with a rectal GIST who underwent transanal wide excision followed by adjuvant therapy with tyrosine kinase inhibitors.

Abstract It is essential to study the robustness and centrality of interdependent networks for building reliable interdependent systems. Here, we consider a nonlinear load-capacity cascading failure model on interdependent networks, where the initial load distribution is not random, as usually assumed, but determined by the influence of each node in the interdependent network. The node influence is measured by an automated entropy-weighted multi-attribute algorithm that takes into account both different centrality measures of nodes and the interdependence of node pairs, then averaging for not only the node itself but also its nearest neighbors and next-nearest neighbors. The resilience of interdependent networks under such a more practical and accurate setting is thoroughly investigated for various network parameters, as well as how nodes from different layers are coupled and the corresponding coupling strength. The results thereby can help better monitoring interdependent systems.

Our previous retrospective observational study demonstrated the safety of laparoscopically assisted subtotal colectomy with ileorectal anastomosis and preservation of the superior rectal artery (SRA), without instances of leakage, in patients with slow-transit constipation (STC). Thus, we extended the enrollment period and enlarged the sample size to detect the differences in the postoperative complications and surgical and functional outcomes between patients who underwent laparoscopically assisted subtotal colectomy with and without SRA preservation. We conducted a retrospective single-center analysis of patients with STC who underwent laparoscopically assisted subtotal colectomy between 2016 and 2020. The diagnosis of STC was based on the colonic transit and anal functional tests and barium enema to exclude secondary causes. Patients were divided into group A, which underwent surgery with SRA preservation, and group B, which underwent ligation of the SRA during surgery. Outcome assessments for both groups included the incidence of anastomotic breakdown, intraoperative complications, length of hospital stay, estimated blood loss, time to first flatus, and complications. Propensity score matching allocated 34 patients to groups A and B each. Postoperative bowel function, including time to first flatus, stool, and oral intake, recovered better in group A than in group B. Anastomotic leakage, a significant postoperative complication, was less frequent in patients with SRA preservation. In conclusion, preservation of the SRA in patients undergoing laparoscopically assisted subtotal colectomy with ileorectal anastomosis for STC is associated with favorable postoperative bowel function recovery and lower anastomotic leakage rates.

Objectives: Teicoplanin has been extensively used in the treatment for infections caused by gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). However, current teicoplanin treatment is challenging due to relatively low and variable concentrations under standard dosage regimens. This study aimed to investigate the population pharmacokinetics (PPK) characteristics of teicoplanin in adult sepsis patients and provide recommendations for optimal teicoplanin dosing regimens.Methods: A total of 249 serum concentration samples from 59 septic patients were prospectively collected in the intensive care unit (ICU). Teicoplanin concentrations were detected, and patients’ clinical data were recorded. PPK analysis was performed using a non-linear, mixed-effect modeling approach. Monte Carlo simulations were performed to evaluate currently recommended dosing and other dosage regimens. The optimal dosing regimens were defined and compared by different pharmacokinetic/pharmacodynamic parameters, including trough concentration (Cmin), the ratio of 24-h area under the concentration-time curve to the minimum inhibitory concentration (AUC0-24/MIC), as well as the probability of target attainment (PTA) and the cumulative fraction of response (CFR) against MRSA.Results: A two-compartment model adequately described the data. The final model parameter estimates for clearance, central compartment volume of distribution, intercompartmental clearance and peripheral compartment volume were 1.03 L/h, 20.1 L, 3.12 L/h and 101 L, respectively. Glomerular filtration rate (GFR) was the only covariate that significantly affected teicoplanin clearance. Model-based simulations revealed that 3 or 5 loading doses of 12/15 mg/kg every 12 h followed by a maintenance dose of 12/15 mg/kg every 24 h–72 h for patients with different renal functions were required to achieve a target Cmin of 15 mg/L and a target AUC0-24/MIC of 610. For MRSA infections, PTAs and CFRs were not satisfactory for simulated regimens. Prolonging the dosing interval may be easier to achieve the target AUC0-24/MIC than reducing the unit dose for renal insufficient patients.Conclusion: A PPK model for teicoplanin in adult septic patients was successfully developed. Model-based simulations revealed that current standard doses may result in undertherapeutic Cmin and AUC, and a single dose of at least 12 mg/kg may be needed. AUC0-24/MIC should be preferred as the PK/PD indicator of teicoplanin, if AUC estimation is unavailable, in addition to routine detection of teicoplanin Cmin on Day 4, follow-up therapeutic drug monitoring at steady-state is recommended.

