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Ting-Yu Hsu,1 Chi-Yung Cheng,1,2,* I-Min Chiu,1,2 Chun-Hung Richard Lin,2 Fu-Jen Cheng,1 Hsiu-Yung Pan,1 Yu-Jih Su,3 Chao-Jui Li1,* 1Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan; 3Department of Internal Medicine, Division of Rheumatology, Allergy and Immunology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan*These authors contributed equally to this workCorrespondence: Chi-Yung Cheng; Chao-Jui Li, Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 833, Taiwan, Tel +886-7-7317123 ext. 8415, Email qzsecawsxd@gmail.com; chaojui@cgmh.org.twBackground: The global aging population presents a significant challenge, with older adults experiencing declining physical and cognitive abilities and increased vulnerability to chronic diseases and adverse health outcomes. This study aims to develop an interpretable deep learning (DL) model to predict adverse events in geriatric patients within 72 hours of hospitalization.Methods: The study used retrospective data (2017– 2020) from a major medical center in Taiwan. It included non-trauma geriatric patients who visited the emergency department and were admitted to the general ward. Data preprocessing involved collecting prognostic factors like vital signs, lab results, medical history, and clinical management. A deep feedforward neural network was developed, and performance was evaluated using accuracy, sensitivity, specificity, positive predictive value (PPV), and area under the receiver operating characteristic curve (AUC). Model interpretation utilized the Shapley Additive Explanation (SHAP) technique.Results: The analysis included 127,268 patients, with 2.6% experiencing imminent intensive care unit transfer, respiratory failure, or death during hospitalization. The DL model achieved AUCs of 0.86 and 0.84 in the validation and test sets, respectively, outperforming the Sequential Organ Failure Assessment (SOFA) score. Sensitivity and specificity values ranged from 0.79 to 0.81. The SHAP technique provided insights into feature importance and interactions.Conclusion: The developed DL model demonstrated high accuracy in predicting serious adverse events in geriatric patients within 72 hours of hospitalization. It outperformed the SOFA score and provided valuable insights into the model’s decision-making process. Keywords: explainable machine learning, deep learning algorithm, adverse events, mortality

Mindy Ming-Huey Guo,1 Liang-Jen Wang,2 Te-Yao Hsu,3 Kuender D Yang,4,5 Ho-Chang Kuo1 1Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung City, Taiwan; 2Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung City, Taiwan; 3Department of Obstetrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung City, Taiwan; 4Department of Pediatrics and Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan; 5Institute of Biomedical Sciences, Mackay Medical School, Taipei, TaiwanCorrespondence: Kuender D YangDepartment of Pediatrics and Department of Medical Research, MacKay Memorial Hospital, Taipei No. 92, Sec. 2, Zhongshan North. Road, Zhongshan District, Taipei City, TaiwanEmail yangkd.yeh@gmail.comHo-Chang KuoDepartment of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital, 123 Da-Pei Road, Niaosong District, Kaohsiung 83301, TaiwanTel +886 7 731-7123 ext. 8795Fax +886 7 733-8009Email erickuo48@yahoo.com.twObjective: Although childhood allergic diseases have been found to be associated with symptoms of attention-deficit hyperactivity disorder, the temporal relationship between these diseases remains unclear. In this study of 97 children, clinical examination and blood samples for total and specific IgE were collected at 6 and 12 years old.Patients and Methods: We followed a total of 97 children from 6 to 12 years old. Clinical examination and blood samples for total and specific IgE were collected at 6 and 12 years old. Attention-deficit hyperactivity disorder and oppositional defiant disorder symptoms at 12 years old were evaluated using the Swanson, Nolan, and Pelham, Version IV Scale Parent Form.Results: After accounting for the affect of confounding variables, we found that allergic rhinitis at 6 years old was associated with higher inattention score at 12 years old (β-coefficient 0.356, 95% CI 0.104– 0.609, p = 0.006). In addition, higher specific IgE levels for peanuts at 6 years of age were correlated with higher hyperactivity/impulsivity scores (β-coefficient 0.088, 95% CI 0.049– 0.126, p < 0.001), and higher specific IgE for peanuts at 12 years of age were correlated with higher opposition/defiance scores (β-coefficient 0.054, 95% CI 0.012– 0.096, p = 0.012) at 12 years old in our final linear regression models.Conclusion: Allergic rhinitis and peanut sensitization in childhood may be associated with more symptoms of attention-deficit hyperactivity and oppositional defiant disorder in adolescence.Keywords: allergic disease, attention deficit hyperactivity disorder, oppositional defiant disorder

We report on the development of a new microelectronic mechanical system (MEMS)-based quartz resonator technology that allows for the processing and integration of VHF to UHF high-Q oscillators and filters with high-speed silicon or III-V electronics. This paper describes the first demonstration of prototype oscillators and filters using this newly developed technology. We present impedance, Q, and temperature sensitivity data of UHF resonators along with phase noise and Allan deviation measurements. Our first 2-pole filter data showing low insertion loss are also presented. Finally, the results of power handling measurements are described for applications where high levels of background signals are present. © 2005 IEEE.

