Liver cancer initiation requires translational activation by an oncofetal regulon involving LIN28 proteins.

It is unknown which post-transcriptional regulatory mechanisms are required for oncogenic competence. Here, we show that the LIN28 family of RNA-binding proteins (RBPs), which facilitate post-transcriptional RNA metabolism within ribonucleoprotein networks, are essential for the initiation of diverse oncotypes of hepatocellular carcinoma (HCC). In HCC models driven by NRASG12V/Tp53, CTNNB1/YAP/Tp53, or AKT/Tp53, mice without Lin28a and Lin28b were markedly impaired in cancer initiation. We biochemically defined an oncofetal regulon of 15 factors connected to Lin28 through direct mRNA and protein interactions. Interestingly, all were RBPs and only 1 of 15 is a Let-7 target. Polysome profiling and reporter assays showed that LIN28B directly increased the translation of 8 of these 15 RBPs. As expected, overexpression of LIN28B and IGFBP1-3 were able to genetically rescue cancer initiation. Using this platform to probe components downstream of LIN28, we found that 8 target RBPs were able to restore NRASG12V/Tp53 cancer formation in Lin28a/b deficient mice. Furthermore, these LIN28B targets promote cancer initiation through an increase in protein synthesis. LIN28B, central to an RNP regulon that increases translation of RBPs, is important for tumor initiation in the liver.

Developing Methods for Assessing Mental Activity Using Human-Smartphone Interactions: Comparative Analysis of Activity Levels and Phase Patterns in General Mental Activities, Working Mental Activities, and Physical Activities.

BACKGROUND: Human biological rhythms are commonly assessed through physical activity (PA) measurement, but mental activity may offer a more substantial reflection of human biological rhythms. OBJECTIVE: This study proposes a novel approach based on human-smartphone interaction to compute mental activity, encompassing general mental activity (GMA) and working mental activity (WMA). METHODS: A total of 24 health care professionals participated, wearing wrist actigraphy devices and using the "Staff Hours" app for more than 457 person-days, including 332 workdays and 125 nonworkdays. PA was measured using actigraphy, while GMA and WMA were assessed based on patterns of smartphone interactions. To model WMA, machine learning techniques such as extreme gradient boosting and convolutional neural networks were applied, using human-smartphone interaction patterns and GPS-defined work hours. The data were organized by date and divided into person-days, with an 80:20 split for training and testing data sets to minimize overfitting and maximize model robustness. The study also adopted the M10 metric to quantify daily activity levels by calculating the average acceleration during the 10-hour period of highest activity each day, which facilitated the assessment of the interrelations between PA, GMA, and WMA and sleep indicators. Phase differences, such as those between PA and GMA, were defined using a second-order Butterworth filter and Hilbert transform to extract and calculate circadian rhythms and instantaneous phases. This calculation involved subtracting the phase of the reference signal from that of the target signal and averaging these differences to provide a stable and clear measure of the phase relationship between the signals. Additionally, multilevel modeling explored associations between sleep indicators (total sleep time, midpoint of sleep) and next-day activity levels, accounting for the data's nested structure. RESULTS: Significant differences in activity levels were noted between workdays and nonworkdays, with WMA occurring approximately 1.08 hours earlier than PA during workdays (P<.001). Conversely, GMA was observed to commence about 1.22 hours later than PA (P<.001). Furthermore, a significant negative correlation was identified between the activity level of WMA and the previous night's midpoint of sleep (ß=-0.263, P<.001), indicating that later bedtimes and wake times were linked to reduced activity levels in WMA the following day. However, there was no significant correlation between WMA's activity levels and total sleep time. Similarly, no significant correlations were found between the activity levels of PA and GMA and sleep indicators from the previous night. CONCLUSIONS: This study significantly advances the understanding of human biological rhythms by developing and highlighting GMA and WMA as key indicators, derived from human-smartphone interactions. These findings offer novel insights into how mental activities, alongside PA, are intricately linked to sleep patterns, emphasizing the potential of GMA and WMA in behavioral and health studies.

Comparing Human-Smartphone Interactions and Actigraphy Measurements for Circadian Rhythm Stability and Adiposity: Algorithm Development and Validation Study.

