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Abstract Background The pathogenesis of chronic active Epstein–Barr virus (EBV) disease (CAEBV) is complex, involving infection, inflammation, and in some cases malignancy. EBV reactivates in some patients, who develop a chronic disease with infectious mononucleosis-like symptoms. On occasion, it might be confused with autoimmune hepatitis (AIH), based on the similar symptoms and elevated liver enzymes. We aimed to describe a similar case to remind reader of this disease. Case Presentation : A 14-year-old girl was diagnosed with AIH based on biopsy and biomarker findings 1 year prior to admission and initially presented with elevated liver enzymes, portal hypertension, and parenchymal liver disease. Despite steroid administration, her condition fluctuated, and she was admitted to the hospital several times. She underwent a renal biopsy because of massive ascites, hypoalbuminemia, and increased renal echogenicity. An evaluation for impaired liver function showed positivity for EBV IgM, IgG, and early antigen (EBEA) antibodies. A PCR-based assay showed 5265 copies/mL of EBV DNA in peripheral blood. Epstein–Barr encoding region (EBER) in situ hybridization revealed abundant positive cells. Immunohistochemistry for CD56 also showed abundant positive cells, and CAEBV was diagnosed on this basis. Chemotherapy, hematopoietic stem cell transplantation (HSCT), and liver transplantation were proposed but her family refused. Conclusions CAEBV should be considered when diagnosing AIH or in cases of treatment-refractory AIH.

Data curation for a hospital-based cancer registry heavily relies on the labor-intensive manual abstraction process by cancer registrars to identify cancer-related information from free-text electronic health records. To streamline this process, a natural language processing system incorporating a hybrid of deep learning-based and rule-based approaches for identifying lung cancer registry-related concepts, along with a symbolic expert system that generates registry coding based on weighted rules, was developed. The system is integrated with the hospital information system at a medical center to provide cancer registrars with a patient journey visualization platform. The embedded system offers a comprehensive view of patient reports annotated with significant registry concepts to facilitate the manual coding process and elevate overall quality. Extensive evaluations, including comparisons with state-of-the-art methods, were conducted using a lung cancer dataset comprising 1428 patients from the medical center. The experimental results illustrate the effectiveness of the developed system, consistently achieving F1-scores of 0.85 and 1.00 across 30 coding items. Registrar feedback highlights the system’s reliability as a tool for assisting and auditing the abstraction. By presenting key registry items along the timeline of a patient’s reports with accurate code predictions, the system improves the quality of registrar outcomes and reduces the labor resources and time required for data abstraction. Our study highlights advancements in cancer registry coding practices, demonstrating that the proposed hybrid weighted neural-symbolic cancer registry system is reliable and efficient for assisting cancer registrars in the coding workflow and contributing to clinical outcomes.

Summary: The experience of pain is complex, involving both sensory and affective components, yet the underlying neural mechanisms remain elusive. Here, we show that formalin-induced pain behaviors coincide with increased responses in glutamatergic neurons within the anterior paraventricular nucleus of the thalamus (PVA). Furthermore, we describe non-overlapping subpopulations of PVAVgluT2 neurons involved in sensory and affective pain processing, whose activity varies across different pain states. Activating PVA glutamatergic neurons is sufficient to induce mechanical hypersensitivity and aversion behaviors, whereas suppression ameliorates formalin-induced pain. Furthermore, we identify the segregation of PVAVgluT2 projections to the bed nucleus of the stria terminalis (BNST) and nucleus accumbens (NAc), each influencing specific aspects of pain-like behavior. This finding provides an important insight into the mechanism of distinct components of pain, highlighting the pivotal role of PVA in mediating different aspects of pain-like behavior with distinct circuits.

BackgroundInternational Classification of Diseases codes are widely used to describe diagnosis information, but manual coding relies heavily on human interpretation, which can be expensive, time consuming, and prone to errors. With the transition from the International Classification of Diseases, Ninth Revision, to the International Classification of Diseases, Tenth Revision (ICD-10), the coding process has become more complex, highlighting the need for automated approaches to enhance coding efficiency and accuracy. Inaccurate coding can result in substantial financial losses for hospitals, and a precise assessment of outcomes generated by a natural language processing (NLP)–driven autocoding system thus assumes a critical role in safeguarding the accuracy of the Taiwan diagnosis related groups (Tw-DRGs). ObjectiveThis study aims to evaluate the feasibility of applying an International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), autocoding system that can automatically determine diagnoses and codes based on free-text discharge summaries to facilitate the assessment of Tw-DRGs, specifically principal diagnosis and major diagnostic categories (MDCs). MethodsBy using the patient discharge summaries from Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUCHH) from April 2019 to December 2020 as a reference data set we developed artificial intelligence (AI)–assisted ICD-10-CM coding systems based on deep learning models. We constructed a web-based user interface for the AI-assisted coding system and deployed the system to the workflow of the certified coding specialists (CCSs) of KMUCHH. The data used for the assessment of Tw-DRGs were manually curated by a CCS with the principal diagnosis and MDC was determined from discharge summaries collected at KMUCHH from February 2023 to April 2023. ResultsBoth the reference data set and real hospital data were used to assess performance in determining ICD-10-CM coding, principal diagnosis, and MDC for Tw-DRGs. Among all methods, the GPT-2 (OpenAI)-based model achieved the highest F1-score, 0.667 (F1-score 0.851 for the top 50 codes), on the KMUCHH test set and a slightly lower F1-score, 0.621, in real hospital data. Cohen κ evaluation for the agreement of MDC between the models and the CCS revealed that the overall average κ value for GPT-2 (κ=0.714) was approximately 12.2 percentage points higher than that of the hierarchy attention network (κ=0.592). GPT-2 demonstrated superior agreement with the CCS across 6 categories of MDC, with an average κ value of approximately 0.869 (SD 0.033), underscoring the effectiveness of the developed AI-assisted coding system in supporting the work of CCSs. ConclusionsAn NLP-driven AI-assisted coding system can assist CCSs in ICD-10-CM coding by offering coding references via a user interface, demonstrating the potential to reduce the manual workload and expedite Tw-DRG assessment. Consistency in performance affirmed the effectiveness of the system in supporting CCSs in ICD-10-CM coding and the judgment of Tw-DRGs.

Abstract Background Containment measures slowed the spread of COVID-19 but led to a global economic crisis. We establish a reinforcement learning (RL) algorithm that balances disease control and economic activities. Methods To train the RL agent, we design an RL environment with 4 semi-connected regions to represent the COVID-19 epidemic in Tokyo, Osaka, Okinawa, and Hokkaido, Japan. Every region is governed by a Susceptible-Exposed-Infected-Quarantined-Removed (SEIQR) model and has a transport hub to connect with other regions. The allocation of the synthetic population and inter-regional traveling is determined by population-weighted density. The agent learns the best policy from interacting with the RL environment, which involves obtaining daily observations, performing actions on individual movement and screening, and receiving feedback from the reward function. After training, we implement the agent into RL environments describing the actual epidemic waves of the four regions to observe the agent’s performance. Results For all epidemic waves covered by our study, the trained agent reduces the peak number of infectious cases and shortens the epidemics (from 165 to 35 cases and 148 to 131 days for the 5th wave). The agent is generally strict on screening but easy on movement, except for Okinawa, where the agent is easy on both actions. Action timing analyses indicate that restriction on movement is elevated when the number of exposed or infectious cases remains high or infectious cases increase rapidly, and stringency on screening is eased when the number of exposed or infectious cases drops quickly or to a regional low. For Okinawa, action on screening is tightened when the number of exposed or infectious cases increases rapidly. Conclusions Our experiments exhibit the potential of the RL in assisting policy-making and how the semi-connected SEIQR models establish an interactive environment for imitating cross-regional human flows.