Rumination is a common symptom in major depressive disorder (MDD). Previous work has connected individual differences in rumination to structural properties in various brain regions. Some of these, such as the dorsolateral prefrontal cortex (dlPFC), have also been highlighted as being altered in MDD, suggesting a connection between structural changes and ruminative symptoms. Although informative, such localised relations have limitations in the context of a network view of the brain. To further investigate rumination-related structural changes in depression, and to situate these within potential functional networks, we acquired T1-weighted structural MRI data from patients with MDD (n = 32) and controls (n = 69). Rumination was measured with the Rumination Response Scale. Surface-based, whole-brain analysis of cortical grey-matter identified group differences in the dlPFC that were, however, not related to rumination. Instead, rumination was correlated with grey-matter properties in the right precuneus. Using normative functional connectivity analysis on an independent sample (n = 100), we show these two regions to be interconnected. Further developing a network-based perspective, it was shown that the rumination-related precuneus region is connected with networks associated with processes such as executive function, autobiographical memory, and visual perception. Notably, these processes have been connected to rumination. These results suggest that rumination in depression may be linked to focal structural changes. The effects of these focal changes on rumination may then be connected to their influence on distributed functional networks., Competing Interests: Declaration of competing interest The authors have no interests to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: The overall prevalence of placenta accreta spectrum (PAS) is approximately 0.17 %, but it accounts for 7 % of maternal mortality and is associated with intraoperative and postoperative morbidity. The pathogenesis mechanisms of PAS include an imbalance between decidualization and trophoblast invasion. The aim of this study is to identify the pathogenesis roles of miR-34a in PAS., Methods: For this purpose, we collected 15 placenta tissues from pregnant subjects with PAS complications and another 15 placenta tissues from normal pregnancy (NP) cases. Then, we conducted in situ hybridization assay to compare miR-34a expression level, followed by in vitro simulations of NP and PAS with miR-34a and scrambled control (SC) mimic transfection in cells, respectively. Next, we conducted in vitro cellular assays to investigate the pathogenesis mechanisms of miR-34a in PAS., Results: We first confirmed significantly lower level of miR-34a in the trophoblast villous (TV) from PAS patients. By in vitro assays, lower miR-34a led to significantly higher cell proliferation and enhanced cell migration in TV epithelial cells. In addition, lower miR-34a resulted in elevated angiogenesis ability in vascular endothelial cells. Finally, to identify the pathway involved by miR-34a in PAS, we used microarray (raw data available via NCBI GEO database with accession number GSE279257) and flow cytometry to confirm that lower miR-34a significantly repressed the apoptosis activity in TV epithelial cells., Discussion: In this study, we not only confirmed miR-34a as a biomarker of PAS but also clarified the in vitro pathogenesis mechanism of miR-34a in PAS., Competing Interests: Declaration of Competing interest The authors declare no commercial or financial conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the residual placental volume and correlated factors using three-dimensional ultrasound (3D) in patients with placenta accreta spectrum (PAS) after conservative management., Materials and Methods: From January 2005 to December 2023, we retrospectively reviewed patients with PAS who underwent prophylactic transcatheter arterial embolization and retained the placenta in situ. The residual placental volume was assessed using 3D ultrasound equipped with virtual organ computer-aided analysis. We determined the resorption rate of the residual placenta (RRRP) and analyzed correlated factors., Results: Eighteen patients with PAS were included. The mean RRRP was 152.64 ± 147.97 cm 3 /month. The median natural resorption time was 5.5 months. According to Spearman's correlation, only the initial placental volume was significantly associated with RRRP (p = 0.001, correlation coefficient = 0.701). Initial placental volume was not associated with postpartum hemorrhage, postpartum infection, resume of menstruation, subsequent pregnancy, or mean white blood cell count., Conclusion: 3D ultrasound is useful for measuring the volume of residual placenta. A larger initial placental volume was associated with a higher RRRP., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Literature demonstrates the detrimental impact of discrimination and microaggressions at personal and institutional levels in the health care workplace. Residents in our program requested curricula to help with addressing manifestations of bias. In response, we designed and implemented an adaptable and reproducible 4-hour virtual simulation session aimed at helping residents identify and constructively respond to microaggressions., Methods: This curriculum, influenced by a preceding needs assessment, was delivered to 68 senior internal medicine residents. It began with a didactic overview to establish foundational knowledge of bias. This was followed by a workshop focused on strategies to address microaggressions. The session culminated with skills practice in a virtual simulation activity where learners addressed microaggressions as bystanders in realistic case scenarios employing simulated participants. We administered pre- and postevaluation individual key-linked surveys assessing learner confidence in responding to microaggressions., Results: A total of 68 residents participated in the curriculum over two academic years, 27 of whom provided complete data for analysis. Overall, there was a statistically significant increase in learner confidence identifying microaggressions. As both a bystander and target/recipient of microaggressions, there were statistically significant increases in learner confidence addressing gender-based microaggressions, race-based microaggressions, and microaggressions reflecting other types of bias. Furthermore, there were statistically significant increases in learner confidence addressing microaggressions in low-acuity contexts, high-acuity contexts, across interprofessional disciplines, with a supervisor, and with a supervisee., Discussion: Our virtual experiential curriculum on responding to microaggressions can help increase learner confidence in addressing microaggressions., (© 2024 Govindraj et al.)

Research Question: What differences exist in the phenotypes of pre-eclampsia, perinatal outcomes and neonatal echocardiography between pregnancies conceived naturally and through IVF?, Design: Six hundred and ten women diagnosed with pre-eclampsia between January 2002 and December 2022 were included in this study. This research was conducted within the IVF and Maternal-Fetal Medicine Department of Kaohsiung Chang Gung Memorial Hospital, Taiwan. Participants were divided into two groups: those who achieved pregnancy through IVF, and those who conceived naturally. The phenotypes of pre-eclampsia and perinatal outcomes were assessed using a propensity-matched sample (n = 218), along with neonatal echocardiography., Results: After conducting propensity score matching, the natural conception group had a higher prevalence of early-onset pre-eclampsia (53.9% versus 37.7%, P = 0.04) and exhibited more severe features of pre-eclampsia (89.1% versus 69.8%, P = 0.01) compared with the IVF group. Regarding perinatal outcomes, neonates in the IVF group had higher placental weights compared with the natural conception group (580 versus 480 g, P = 0.031). The prevalence of abnormal findings on neonatal echocardiography was similar between the groups. Multivariate analysis showed that greater gestational age at delivery reduced the likelihood of abnormal findings on echocardiography [adjusted risk ratio (aRR) 0.950, P = 0.001], while pregestational diabetes mellitus increased the likelihood of abnormal findings (aRR 1.451, P = 0.044). Septal defects were the most common type of defect, occurring in 16.1% of infants., Conclusion: The impact of IVF conception on the severity of pre-eclampsia is not as expected. Neonatal echocardiography revealed a higher prevalence of abnormalities in offspring of women with pre-eclampsia compared with the general population. However, these issues were not linked to the method of conception, suggesting the existence of undisclosed factors that could influence the clinical features and perinatal outcomes of pre-eclampsia., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

We hypothesized and investigated whether prenatal exposure to preeclampsia (PE) would simultaneously affect perinatal cardiovascular features and angiotensin system expressions. This prospective study was composed of mother-neonate dyads with (n = 49) and without maternal preeclampsia (n = 48) in a single tertiary medical center. The neonates exposed to PE had significantly larger relative sizes for the left and right coronary arteries and a higher cord plasma level of aminopeptidase-N, which positively correlated with the maternal diastolic blood pressures and determined the relative sizes of the left and right coronary arteries, whereas the encoding aminopeptidase-N ( ANPEP ) mRNA level in the PE cord blood leukocytes was significantly decreased, positively correlated with the neonatal systolic blood pressures (SBPs), and negatively correlated with the cord plasma-induced endothelial vascular cell adhesion molecule-1 mRNA levels. The PE cord plasma significantly induced higher endothelial mRNA levels of angiotensin II type 1 receptor ( AT1R) and AT4R, whereas in the umbilical arteries, the protein expressions of AT2R and AT4R were significantly decreased in the PE group. The endothelial AT1R mRNA level positively determined the maternal SBPs, and the AT4R mRNA level positively determined the neonatal chamber size and cardiac output. In conclusion, PE may influence perinatal angiotensin system and cardiovascular manifestations of neonates across placentae. Intriguing correlations between these two warrant further mechanistic investigation.