BACKGROUND: This study aimed to investigate the relationships between adiposity and circadian rhythm and compare the measurement of circadian rhythm using both actigraphy and a smartphone app that tracks human-smartphone interactions. OBJECTIVE: We hypothesized that the app-based measurement may provide more comprehensive information, including light-sensitive melatonin secretion and social rhythm, and have stronger correlations with adiposity indicators. METHODS: We enrolled a total of 78 participants (mean age 41.5, SD 9.9 years; 46/78, 59% women) from both an obesity outpatient clinic and a workplace health promotion program. All participants (n=29 with obesity, n=16 overweight, and n=33 controls) were required to wear a wrist actigraphy device and install the Rhythm app for a minimum of 4 weeks, contributing to a total of 2182 person-days of data collection. The Rhythm app estimates sleep and circadian rhythm indicators by tracking human-smartphone interactions, which correspond to actigraphy. We examined the correlations between adiposity indices and sleep and circadian rhythm indicators, including sleep time, chronotype, and regularity of circadian rhythm, while controlling for physical activity level, age, and gender. RESULTS: Sleep onset and wake time measurements did not differ significantly between the app and actigraphy; however, wake after sleep onset was longer (13.5, SD 19.5 minutes) with the app, resulting in a longer actigraphy-measured total sleep time (TST) of 20.2 (SD 66.7) minutes. The obesity group had a significantly longer TST with both methods. App-measured circadian rhythm indicators were significantly lower than their actigraphy-measured counterparts. The obesity group had significantly lower interdaily stability (IS) than the control group with both methods. The multivariable-adjusted model revealed a negative correlation between BMI and app-measured IS (P=.007). Body fat percentage (BF%) and visceral adipose tissue area (VAT) showed significant correlations with both app-measured IS and actigraphy-measured IS. The app-measured midpoint of sleep showed a positive correlation with both BF% and VAT. Actigraphy-measured TST exhibited a positive correlation with BMI, VAT, and BF%, while no significant correlation was found between app-measured TST and either BMI, VAT, or BF%. CONCLUSIONS: Our findings suggest that IS is strongly correlated with various adiposity indicators. Further exploration of the role of circadian rhythm, particularly measured through human-smartphone interactions, in obesity prevention could be warranted.

Metabolic inflexibility promotes mitochondrial health during liver regeneration.

Mitochondria are critical for proper organ function and mechanisms to promote mitochondrial health during regeneration would benefit tissue homeostasis. We report that during liver regeneration, proliferation is suppressed in electron transport chain (ETC)-dysfunctional hepatocytes due to an inability to generate acetyl-CoA from peripheral fatty acids through mitochondrial ß-oxidation. Alternative modes for acetyl-CoA production from pyruvate or acetate are suppressed in the setting of ETC dysfunction. This metabolic inflexibility forces a dependence on ETC-functional mitochondria and restoring acetyl-CoA production from pyruvate is sufficient to allow ETC-dysfunctional hepatocytes to proliferate. We propose that metabolic inflexibility within hepatocytes can be advantageous by limiting the expansion of ETC-dysfunctional cells.

Association of Childhood Attention Deficit/Hyperactivity Disorder With Adolescent Traditional and Cyberbullying Victimization in the Digital Generation: A Population-Based Cohort Study.

PURPOSE: This population-based cohort study aimed to examine the association with childhood attention deficit/hyperactivity disorder (ADHD) and bullying experiences during adolescence among Digital Generation individuals, exploring both traditional and cyberbullying. METHODS: This study included data from 15,240 participants, collected from the Taiwan Adolescent to Adult Longitudinal Study project. Participants, initially in seventh and 10th grade in 2015, were selected through a multistage stratified sampling approach. Self-report questionnaires assessed traditional and cyberbullying victimization experiences during adolescence, with 5-year longitudinal follow-up. Childhood ADHD diagnoses were identified by linking data to Taiwan's National Health Insurance Research Database from 2000 to 2015. Logistic regression models were employed to examine the relationship between childhood ADHD and bullying victimization while controlling for relevant covariates. RESULTS: Individuals diagnosed with childhood ADHD exhibited a significantly higher likelihood of experiencing bullying during adolescence (adjusted odds ratio (aOR) = 1.52, 95% confidence interval (CI): 1.28-1.80). This association extended to various forms of bullying, including physical (aOR = 1.42, 95% CI: 1.20-1.68), verbal (aOR = 1.42, 95% CI: 1.20-1.67), relational (aOR = 1.45, 95% CI: 1.22-1.71), and cyber (aOR = 1.35, 95% CI: 1.14-1.61). Additional factors positively associated with bullying victimization included male, binge drinking, and depression, while a positive campus atmosphere was protective against bullying. However, there is no evidence for interactions between these factors and ADHD in their associations with bullying. DISCUSSION: Childhood ADHD increases the risk of both traditional and cyberbullying during adolescence. Recognizing this risk is essential for targeted interventions and further research on underlying mechanisms.