Background: With the widespread use of abdominal ultrasonography (US), incidental detection of common bile duct (CBD) dilatation is common in pediatric populations. This study investigated the causes and clinical significance of CBD dilatation in children without biliary symptoms, jaundice, or causative lesions in US. Methods: We retrospectively reviewed pediatric patients with CBD dilatation from July 2013 to June 2023. All cases were detected via abdominal US. We analyzed the patients’ clinical manifestations, laboratory data, diagnosis, underlying diseases, and clinical course. Results: In a total of 687 patients enrolled, 338 met inclusion criteria (90 in hepatobiliary, 248 in CBD dilatation group). Of 128 patients with incidental CBD dilatation who underwent regular US examinations, 91 (71.1%) experienced resolution during follow-up. The proportion of patients with intrahepatic duct dilatation was significantly higher in the non-resolution group (p = 0.038). General health examination group had significant smaller CBD diameter compared to the gastrointestinal and infection groups. Correlation analysis found starting point of resolution decline at 3.24 mm (all-inclusive) and 2.51 mm (infant group) CBD diameter. Conclusions: Most children with incidental CBD dilatation did not have abnormal hepatobiliary function or other sonographic abnormalities. They usually remained asymptomatic and experienced uneventful clinical courses.

Background: Previous studies have determined that up to 6% of patients with aspirin-exacerbated respiratory disease (AERD) have family history of AERD, indicating a possible link with genetic polymorphisms. However, whole exome sequencing (WES) studies of such associations are currently lacking. Objectives: We sought to examine whether WES can identify pathogenic variants associated with AERD. Methods: Diagnoses of AERD were confirmed in patients with nasal polyps and asthma. WES was performed using an Illumina sequencing platform. Human Phenotype Ontology terms were used to define the patients’ phenotypes. Exomiser was used to annotate, filter, and prioritize possible disease-causing genetic variants. Results: Of 39 patients with AERD, 41% reported a family history of asthma and 5% reported a family history of AERD. Pathogenic exome variants in the filaggrin gene (FLG) were found in 2 patients (5%). Other variants not known to be pathogenic were detected in an additional 16 patients (41%) in genes related to epithelial integrity and cellular interactions, including genes encoding desmoglein 3 (DSG3), dynein axonemal heavy chain 9 (DNAH9), collagen type VII alpha 1 chain (COL7A1), collagen type XVII alpha 1 chain (COL17A1), chromodomain helicase DNA binding protein-7 (CHD7), TSC complex subunit 2/tuberous sclerosis-2 protein (TSC2), P-selectin (SELP), and platelet-derived growth factor receptor-alpha (PDGFRA). Conclusion: WES identified a monogenic susceptibility to AERD in 5% of patients with FLG pathogenic variants. Other variants not previously identified as pathogenic were found in genes relevant to epithelial integrity and cellular interactions and may further reveal genetic factors that contribute to this condition.

Clostridioides difficile infection (CDI) worsens inflammatory bowel disease (IBD) prognosis. While fecal microbiota transplantation (FMT) is effective for refractory or recurrent CDI (rrCDI), comparative success rates between IBD and non-IBD patients are scarce. This study addresses this gap. A retrospective cohort study was conducted at Chang Gung Memorial Hospital from April 2019 to October 2023. Patients receiving FMT for rrCDI were categorized into IBD and non-IBD groups. Baseline characteristics and outcomes were compared at one month and one year, with successful FMT defined as the resolution of diarrhea without CDI recurrence. The study included 88 patients: 30 with IBD and 58 without IBD. The IBD group was younger, with fewer comorbidities. Success rates at one month were similar between groups (IBD: 80.0% vs. non-IBD: 78.9%, p = 0.908), as were negative toxin tests (IBD: 83.3% vs. non-IBD: 63.8%, p = 0.174). One-year success rates (IBD: 70.0% vs. non-IBD: 67.6%, p = 0.857) and eradication rates (IBD: 94.4% vs. non-IBD: 73.9%, p = 0.112) were also similar. Poor bowel preparation predicted FMT failure at one month (OR = 0.23, p = 0.019). No safety issues were reported. FMT is a safe, effective treatment for rrCDI, demonstrating similar success rates in patients with and without IBD.

Abstract We demonstrate that isomorphically mapping gray-level medical image matrices onto energy spaces underlying the framework of fast data density functional transform (fDDFT) can achieve the unsupervised recognition of lesion morphology. By introducing the architecture of geometric deep learning and metrics of graph neural networks, gridized density functionals of the fDDFT establish an unsupervised feature-aware mechanism with global convolutional kernels to extract the most likely lesion boundaries and produce lesion segmentation. An AutoEncoder-assisted module reduces the computational complexity from $$\mathcal{O}\left({N}^{3}\right)$$ O N 3 to $$\mathcal{O}\left(N\mathrm{log}N\right)$$ O N log N , thus efficiently speeding up global convolutional operations. We validate their performance utilizing various open-access datasets and discuss limitations. The inference time of each object in large three-dimensional datasets is 1.76 s on average. The proposed gridized density functionals have activation capability synergized with gradient ascent operations, hence can be modularized and embedded in pipelines of modern deep neural networks. Algorithms of geometric stability and similarity convergence also raise the accuracy of unsupervised recognition and segmentation of lesion images. Their performance achieves the standard requirement for conventional deep neural networks; the median dice score is higher than 0.75. The experiment shows that the synergy of fDDFT and a naïve neural network improves the training and inference time by 58% and 51%, respectively, and the dice score raises to 0.9415. This advantage facilitates fast computational modeling in interdisciplinary applications and clinical investigation.

Background: The coronavirus disease 2019 (COVID-19) outbreak that began in late 2019 has significantly affected quality of life and healthcare. Approaches to prevent the spread of COVID-19 have also affected the prevalence of other diseases. This retrospective review evaluated pediatric emergency department (PED) volume, in terms of children with acute gastroenteritis (AGE), and changes in AGE severity before versus during the COVID-19 pandemic in a tertiary medical center in Taiwan. Methods: Patients who visited the PED and were diagnosed with AGE during the 70-day COVID-19 lockdown in 2021, or the identical period in 2020, were compared using a clinically validated AGE severity score, the modified Vesikari score (MVS), and additional parameters. Results: During the COVID-19 outbreak, there was a 61.4% reduction in the number of children with AGE visiting the PED. In that period, the AGE severity score was similar compared to the pre-pandemic period (9.00 vs. 8.57, p = 0.273). The mean C-reactive protein (CRP) level (55.7 vs. 40.6 mg/L, p

Background: Human adenoviruses are the most common pathogens to be isolated from cases of pediatric intussusception. However, the specific clinical characteristics of pediatric intussusception associated with adenovirus infection are poorly known. Methods: We reviewed the medical records of pediatric patients (≤18 years of age) with intussusception treated between January 2014 and December 2020. We enrolled patients with febrile episodes, 27 with and 29 without adenovirus infections (the latter serving as control group). The demographic data, clinical characteristics, and the diagnoses and management strategies were evaluated. Results: The adenovirus group exhibited a significantly longer febrile duration (4.3 ± 1.9 vs. 3.3 ± 1.1 days, p = 0.020) than the control group, with an odds ratio (OR) of 5.098 (95% confidence interval [CI] 1.223–21.254, p = 0.025). The recurrence rates were 48.1% and 13.8% in the two groups (OR 5.804; 95% CI: 1.585–21.245, p = 0.008). Most adenoviruses were non-enteric (85.2%). Conclusion: Adenovirus-related intussusception is associated with a longer febrile period and a higher rate of intussusception recurrence. It is recommended that patients suspected of adenovirus-related intussusception should be observed for longer than others prior to discharge.