Abstract Psoriasis is a chronic inflammatory disease with characteristic skin manifestations. Several pathogens can cause flare‐ups of psoriasis. The risks of skin infections are increased in patients receiving immunomodulators. A patient with chronic psoriasis presented with human papillomavirus infection and anogenital warts and was treated surgically with acceptable results.

Background and Objectives: Although human papillomavirus (HPV) is a major etiology of cervical and anogenital cancers, whether it is associated with colorectal carcinogenesis is yet undetermined. Materials and Methods: The longitudinal association of HPV infection with colorectal cancer (CRC) was evaluated using 2000–2013 data from a nationwide Taiwanese claims database. In this retrospective cohort study, 358 patients with primary HPV diagnoses (HPV-infected cohort) and 1432 patients without such a diagnosis (HPV-uninfected cohort) were recruited between 2000 and 2006. Both cohorts were followed up to identify CRC incidences from 2006 to 2013. Hazard ratios (HRs) and their 95% confidence intervals (CIs) derived from Cox proportional hazards models were used to estimate the association between HPV and CRC risk. Results: The HPV-infected cohort had a significantly higher cumulative incidence of CRC than the HPV-uninfected cohort. The presence of HPV was associated with an increased risk of CRC (adjusted HR, 1.63; 95% CI, 1.02–3.62). Furthermore, the significant HPV–CRC risk association was evident in both sexes. Conclusions: This population-based cohort study reveals longitudinal evidence that HPV is associated with an increased risk of CRC. Further studies are required to verify the role of HPV in colorectal carcinogenesis.

Background: The association between attention-deficit hypersensitivity disorder (ADHD) and the risk of developing colorectal cancer (CRC) is, as yet, to be investigated, and thus, we have conducted this nationwide, cohort study to examine the association in patients from Taiwan.Methods: In this study, 798 individuals with newly diagnosed ADHD and 2,394 (1:3) age-, gender-, and index year- matched controls without ADHD were enrolled, between 2000 and 2013, from the Longitudinal Health Insurance Database, a subset of the National Health Insurance Research Database in Taiwan. The cumulative incidence of CRC was assessed in each cohort by the Kaplan–Meier method. The multivariate Cox proportional hazards model was used to estimate the crude, and the adjusted hazards ratios (HRs) with 95% confidence intervals (CIs), was conducted to estimate the association between ADHD and CRC.Results: The Kaplan–Meier analysis revealed that the cumulative incidence of CRC was significantly higher in patients with ADHD than in those without it (log rank test, p < 0.001). After adjustments for age, gender, comorbidities, and other covariates, the ADHD group was associated with an increased risk of CRC in comparison to the non-ADHD group (adjusted HR = 3.458, 95% CI = 1.640–7.293, p < 0.001). In addition, the usage of methylphenidate was not associated with the risk of developing CRC in patients with ADHD.Conclusion: This retrospective cohort study depicts the evidence that ADHD was associated with the increased risk of CRC. Further studies are needed to confirm the association and the underlying mechanisms.

This paper pays close attention to the adaptive neural network tracking control. Aiming at a class of uncertain nonlinear systems with completely unknown output disturbance and unknown time delay, a corresponding robust control method is proposed based on the backstepping design technology. Neural network approximation is introduced as a very effective estimation technique for modeling uncertain partitions in the design process of virtual controller. The suitable Lyapunov–Krasovskii function is constructed, and by using the organic combination of Young’s inequality, unknown time delays are compensated. Nussbaum function is used to handle unknown virtual control directions. A practical robust control method is proposed to deal with the controller singularity problems. A priori knowledge is not required for this method. In this method, all signals achieve semi-global uniform ultimate boundedness, and it is demonstrated that the tracking error eventually converges the region around the origin. The simulation results verify this method’s feasibility and effectiveness.

This paper focuses on the leader-following bipartite consensus problem for second order multi-agent systems (MASs) subject to the disturbance generated from exosystem. Different from some related works on this topic, the upper bound of disturbance is not required and the disturbance observer is proposed to estimate the exogenous disturbance. To guarantee the bipartite consensus of nonlinear MASs, both pinning control and disturbance observer strategy are employed. With the help of linear matrix inequality and Lyapunov stability theory, it is demonstrated that leader-following bipartite consensus for nonlinear MASs can be realized if a fraction of the agents are controlled under some sufficient conditions. The effectiveness of the developed approach is verified via simulations.

This paper generates an augmented hyperchaotic system from the famous Lorenz system. The hyperchaotic system has complex dynamic properties, including stability, periodicity, multiple coexisting attractors, period-doubling and Hopf bifurcations, and hyperchaos for different parameter conditions and all these dynamic properties are presented by detailed theoretical and numerical analysis. Moreover, the finite-time synchronization of the hyperchaotic system is considered by using the state-error controller. Both the sufficient conditions for finite-time synchronization and the corresponding finite time are strictly established.