The greatest loss of unpleasant smells may be related to the risk of more severe PD symptoms.

Background: Limited research has explored the relationship between the valence of olfactory dysfunction and PD clinical symptoms. This study aimed to investigate correlations between the emotional valence of olfactory impairment and different domains of PD symptoms. Methods: PD patients who fulfilled the clinically probable PD diagnostic criteria of the International Parkinson and Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's Disease were recruited from the Center for Parkinson and Movement Disorders at Taichung Veterans General Hospital between October 2016 and April 2022. Demographic data and serial clinical assessments were collected, including the traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC) and Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Thirty-five odors from the UPSIT-TC were classified into neutral, pleasant or unpleasant groups. Group comparisons, correlation analyses, and linear regression analyses were conducted to examine the relationship between olfactory impairment of UPSIT-TC odors, considering emotional valence, and MDS-UPDRS subscores across various domains. Results: A total of 176 PD patients were recruited for analysis. Patients in the predominantly neutral/unpleasant odor impairment groups had higher MDS-UPDRS part III scores compared to those in the predominantly pleasant odor impairment group (pleasant vs. neutral vs. unpleasant odor impairment groups: 26.79 ± 13.59 vs. 35.33 ± 16.36 vs. 31.57 ± 12.37, p = 0.009). This trend was also noted in MDS-UPDRS rigidity, bradykinesia, and akinetic-rigid subscores (p = 0.003, p = 0.012, and p = 0.001, respectively). Correlation analysis revealed a weak but significant correlation between rigidity/akinetic-rigid subscores and misidentification numbers for neutral/unpleasant odors (all p < 0.05), with age, gender, LEDD, and disease duration as covariates. All significances were retained in the linear regression analysis. Conclusion: Our results emphasize the link between olfactory impairment of specific emotional valence, neutral/unpleasant odors, and PD severity, particularly with respect to akinetic-rigid symptoms. A concise olfactory test that focuses on both neutral and unpleasant odors may offer deeper insights into PD symptoms.

Suppression of the alpha, delta, and omicron variants of SARS-Cov-2 in Taiwan.

BACKGROUND: Taiwan was a coronavirus disease 2019 (COVID-19) outlier, with an extraordinarily long transmission-free record: 253 days without locally transmitted infections while the rest of the world battled wave after wave of infection. The appearance of the alpha variant in May 2021, closely followed by the delta variant, disrupted this transmission-free streak. However, despite low vaccination coverage (<1%), outbreaks were well-controlled. METHODS: This study analyzed the time to border closure and conducted one-sample t test to compare between Taiwan and Non-Taiwan countries prior to vaccine introduction. The study also collected case data to observe the dynamics of omicron transmission. Time-varying reproduction number,Rt, was calculated and was used to reflect infection impact at specified time points and model trends of future incidence. RESULTS: The study analyzed and compare the time to border closure in Taiwan and non-Taiwan countries. The mean times to any border closure from the first domestic case within each country were -21 and 5.98 days, respectively (P < .0001). The Taiwanese government invested in quick and effective contact tracing with a precise quarantine strategy in lieu of a strict lockdown. Residents followed recommendations based on self-discipline and unity. The self-discipline in action is evidenced in Google mobility reports. The central and local governments worked together to enact non-pharmaceutical interventions (NPIs), including universal masking, social distancing, limited unnecessary gatherings, systematic contact tracing, and enhanced quarantine measures. The people cooperated actively with pandemic-prevention regulations, including vaccination and preventive NPIs. CONCLUSIONS: This article describes four key factors underlying Taiwan's success in controlling COVID-19 transmission: quick responses; effective control measures with new technologies and rolling knowledge updates; unity and cooperation among Taiwanese government agencies, private companies and organizations, and individual citizens; and Taiwanese self-discipline.