BackgroundThe widespread use of electronic health records in the clinical and biomedical fields makes the removal of protected health information (PHI) essential to maintain privacy. However, a significant portion of information is recorded in unstructured textual forms, posing a challenge for deidentification. In multilingual countries, medical records could be written in a mixture of more than one language, referred to as code mixing. Most current clinical natural language processing techniques are designed for monolingual text, and there is a need to address the deidentification of code-mixed text. ObjectiveThe aim of this study was to investigate the effectiveness and underlying mechanism of fine-tuned pretrained language models (PLMs) in identifying PHI in the code-mixed context. Additionally, we aimed to evaluate the potential of prompting large language models (LLMs) for recognizing PHI in a zero-shot manner. MethodsWe compiled the first clinical code-mixed deidentification data set consisting of text written in Chinese and English. We explored the effectiveness of fine-tuned PLMs for recognizing PHI in code-mixed content, with a focus on whether PLMs exploit naming regularity and mention coverage to achieve superior performance, by probing the developed models’ outputs to examine their decision-making process. Furthermore, we investigated the potential of prompt-based in-context learning of LLMs for recognizing PHI in code-mixed text. ResultsThe developed methods were evaluated on a code-mixed deidentification corpus of 1700 discharge summaries. We observed that different PHI types had preferences in their occurrences within the different types of language-mixed sentences, and PLMs could effectively recognize PHI by exploiting the learned name regularity. However, the models may exhibit suboptimal results when regularity is weak or mentions contain unknown words that the representations cannot generate well. We also found that the availability of code-mixed training instances is essential for the model’s performance. Furthermore, the LLM-based deidentification method was a feasible and appealing approach that can be controlled and enhanced through natural language prompts. ConclusionsThe study contributes to understanding the underlying mechanism of PLMs in addressing the deidentification process in the code-mixed context and highlights the significance of incorporating code-mixed training instances into the model training phase. To support the advancement of research, we created a manipulated subset of the resynthesized data set available for research purposes. Based on the compiled data set, we found that the LLM-based deidentification method is a feasible approach, but carefully crafted prompts are essential to avoid unwanted output. However, the use of such methods in the hospital setting requires careful consideration of data security and privacy concerns. Further research could explore the augmentation of PLMs and LLMs with external knowledge to improve their strength in recognizing rare PHI.

Quantitative ultrasound (QUS) envelope statistics imaging is an emerging technique for the assessment of hepatic steatosis in adults. Blood tests are currently recommended as the screening tool for pediatric hepatic steatosis, a condition that can lead to liver fibrosis in children. This study examined the utility of QUS envelope statistics imaging in grading biomarker-diagnosed hepatic steatosis and detecting liver fibrosis in a pediatric population. A total of 173 subjects was enrolled (Group A) for QUS envelope statistics imaging using two statistical distributions, Nakagami and homodyned K (HK) models, and information entropy. QUS parameter values were compared with the hepatic steatosis index (HSI) and steatosis grade (G0: HSI

Background: Cytomegalovirus (CMV) gastrointestinal (GI) diseases impact both immunocompromised and immunocompetent individuals, yet comprehensive studies highlighting the differences between these groups are lacking. Methods: In this retrospective study (January 2000 to July 2022) of 401 patients with confirmed CMV GI diseases, we categorized them based on immunological status and compared manifestations, treatments, outcomes, and prognostic factors. Results: The immunocompromised patients (n = 193) showed older age, severe illnesses, and higher comorbidity rates. GI bleeding, the predominant manifestation, occurred more in the immunocompetent group (92.6% vs. 63.6%, p = 0.009). Despite longer antiviral therapy, the immunocompromised patients had higher in-hospital (32.2% vs. 18.9%, p = 0.034) and overall mortality rates (91.1% vs. 43.4%, p < 0.001). The independent factors influencing in-hospital mortality in the immunocompromised patients included GI bleeding (OR 5.782, 95% CI 1.257–26.599, p = 0.024) and antiviral therapy ≥ 14 days (OR 0.232, 95% CI 0.059–0.911, p = 0.036). In the immunocompetent patients, age (OR 1.08, 95% CI 1.006–1.159, p = 0.032), GI bleeding (OR 10.036, 95% CI 1.183–85.133, p = 0.035), and time to diagnosis (OR 1.029, 95% CI 1.004–1.055, p = 0.021) were significant prognostic factors, with the age and diagnosis time cut-offs for survival being 70 years and 31.5 days, respectively. Conclusions: GI bleeding is the most common manifestation and prognostic factor in both groups. Early diagnosis and effective antiviral therapy can significantly reduce in-hospital mortality.

Summary: Differentiated cardiomyocytes (CMs) must undergo diverse morphological and functional changes during postnatal development. However, the mechanisms underlying initiation and coordination of these changes remain unclear. Here, we delineate an integrated, time-ordered transcriptional network that begins with expression of genes for cell-cell connections and leads to a sequence of structural, cell-cycle, functional, and metabolic transitions in mouse postnatal hearts. Depletion of histone H2B ubiquitin ligase RNF20 disrupts this gene network and impairs CM polarization. Subsequently, assay for transposase-accessible chromatin using sequencing (ATAC-seq) analysis confirmed that RNF20 contributes to chromatin accessibility in this context. As such, RNF20 is likely to facilitate binding of transcription factors at the promoters of genes involved in cell-cell connections and actin organization, which are crucial for CM polarization and functional integration. These results suggest that CM polarization is one of the earliest events during postnatal heart development and provide insights into how RNF20 regulates CM polarity and the postnatal gene program.

BackgroundCompared to antibiotic treatment, fecal microbiota transplantation (FMT) is a more effective treatment for refractory or recurrent CDI (rCDI). Patients with inflammatory bowel disease (IBD) have a higher incidence of CDI and worse outcomes. There has been no study from Asia to evaluate the cost-effectiveness of FMT for overall rCDI patients and rCDI patients with IBD.MethodsWe applied a Markov model with deterministic and probabilistic sensitivity analyses to evaluate the cost and effectiveness of different treatments for rCDI patients with a time horizon of 1 year from the payer's perspective. We compared the cost and clinical outcomes of FMT through colonoscopy to two antibiotics (vancomycin and fidaxomicin) using data from Chang Gung Memorial Hospital, Taoyuan, Taiwan.ResultsCompared to vancomycin, FMT was cost-effective in overall rCDI patients as well as IBD patients with rCDI [USD 39356 (NT$1,101,971.98)/quality-adjusted life year (QALY) gained in overall patients; USD65490 (NT$1,833,719.14)/QALY gained in IBD patients]. Compared to fidaxomicin, FMT was only cost-effective in overall rCDI patients [USD20255 (NT$567,133.45)/QALY gained] but slightly increased QALY (0.0018 QALY gained) in IBD patients with rCDI.ConclusionFMT is cost-effective, compared to vancomycin or fidaxomicin, for the treatment of rCDI in most scenarios from the payers' perspective in Taiwan.

Background: To examine factors that affect the severity of pyloric hypertrophy, post-operative feeding and nutritional recovery in infantile hypertrophic pyloric stenosis (IHPS). Methods: Medical records of infants diagnosed with IHPS at a single tertiary center between 2009 and 2018 were retrospectively reviewed. Clinical characteristics, biochemistry data and outcome were assessed for their association with the severity of pyloric hypertrophy and post-operative recovery. Nutritional recovery was assessed using weight-for-age status improvement after surgery. Results: Eighty-five patients were recruited in this study. The mean pre-operative weight-for-age percentile was 18.2. Elevated bicarbonate was positively correlated with symptom duration (p = 0.007). Pyloric muscle thickness was significantly correlated with age, weight, and symptom duration (p = 0.004, 0.003, 0.008, respectively). The mean weight-for-age percentile increased to 41.6 by post-operative weeks 6–8. Pyloric muscle thickness was negatively correlated with nutritional recovery by post-operative weeks 6–8 (p = 0.003). In multivariable analysis, pyloric length related to nutritional recovery at week 1–2 postoperatively (OR = 1.42, p = 0.030, 95% CI = 0.03–1.94), and pyloric muscle thickness related to nutritional recovery at week 6–8 postoperatively (OR = 4.08, p = 0.032, 95% CI = 1.13–14.7). Conclusion: Our study indicated that favorable nutritional outcome and successful weight gain was observed 6–8 weeks after surgery in children with IHPS. Pyloric muscle thickness positively correlated with age, weight, symptom duration, and favorable nutritional recovery. Serum bicarbonate showed a positive correlation with symptom duration.