Intestinal intussusception is relatively rare in adults and accounts for approximately 5% of intestinal obstruction. Intussusception is classified into subtypes according to the location, including ileoileal, ileocolic, ileo-ileocolic, colo-colic, jejuno-ileal, or jejuno-jejunal; the ileocolic type being the most common. However, intussusception of a combination of different subtypes has rarely been reported in the available literature. Abdominal computed tomography (CT) is the most accurate tool to evaluate intestinal intussusception. The pathological lead point in the intestine typically results in adult intussusception. Surgical intervention is usually adopted in cases of adult intussusception due to a high incidence of underlying bowel malignancy. An inflammatory fibroid polyp (IFP) is one of the uncommon benign neoplasms of the gastrointestinal (GI) system, which can result in intestinal intussusception. Herein, we present a case of a 50-year-old female with combined ileoileal and ileocolic intussusception, which was initially diagnosed by abdominal CT. Therefore, laparoscopic right hemicolectomy surgery was performed, confirming the final diagnosis as ileoileal and ileocolic intussusception secondary to IFP.

Plasma cell neoplasms are characterized by dysregulated proliferation of mature B cells, which can present with either single (solitary plasmacytoma) or systemic (multiple myeloma (MM)) involvement. MM with extramedullary plasmacytoma (EMP) is a rare disease that accounts for approximately 3–5% of all plasmacytomas. EMP with gastrointestinal (GI) system involvement is an even rarer entity, accounting for

BACKGROUND:Colorectal cancer (CRC) is regarded as a multifactorial disease and shares many risk factors with alcoholism. However, the association between alcoholism and CRC remains controversial. OBJECTIVES:In this study, we aimed to evaluate the association between alcoholism and risk of CRC. METHODS:We performed a large-scale, population-based nested case-control study using the Longitudinal Health Insurance Database 2013, derived from Taiwan's National Health Insurance Research Database, and collected data from 2000 to 2013. There were 49,095 diagnosed cases of CRC defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification. Each case was matched with three controls by sex, age, index date of CRC, and annual medical visits; a total of 147,285 controls were identified. Multiple risk factors of CRC in alcoholism cases were investigated using unconditional multiple logistic regression analysis. RESULTS:Among 49,095 cases of CRC, alcoholism was associated with a significantly higher risk of CRC (adjusted odds ratio (OR), 1.631; 95% CI, 1.565-1.699) in multivariate logistic regression, after adjusting other CRC risk factors, and in stratified analysis with multivariate logistic regression. In addition, there was a time-dependent relationship between alcoholism duration and CRC risk in >1 year, > 2 years, >5 years, and > 11 years groups (adjusted ORs, 1.875, 2.050, 2.662 and 2.670; 95% CI, 1.788-1.967, 1.948-2.158, 2.498-2.835, and 2.511-2.989 respectively). CONCLUSION:An association between alcoholism and risk of CRC was found in this study. Furthermore, patients with longer alcoholism history showed higher likelihood of developing CRC, which indicates a time-dependent relationship between alcoholism exposure and CRC. Further research on colorectal tumorigenesis is needed.

This paper investigates both the time-varying formation and multiple time-varying formation tracking problems of networked heterogeneous robotic systems (NHRSs) with parameter uncertainties and external disturbances in the task space. Each robot inside can be either redundant or nonredundant. Several novel estimator-based hierarchical cooperative (EBHC) algorithms are designed to achieve both the tracking task and the possible preset subtasks for redundant robots. Besides, the designed estimator algorithms guarantee that each robot can obtain the accurate information of their corresponding leaders. By employing Lyapunov stability and input-to-state stability, sufficient conditions on the asymptotic stability of the error closed-loop system are derived. Finally, two simulation examples are presented to verify the effectiveness of the proposed algorithms.

This paper deals with the problem of stochastic stability for a class of neutral distributed parameter systems with Markovian jump. In this model, we only need to know the absolute maximum of the state transition probability on the principal diagonal line; other transition rates can be completely unknown. Based on calculating the weak infinitesimal generator and combining Poincare inequality and Green formula, a stochastic stability criterion is given in terms of a set of linear matrix inequalities (LMIs) by the Schur complement lemma. Because of the existence of the neutral term, we need to construct Lyapunov functionals showing more complexity to handle the cross terms involving the Laplace operator. Finally, a numerical example is provided to support the validity of the mathematical results.