Unplanned Emergency Department Visits Following Revision Total Joint Arthroplasty: Incidences, Risk Factors, and Mortalities.

BACKGROUND: The incidence of unplanned emergency department (ED) visits following revision total joint arthroplasty is an indicator of the quality of postoperative care. The aim of this study was to investigate the incidences, timings, and characteristics of ED visits within 90 days after revision total joint arthroplasty. METHODS: A retrospective review of 457 consecutive cases, including 254 revision total hip arthroplasty (rTHA) and 203 revision total knee arthroplasty (rTKA) cases, was conducted. Data regarding patient demographics, timings of the ED encounter, chief complaints, readmissions, and diagnoses indicating reoperation were analyzed. RESULTS: The results showed that 41 patients who had rTHA (16.1%) and 14 patients who had rTKA (6.9%) returned to the ED within 90 days postoperatively. The incidence of ED visits was significantly higher in the rTHA group than in the rTKA group (P = .003). The most common surgery-related complications were dislocation among rTHA patients and wound conditions among rTKA patients. Apart from elevated calculated comorbidity scores, peptic ulcer in rTHA patients and cerebral vascular events and chronic obstructive pulmonary disease in rTKA patients might increase chances of unplanned ED visits. Patients who had ED visits showed significantly higher mortality rates than the others in both rTHA and rTKA cohorts (P = .050 and P = .008, respectively). CONCLUSIONS: The ED visits within 90 days are more common after rTHA than after rTKA. Patients in both ED visit groups after rTHA and rTKA demonstrated worse survival. Efforts should be made to improve quality of care to prevent ED visits.

Use of dipeptidyl peptidase-4 inhibitors was associated with a lower risk of Parkinson's disease in diabetic patients.

Diabetes mellitus is a risk factor for Parkinson's disease (PD). While animal studies have supported the benefits of incretin-based therapies, including dipeptidyl peptidase-4 (DPP4) inhibitors, in PD, clinical research has yielded controversial results. This cohort study aimed to assess the relationship between PD incidence and the utilization of DPP4 inhibitor in diabetic patients. Using Taiwan's National Health Insurance Research Database from 2009 to 2018, diabetic patients receiving metformin plus at least one second-line oral antidiabetic (OAD) were enrolled. The patients were categorized as DPP4 inhibitor users and non-users. Propensity score matching was employed to establish a 1:1 ratio between DPP4 inhibitor users and non-users. Among the 205,910 patients enrolled, 149 were diagnosed with PD during follow-up. The incidence rate was 0.29 per 1000 person-years for DPP4 inhibitor users and 0.55 per 1000 person-years for the non-users. DPP4 inhibitor users exhibited a significantly lower risk of PD (adjusted hazard ratio, 0.51; 95% CI 0.39-0.68). Among DPP4 inhibitor users, vildagliptin showed the strongest correlation with a reduction in the risk of PD. This study demonstrates that the use of DPP4 inhibitors along with metformin in diabetic patients is associated with a lower risk of PD compared to those using other OADs.

Developing a Machine Learning Algorithm to Predict the Probability of Medical Staff Work Mode Using Human-Smartphone Interaction Patterns: Algorithm Development and Validation Study.