Cytomegalovirus (CMV) is a potential pathogen that causes gastrointestinal (GI) tract diseases regardless of host immunity. In contrast to immunocompromised individuals, immunocompetent patients lack a comprehensive overview of the gastrointestinal manifestations. This study aims to provide a comprehensive summary of the current evidence regarding presentations, diagnostics, management, risk assessment, and outcomes in immunocompetent patients with CMV GI disease. A thorough literature search of English publications up to April 2022 was conducted across electronic databases to identify relevant articles, with eligible case series selected for detailed analysis. The majority of immunocompetent patients affected by CMV GI disease are typically elderly, critically ill, or burdened with comorbidities that compromise immunity. Clinical presentations range from subtle symptoms to severe surgical conditions, including instances of mortality. Specific clinical presentations, blood test results, or endoscopic features are lacking, necessitating reliance on histopathological tests such as immunohistochemistry staining for diagnosis. While antiviral therapy may offer benefits in improving outcomes, careful individual assessment is warranted due to diverse comorbidities and potential side effects. Mortality rates vary considerably based on underlying medical conditions and therapeutic approaches. It is imperative for clinicians to maintain vigilance for CMV GI disease among high-risk groups, despite their baseline immunocompetence, in order to enhance clinical outcomes.

Background/Purpose: Esophageal variceal bleeding (EVB) is a medical emergency in patients with portal hypertension (PHT). However, studies on the long-term outcomes of prophylactic endoscopic variceal ligation (EVL) in pediatric-onset PHT are lacking. Methods: Between 1999 and 2020, patients who received EVL in the Electronic Report System of the Pediatric Endoscopy Unit were included in this retrospective study. EVL was classified as primary prophylaxis when it was performed for esophageal varices (EVs) without previous bleeding. If it was implemented in acute EVB, the subsequent EVL was classified as secondary prophylaxis. Results: Fifty-eight patients aged 10 months to 33 years with 31 males were included. Thirty-eight patients were classified as primary prophylaxis group, and twenty, secondary prophylaxis group. The primary prophylaxis group experienced fewer 5-year EVB events than the secondary prophylaxis group (cumulative risk: 14.4% versus 32.4%). Still, it didn't significantly affect overall survival and biliary atresia transplant-free survival. Long-term mortality was significantly associated with higher serum direct bilirubin levels (≥0.55 mg/dL) and lower albumin levels (≤2.54 mg/dL) at the first EVL. Aspartate aminotransferase-to-platelet ratio index (APRI) with a cut-off value of 1.24 helped to predict EV presence at the initial esophagogastroduodenoscopy (EGD) (AUROC = 0.762, sensitivity 75.0%, and specificity 66.7%). Conclusion: Primary prophylactic EVL, despite reducing acute EVB, may not change overall survival and biliary atresia transplant-free survival. APRI > 1.24 may predict EV presence at the first EGD and help to schedule a surveillance EGD. Higher direct bilirubin and lower albumin levels at the first EVL may relate to long-term mortality.

Background: Fecal microbiota transplantation (FMT) has been shown to highly effective in the treatment of recurrent or refractory Clostridioides difficile infection (rCDI) in many countries of the world. Not until 2018, Ministry of Health and Welfare, Taiwan approved the application of FMT for rCDI under a special law. The study reported the first implementation of the technology in the medical center in Taiwan and the preliminary outcome. Methods: FMT was used to treat patients with rCDI in Chang Gung Memorial Hospital. FMT was delivered by gastroenterologists using colonoscope. Strict donor screening was performed according to the guidelines. We followed up the clinical course of patients after FMT. 16S rRNA sequencing of fecal samples for donor, and also recipient before and after FMT was carried out. Results: From September 2018 to June 2020, 39 patients with rCDI received FMT, with a successful rate of 89.7%. Two patients died due to causes unrelated to FMT, and two other cases showed no clinical improvement after the procedure. High school and college students showed the best pass rate during donor screening. The presence of multi-drug resistant pathogen was the most common cause for screening failure. We demonstrated in a case the use of rRNA sequencing as a biomarker indicating for the improvement of dysbiosis in a patient after FMT. Conclusions: FMT was successfully implemented in a medical center in Taiwan and showed a comparable successful rate in treating rCDI, compared to other countries. Safety remains the most important issue when applying FMT in the clinical setting.

The Cav3.2 T-type calcium channel is implicated in various pathological conditions, including cardiac hypertrophy, epilepsy, autism, and chronic pain. Phosphorylation of Cav3.2 by multiple kinases plays a pivotal role in regulating its calcium channel function. The calcium/calmodulin-dependent serine/threonine phosphatase, calcineurin, interacts physically with Cav3.2 and modulates its activity. However, it remains unclear whether calcineurin dephosphorylates Cav3.2, the specific spatial regions on Cav3.2 involved, and the extent of the quantitative impact. In this study, we elucidated the serine/threonine residues on Cav3.2 targeted by calcineurin using quantitative mass spectrometry. We identified six serine residues in the N-terminus, II–III loop, and C-terminus of Cav3.2 that were dephosphorylated by calcineurin. Notably, a higher level of dephosphorylation was observed in the Cav3.2 C-terminus, where calcineurin binds to this channel. Additionally, a previously known CaMKII-phosphorylated site, S1198, was found to be dephosphorylated by calcineurin. Furthermore, we also discovered that a novel CaMKII-phosphorylated site, S2137, underwent dephosphorylation by calcineurin. In CAD cells, a mouse central nervous system cell line, membrane depolarization led to an increase in the phosphorylation of endogenous Cav3.2 at S2137. Mutation of S2137 affected the calcium channel function of Cav3.2. Our findings advance the understanding of Cav3.2 regulation not only through kinase phosphorylation but also via calcineurin phosphatase dephosphorylation.

Fecal microbiota transplantation (FMT) is a new and adequate route to modify the microbial ecosystem in gastrointestinal tract of the hosts. Intestinal microbiota is highly associated with human health and disease. According to the reports of human clinical trials or case series, the application of FMT ranged from Clostridiodes difficile infection (CDI), inflammatory bowel disease (IBD), irritable bowel syndrome, refractory diarrhea, diabetes mellitus, metabolic syndrome, and even neurologic diseases, including Parkinson disease, and neuropsychiatric disorder (autism spectrum disorder, ASD). Although the current allowed indication of FMT is CDI in Taiwan, more application and development are expectable in the future. There is a relative rare data available for children in application of fecal microbiota transplantation. Thus, we review previous published research inspecting FMT in children, and address particular considerations when conducting FMT in pediatric patients.

Background: Cardiac pressure overload induces cardiac hypertrophy and eventually leads to heart failure. One distinct feature of pathological cardiac hypertrophy is fetal-gene re-expression, but not every cardiomyocyte exhibits fetal gene re-expression in the diseased heart. Adult cardiomyocytes are terminally differentiated cells, so we do not know how the heterogeneity is determined and whether the differential fetal-gene reprogramming indicates a different degree of remodeling among cardiomyocytes. We hypothesized that fetal gene-expressed cardiomyocytes show more pathological features in the pressure-overloaded heart. Results: We induced pressure overload in mice by transverse aortic constriction (TAC) and observed a cardiomyocyte population with expression of β-myosin heavy chain (βMHC, a fetal gene encoded by Myh7) after TAC for 3 days. On transcriptomic and proteomic analyses, βMHC-expressed cardiomyocytes of 3-day TAC hearts were enriched in genes in cardiomyopathy-associated pathways and glycolytic processes. Moreover, results of immunoblotting and enzyme activity assay suggested higher glycolytic activity in βMHC-expressed than non-expressed cardiomyocytes. When we inhibited the glycolytic flux by 2-deoxy-d-glucose, a widely used glycolysis inhibitor, the number of βMHC-expressed cardiomyocytes was reduced, and the level of TEA domain family member 1 (TEAD1), a transcriptional enhancer, was decreased. Also, our spatial transcriptomic results demonstrated that naïve and 3-day TAC hearts had fetal-gene–rich tissue domains that were enriched in pathways in extracellular matrix organization and tissue remodeling. As well, gene levels of glycolytic enzymes were higher in Myh7-positive than Myh7-negative domains. Conclusions: Our data suggest that βMHC-expressed cardiomyocytes progress to pathological remodeling in the early stages of cardiac hypertrophy. In addition, the diverse glycolytic activity among cardiomyocytes might play a role in regulating gene expression via TEAD1 signaling.

