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This study evaluates longitudinal and transversal intramuscular variations in muscle fiber and meat quality characteristics in bovine M. longissimus thoracis et lumborum (LTL). The LTL muscles (n = 5) from the left side of the beef carcass were cut at intervertebral segment intervals (between 1st thoracic vertebra (TV) and 6th lumbar vertebra (LV)). The pennation angle demonstrated an increasing trend from the anterior to posterior regions regardless of the medial (M-zone) and lateral (L-zone) regions (P < 0.05). The M -zone had a higher pennation angle than the L-zone in the TV and 1st LV (P < 0.05). The cross-sectional area (CSA) of muscle fibers, excluding type I, was larger in the posterior region than the anterior region (P < 0.05). A larger CSA of type I/IIA, IIA, IIAX, and IIX was observed on the lateral side than on the medial side of the 13th TV (P < 0.05). Fiber types were more oxidative (types I and IIA) in the anterior region and more glycolytic (types IIA/IIX and IIX) in the posterior region. Fat content was higher in the anterior region than in the posterior region (P < 0.05). The lowest redness, yellowness, and Warner-Bratzler shear force values were observed in the middle of the muscle, whereas the lightness value was lower in the posterior region regardless of the transversal region (P < 0.05). Therefore, bovine LTL muscles exhibit unique morphological properties and contribute to understanding meat quality associated with morphological and muscle fiber characteristics in relation to their intramuscular variations., 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 Ltd. All rights reserved.)

Background: Obesity is a major health concern worldwide. Previous studies have suggested that phthalate plasticizers are obesogens. However, the relationship between early-life phthalate exposure and long-term obesity development remains unknown., Objective: We investigated the association between prenatal phthalate exposure and children's body mass index (BMI) patterns in an 18-year birth cohort follow-up study in Taiwan., Methods: Our analytical lab quantified seven phthalate metabolites in maternal urine during pregnancy using quantitative liquid chromatography-tandem mass spectrometry. In addition, we calculated BMI z scores for participated children at each follow-up, utilized trajectory analysis to describe children's BMI z-score patterns at 2-18 years of age, and adopted generalized estimating equations (GEE) and multivariate logistic regression models to assess the association between prenatal phthalate exposure and BMI z scores in children., Results: A total of 208 mother-child pairs were included in the analysis. Maternal urinary diethyl phthalate (DEP) metabolites were associated with the increase of BMI z scores in children aged 2-18 years in the GEE model. Doubled maternal urinary ∑mDEHP (3 mono hexyl-metabolites of di-ethyl-hexyl phthalate (DEHP) increased the risk of children being in the stable-high BMI trajectory group until the age of eighteen., Impact Statement: We observed that BMI trajectories of children remained stable after the age of 5 years. During each follow-up, a higher frequency of overweight or obese was observed in children, ranging from 15.9% to 35.6% for girls and 15.2-32.0% for boys, respectively. Prenatal phthalate exposure was associated with increasing BMI z scores in children. Prenatal DEHP exposure was associated with a stable-high BMI trajectory in children up to the age of 18 years., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Pig-to-human xenotransplantation is rapidly approaching the clinical arena; however, it is unclear which immunomodulatory regimens will effectively control human immune responses to pig xenografts. Here, we transplant a gene-edited pig kidney into a brain-dead human recipient on pharmacologic immunosuppression and study the human immune response to the xenograft using spatial transcriptomics and single-cell RNA sequencing. Human immune cells are uncommon in the porcine kidney cortex early after xenotransplantation and consist of primarily myeloid cells. Both the porcine resident macrophages and human infiltrating macrophages express genes consistent with an alternatively activated, anti-inflammatory phenotype. No significant infiltration of human B or T cells into the porcine kidney xenograft is detectable. Altogether, these findings provide proof of concept that conventional pharmacologic immunosuppression may be able to restrict infiltration of human immune cells into the xenograft early after compatible pig-to-human kidney xenotransplantation., (© 2024. The Author(s).)

Osteoporosis is a prevalent chronic disease worldwide, particularly affecting the aging population. The gold standard diagnostic tool for osteoporosis is Dual-energy X-ray Absorptiometry (DXA). However, the expensive cost of the DXA machine and the need for skilled professionals to operate it restrict its accessibility to the general public. This paper builds upon previous research and proposes a novel approach for rapidly screening bone density. The method involves utilizing near-infrared light to capture local body information within the human body. Deep learning techniques are employed to analyze the obtained data and extract meaningful insights related to bone density. Our initial prediction, utilizing multi-linear regression, demonstrated a strong correlation (r = 0.98, p-value = 0.003**) with the measured Bone Mineral Density (BMD) obtained from Dual-energy X-ray Absorptiometry (DXA). This indicates a highly significant relationship between the predicted values and the actual BMD measurements. A deep learning-based algorithm is applied to analyze the underlying information further to predict bone density at the wrist, hip, and spine. The prediction of bone densities in the hip and spine holds significant importance due to their status as gold-standard sites for assessing an individual's bone density. Our prediction rate had an error margin below 10% for the wrist and below 20% for the hip and spine bone density., (© 2024 The Authors.)