BACKGROUND: Traditional methods for investigating work hours rely on an employee's physical presence at the worksite. However, accurately identifying break times at the worksite and distinguishing remote work outside the worksite poses challenges in work hour estimations. Machine learning has the potential to differentiate between human-smartphone interactions at work and off work. OBJECTIVE: In this study, we aimed to develop a novel approach called "probability in work mode," which leverages human-smartphone interaction patterns and corresponding GPS location data to estimate work hours. METHODS: To capture human-smartphone interactions and GPS locations, we used the "Staff Hours" app, developed by our team, to passively and continuously record participants' screen events, including timestamps of notifications, screen on or off occurrences, and app usage patterns. Extreme gradient boosted trees were used to transform these interaction patterns into a probability, while 1-dimensional convolutional neural networks generated successive probabilities based on previous sequence probabilities. The resulting probability in work mode allowed us to discern periods of office work, off-work, breaks at the worksite, and remote work. RESULTS: Our study included 121 participants, contributing to a total of 5503 person-days (person-days represent the cumulative number of days across all participants on which data were collected and analyzed). The developed machine learning model exhibited an average prediction performance, measured by the area under the receiver operating characteristic curve, of 0.915 (SD 0.064). Work hours estimated using the probability in work mode (higher than 0.5) were significantly longer (mean 11.2, SD 2.8 hours per day) than the GPS-defined counterparts (mean 10.2, SD 2.3 hours per day; P<.001). This discrepancy was attributed to the higher remote work time of 111.6 (SD 106.4) minutes compared to the break time of 54.7 (SD 74.5) minutes. CONCLUSIONS: Our novel approach, the probability in work mode, harnessed human-smartphone interaction patterns and machine learning models to enhance the precision and accuracy of work hour investigation. By integrating human-smartphone interactions and GPS data, our method provides valuable insights into work patterns, including remote work and breaks, offering potential applications in optimizing work productivity and well-being.

Examining Human-Smartphone Interaction as a Proxy for Circadian Rhythm in Patients With Insomnia: Cross-Sectional Study.

BACKGROUND: The sleep and circadian rhythm patterns associated with smartphone use, which are influenced by mental activities, might be closely linked to sleep quality and depressive symptoms, similar to the conventional actigraphy-based assessments of physical activity. OBJECTIVE: The primary objective of this study was to develop app-defined circadian rhythm and sleep indicators and compare them with actigraphy-derived measures. Additionally, we aimed to explore the clinical correlations of these indicators in individuals with insomnia and healthy controls. METHODS: The mobile app "Rhythm" was developed to record smartphone use time stamps and calculate circadian rhythms in 33 patients with insomnia and 33 age- and gender-matched healthy controls, totaling 2097 person-days. Simultaneously, we used standard actigraphy to quantify participants' sleep-wake cycles. Sleep indicators included sleep onset, wake time (WT), wake after sleep onset (WASO), and the number of awakenings (NAWK). Circadian rhythm metrics quantified the relative amplitude, interdaily stability, and intradaily variability based on either smartphone use or physical activity data. RESULTS: Comparisons between app-defined and actigraphy-defined sleep onsets, WTs, total sleep times, and NAWK did not reveal any significant differences (all P>.05). Both app-defined and actigraphy-defined sleep indicators successfully captured clinical features of insomnia, indicating prolonged WASO, increased NAWK, and delayed sleep onset and WT in patients with insomnia compared with healthy controls. The Pittsburgh Sleep Quality Index scores were positively correlated with WASO and NAWK, regardless of whether they were measured by the app or actigraphy. Depressive symptom scores were positively correlated with app-defined intradaily variability (ß=9.786, SD 3.756; P=.01) and negatively correlated with actigraphy-based relative amplitude (ß=-21.693, SD 8.214; P=.01), indicating disrupted circadian rhythmicity in individuals with depression. However, depressive symptom scores were negatively correlated with actigraphy-based intradaily variability (ß=-7.877, SD 3.110; P=.01) and not significantly correlated with app-defined relative amplitude (ß=-3.859, SD 12.352; P=.76). CONCLUSIONS: This study highlights the potential of smartphone-derived sleep and circadian rhythms as digital biomarkers, complementing standard actigraphy indicators. Although significant correlations with clinical manifestations of insomnia were observed, limitations in the evidence and the need for further research on predictive utility should be considered. Nonetheless, smartphone data hold promise for enhancing sleep monitoring and mental health assessments in digital health research.

UPSIT subitems may predict motor progression in Parkinson's disease.