Rowing competitions require consistent rowing strokes among crew members to achieve optimal performance. However, existing motion analysis techniques often rely on wearable sensors, leading to challenges in sporter inconvenience. The aim of our work is to use a graph-matching network to analyze the similarity in rowers’ rowing posture and further pair rowers to improve the performance of their rowing team. This study proposed a novel video-based performance analysis system to analyze paired rowers using a graph-matching network. The proposed system first detected human joint points, as acquired from the OpenPose system, and then the graph embedding model and graph-matching network model were applied to analyze similarities in rowing postures between paired rowers. When analyzing the postures of the paired rowers, the proposed system detected the same starting point of their rowing postures to achieve more accurate pairing results. Finally, variations in the similarities were displayed using the proposed time-period similarity processing. The experimental results show that the proposed time-period similarity processing of the 2D graph-embedding model (GEM) had the best pairing results.

Background: Necrotizing enterocolitis (NEC) is one of the most serious complications in preterm infants. Probiotics have been used to prevent NEC. Safety is a major concern for this practice. Methods: We reported a female preterm infant who received oral Lactobacillus rhamnosus GG but developed sepsis 12 days after the treatment. Cultures of blood and the catheter tip yielded L. rhamnosus. Next-generation sequencing was performed to analyze isolates from blood, stool, catheter, and product capsules. We also determined the capacities of these isolates to form biofilms. A literature review was performed. Results: The patient was treated with ampicillin and piperacillin/tazobactam, and she subsequently recovered without complications. The analysis of genome sequences indicated that all the isolates belonged to the clone of L. rhamnosus GG (ATCC 53103), suggesting that sepsis was a catheter-related infection caused by the oral probiotic. L. rhamnosus GG (ATCC 53103) and the probiotic strain tested formed biofilms under all growth conditions. Isolates from the blood and catheter tip also formed biofilms, but the stool isolate did not. The capacity of intrinsic biofilm formation in L. rhamnosus GG depended on environmental factors and the type of culture medium. Literature review of L. rhamnosus GG sepsis in preterm and young infants found that nearly 60% of the patients had a suspected or confirmed infected catheter. Conclusion: The study showed that the capacity of L. rhamnosus GG to form biofilms, especially in the presence of glucose, is a critical factor leading to the probiotic-related sepsis in preterm infants.

BackgroundSurgery is required for the treatment of intussusception when enema reduction is unsuccessful, or when the patient develops peritonitis, bowel perforation, or intestinal damage. We aimed to evaluate the clinical and laboratory parameters that may be used to predict the need for bowel resection in children with intussusception.MethodsThis observational retrospective study included children who were admitted to the pediatric emergency department with intussusception. Univariate and multivariate logistic regression models were used to evaluate factors associated with bowel resection.ResultsIn total, 584 children with intussusception were admitted to the pediatric emergency department; 129 of these children underwent surgery. Multivariate analysis revealed the following independent predictors of bowel resection for intussusception: symptoms for at least 2 days before surgery (OR = 6.863; p = 0.009), long intussusception (OR = 5.088; p = 0.014), pathological lead point (OR = 6.926; p = 0.003), and intensive care unit admission (OR = 11.777; p = 0.001) were factors independently associated with bowel resection.ConclusionSymptoms for at least 2 days before surgery, long intussusception, pathological lead, and intensive care unit admission were predictors of bowel resection in children with intussusception. These findings can be used to identify patients at high risk of needing surgery and bowel resection.

Alzheimer's disease (AD) is one of the most common progressive neurodegenerative disorders that cause deterioration of cognitive functions. Recent studies suggested that the accumulation of inflammatory molecules and impaired protein degradation mechanisms might both play a critical role in the progression of AD. Autophagy is a major protein degradation pathway that can be controlled by several HECT-E3 ligases, which then regulates the expression of inflammatory molecules. E3 ubiquitin ligases are known to be upregulated in several neurodegenerative diseases. Here, we studied the expressional change of HECT-E3 ligase using M01 on autophagy and inflammasome pathways in the context of AD pathogenesis. Our results demonstrated that the M01 treatment reversed the working memory deficits in 3xTg-AD mice when examined with the T-maze and reversal learning with the Morris water maze. Additionally, the electrophysiology recordings indicated that M01 treatment enhanced the long-term potentiation in the hippocampus of 3xTg-AD mice. Together with the improved memory performance, the expression levels of the NLRP3 inflammasome protein were decreased. On the other hand, autophagy-related molecules were increased in the hippocampus of 3xTg-AD mice. Furthermore, the protein docking analysis indicated that the binding affinity of M01 to the WWP1 and NEDD4 E3 ligases was the highest among the HECT family members. The western blot analysis also confirmed the decreased expression level of NEDD4 protein in the M01-treated 3xTg-AD mice. Overall, our results demonstrate that the modulation of HECT-E3 ligase expression level can be used as a strategy to treat early memory deficits in AD by decreasing NLRP3 inflammasome molecules and increasing the autophagy pathway.

Abstract Fear dysregulation is one of the symptoms found in post-traumatic stress disorder (PTSD) patients. The functional abnormality of the hippocampus is known to be implicated in the development of such pathology. Peroxiredoxin 6 (PRDX6) belongs to the peroxiredoxin family. This antioxidant enzyme is expressed throughout the brain, including the hippocampus. Recent evidence reveals that PRDX6 plays an important role in redox regulation and the modulation of several signaling molecules involved in fear regulation. Thus, we hypothesized that PRDX6 plays a role in the regulation of fear memory. We subjected a systemic Prdx6 knockout (Prdx6 −/− ) mice to trace fear conditioning and observed enhanced fear response after training. Intraventricular injection of lentivirus-carried mouse Prdx6 into the 3rd ventricle reduced the enhanced fear response in these knockout mice. Proteomic analysis followed by validation of western blot analysis revealed that several proteins in the MAPK pathway, such as NTRK2, AKT, and phospho-ERK1/2, cPLA2 were significantly upregulated in the hippocampus of Prdx6 −/− mice during the retrieval stage of contextual fear memory. The distribution of PRDX6 found in the astrocytes was also observed throughout the hippocampus. This study identifies PRDX6 as a participant in the regulation of fear response. It suggests that PRDX6 and related molecules may have important implications for understanding fear-dysregulation associated disorders like PTSD.

Background: Inflammatory bowel diseases (IBD) include ulcerative colitis (UC) and Crohn's disease (CD). The incidence in children and adolescents has risen since the 21st century globally, including Taiwan. The study aimed to disclose the characteristics and outcome of pediatric IBD (pIBD) patients in a tertiary center for the past two decades. Methods: We retrospectively reviewed the charts of pIBD children from 2000 to 2018 in a tertiary center in Northern Taiwan. Demographics, presentations, diagnostic modalities, treatment, and outcomes were analyzed. Results: A total of 38 cases were enrolled, including 27 CD and 11 UC patients. An almost 3-folds increase in incidence after 2010 was observed. Twelve cases (32%) were early-onset, and six of them (16%) were very-early-onset; four of them were detected with single-gene mutations [XIAP, TTC7A (2 siblings), and ZAP70]. Eleven CD patients (40.7%) received bowel resection at the onset, and another two (7.4%) had bowel resection years after the diagnosis. Initial bowel resection was associated with fibrostenotic/penetrating behavior, early-onset disease, and growth failure. Conclusion: This study demonstrated an increased incidence of pIBD in the past two decades in Taiwan, a low-prevalence region. The initial high bowel resection rate in CD was related to the fibrostenotic and/or penetrating behavior, younger age at diagnosis, and growth failure.