Because the mechanotransduction by stromal stiffness stimulates the rupture and repair of the nuclear envelope in pancreatic progenitor cells, accumulated genomic aberrations are under selection in the tumor microenvironment. Analysis of cell growth, micronuclei, and phosphorylated Ser-139 residue of the histone variant H2AX (γH2AX) foci linked to mechanotransduction pressure in vivo during serial orthotopic passages of mouse Kras LSL-G12D/+ ;Trp53 flox/flox ;Pdx1-Cre (KPC) cancer cells in the tumor and in migrating through the size-restricted 3-μm micropores. To search for pancreatic cancer cell-of-origin, analysis of single-cell data sets revealed that the extracellular matrix shaped an alternate route of acinar-ductal transdifferentiation of acinar cells into topoisomerase II α (TOP2A)-overexpressing cancer cells and derived subclusters with copy number amplifications in MYC-PTK2 (protein tyrosine kinase 2) locus and PIK3CA. High-PTK2 expression is associated with 171 differentially methylated CpG loci, 319 differentially expressed genes, and poor overall survival in The Cancer Genome Atlas-Pancreatic Adenocarcinoma cohort. Abolished RGD-integrin signaling by disintegrin KG blocked the PTK2 phosphorylation, increased cancer apoptosis, decreased vav guanine nucleotide exchange factor 1 (VAV1) expression, and prolonged overall survival in the KPC mice. Reduction of α-smooth muscle actin deposition in the CD248 knockout KPC mice remodeled the tissue stroma and down-regulated TOP2A expression in the epithelium. In summary, stromal stiffness induced the onset of cancer cells-of-origin by ectopic TOP2A expression, and the genomic amplification of MYC-PTK2 locus via alternative transdifferentiation of pancreatic progenitor cells is the vulnerability useful for disintegrin KG treatment., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

The aerodynamic sizes of bioaerosols may significantly affect their behaviors, respiratory deposition and biodiversity. The respirable bacterial size, biodiversity, and human-associated bacteria (HAB) related bioaerosols were evaluated at three kindergartens in Taiwan. Kindergartens A, B, and C were in urban, semi-urban, and rural areas, respectively. A six-stage viable Andersen cascade impactor was used to collect bioaerosols and to determine their size distributions. The geometric mean diameter (GMD), geometric standard deviation (GSD), heat maps, and uniformity were used to evaluate the association of bacteria characteristics. A BD Phoenix-100 automated interpretation system was used to identify the airborne bacteria species. The results revealed that 1425 colonies of the sampled airborne bacteria contained 63 species in 29 genera, and overall, 63.0% were HABs. The most abundant phylum was Actinobacteria (56.6 ± 22.2%) and Firmicutes (31.6 ± 22.3%), and from the taxonomic analysis, both airborne Micrococcus and the Staphylococcus aureus are the dominant genus. All the bacteria aerodynamic particle size distributions were polydisperse distributions. The heat map and uniformity analysis had revealed most of the sampled bioaerosols distributed between 1.1-3.3 μm, and most of the polydisperse airborne Streptococcus spp. had a size in the respirable range, due to urbanization, they have potentially contributed to respiratory risk in the kindergartens. The Shannon diversity index (H) and inverse Simpson diversity index (D) of the bioaerosols in urban kindergarten were negatively correlated with GMD and GSD. The Pearson correlations revealed that the kindergarten in the rural area, with a higher temperature, a lower relative humidity, and a lower CO 2 concentration than the others, tended to have the largest H and D values (P < 0.05). Multiple and stepwise regression revealed that bioaerosol aerodynamic size was statistically significantly correlated with H (P = 0.001) and D values (P = 0.002). This study sheds light on the characteristics of bioaerosols and their associations with microbiome., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ischemic stroke is a leading cause of mortality and disability. The relationships of heart rate variability (HRV) and stroke-related factors with mortality and functional outcome are complex and not fully understood. Understanding these relationships is crucial for providing better insights regarding ischemic stroke prognosis. The objective of this study is to examine the relationship between HRV, neurological function, and clinical factors with mortality and 3-month behavioral functional outcome in ischemic stroke. We prospectively collected the HRV data and monitored the behavioral functional outcome of patients with ischemic stroke. The behavioral functional outcome was represented by a modified Rankin Scale (mRS) score. This study population consisted of 58 ischemic stroke patients (56.9% male; mean age 70) with favorable (mRS score ≤ 2) and unfavorable (mRS score ≥ 3) outcome. The analysis indicated that the median of the mean RR interval (RR mean) showed no statistical difference between mortality groups. Conversely, the median of the RR mean had significant association with unfavorable outcome (OR = 0.989, p = 0.007). Lower hemoglobin levels had significant association with unfavorable outcome (OR = 0.411, p = 0.010). Higher National Institute of Health Stroke Scale (NIHSS) score at admission had significant association with unfavorable outcome (OR = 1.396, p = 0.002). In contrast, age, stroke history, NIHSS score at admission, and hemoglobin showed no significant association with mortality in ischemic stroke. These results imply that HRV, as indicated by the median of RR mean, alongside specific clinical factors and neurological function at admission (measured by NIHSS score), may serve as potential prognostic indicators for 3-month behavioral functional outcome in ischemic stroke.

Atmospheric rivers (ARs), responsible for extreme weather conditions, are mid-latitude systems that can cause significant damage to coastal areas. While forecasting ARs beyond two weeks remains a challenge, past research suggests potential benefits may come from properly accounting for the changes in sea surface temperature (SST) through air-sea interactions. In this paper, we investigate the impact of ARs on SST over the North Pacific by analyzing 25 years of ocean reanalysis data using an SST budget equation. We show that in the region of strong ocean modification, ocean dynamics can offset over 100% of the anomalous SST warming that would otherwise arise from atmospheric forcing. Among all ocean processes, ageostrophic advection and vertical mixing (diffusion and entrainment) are the most important factors in modifying the SST tendency response. The SST tendency response to ARs varies spatially. For example, in coastal California, the driver of enhanced SST warming is the reduction in ageostrophic advection due to anomalous southerly winds. Moreover, there is a large region where the SST shows a warming response to ARs due to the overall reduction in the total clouds and subsequent increase in total incoming shortwave radiation., (© 2024. The Author(s).)

The integration of a silicon (Si) anode into lithium-ion batteries (LIBs) holds great promise for energy storage, but challenges arise from unstable electrochemical reactions and volume changes during cycling. This study investigates the influence of reduced graphene oxide (rGO) size on the performance of rGO-protected Si composite (Si@rGO) anodes. Two sizes of graphene oxide (GO(L) and GO(S)) are used to synthesize Si@rGO composites with a core-shell structure by spray drying and thermal reduction. Electrochemical evaluations show the advantages of the Si@rGO(S) anode with improved cycle life and cycling efficiency over Si@rGO(L) and pure Si. The Si@rGO(S) anode facilitates the formation of a stable LiF-rich solid electrolyte interface (SEI) after cycling, ensuring enhanced capacity retention and swelling control. Rate capability tests also demonstrate the superior high-power performance of Si@rGO(S) with low and stable resistances in Si@rGO(S) over extended cycles. This study provides critical insights into the tailoring of graphene-protected Si composites, highlighting the critical role of rGO size in shaping structural and electrochemical properties. The Si material wrapped by graphene with an optimal lateral size of graphene emerges as a promising candidate for high-performance LIB anodes, thereby advancing electrochemical energy storage technologies.