Background: The relationship between hyposmia and motor progression is controversial in Parkinson's disease (PD). The aim of this study was to investigate whether preserved identification of Chinese-validated University of Pennsylvania Smell Identification Test (UPSIT) odors could predict PD motor progression. Methods: PD patients with two consecutive clinical visits while taking medication were recruited. Based on mean changes in Movement Disorder Society Unified Parkinson's Disease Rating Scale part 3 score and levodopa equivalent daily dosage, the participants were categorized into rapid progression, medium progression, and slow progression groups. Odors associated with the risk of PD motor progression were identified by calculating the odds ratios of UPSIT item identification between the rapid and slow progression groups. Receiver operating characteristic curve analysis of these odors was conducted to determine an optimal threshold for rapid motor progression. Results: A total of 117 PD patients were screened for group classification. Preserved identification of neutral/pleasant odors including banana, peach, magnolia, and baby powder was significantly correlated with rapid motor progression. The risk of rapid progression increased with more detected risk odors. Detection of ≥1.5 risk odors could differentiate rapid progression from slow progression with a sensitivity of 85.7%, specificity of 45.8%, and area under the receiver operating characteristic curve of 0.687. Conclusion: Preserved identification of neutral/pleasant odors may help to predict PD motor progression, and detection of ≥1.5 UPSIT motor progression risk odors could improve the predictive power. In PD patients with a similar level of motor disability during initial screening, preserved pleasant/neutral odor identification may imply relatively better cortical odor discriminative function, which may suggest the body-first (caudo-rostral) subtype with faster disease progression.

Effect of Endoscopic Posterior Nasal Neurectomy on Laryngectomy-associated Rhinorrhea: A Feasibility Study.

BACKGROUND/AIM: Refractory rhinorrhea is common after total laryngectomy (TL). Because botulinum toxin injection and ipratropium bromide nasal spray have shown success in it, suggesting a hyperactive parasympathetic tone may play a role. Therefore, we sought to evaluate whether endoscopic posterior nasal neurectomy (ePNN) to include more nasal secretomotor fibers is a treatment option for laryngectomy-associated rhinorrhea. PATIENTS AND METHODS: Laryngectomized patients with persistent rhinorrhea who underwent ePNN at both the middle and inferior meatus were enrolled. We evaluated the changes in 2-week Total Nasal Symptoms Score (TNSS) and rhinorrhea subscore over 6 and 12 months post ePNN treatment, as well as self-rated rhinorrhea using the visual analogue scale (VAS) at pretreatment and 12 months post-treatment. Adverse events, post-procedure medication reliance, and patient satisfaction were recorded. RESULTS: Five males (mean age, 62.4 years) with elapsed time from TL of 97.56±89.91 months were identified. ePNN significantly improved the average rhinorrhea subscore of TNSS at six months (p=0.037, Wilcoxon sign-rank test) and twelve months (p=0.047) compared to baseline. There were marginally significant improvements between baseline and at 12 months for overall TNSS (6.60±2.30 to 2.00±1.22, p=0.056) and VAS for rhinorrhea (7.80±0.84 to 2.00±1.58, p=0.062). No adverse event was reported, and four patients had excellent outcomes. CONCLUSION: Endoscopic posterior nasal neurectomy is a safe and efficient alternative treatment for laryngectomy-associated rhinorrhea, with lasting improvement over one year. However, a large-scale study with more comprehensive measurements is needed to verify its long-term efficacy.

Bidirectional association between infectious gastroenteritis and inflammatory bowel disease: a population-based study.

BACKGROUND: Intertwined association between infectious gastroenteritis (IGE) and inflammatory bowel disease (IBD) has not been investigated clearly. We aimed to examine the bidirectional association between IGE and IBD. METHODS: A bidirectional study using the Taiwan National Health Insurance Research Database was designed. Through a case-control design, we identified 2899 new IBD cases during 2006-2017 and matched to 28,990 non-IBD controls. We used conditional logistic regression model to estimate odds ratios (OR) of IBD for previous IGE in different exposure time-windows within 5-years before IBD diagnosis and Poisson regression model to estimate incidence rate ratio (IRR) of subsequent IGE for IBD group to non-IBD group. RESULTS: The mean age at the initial IBD diagnosis was 41 years. More IBD patients (21.49%) than controls (12.60%) had been exposed to IGE during > 6 months to 5 years before IBD diagnosis, the OR of IBD for IGE was 1.89 [95% confidence interval: 1.69-2.11]. Excess OR decreased as IGE exposure time before the index date increased. More IGE episodes were associated with additional increase in IBD risk (OR: 1.64, 2.19, 2.57, 3.50, and 4.57 in patients with 1, 2, 3, 4, and ≥ 5 IGE episodes, respectively). The IRR of having IGE for IBD group to non-IBD group was 2.42 before IBD diagnosis and increased to 5.74 after IBD diagnosis. CONCLUSIONS: These findings suggested an IGE-IBD bidirectional association. More attention is needed for physicians to develop preventive strategies and be aware of the higher risk of subsequent IGE in IBD patients.