Background: This study aimed to investigate whether fecal human beta-defensins (HBD)-2 and eosinophil cationic protein (ECP) expression in preterm infants are associated with allergic disease development by age 2 years. Methods: Preterm infants' stool samples were collected at the age of 6 and 12 months postnatally. Information regarding medication exposure histories (antibiotics, antipyretics, probiotics) and physician-diagnosed allergic diseases was obtained using age-specific questionnaires and medical records. We compared the 6-month and 12-month fecal HBD-2 and ECP concentrations between the medication exposure and non-exposure group, respectively, and between children who developed allergic diseases and those who did not by 2 years of age. Univariate and multivariable logistic regression analyses were performed to investigate independent variables related to physician-diagnosed allergic diseases by 2 years of age. Results: Seventy-four preterm infants (gestational age, 31–36 weeks) were included. Fecal HBD-2 levels were significantly increased at 12 months of age among children who developed allergic diseases compared to those who did not (37.18 ± 11.80 ng/g vs. 8.56 ± 4.33 ng/g, P = 0.011). This association was more apparent among allergic children given antibiotics (50.23 ± 16.15 ng/g vs. 9.75 ± 7.16 ng/g, P = 0.008) or antipyretics (46.12 ± 14.22 ng/g vs. 10.82 ± 6.81 ng/g, P = 0.018) during the first year, whereas among allergic children who were previously not exposed to antibiotics or antipyretics, the differences were not significant. Results of the multivariable logistic regression analysis indicated that HBD-2 concentration in 12-month stools was an independent indicator associated with physician-diagnosed allergic diseases by 2 years of age (adjusted odds ratio: 1.03 [95% confidence interval: 1.00–1.05], P = 0.036). Our data revealed a lack of association between fecal ECP and allergic diseases. Conclusions: We found that preterm infants who expressed high fecal HBD-2 at 12 months of age were associated with physician-diagnosed allergic diseases by the age of 2 years. Further studies are needed to determine the role of fecal HBD-2 in the development of allergic diseases.

BackgroundArgon plasma coagulation (APC) has been applied in adults to treat various diseases, including vascular lesions in the gastrointestinal (GI) tract. However, angiodysplasia (AD) is an uncommon cause of pediatric GI bleeding, while the experience of treating AD with APC was rarely reported.MethodsFive children with AD in the GI tract successfully treated with APC were reviewed.ResultsThree of the five patients were girls, and the age at diagnosis ranged from 1.5 months to 10.5 years of age. One patient with gastric AD manifested with tarry stool, and the rest had colonic AD, which caused various degrees of bloody stool. Three patients had evident anemia. All patients received an endoscopic diagnosis, and two had compatible findings in radiographic exams. Each patient underwent one APC treatment session, and none encountered procedure-related complications or re-bleeding.ConclusionAD can be an etiology of GI bleeding even in neonates. APC is an effective and safe therapy for symptomatic AD in children.

Abstract Background Our previous studies demonstrated that adipose-derived mesenchymal stromal cells (ASCs) have immunomodulatory effects that prolong allograft survival in a rodent hind-limb allotransplant model. In this study, we investigated whether the effects of immunomodulation by ASCs on allograft survival are correlated with B cell regulation. Methods B cells isolated from splenocytes were cocultured with ASCs harvested from adipose tissue from rodent groin areas for in vitro experiments. In an in vivo study, hind-limb allotransplantation from Brown-Norway to Lewis rats was performed, and rats were treated with ASCs combined with short-term treatment with anti-lymphocyte serum (ALS)/cyclosporine (CsA) as immunosuppressants. Peripheral blood and transplanted tissue were collected for further analysis. Result An in vitro study revealed that ASCs significantly suppressed lipopolysaccharide-activated B cell proliferation and increased the percentage of Bregs. The levels of immunoregulatory cytokines, such as TGF-β1 and IL-10, were significantly increased in supernatants of stimulated B cells cocultured with ASCs. The in vivo study showed that treatment with ASCs combined with short-term ALS/CsA significantly reduced the B cell population in alloskin tissue, increased the proportion of circulating CD45Ra+/Foxp3+ B cells, and decreased C4d expression in alloskin. Conclusion ASCs combined with short-term immunosuppressant treatment prolong allograft survival and are correlated with B cell regulation, C4d expression and the modulation of immunoregulatory cytokines.

Background: The ingestion of multiple magnets may lead to severe complications including bowel obstruction, perforation, fistula, peritonitis, short bowel syndrome, life-threatening injuries, and even death. The annual case number of high-powered neodymium magnets ingestion has been increasing in the western world and the dearth of available data demonstrates that this issue has been neglected in Taiwan. Methods: We searched the electronic medical records of our institution for patients younger than 18 years old who were diagnosed with, who had ever visited our emergency department, or been hospitalized for magnetic foreign body ingestion between January 2009 and March 2018. Demographic data including the number, shape, and size of magnets ingested, the clinical presentation, type of intervention, and complications were reviewed. Results: Thirteen patients who met the enrollment criteria were analyzed. One patient was documented between 2009 and 2013, and twelve were documented between January 2014 and March 2018. Five of the cases documented between 2014 and 2018 had ingested Buckyballs. The median age of the patients was 5 years. All of the patients with clinical symptoms had ingested more than one magnet and required endoscopic or surgical intervention. Bowel perforation or deep ulcer with impending perforation was found in three patients during surgery. Conclusion: The number of children who visited our emergency department or were hospitalized due to the ingestion of magnets has increased recently. The presence of high power of neodymium magnets in many products increases the risk of ingesting multiple magnets resulting in serious complications. Therefore, stricter policies are needed to prevent children from obtaining products that contain magnets.

Abstract Background Neuropathic pain is an abnormally increased sensitivity to pain, especially from mechanical or thermal stimuli. To date, the current pharmacological treatments for neuropathic pain are still unsatisfactory. The gut microbiota reportedly plays important roles in inducing neuropathic pain, so probiotics have also been used to treat it. However, the underlying questions around the interactions in and stability of the gut microbiota in a spared nerve injury-induced neuropathic pain model and the key microbes (i.e., the microbes that play critical roles) involved have not been answered. We collected 66 fecal samples over 2 weeks (three mice and 11 time points in spared nerve injury-induced neuropathic pain and Sham groups). The 16S rRNA gene was polymerase chain reaction amplified, sequenced on a MiSeq platform, and analyzed using a MOTHUR- UPARSE pipeline. Results Here we show that spared nerve injury-induced neuropathic pain alters gut microbial diversity in mice. We successfully constructed reliable microbial interaction networks using the Metagenomic Microbial Interaction Simulator (MetaMIS) and analyzed these networks based on 177,147 simulations. Interestingly, at a higher resolution, our results showed that spared nerve injury-induced neuropathic pain altered both the stability of the microbial community and the key microbes in a gut micro-ecosystem. Oscillospira, which was classified as a low-abundance and core microbe, was identified as the key microbe in the Sham group, whereas Staphylococcus, classified as a rare and non-core microbe, was identified as the key microbe in the spared nerve injury-induced neuropathic pain group. Conclusions In summary, our results provide novel experimental evidence that spared nerve injury-induced neuropathic pain reshapes gut microbial diversity, and alters the stability and key microbes in the gut.

Fusing object detection techniques and stochastic variational inference, we proposed a new scheme for lightweight neural network models, which could simultaneously reduce model sizes and raise the inference speed. This technique was then applied in fast human posture identification. The integer-arithmetic-only algorithm and the feature pyramid network were adopted to reduce the computational complexity in training and to capture features of small objects, respectively. Features of sequential human motion frames (i.e., the centroid coordinates of bounding boxes) were extracted by the self-attention mechanism. With the techniques of Bayesian neural network and stochastic variational inference, human postures could be promptly classified by fast resolving of the Gaussian mixture model for human posture classification. The model took instant centroid features as inputs and indicated possible human postures in the probabilistic maps. Our model had better overall performance than the baseline model ResNet in mean average precision (32.5 vs. 34.6), inference speed (27 vs. 48 milliseconds), and model size (46.2 vs. 227.8 MB). The model could also alert a suspected human falling event about 0.66 s in advance.