Background: Controversy exists over whether aggressive surgical resection of the primary tumor without metastasectomy first or chemotherapy first in stage IV colon cancer with unresectable synchronous liver-only-metastases (CLM) improves patients. Materials and Methods: We retrospectively reviewed the outcome of 156 patients initially diagnosed with unresectable synchronous CLM who were under treatment in our institution from January 2004 to December 2012. Patients with extrahepatic diseases or previous hepatic resection were excluded. All patients with a follow-up of at least 3 months were included. Progression-free survival (PFS) and 5-year overall survival (OS) curves were calculated using the Kaplan–Meier method. Results: Among the 156 patients with CLM, 43 (27.56%) received aggressive surgical resection of the primary tumor without metastasectomy first, 113 (72.43%) received systemic chemotherapy first. At 5 years, the adjusted PFS and OS in stage IV colon cancer with inoperable metastases were 24.2% and 20.4%, respectively, in the surgical resection of the primary tumor first group and 46.0% and 16.9% in the chemotherapy first group (P = 0.515 and P= 0.742, respectively). In multivariate analysis, there was no statistical difference in the PFS and 5-year OS between the surgical resection of the primary tumor first group and chemotherapy first. Conclusion: Surgical resection of the primary tumor without metastasectomy first in CLM is not associated with improved survival as compared with chemotherapy first. Additional research is necessary to determine which patients may benefit from this intervention.

Mis-swallowing of a foreign body in the esophagus coexisting with sliding hernia might be misdiagnosed as esophageal perforation with mediastinal abscess. We report an 89-year-old woman, bedridden for a long period in a nursing home after a previous cerebrovascular accident, who was sent to our emergency department in a state of sepsis because she had swallowed a radio-opaque partial denture. The retention of the denture as an esophageal foreign body was complicated with mediastinitis and bilateral pleural effusion. The inability of the patient to give a reliable clinical history delayed the diagnosis. This report highlights the difficulty in precisely locating a partial denture because of conflicting radiologic findings and the coexistence of esophageal sliding hernia, all of which led to a misdiagnosis of possible esophageal perforation. A right posterolateral thoracotomy with gastrostomy was performed to remove the lower esophageal foreign body after esophagoscopy failed. The surgical finding of a coincidental sliding esophageal hiatal hernia correlated well with the clinical presentation. Managing such a complicated esophageal foreign body in this elderly patient was challenging.

The optimal regulation properties of multi-input and multioutput (MIMO) discrete-time networked control systems (NCSs), over additive white Gaussian noise (AWGN) fading channels, based on state space representation, are investigated. The average performance index is introduced. Moreover, the regulation performance is measured by the control energy and the error energy of the system, and fundamental limitations are obtained. Two kinds of network parameters, fading and the additive white Gaussian noise, are considered. The best attainable regulation performance limitations can be obtained by the limiting steady state solution of the corresponding algebraic Riccati equation (ARE). The simulation results are given to demonstrate the main results of the theoretical development.

The records of the death times of the people of the Jin dynasty in Jianyan Yilai Xinian Yaolu (the Chronological Record of Important Events since 1127, hereinafter referred to as "Yaolu") were sorted in the study. The descriptions of these people were explained and compared with the literature of the Southern Song Dynasty and the Jin Dynasty in order to identify the differences among them. The causes of the differences were also discussed. Most of the records in Yaolu relates to the important figures in the political world of the Jin Dynasty, due perhaps to Li Xinchuan's motive to record the important political events of the Jin Dynasty. There are various narrative styles in Yaolu, which shows that its author had different levels of understanding of individual incidents. Compared with the history books of the Southern Song Dynasty, Yaolu has the most records about the death times of the Jin people, and it contains the most articles corresponding to Jinshi. Therefore, Yaolu has the most articles with the top quality among all the Southern Song Dynasty history books. Based on further analysis, Yaolu played an essential role in the transmission of the incidents of the Jin Dynasty among the history books of the Southern Song Dynasty and became the basis of later history books of the Southern Song Dynasty because its author was able to widely adopt the descriptions made by former scholars and select the ones which were closer to the facts. Although many articles are correct in Yaolu, there are still problems of obscure passages, errors, and omissions. The causes of these problems should be related to the limited literature that Li Xinchuan could refer to, and the literature referred to by Li Xinchuan could not help him to write precise articles. Finally, considering the influence of references on Yaolu, the challenge for Yaolu to correctly record the death times of the Jin people was caused by the indirect transmission of the incidents of the Jin people of the Southern Song dynasty, and the political barriers between the sources of Yaolu and the political field of the Jin dynasty. [ABSTRACT FROM AUTHOR]