The relationship between exposure to air pollutants and fetal growth outcomes has shown inconsistency, and only a limited number of studies have explored the impact of air pollution on gestational hypertension and birth outcomes. This study aimed to evaluate how maternal exposure to air pollutants and blood pressure could influence fetal birth outcomes. A total of 55 women with gestational hypertension and 131 healthy pregnant women were enrolled in this study. Data pertaining to personal characteristics, prenatal examinations, outdoor air pollutant exposure, and fetal birth outcomes were collected. The study revealed that fetal birth weight and abdominal circumference exhibited a significant reduction among women with gestational hypertension compared to healthy pregnant women, even after adjustments for body mass index, gestational age, and exposure to air pollutants had been made. Moreover, maternal exposure to outdoor air pollutants displayed a notable correlation with decreased birth length of fetuses. Consequently, the study concluded that maternal blood pressure and exposure to outdoor air pollutants during pregnancy potentially stand as pivotal factors influencing fetal birth outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Oranges contain many natural active chemicals, organic acids, and polysaccharides. Aging processing is commonly used to modify the color, quality, functional components, and stability of fruits. This study assesses the preparation of aging black oranges using various pre-treatments and solid fermentation. Oranges were aged for six weeks in fresh, non-blanching, blanching, and hot air-assisted aging cycle (AA) groups. The oranges' shrinkage ratio, color difference values, and soluble solids content changed significantly ( p < 0.05). Principal component analysis indicated that aging fermentation treatment accelerated glycolysis and increased the ratio of reducing sugars. The enhanced browning can be associated with the oxidation of ascorbic acid (0.66-0.47 mg/g) and the formation of 5-hydroxymethylfurfural (5-HMF) (0.09 mg/g). Furthermore, the presence of free polyphenols led to an increase in the total polyphenol and total flavonoid content. It also had a synergistic effect with 5-HMF in increasing the 2,2-diphenyl-1-picrylhydrazyl free radical-scavenging capacity and ferric ion-reducing antioxidant power ( p < 0.05). AA had superior α-glucosidase inhibitory ability increasing from 67.31 to 80.48%. It also reduced the development time by 33%. Therefore, aging technology can enhance the bioactive compounds in oranges and provide a reference for future whole-fruit aging fermentation and health product creation.

There has been a significant increase in robot-assisted dental procedures in the past decade, particularly in the area of robot-assisted implant placement. The objective of this case report was to assess the initial use of the Yomi Robot's assistance and haptic guidance during endodontic microsurgery. The robot was used during the osteotomy and root-end resection of the first and second upper left premolars. The report aims to inform clinicians of the initial implementation of this cutting-edge technology in endodontics and its potential to enhance endodontic microsurgery. The Yomi Robot was used in performing osteotomy and root-end resection during apical surgery in a patient presenting with symptomatic upper left first and second premolars. The treatment procedure was decided after clinical examination, chart data, and radiographic examinations, which showed periapical lesions on both premolars, taking into consideration the failed endodontic retreatment on the first premolar, the post and ceramic coronal restorations on both teeth, and the desire of the patient to save them. The Yomi Robot system provides auditory, visual, and physical guidance to clinicians during surgery while using a cone-beam computed tomography scan for precision planning with greater accuracy and minimized potential for human error. Further studies are needed to prepare a protocol for robotic-guided procedures in endodontics., (Copyright © 2024 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Background: Ritodrine hydrochloride is a widely used beta-adrenergic agonist used to stop preterm labor in Taiwan. Many side effects causing maternal morbidity and mortality have been reported. We report a case complicated with ritodrine-induced side effects and mirror syndrome that was associated with placental chorioangioma., Case Presentation: A 36-year-old singleton pregnant woman at 25 6/7 weeks of gestation, with an undiagnosed placental chorioangioma, underwent tocolysis due to preterm uterine contractions. Her clinical condition deteriorated, attributed to mirror syndrome and adverse events induced by ritodrine. An emergency cesarean section was performed at 27 1/7 weeks of gestation, delivering an infant with generalized subcutaneous edema. A placental tumor measuring 8.5 cm was discovered during the operation, and pathology confirmed chorioangioma. Gradual improvement in her symptoms and laboratory data was observed during the postpartum period. Identifying mirror syndrome and ritodrine-induced side effects poses challenges. Therefore, this case is educational and warrants discussion., Conclusion: Our case demonstrates mirror syndrome induced by chorioangioma, which is rare, and ritodrine-induced side effects. The cessation of intravenous ritodrine and delivery are the best methods to treat maternal critical status due to fluid overload., (© 2024. The Author(s).)

A 36-year-old woman, gravida 3, para 1 (previous cesarean section), with one medical abortion, and no history of systemic diseases presented an unremarkable medical history during prenatal visits. The final prenatal ultrasound at 38 weeks of gestation showed a vertex presentation, a weight of 2600 g, a normal amniotic fluid level, and the placenta located on the posterior wall of the uterus. Fetal cardiotocography conducted before delivery reported a reactive heart rate without decelerations. The Doppler wave analysis of the fetal umbilical artery was normal (the ratio of peak-systolic flow velocity to the end-diastolic flow velocity was 2.5) without the absence or reversal of end-diastolic velocity. The total score of the fetal biophysical profile by ultrasound was 8. The night before the scheduled cesarean section, she experienced heightened anxiety and was unable to sleep, noting "crazy" fetal movements throughout the night. During the cesarean section, it was discovered that the umbilical cord was wrapped around the newborn's legs, resembling ankle shackles. The fetal weight was 2740 g, and Apgar scores were 9 at the first minute and 10 at the fifth minute. The motility of the neonatal legs was normal without cyanosis or neurological adverse outcomes.

Lanthanum (La) and cerium (Ce), rare earth elements with physical properties similar to calcium (Ca), are generally considered non-toxic when used appropriately. However, their ions possess anti-tumor capabilities. This investigation explores the potential applications and mechanisms of LaCl 3 or CeCl 3 treatment in triple-negative breast cancer (TNBC) cell lines. TNBC, characterized by the absence of estrogen receptor (ERα), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression, is prone to early metastasis and resistant to hormone therapy. Our results demonstrate that La/Ce treatment reduces cell growth, and when combined with cisplatin, it synergistically inhibits cell growth and the PI3K/AKT pathway. La and Ce induce oxidative stress by disrupting mitochondrial function, leading to protein oxidation. Additionally, they interfere with protein homeostasis and induce nucleolar stress. Furthermore, disturbance in F-actin web formation impairs cell migration. This study delves into the mechanism by which calcium-like elements La and Ce inhibit breast cancer cell growth, shedding light on their interference in mitochondrial function, protein homeostasis, and cytoskeleton assembly., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The aim of the study is to assess the effectiveness of transcranial direct current stimulation in knee osteoarthritis., Methods: The study searched PubMed, Cochrane Library, Embase, and Scopus databases until August 3, 2023, and identified randomized controlled trials evaluating the effects of transcranial direct current stimulation in knee osteoarthritis whose outcomes using pain scores or functional scales. The selected randomized controlled trials were subjected to meta-analysis and risk of bias assessment., Results: Seven randomized controlled trials involving 488 patients were included in this meta-analysis. Compared with the control group, the transcranial direct current stimulation group exhibited significant improvement in pain scores after treatment (standardized mean difference = 1.03; 95% confidence interval: 0.70 to 1.35; n = 359; I2 = 46%), pain scores during follow-up (standardized mean difference = 0.83; 95% confidence interval: 0.21 to 1.45; n = 358; I2 = 86%), and Western Ontario and McMaster Universities Osteoarthritis scores after treatment (standardized mean difference = 4.76; 95% confidence interval: 0.16 to 9.53; n = 319; I2 = 74 % ), but Western Ontario and McMaster Universities Osteoarthritis scores during follow-up did not differ significantly between the groups (standardized mean difference = 0.06; 95% confidence interval: -0.2 to 0.32; n = 225; I2 = 0%)., Conclusions: Transcranial direct current stimulation is a promising therapy for knee osteoarthritis. Further investigation using large-scale, high-quality randomized controlled trials is necessary for optimal transcranial direct current stimulation approach in knee osteoarthritis., Competing Interests: Author Disclosures: The authors have no conflicts of interest to declare. This article is original and has not been published elsewhere. The authors received no financial support for the authorship and publication of this article. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: To describe and explore the risk factors, clinical presentations, timely diagnostic approaches, and management in patients experiencing unscarred uterine rupture with catastrophic hemorrhage., Methods: We retrospectively analyzed clinical and imaging data from women who encountered postpartum hemorrhage (PPH) and were diagnosed with unscarred uterine rupture within a three-year timeframe (2018-2020). The data were extracted from medical records obtained from a multi-hospital 24-hour emergency PPH transfer system., Results: Six patients were identified as having unscarred uterine rupture after vaginal delivery. All six women were para 2, with four of them undergoing vacuum-assisted delivery. One patient experienced out-of-hospital cardiac arrest (OHCA), while five patients presented with hypovolemic shock. Abdominopelvic ultrasound revealed a boggy lower uterine segment. Initially, five patients underwent transarterial embolization (TAE) of the internal iliac arteries in an attempt to achieve hemostasis, but this approach proved unsuccessful. Abdominopelvic computed tomography (CT) confirmed the diagnosis of ruptured uterus by demonstrating disrupted myometrium and hemoperitoneum. Immediate exploratory laparotomy followed by life-saving hysterectomy was performed in all cases. The median estimated total blood loss was 2725 mL ± 900 mL (ranging from 1600 mL to 7100 mL). Lower segment lacerations were observed in all patients, with more extensive uterine damage noted in those who underwent vacuum extraction. The length of hospital stay varied between 9 and 38 days., Conclusion: Instrument-assisted obstetric delivery is a possible contributing factor to unscarred uterine rupture in our study. In specific cases, the use of abdominopelvic CT prior to initiating transarterial embolization (TAE) offers valuable information to complement ultrasound findings. This comprehensive approach helps in accurately identifying the underlying cause of intractable postpartum hemorrhage (PPH). Immediate conversion to laparotomy is essential to explore the intra-abdominal factors causing PPH that cannot be controlled by TAE. The rational etiologies of uterine rupture must be clarified while generating practical guideline in the future.