Background: Antral web is a rare cause of gastric outlet obstruction in children. The presentation is diverse, depending on the degree of obstruction. Unfortunately, the guidance of management is still lacking.Methods: This study retrospectively evaluated the presentations, management, and outcomes of the pediatric antral web based on a 20-year experience in a referral center.Results: A total of 23 cases were included. The median age of diagnosis was 10 months (interquartile range, IQR, 0.8–23 months). Main presentations comprised vomiting (83%) and upper gastrointestinal (UGI) bleeding (48%). Concurrent gastric ulcers were common (68%). A total of 13 cases (57%) underwent interventional treatment. The median duration from diagnosis to intervention (DtI) was 10 days, but five with longer DtI, ranged from 30 to 755 days. Among the 15 cases with concurrent gastric ulcers, 10 patients received intervention, immediately in six but delayed in four. Surgical treatments (N = 12) achieved a cure in 11, with one rescued by endoscopic treatment.Conclusions: Children who suffer from early gastric ulcers with outlet obstruction shall raise the suspicion of the antral web. Complete obstruction madates early intervention. Around half of the cases with adequate feeding and growth need no intervention. Recurrent obstructive symptoms or adjacent ulcers justify a switch from observation to intervention to avoid complications or growth faltering.

This research demonstrates the preparation of composite membranes containing graphene oxide (GO) and investigates the separation mechanisms of various salts and bovine serum albumin (BSA) solutions. A microporous polyvinylidene fluoride–polyacrylic acid–GO (PVDF-PAA-GO) separation layer was fabricated on non-woven support. The GO-incorporating composite resulted in enlarged pore size (0.16 μm) compared with the control membrane (0.12 μm). The zeta potential of the GO composite was reduced to –31 from –19 mV. The resulting membranes with and without GO were examined for water permeability and rejection efficiency with single salt and BSA solutions. Using the non-woven/PVDF-PAA composite, the permeance values were 88–190 kg/m2hMPa, and the salt rejection coefficients were 9–28% for Na2SO4, MgCl2, MgSO4, and NaCl solutions. These salt removals were based on the Donnan exclusion mechanism considering the ion radii and membrane pore size. Incorporating GO into the separation layer exhibited limited impacts on the filtration of salt solutions, but significantly reduced BSA membrane adhesion and increased permeance. The negatively charged protein reached almost complete removal (98.4%) from the highly negatively charged GO-containing membrane. The GO additive improved the anti-fouling property of the composite membrane and enhanced BSA separation from the salt solution.

Aim: The present study evaluates the long-term clinical and nutritional effect to endoscopic balloon dilatation (EBD) in pediatric esophageal stricture. Methods: This was a 15-year retrospective study involving pediatric patients with esophageal stricture treated with EBD. Outcome parameters included the number of dilatations, procedural success rates, nutritional status, and complications. EBD was performed in patients with a dysphagia score greater than 2. The nutritional status was assessed by weight-for-age z-score. Clinical success was defined as no requirement for EBD for at least 1 year and/or increasing interval between dilatation and the numbers of EBD was fewer than 4 times per year. Results: A total of 50 cases (mean age, 4.41 ± 4.9 years) were enrolled. During a mean follow-up of 3.2 ± 1.9 years, a total of 268 EBD sessions were performed, with an average of 5.36 sessions per patient (range, 1–33). Patients who had short segment stricture (

Background: There is limited information on therapeutic benefits and tube-related complications of pediatric nasoenteric (NE) tube feeding. We viewed, from different clinical aspects, NE tube feeding in children who are under intolerable conditions.Methods: A 10-years retrospective study enrolled 77 pediatric patients who underwent an endoscopic-guided placement of the NE tube for enteral nutrition. The evaluated data, including growth parameters, feeding volume, parenteral nutrition (PN) dependence, and nutritional markers [serum hemoglobin (Hb) and albumin] before and after NE tube feeding were compared. Tube-related complications and major adverse events were also recorded.Results: A total of 77 patients (including 50 males) underwent 176 endoscopic-guided placements of the NE tube with an average duration of 133.7 (6.0–1,847.3) days. The gastroesophageal reflux disease-related symptoms (vomiting, desaturations, and aspiration pneumonia) improved in 71.4% of patients. Feeding volume increased significantly after intervention, especially in patients with delayed gastric emptying, from 144.8 ± 28.5 to 1,103.1 ± 524.7 ml/days (p < 0.001). Weaning from PN was successfully achieved in 84.3% of patients with an average of 9.33 ± 7.30 days. About 16 patients (20.8%) were subsequently highly compatible with oral feeding after NE tube placement for an average of 24.7 ± 14.1 days. Patients either without neurologic dysfunction or with no ventilator-dependent status had a higher chance of shifting to oral feeding. Weight-for-age z-scores increased by 0.15 ± 1.33 after NE tube intervention. One NE tube-related adverse event, which caused bowel perforation at 6 days post-insertion, was recorded. No direct tube-related mortality was observed.Conclusions: Endoscopic-guided NE tube placement is a relatively safe, non-invasive procedure for pediatric patients who require enteral nutrition. Feeding via NE tube showed beneficial effects such as improvement in symptoms, PN weaning, and maintenance of body growth without major tube-related complications.

Congenital short bowel syndrome (CSBS) is a rare condition characterized by an inborn shortening of bowel length with loss of intestinal functions, which often combines malrotation. CXADR-like membrane protein (CLMP) and filamin A (FLNA) gene mutations are the two major causes of this inherited defect. We presented two siblings with the older brother suffering from a laparotomy for bowel obstruction due to malrotation on the 17th day after birth. The younger sister encountered a laparotomy for lactobezoar at 6 months old. CSBS was diagnosed by measurement of the bowel length during the operations. Compound heterozygous CLMP mutations with the paternal allele harboring a long deletion across exon 3–5 and the maternal allele bearing a non-sense mutation of exon 3 (c.235C > T, p.Q79∗) were identified in both cases. They are the first reported familial CSBS caused by novel CLMP mutations in Taiwan.

Propofol and fentanyl are commonly used agents for the induction of anesthesia, and are often associated with hemodynamic disturbances. Understanding pharmacodynamic impacts is vital for parasympathetic and sympathetic tones during the anesthesia induction period. Inspired by the thermodynamic interaction between drug concentrations and effects, we established a machine-learning-based response surface model (MLRSM) to address this predicament. Then, we investigated and modeled the biomedical phenomena in the autonomic nervous system. Our study prospectively enrolled 60 patients, and the participants were assigned to two groups randomly and equally. Group 1 received propofol first, followed by fentanyl, and the drug sequence followed an inverse procedure in Group 2. Then, we extracted and analyzed the spectrograms of electrocardiography (ECG) and pulse photoplethysmography (PPG) signals after induction of propofol and fentanyl. Eventually, we utilized the proposed MLRSM to evaluate the relationship between anesthetics and the integrity/balance of sympathetic and parasympathetic activity by employing the power of high-frequency (HF) and low-frequency (LF) bands and PPG amplitude (PPGA). It is worth emphasizing that the proposed MLRSM exhibits a similar mathematical form to the conventional Greco model, but with better computational performance. Furthermore, the MLRSM has a theoretical foundation and flexibility for arbitrary numbers of drug combinations. The modeling results are consistent with the previous literature. We employed the bootstrap algorithm to inspect the results’ consistency and measure the various statistical fluctuations. Then, the comparison between the modeling and the bootstrapping results was used to validate the statistical stability and the feasibility of the proposed MLRSM.

Inhibition of T-type calcium channels (CaV3) prevents development of diseases related to cardiovascular and nerve systems. Further, knockout animal studies have revealed that some diseases are mediated by specific subtypes of CaV3. However, subtype-specific CaV3 inhibitors for therapeutic purposes or for studying the physiological roles of CaV3 subtypes are missing. To bridge this gap, we employed our spider venom library and uncovered that Avicularia spec. (“Amazonas Purple”, Peru) tarantula venom inhibited specific T-type CaV channel subtypes. By using chromatographic and mass-spectrometric techniques, we isolated and sequenced the active toxin ω-Avsp1a, a C-terminally amidated 36 residue peptide with a molecular weight of 4224.91 Da, which comprised the major peak in the venom. Both native (4.1 μM) and synthetic ω-Avsp1a (10 μM) inhibited 90% of CaV3.1 and CaV3.3, but only 25% of CaV3.2 currents. In order to investigate the toxin binding site, we generated a range of chimeric channels from the less sensitive CaV3.2 and more sensitive CaV3.3. Our results suggest that domain-1 of CaV3.3 is important for the inhibitory effect of ω-Avsp1a on T-type calcium channels. Further studies revealed that a leucine of T-type calcium channels is crucial for the inhibitory effect of ω-Avsp1a.