Vitrimer synthesis from recycled polyurethane gylcolysate.

Polyurethanes and plastics have become ubiquitous in modern society, finding use in a wide variety of applications such as clothing, automobiles, and shoes. While these materials provide numerous benefits to human life, their persistence in the environment has caused ecological imbalances. Therefore, new processes are needed to make these materials more sustainable and re-usable. In 2011, Ludwik Leibler introduced a new class of covalent adaptable network (CAN) polymers called Vitrimers. Vitrimers possess self-repairing properties and are capable of being reprocessed due to dynamic exchange or breaking/recombination of covalent bonds, similar to thermoset materials. This study explores the synthesis of Vitrimers using waste polyurethane or plastics as feedstock. The raw materials were glycolysed to obtain the glycolysate, which was then used as a reagent for the Vitrimers synthesis. The main objective of this study was to achieve the maximum self-repairable rate of the prepared sample. The Taguchi orthogonal analysis was employed to guide the experiments. The optimized experimental conditions for polyurethane glycolysis were determined to be under ethylene glycol and catalyzed by sodium hydroxide at 180°C for 1 h, resulting in the highest hydroxyl concentration in the glycolysate. In the second stage of the experiment, the ratio of hexamethylene diisocyanate (HDI) to solvent was set to 2, HDI trimer to solvent was 2, and PGE/glycolysate was 0.5, with equal amounts of PEG and glycolysate used as the solvent. The reaction was carried out at 80°C for 1 h, achieving a self-repair ability of 47.5% in the prepared sample. The results of this study show that waste polyurethane or plastics can be effectively recycled and transformed into vitrimers with self-repairing properties. The use of glycolysis as a feedstock is a promising method for the sustainable recycling of polyurethane waste. The Taguchi orthogonal analysis is an effective approach for optimizing experimental conditions and improving the reproducibility of the results.

Analysis of Aldehyde Dehydrogenase 2 as a Prognostic Marker Associated with Immune Cell infiltration and Chemotherapy Efficacy in Head and Neck Squamous Cell Carcinoma.

Background: Previous investigations have demonstrated the role of Aldehyde Dehydrogenase 2 (ALDH2) levels in the cancer initiation and progression, prognosis, and treatment response in kinds of malignancies. However, its significance in the head and neck squamous cell carcinoma (HNSC) by different human papillomavirus (HPV) statuses remains unclear. Methods: We conducted an in-depth analysis of ALDH2 in HNSC using various bioinformatics tools, investigating its expression, alteration, differential levels, prognostic significance, molecular interactions, immune characteristics, and conducting experimental validation through immunohistochemistry (IHC) arrays and Western blot to compare expression levels between tumor and normal tissues, analyze the associations with clinicopathological features, and investigate its responses to chemotherapies. Results: ALDH2 levels are downregulated in HNSC tissues and associated with higher American Joint Committee on Cancer (AJCC) T classification and worse overall survival in HPV-unrelated HNSC, yet not in HPV-related HNSC. ALDH2 is positively regulated by copy-number variation and negatively regulated by DNA methylation. The association of ALDH2 with prognosis may be due to its interaction with ALDH6A1, and its co-expressed genes are predictive biomarkers of HNSC. We also found high ALDH2 levels in bulk tumors are associated with increased immune surveillance cells, such as naïve B cells and M1 macrophages in HPV-unrelated HNSC. IHC and western blot showed that ALDH2 is downregulated in the oral cavity, hypopharyngeal cancers, and well-differentiated carcinoma. In vitro, low ALDH2 levels showed reduced response to 5-fluorouracil in HNSC-derived cell lines. Conclusion: Our analyses revealed the genetic and cellular targets and drug response of ALDH2 in HNSC. We also found ALDH2 is involved in regulating the immune response of the tumor microenvironment, and high levels of ALDH2 in bulk HNSC may enhance antitumor immunity, which could improve prognosis. These findings suggest that ALDH2 could be a potential biomarker in improving risk stratification and tailoring treatment strategies in HNSC patients, especially in the HPV-unrelated subgroup.