Competing Interests: None

Background: Neuroimaging and lesion studies suggested that the dorsolateral prefrontal and posterior parietal cortices mediate visual metacognitive awareness. The causal evidence provided by non-invasive brain stimulation, however, is inconsistent., Objective/hypothesis: Here we revisit a major figure discrimination experiment adding a new Kanizsa figure task trying to resolve whether bilateral continuous theta-burst transcranial magnetic stimulation (cTBS) over these regions affects perceptual metacognition. Specifically, we tested whether subjective visibility ratings and/or metacognitive efficiency are lower when cTBS is applied to these two regions in comparison to an active control region., Methods: A within-subjects design including three sessions spaced by one-week intervals was implemented. In each session, every participant was administered bilateral cTBS to either prefrontal, control or parietal cortices. Two concurrent tasks were performed, a real and an illusory figure task, stabilising objective performance with use of an adaptive staircase procedure., Results: When performing the replicated task, cTBS was found insufficient to disrupt neither visibility ratings nor metacognitive efficiency. However, with use of Kanizsa style illusory figures, cTBS over the dorsolateral prefrontal, but not over the posterior parietal cortex, was observed to significantly diminish metacognitive efficiency., Conclusion(s): Real and illusory figure tasks demonstrated different cTBS effects. A possible explanation is the involvement of the prefrontal cortex in the creation of expectations, which is necessary for efficient metacognition. Failure to replicate previous findings for the real figure task, however, cannot be said to support, conclusively, the notion that these brain regions have a causal role in metacognitive awareness. This inconsistent finding may result from certain limitations of our study, thereby suggesting the need for yet further investigation., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Sleep disturbance and insufficient sleep have been linked to metabolic syndrome, increasing cardiovascular disease and mortality risk. However, few studies investigate the joint effect of sleep and exercise on metabolic syndrome. We hypothesized that regular exercise can mitigate the exacerbation of metabolic syndrome by sleep insufficiency., Objective: The aim of this study was to investigate whether exercise can attenuate or eliminate the relationship between sleep insufficiency and metabolic syndrome., Method: A total of 6,289 adults (mean age = 33.96 years; women: 74.81%) were included in the study, a cross-sectional study conducted based on the results of employee health screening questionnaires and databases from a large healthcare system in central Taiwan. Participants reported sleep insufficiency or not. Self-reported exercise habits were classified into 3 levels: no exercise, exercise <150 min/week, and exercise ≧150 min/week. Multiple logistic regression and sensitivity analyses were conducted to understand the joint associations of sleep patterns and exercise with metabolic syndrome with exposure variables combining sleep duration/disturbances and PA., Results: Compared with the reference group (sufficient sleep), individuals with sleep insufficiency had a higher risk for metabolic syndrome [adjusted odds ratio (AOR) = 1.40, 95% confidence interval (95% CI): 1.01-1.94, p  < 0.05] in females aged 40-64 years, but not in other populations. Sleep insufficiency was not associated with the risk of metabolic syndrome among individuals achieving an exercise level of <150 min/week, and in particular among those achieving ≧150 min/week in all populations in our study., Conclusion: Sleep insufficiency was related to a higher risk of metabolic syndrome in female healthcare staff aged 40-64 years. Being physically active with exercise habits in these individuals, the risk of metabolic syndrome was no longer significant., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Chou, Chiu, Huang, Hsu, Liu, Lin, Huang, Lin and Wu.)

Introduction: Recent developments in artificial intelligence large language models (LLMs), such as ChatGPT, have allowed for the understanding and generation of human-like text. Studies have found LLMs abilities to perform well in various examinations including law, business and medicine. This study aims to evaluate the performance of ChatGPT in the United Kingdom Medical Licensing Assessment (UKMLA)., Methods: Two publicly available UKMLA papers consisting of 200 single-best-answer (SBA) questions were screened. Nine SBAs were omitted as they contained images that were not suitable for input. Each question was assigned a specialty based on the UKMLA content map published by the General Medical Council. A total of 191 SBAs were inputted in ChatGPT-4 through three attempts over the course of 3 weeks (once per week)., Results: ChatGPT scored 74.9% (143/191), 78.0% (149/191) and 75.6% (145/191) on three attempts, respectively. The average of all three attempts was 76.3% (437/573) with a 95% confidence interval of (74.46% and 78.08%). ChatGPT answered 129 SBAs correctly and 32 SBAs incorrectly on all three attempts. On three attempts, ChatGPT performed well in mental health (8/9 SBAs), cancer (11/14 SBAs) and cardiovascular (10/13 SBAs). On three attempts, ChatGPT did not perform well in clinical haematology (3/7 SBAs), endocrine and metabolic (2/5 SBAs) and gastrointestinal including liver (3/10 SBAs). Regarding to response consistency, ChatGPT provided correct answers consistently in 67.5% (129/191) of SBAs but provided incorrect answers consistently in 12.6% (24/191) and inconsistent response in 19.9% (38/191) of SBAs, respectively., Discussion and Conclusion: This study suggests ChatGPT performs well in the UKMLA. There may be a potential correlation between specialty performance. LLMs ability to correctly answer SBAs suggests that it could be utilised as a supplementary learning tool in medical education with appropriate medical educator supervision., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lai, Wu, Hsu and Kan.)