Multi-secret image sharing technology shares multiple secret images among shared images for participants and the recovery requires enough shared images for fulfilling the security property. Simultaneously, the adopted Boolean method preserves high performance. The proposed (k, n, m) multi-secret image sharing scheme shares m secret images among n participants and gathering k participants’ shared images perfectly recovers these m secret images. The proposed scheme exhibits high performance because of the usage of Boolean-based processing. Moreover, the usage of a sharing matrix based strategy acquires perfect reconstruction of the secret images under (k, n) thresholds. Two proposed schemes, the source-random-mixed (SRM) and the source-random-separate (SRS) methods, are presented in this study from different strategies of sharing the random image mixed with the secret images or separated to the secret images, respectively. Moreover, the proposed SRS method exhibits the better sharing capacity. Experimental results show that the proposed schemes perform well on sharing efficiency and security.

Spherical silver nanoparticles (Ag NPs) and silver nanoprisms (Ag NPrsms) were synthesized and decorated on graphene oxide (GO) nanosheets. The Ag contents were 29% and 23% in the GO–Ag NPs and GO–Ag NPrsms, respectively. The Ag NPrsms exhibited stronger (111) crystal signal than Ag NPs. The GO–Ag NPrsms exhibited higher Ag (I) content (75.6%) than GO-Ag NPs (69.9%). Increasing the nanomaterial concentration from 25 to 100 µg mL−1 improved the bactericidal efficiency, and the antibacterial potency was in the order: GO–Ag NPrsms > GO–Ag NPs > Ag NPrsms > Ag NPs > GO. Gram-positive Staphylococcus aureus (S. aureus) was more vulnerable than Gram-negative Escherichia coli (E. coli) upon exposure to these nanomaterials. The GO–Ag NPrsms demonstrated a complete (100%) bactericidal effect against S. aureus at a concentration of 100 µg mL−1. The GO–Ag composites outperformed those of Ag or GO due to the synergistic effect of bacteriostatic Ag particles and GO affinity toward bacteria. The levels of reactive oxygen species produced in the bacteria–nanomaterial mixtures were highly correlated to the antibacterial efficacy values. The GO–Ag NPrsms are promising as bactericidal agents to suppress biofilm formation and inhibit bacterial infection.

Vasoactive intestinal peptide (VIP) secreting tumor (VIPoma) is a rare disease, presenting with profuse diarrhea, electrolyte imbalance, and possibly fatal outcome. The diagnosis and treatment are challenging, and no consensus guideline of management is available. The pediatric incidence remains unclear. This study comprises two pediatric case reports from a tertiary center and a literature-based case series investigating the characteristics among children. The two reported cases both presented with severe diarrhea and laboratory abnormalities, including electrolyte imbalance and elevated plasma VIP level. Case 1 received several imaging investigations, partial pancreatectomy, octreotide, and everolimus, reflecting her complicated and refractory course. Case 2 underwent total excision of suprarenal ganglioneuroblastoma, and the clinical response was significant. In both cases, varied degrees of symptomatic control, reduced plasma VIP level, and correction of electrolyte imbalance were achieved. A literature review-based case series analyzed 45 pediatric cases retrieved from the PubMed database until December 31, 2019. Demographics, clinical features, diagnostic modalities, treatments, and outcomes were presented.

Background: Liver abscess is an important but relatively rare disease in children. This study investigated the clinical characteristics of eligible patients at a referral tertiary center over the past two decades.Method: A 20-year retrospective study (January 2000–December 2019) enrolled 38 children diagnosed with liver abscess. Demographic data; clinical features; laboratory, imaging, and microbiological findings; management strategy; and outcomes were reviewed from the patients' medical records.Results: Thirty-eight cases of pyogenic liver abscess were identified without a culture-proven amebic or fungal abscess. The mean age of diagnosis was 9.6 ± 6.2 years, and the male-to-female ratio was 1.92: 1. Hemato-oncological (28.9%) and predisposing hepatobiliary diseases (23.7%) were the two most common predisposing factors. Fever (94.7%) was the most common presentation followed by right upper quadrant abdominal pain (42.1%) and pleural effusion (34.2%). Among the laboratory parameters, leukocytosis was common (70.3%), and all patients had elevated serum C-reactive protein levels. Increased serum levels of alanine aminotransferase, aspartate aminotransferase, direct bilirubin, and total bilirubin were found in 40.5, 48.6, 23.1, and 42.9% of the cases, respectively. The most common pathogen in blood and pus cultures was Klebsiella pneumoniae. The mean durations of intravenous antibiotic and total antibiotic use were 29.0 ± 15.7 and 45.1 ± 22.1 days, respectively. Twelve patients (31.6%) were treated with antibiotics alone, while percutaneous needle aspiration, percutaneous pigtail drainage, and surgical intervention were performed in 12 (31.6%), 10 (26.3%), and 5 (13.2%) patients, respectively. No mortality was documented in this series.Conclusion: The present study reflects a relatively declining incidence of liver abscess compared with prior studies in Taiwan. K. pneumoniae remains the most prevalent pathogen in both blood and abscess cultures in Taiwan. Proper antimicrobial therapy with timely drainage generally yielded an adequate treatment response without any mortality.

Lung cancer has the highest global mortality rate of any cancer. Although targeted therapeutic drugs are commercially available, the common drug resistance and insensitivity to cisplatin-based chemotherapy, a common clinical treatment for lung cancer, have prompted active research on alternative lung cancer therapies and methods for mitigating cisplatin-related complications. In this study, we investigated the effect of WSG, a glucose-rich, water soluble polysaccharide derived from Ganoderma lucidum, on cisplatin-based treatment for lung cancer. Murine Lewis lung carcinoma (LLC1) cells were injected into C57BL/6 mice subcutaneously and through the tail vein. The combined administration of WSG and cisplatin effectively inhibited tumor growth and the formation of metastatic nodules in the lung tissue of the mice. Moreover, WSG increased the survival rate of mice receiving cisplatin. Co-treatment with WSG and cisplatin induced a synergistic inhibitory effect on the growth of lung cancer cells, enhancing the apoptotic responses mediated by cisplatin. WSG also reduced the cytotoxic effect of cisplatin in both macrophages and normal lung fibroblasts. Our findings suggest that WSG can increase the therapeutic effectiveness of cisplatin. In clinical settings, WSG may be used as an adjuvant or supplementary agent.

Background: Acute acalculous cholecystitis (AAC) is generally considered to be a mild disease in children; however, if left untreated or treated without caution, AAC can lead to severe outcomes, such as death. The objectives of this study were to present the clinical features and identify the predictors of mortality in pediatric AAC. Methods: Patients diagnosed with AAC between 2005 and 2012 were enrolled. AAC was defined by the presence of fever and an echo-proven thickened gallbladder wall exceeding 4 mm. A poor health outcome was defined as death. Further information related to the demographics, clinical manifestations, laboratory results, ultrasound findings, and pathogens present in the AAC patients was also collected. Predictors of mortality were identified by association analyses and confirmed by multivariate logistic regression. Results: A total of 147 pediatric AAC patients (male/female = 1.01, mean age = 5.2 years) were included in this retrospective study. The most common clinical presentation was an elevated C-reactive protein level (84%) followed by hepatomegaly (80%) and anorexia (78%). AAC in children was associated with various diseases, including infectious diseases (70%), systemic diseases (13%), and malignancy (11%). Fourteen of the 147 (9.25%) patients died during the study period. The presences of thrombocytopenia, anemia, gallbladder sludge, hepatitis, and/or sepsis plus hepatitis were found to be the important predictors of AAC mortality. Conclusions: The factors associated with AAC mortality were anemia, thrombocytopenia, gallbladder sludge, hepatitis, and sepsis plus hepatitis. These predictors are likely to help clinicians identify patients who are at a high risk of poor prognoses and make appropriate clinical decisions. Key Words: acute acalculous cholecystitis (AAC), children, risk factor

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