Ethylene Glycol-Manipulated Syntheses of Calcium Carbonate Particles and DNA Capsules toward Efficient ATP-Responsive Cargo Release.

Cargo molecule-encapsulated DNA capsules synthesized with a solid sacrificial template have elicited significant interest in the last decade and have been used for active materials in applications ranging from biosensors to drug delivery. However, the correlation between template properties and the subsequent assembly and triggered release behavior of the resultant carriers remain uninvestigated. In this study, ethylene glycol (EG) was added during the CaCO3 precipitation synthesis to yield particles of various sizes and surface properties, and the adenosine triphosphate (ATP)-responsive release characteristics of the fabricated DNA capsules affected by these particle properties were investigated. The geometry, crystallization, and surface morphology of the CaCO3 particles co-precipitated at various EG concentrations were characterized. We discuss the integrity of cross-linking hybridization, fluorescent molecule internalization, degree of leakage, and release efficiency of the resulting DNA capsules and their relevance brought by particle properties. To achieve efficient encapsulation and cargo release, the surface roughness of the CaCO3 particles was explored and was deemed a key determinant of the compactness of the DNA shell after template removal. This effect was particularly strong in CaCO3 particles in connection with high EG concentrations. The DNA capsules fabricated using 83% EG exhibited low leakage, high loading, and moderate release efficiencies as well as a greater apparent association constant with ATP due to their small particle size and the high-integrity DNA shells.

Dual trigger improves the pregnancy rate in fresh in vitro fertilization (IVF) cycles compared with the human chorionic gonadotropin (hCG) trigger: a systematic review and meta-analysis of randomized trials.

PROPOSE: The purpose of this study was to assess whether the implementation of a "dual trigger" approach, utilizing gonadotropin-releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG) in the GnRH antagonist protocol for in vitro fertilization (IVF), leads to improved pregnancy outcomes compared to the conventional hCG trigger alone. Previous meta-analyses have not provided sufficient evidence to support the superiority of the dual trigger over the hCG trigger in fresh or frozen embryo transfer cycles. Thus, a systematic review and meta-analysis of randomized trials were conducted to provide a comprehensive evaluation of the impact of the dual trigger on pregnancy outcomes in fresh or frozen embryo transfer cycles. METHOD: A systematic review and meta-analysis of randomised controlled trials (RCTs) were conducted. We searched the Medline and Embase databases for articles up to 2023 by using search terms: "dual trigger," "GnRHa," "hCG," "IVF." Eligible RCTs comparing the dual trigger with the hCG trigger were included. The primary outcome was the live birth rate (LBR) per cycle. The secondary outcomes were the number of oocytes retrieved, number of mature oocytes retrieved, implantation rate, biochemical pregnancy rate, CPR, miscarriage rate and ovarian hyperstimulation syndrome (OHSS) rate per started cycle We compared the oocyte maturation and pregnancy outcomes in the dual trigger and hCG trigger groups. In patients undergoing fresh embryo transfer (ET) and frozen-thawed ET, we also conducted a subgroup analysis to evaluate whether dual trigger improves the clinical pregnancy rate (CPR). RESULTS: We included 10 randomised studies, with 825 participants in the dual trigger group and 813 in the hCG trigger group. Compared with the hCG trigger, dual trigger was associated with a significant increase in the LBR per cycle (odds ratio (OR) = 1.61[1.16, 2.25]), number of oocytes retrieved (mean difference [MD] = 1.05 [0.43, 1.68]), number of mature oocytes retrieved (MD = 0.82 [0. 84, 1.16]), and CPR (OR = 1.48 [1.08, 2.01]). Subgroup analyses revealed that dual trigger was associated with a significantly increased CPR in patients who received fresh ET (OR = 1.68 [1.14, 2.48]). By contrast, the dual trigger was not associated with an increased CPR in the patient group with frozen-thawed ET (OR = 1.15 [0.64, 2.08]). CONCLUSION: The dual trigger was associated with a significantly higher number of retrieved oocytes, number of mature oocytes, CPR, and LBR in IVF than the hCG trigger. The beneficial effect for fresh ET cycles compared with frozen-thawed ET might be associated with increased endometrial receptivity. RELEVANCE: After dual trigger, delaying ET due to the concern of endometrial receptivity might not be needed.