Integration of light and phytohormones is essential for plant growth and development. FAR-RED INSENSITIVE 219 (FIN219)/JASMONATE RESISTANT 1 (JAR1) participates in phytochrome A (phyA)-mediated far-red (FR) light signaling in Arabidopsis and is a jasmonate (JA)-conjugating enzyme for the generation of an active JA-isoleucine. Accumulating evidence indicates that FR and JA signaling integrate with each other. However, the molecular mechanisms underlying their interaction remain largely unknown. Here, the phyA mutant was hypersensitive to JA. The double mutant fin219-2phyA-211 showed a synergistic effect on seedling development under FR light. Further evidence revealed that FIN219 and phyA antagonized with each other in a mutually functional demand to modulate hypocotyl elongation and expression of light- and JA-responsive genes. Moreover, FIN219 interacted with phyA under prolonged FR light, and MeJA could enhance their interaction with CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) in the dark and FR light. FIN219 and phyA interaction occurred mainly in the cytoplasm, and they regulated their mutual subcellular localization under FR light. Surprisingly, the fin219-2 mutant abolished the formation of phyA nuclear bodies under FR light. Overall, these data identified a vital mechanism of phyA-FIN219-COP1 association in response to FR light, and MeJA may allow the photoactivated phyA to trigger photomorphogenic responses., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives . Microstate studies of electroencephalograms (EEGs) on schizophrenia (SCZ) and bipolar disorder (BD) demonstrated categorical differences. The relationship between microstate indices and clinical symptoms in each group, however, remained unclear. Our objective was to examine associations between EEG microstates and the core features of SCZ and BD. Methods . This study examined the resting EEG data of 40 patients with SCZ, 19 patients with BD (12 BD type I and 7 BD type II), and 16 healthy controls. EEG topographic maps were divided into four canonical microstate classes: A, B, C, and D. The Positive and Negative Syndrome Scale (PANSS), Young Mania Rating Scale, Hamilton Depression Rating Scale (HAMD), and Global Assessment of Functioning (GAF) were used to measure clinical symptoms and global functioning. Results . There was a significant inverse correlation between the proportion of time spent in microstate class A and GAF in patients with SCZ but not BD. Furthermore, the occurrence of microstate class A was positively correlated with the Positive Scale scores of the PANSS. Nevertheless, there were no group differences between the microstate classes. Conclusions . The results of this study indicate a negative correlation between microstate class A and global functioning in SCZ but not in BD. The association may be mediated by positive symptoms of SZ. Neural mechanisms underlying this relationship require further investigation.

Preterm birth is a major challenge in pregnancy worldwide. Prematurity is the leading cause of death in infants and may result in severe complications. Nearly half of preterm births are spontaneous, but do not have recognizable causes. This study investigated whether the maternal gut microbiome and associated functional pathways might play a key role in spontaneous preterm birth (sPTB). Two hundred eleven women carrying singleton pregnancies were enrolled in this mother-child cohort study. Fecal samples were freshly collected at 24-28 weeks of gestation before delivery, and the 16S ribosomal RNA gene was sequenced. Microbial diversity and composition, core microbiome, and associated functional pathways were then statistically analyzed. Demographic characteristics were collected using records from the Medical Birth Registry and questionnaires. The result showed that the gut microbiome of mothers with over-weight (BMI ≥ 24) before pregnancy have lower alpha diversity than those with normal BMI before pregnancy. A higher abundance of Actinomyces spp. was filtered out from the Linear discriminant analysis (LDA) effect size (LEfSe), Spearman correlation, and random forest model, and was inversely correlated with gestational age in sPTB. The multivariate regression model showed that the odds ratio of premature delivery was 3.274 [95% confidence interval (CI): 1.349; p = 0.010] in the group with over-weight before pregnancy with a cutoff Hit% > 0.022 for Actinomyces spp. The enrichment of Actinomyces spp. was negatively correlated with glycan biosynthesis and metabolism in sPTB by prediction from the Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) platform. Maternal gut microbiota showing a lower alpha diversity, increased abundance of Actinomyces spp., and dysregulated glycan metabolism may be associated with sPTB risk.

Objectives: Acute cholecystitis is a gallbladder inflammation, and the Tokyo Guidelines 2018 (TG18) can be used to predict its presence and severity with high sensitivity and specificity. However, TG18 grading require the collection of excessive parameters. Monocyte distribution width (MDW) is a parameter used to detect sepsis early. Therefore, we investigated the correlation between MDW and cholecystitis severity., Methods: We conducted a retrospective study of patients with cholecystitis admitted to our hospital from November 1, 2020, to August 31, 2021. The primary outcome was severe cholecystitis analyzed as a composite of intensive care unit (ICU) admission and mortality. The secondary outcomes were length of hospital stay, ICU stay, and TG18 grade., Results: A total of 331 patients with cholecystitis were enrolled in this study. The average MDWs for TG18 grades 1, 2, and 3 were 20.21 ± 3.99, 20.34 ± 3.68, and 25.77 ± 6.61, respectively. For patients with severe cholecystitis, the average MDW was 25.42 ± 6.83. Using the Youden J statistic, we set a cutoff MDW of 21.6. Multivariate logistic regression revealed that patients with an MDW≥21.6 had a higher risk of severe cholecystitis (odds ratio=4.94; 95 % CI, 1.71-14.21; p=0.003). The Cox model revealed that patients with an MDW≥21.6 were more likely to have a prolonged hospital stay., Conclusions: MDW is a reliable indicator of severe cholecystitis and prolonged length of stay. Additional MDW testing and a complete blood count may provide simple information for predicting severe cholecystitis early., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Promoting physical activity (PA) in different populations experiencing sleep disturbance may increase population PA levels and improve sleep. This scoping review aimed to examine the effect of various PA intervention strategies on sleep across different populations, identify key sleep outcomes, and analyze knowledge gaps by mapping the relevant literature., Methods: For this study, we systematically searched articles published till March 2022 from PubMed, Web of Science, Cochrane Library, and Embase databases for randomized clinical trials (RCTs) regarding the effect of physical activity on sleep. Two authors extracted key data and descriptively analyzed the data. Thematic analysis was used to categorize the results into themes by all authors. Arksey and O'Malley's scoping review framework was used to present the findings., Results: Twenty-one randomized controlled trials out of 3052 studies were finally included with 3677 participants (2852 females (78%)). Five trials were conducted in healthy working-age adults with sleep disturbance but without the diagnosis of insomnia, five in healthy older adults, two in perinatal women, four in patients with cancer, three in mental illness related subjects, and another two in other disease-related areas. PA interventions were diverse, including walking, resistance training, aerobic exercise, housework, water exercise, basketball, smartphone/tablet "apps", web, online videos or wearable actigraphy, and self-determined exercise. Three major themes were identified: (1) Sleep environment may be important to address prior to instituting PA interventions, (2) All types of PA were effective for improving sleep in all populations studied, (3) Self-tolerated PA is safe for improving sleep in the elderly and in co-morbid or perinatal populations., Conclusions: PA is effective and safe for improving sleep in both healthy and co-morbid populations with sleep disturbance by increasing daily activity levels using a variety of strategies, even low intensity, such as housekeeping, sit-to-stand repetitions, along with encouraging PA through web pages, videos, and self-goal setting apps. In addition, this scoping review identifies the need for further therapeutic research and future exploration in populations with sleep initiation or sleep maintenance disturbance., (© 2023. The Author(s).)

The droplet epitaxy of indium gallium nitride quantum dots (InGaN QDs), the formation of In-Ga alloy droplets in ultra-high vacuum and then surface nitridation by plasma treatment, is firstly investigated by using plasma-assisted molecular beam epitaxy. During the droplet epitaxy process, in-situ reflection high energy electron diffraction patterns performs the amorphous In-Ga alloy droplets transform to polycrystalline InGaN QDs, which are also confirmed by the characterizations of transmission electron microscopy and X-ray photoelectron spectroscopy. The substrate temperature, In-Ga droplet deposition time, and duration of nitridation are set as parameters to study the growth mechanism of InGaN QDs on Si. Self-assembled InGaN QDs with a density of 1.33 × 10 11  cm -2 and an average size of 13.3 ± 3 nm can be obtained at the growth temperature of 350 °C. The photoluminescence emissions of uncapped InGaN QDs in wavelength of the visible red (715 nm) and infrared region (795 and 857 nm) are observed. The formation of high-indium composition of InGaN QDs via droplet epitaxy technique could be applied in long wavelength optoelectronic devices., (© 2023. The Author(s).)

Background: Colonic diverticulitis is a leading cause of abdominal pain. The monocyte distribution width (MDW) is a novel inflammatory biomarker with prognostic significance for coronavirus disease and pancreatitis; however, no study has assessed its correlation with the severity of colonic diverticulitis., Methods: This single-center retrospective cohort study included patients older than 18 years who presented to the emergency department between November 1, 2020, and May 31, 2021, and received a diagnosis of acute colonic diverticulitis after abdominal computed tomography. The characteristics and laboratory parameters of patients with simple versus complicated diverticulitis were compared. The significance of categorical data was assessed using the chi-square or Fisher's exact test. The Mann-Whitney U test was used for continuous variables. Multivariable regression analysis was performed to identify predictors of complicated colonic diverticulitis. Receiver operator characteristic (ROC) curves were used to test the efficacy of inflammatory biomarkers in distinguishing simple from complicated cases., Results: Of the 160 patients enrolled, 21 (13.125%) had complicated diverticulitis. Although right-sided was more prevalent than left-sided colonic diverticulitis (70% versus 30%), complicated diverticulitis was more common in those with left-sided colonic diverticulitis (61.905%, p = 0.001). Age, white blood cell (WBC) count, neutrophil count, C-reactive protein (CRP) level, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and MDW were significantly higher in the complicated diverticulitis group (p < 0.05). Logistic regression analysis indicated that the left-sided location and the MDW were significant and independent predictors of complicated diverticulitis. The area under the ROC curve (AUC) was as follows: MDW, 0.870 (95% confidence interval [CI], 0.784-0.956); CRP, 0.800 (95% CI, 0.707-0.892); NLR, 0.724 (95% CI, 0.616-0.832); PLR, 0.662 (95% CI, 0.525-0.798); and WBC, 0.679 (95% CI, 0.563-0.795). When the MDW cutoff was 20.38, the sensitivity and specificity were maximized to 90.5% and 80.6%, respectively., Conclusions: A large MDW was a significant and independent predictor of complicated diverticulitis. The optimal cutoff value for MDW is 20.38 as it exhibits maximum sensitivity and specificity for distinguishing between simple and complicated diverticulitis The MDW may aid in planning antibiotic therapy for patients with colonic diverticulitis in the emergency department., (© 2023. The Author(s).)

Neonates who are born preterm (PT) are usually characterized by immature physiological development, and preterm birth (PTB) is the leading cause of neonatal morbidity and mortality if intensive medical care is not available to PTB neonates. Early prediction of a PTB enables medical personnel to make preparations in advance, protecting the neonate from the subsequent health risks. Therefore, many studies have worked on identifying invasive or noninvasive PT biomarkers. In this study, we collected amniocentesis-derived (at the second trimester of gestation) amniotic fluid (AF) samples. At delivery, AF samples were classified into PTB or full-term birth (FTB). We first applied protein mass spectrometry technology to globally screen AF proteins, followed by specific protein validation with ELISA. We identified four protein biomarkers of PTB, including lactotransferrin (LTF), glutathione-disulfide reductase (GSR), myeloperoxidase (MPO) and superoxide dismutase 2 (SOD2). Further analyses demonstrated that their abundances were negatively correlated with neonatal weight and gestational age. In addition, by mimicking survival rate analysis widely used in tumor biology, we found that LTF and SOD2 were prognostic factors of gestational age, with higher levels denoting shorter gestational age. Finally, using the abundances of the four protein biomarkers, we developed a prediction model of PTB with an auROC value of 0.935 (sensitivity = 0.94, specificity = 0.89, p value = 0.0001). This study demonstrated that the abundances of specific proteins in amniotic fluid were not only the prognostic factors of gestational age but also the predictive biomarkers of PTB. These four AF proteins enable identification of PTB early in the second trimester of gestation, facilitating medical intervention to be applied in advance., (© 2023. The Author(s).)

Chronic pruritus is an unpleasant sensory perception that negatively affects quality of life and is common among patients with type 2 diabetes mellitus. Current antipruritic therapies are insufficiently effective. Thus, the mediation of diabetic pruritus by histamine-independent pathways is likely. The aim of this study was to identify possible mediators responsible for diabetic pruritus. A total of 87 patients with type 2 diabetes mellitus were analysed, of whom 59 had pruritus and 28 did not. The 2 groups were assessed for baseline demographics, serum biochemistry parameters, cytokines, and chemokines. This study also investigated the associations of these factors with the severity of itching. Neither haemoglobin A1c nor serum creatinine levels were correlated with severity of itching. Significantly higher levels of interleukin-4 (p = 0.004), interleukin-13 (p = 0.006), granulocyte-macrophage colony-stimulating factor (p < 0.001) and C-X-C motif chemokine ligand 10 (p = 0.028) were observed in the patients with pruritus than in those without pruritus. Moreover, the levels of these mediators were positively correlated with the severity of itching. Thus, novel antipruritic drugs can be developed to target these molecules. This is the first study to compare inflammatory mediators comprehensively in patients with diabetes mellitus with pruritus vs those without pruritus.

Background: Autophagy is a catabolic process that recycles damaged organelles and acts as a pro-survival mechanism, but little is known about autophagy dysfunction and epigenetic regulation in patients with obstructive sleep apnea (OSA)., Methods: Protein/gene expressions and DNA methylation levels of the autophagy-related genes (ATG) were examined in blood leukocytes from 64 patients with treatment-naïve OSA and 24 subjects with primary snoring (PS)., Results: LC3B protein expression of blood monocytes, and ATG5 protein expression of blood neutrophils were decreased in OSA patients versus PS subjects, while p62 protein expression of cytotoxic T cell was increased, particularly in those with nocturia. ATG5, ULK1, and BECN1 gene expressions of peripheral blood mononuclear cells were decreased in OSA patients versus PS subjects. LC3B gene promoter regions were hypermethylated in OSA patients, particularly in those with excessive daytime sleepiness, while ATG5 gene promoter regions were hypermethylated in those with morning headache or memory impairment. LC3B protein expression of blood monocytes and DNA methylation levels of the LC3B gene promoter region were negatively and positively correlated with apnea hyponea index, respectively. In vitro intermittent hypoxia with re-oxygenation exposure to human THP-1/HUVEC cell lines resulted in LC3B/ATG5/ULK1/BECN1 down-regulations and p62 up-regulation along with increased apoptosis and oxidative stress, while rapamycin and umbilical cord-mesenchymal stem cell treatment reversed these abnormalities through de-methylation of the ATG5 gene promoter., Conclusions: Impaired autophagy activity in OSA patients was regulated by aberrant DNA methylation, correlated with clinical phenotypes, and contributed to increased cell apoptosis and oxidative stress. Autophagy enhancers may be novel therapeutics for OSA-related neurocognitive dysfunction., (© 2023. The Author(s).)

Background: Liver cancer is ranked fifth in incidence and second in mortality among cancers in Taiwan. Nevertheless, the Taiwan government does not screen for liver cancer in its free cancer screening and preventive health examination service. This study compared the differences in cancer stage and survival between patients who received an initial liver cancer diagnosis in outpatient departments (OPDs) and those who received such a diagnosis in emergency departments (EDs)., Methods: This retrospective cohort study used the 2000-2016 National Health Insurance Database to obtain a sample from 2 million Taiwanese residents. To evaluate the effect of the utilization of the adult health examination offered to people aged ≥ 40 years, patients aged ≥ 40 years who received an initial liver cancer diagnosis between 2003 and 2015 were followed up until December 31, 2016., Results: In total, 2,881 patients were included in this study. A greater proportion of cancer cases in the OPD group were non-advanced than those in the ED group (75.26% vs. 54.23%). Having stage C or D cancer, having a low monthly salary, and a Charlson comorbidity index score ≥ 8, not having hepatitis B, being divorced, and attending a non-public hospital as the primary care institution were risk factors for initial ED diagnosis. The risk of liver cancer-specific death among the ED group patients was 1.38 times that among the OPD group patients (adjusted hazard ratio = 1.38, 95% confidence interval [CI] = 1.14-1.68, P < 0.001). However, the use of health examination did not exert a significant effect on the likelihood of liver cancer diagnosis in an ED (adjusted odds ratio = 0.86, 95% CI = 0.61-1.21, P = 0.381)., Conclusion: Government-subsidized health examinations are insufficient to prevent first-ever diagnosed liver cancers in EDs. Patients with liver cancers diagnosed in EDs had a higher risk of advanced stage and mortality. For early detection and treatment, the government may consider implementing liver cancer screening for high-risk and low-socioeconomic people., (© 2023. The Author(s).)

No consistent results from past studies have been found on the relationship between the effects of air pollutant exposure, preterm birth (PTB) and low birth weight (LBW) in fetuses. This study aimed to analyze the impact of high concentrations of air pollutants on the health outcomes of fetuses, especially regarding PTB and LBW. This study used keywords related to air pollutants, pregnancy, and birth outcomes, to search the literature within the databases of the Cochrane Library, PubMed, and Embase, which were published as of July 26, 2022. A total of 24 studies were included in this meta-analysis. This meta-analysis revealed that nitrogen dioxide (NO 2 ) exposure throughout pregnancy was associated with an increased risk of PTB. Maternal exposure to PM 2.5 (particulate matter sized less than 2.5 μm) during gestation was associated with the risk of LBW. The findings of this meta-analysis provide an important foundation for evaluating the relationship between exposure of air pollutants and fetal birth outcomes in countries with severe air pollution in the future., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To determine the association between race/ethnicity and COVID-19 outcomes in individuals with systemic lupus erythematosus (SLE)., Methods: Individuals with SLE from the US with data entered into the COVID-19 Global Rheumatology Alliance registry between March 24, 2020 and August 27, 2021 were included. Variables included age, sex, race, and ethnicity (White, Black, Hispanic, other), comorbidities, disease activity, pandemic time period, glucocorticoid dose, antimalarials, and immunosuppressive drug use. The ordinal outcome categories were: not hospitalized, hospitalized with no oxygenation, hospitalized with any ventilation or oxygenation, and death. We constructed ordinal logistic regression models evaluating the relationship between race/ethnicity and COVID-19 severity, adjusting for possible confounders., Results: We included 523 patients; 473 (90.4%) were female and the mean ± SD age was 46.6 ± 14.0 years. A total of 358 patients (74.6%) were not hospitalized; 40 patients (8.3%) were hospitalized without oxygen, 64 patients (13.3%) were hospitalized with any oxygenation, and 18 (3.8%) died. In a multivariable model, Black (odds ratio [OR] 2.73 [95% confidence interval (95% CI) 1.36-5.53]) and Hispanic (OR 2.76 [95% CI 1.34-5.69]) individuals had higher odds of more severe outcomes than White individuals., Conclusion: Black and Hispanic individuals with SLE experienced more severe COVID-19 outcomes, which is consistent with findings in the US general population. These results likely reflect socioeconomic and health disparities and suggest that more aggressive efforts are needed to prevent and treat infection in this population., (© 2022 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: We present mosaic trisomy 21 at amniocentesis in a twin pregnancy associated with a favorable fetal outcome, maternal uniparental disomy (UPD) 21 and postnatal decrease of the trisomy 21 cell line., Case Report: A 36-year-old woman underwent elective amniocentesis at 16 weeks of gestation because of advanced maternal age, and an abnormal non-invasive prenatal testing (NIPT) result suggesting trisomy 21. Amniocentesis revealed the karyotype of 46, XX in co-twin A and the karyotype of 47,XY,+21[12]/46,XY[21] in co-twin B in the cultured amniocytes by in situ culture method. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed the result of arr (21) × 3 [0.40] in co-twin B, consistent with 40% mosaicism for trisomy 21. Prenatal ultrasound was unremarkable, and the parental karyotypes were normal. Following genetic counseling, the parents decided to continue the pregnancy. At 36 weeks of gestation, a 2140-g female co-twin A and a 1800-g male co-twin B were delivered without any phenotypical abnormality. The karyotypes of the umbilical cord and placenta of co-twin B were 47,XY,+21[16]/46,XY[24] and 47,XY,+21 (40/40 cells), respectively. Quantitative fluorescence polymerase chain reaction (QF-PCR) analysis on the DNA extracted from parental bloods and umbilical cord, cord blood and placenta and peripheral blood at age five months of co-twin B confirmed a maternal origin of trisomy 21 and maternal uniparental isodisomy 21. aCGH analysis on the cord blood revealed the result of arr 21q11.2q22.3 × 2.25 consistent with 20%-25% (log 2 ratio = 0.15-0.2) mosaicism for trisomy 21. When follow-up at age five months, the co-twin B was phenotypically normal. His peripheral blood had a karyotype of 47,XY,+21[3]/46,XY[37]. Interphase fluorescence in situ hybridization (FISH) on 100 buccal mucosal cells detected no trisomy 21 signals. The peripheral blood had uniparental isodisomy 21., Conclusion: Mosaic trisomy 21 at amniocentesis can be a transient and benign condition and should alert the possibility of UPD 21. The abnormal trisomy 21 cell line in mosaic trisomy 21 at amniocentesis may decrease and disappear after birth., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023. Published by Elsevier B.V.)