Objective: To analyze the clinical characteristics of patients with Vibrio vulnificus infection, share diagnosis and treatment experience, and establish a rapid diagnosis procedure for this disease. Methods: This study was a retrospective case series study. From January 2009 to November 2022, 11 patients with Vibrio vulnificus infection who met the inclusion criteria were admitted to the Department of Burns and Wound Repair of Guangdong Provincial People's Hospital Affiliated to Southern Medical University. The gender, age, time of onset of illness, time of admission, time of diagnosis, route of infection, underlying diseases, affected limbs, clinical manifestations and signs on admission, white blood cell count, hemoglobin, platelet count, C-reactive protein (CRP), alanine transaminase (ALT), aspartate transaminase (AST), creatinine, procalcitonin, albumin, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and blood sodium levels on admission, culture results and metagenomic next-generation sequencing (mNGS) results of pathogenic bacteria and the Vibrio vulnificus drug susceptibility test results during hospitalization, treatment methods, length of hospital stay, and outcomes of all patients were recorded. Comparative analysis was conducted on the admission time and diagnosis time of patients with and without a history of exposure to seawater/marine products, as well as the fatality ratio and amputation of limbs/digits ratio of patients with and without early adequate antibiotic treatment. For the survived patients with hand involvement, the hand function was assessed using Brunnstrom staging at the last follow-up. Based on patients' clinical characteristics and treatment conditions, a rapid diagnosis procedure for Vibrio vulnificus infection was established. Results: There were 7 males and 4 females among the patients, aged (56±17) years. Most of the patients developed symptoms in summer and autumn. The admission time was 3.00 (1.00, 4.00) d after the onset of illness, and the diagnosis time was 4.00 (2.00, 8.00) d after the onset of illness. There were 7 and 4 patients with and without a history of contact with seawater/marine products, respectively, and the admission time of these two types of patients was similar ( P >0.05). The diagnosis time of patients with a history of contact with seawater/marine products was 2.00 (2.00, 5.00) d after the onset of illness, which was significantly shorter than 9.00 (4.25, 13.00) d after the onset of illness for patients without a history of contact with seawater/marine products ( Z =-2.01, P <0.05). Totally 10 patients had underlying diseases. The affected limbs were right-hand in 8 cases, left-hand in 1 case, and lower limb in 2 cases. On admission, a total of 9 patients had fever; 11 patients had pain at the infected site, and redness and swelling of the affected limb, and 9 patients each had ecchymosis/necrosis and blisters/blood blisters; 6 patients suffered from shock, and 2 patients developed multiple organ dysfunction syndrome. On admission, there were 8 patients with abnormal white blood cell count, hemoglobin, and albumin levels, 10 patients with abnormal CRP, procalcitonin, and NT-proBNP levels, 5 patients with abnormal creatinine and blood sodium levels, and fewer patients with abnormal platelet count, ALT, and AST levels. During hospitalization, 4 of the 11 wound tissue/exudation samples had positive pathogenic bacterial culture results, and the result reporting time was 5.00 (5.00, 5.00) d; 4 of the 9 blood specimens had positive pathogenic bacterial culture results, and the result reporting time was 3.50 (1.25, 5.00) d; the mNGS results of 7 wound tissue/exudation or blood samples were all positive, and the result reporting time was 1.00 (1.00, 2.00) d. The three strains of Vibrio vulnificus detected were sensitive to 10 commonly used clinical antibiotics, including ciprofloxacin, levofloxacin, and amikacin, etc. A total of 10 patients received surgical treatment, 4 of whom had amputation of limbs/digits; all patients received anti-infection treatment. The length of hospital stay of 11 patients was (26±11) d, of whom 9 patients were cured and 2 patients died. Compared with that of the 6 patients who did not receive early adequate antibiotic treatment, the 5 patients who received early adequate antibiotic treatment had no significant changes in the fatality ratio or amputation of limbs/digits ratio ( P >0.05). In 3 months to 2 years after surgery, the hand function of 8 patients was assessed, with results showing 4 cases of disabled hands, 2 cases of incompletely disabled hands, and 2 cases of recovered hands. When a patient had clinical symptoms of limb redness and swelling and a history of contact with seawater/marine products or a pre-examination triage RiCH score of Vibrio vulnificus sepsis ≥1, the etiological testing should be initiated immediately to quickly diagnose Vibrio vulnificus infection. Conclusions: Vibrio vulnificus infection occurs most frequently in summer and autumn, with clinical manifestations and laboratory test results showing obvious infection characteristics, and may be accompanied by damage to multiple organ functions. Both the fatality and disability ratios are high and have a great impact on the function of the affected limbs. Early diagnosis is difficult and treatment is easily delayed, but mNGS could facilitate rapid detection. For patients with red and swollen limbs accompanied by a history of contact with seawater/marine products or with a pre-examination triage RiCH score of Vibrio vulnificus sepsis ≥1, the etiological testing should be initiated immediately to quickly diagnose Vibrio vulnificus infection.

Background: Newborn anogenital distance (AGD) has been associated with prenatal exposure of phthalates. The association between prenatal phthalate exposure and sex steroid hormones in newborns is unclear., Object: This study aimed to examine whether cord-blood sex hormone levels were associated with prenatal phthalate exposure and newborn anogenital distance (AGD)., Methods: In the Taiwan Maternal and Infant Cohort Study, we recruited 1,676 pregnant women in their third trimester in 2012-2015 in Taiwan. We determined 11 urinary phthalate metabolites in pregnant women, three maternal and five cord-blood steroid sex-hormone concentrations. Five hundred and sixty-five mother-infant pairs with sufficient data were included. Trained neonatologists measured 263 newborns' AGD. We examined the associations of prenatal phthalate metabolite levels with AGD and hormones using linear regression models and evaluated correlations between maternal and cord-blood sex hormone levels and AGD., Results: Compared with the male newborns exposed to maternal phthalate metabolites at the first tertile, AGD was -3.75, -3.43, and -3.53 mm shorter among those exposed at the median tertile of di-2-ethylhexyl phthalate (DEHP) metabolites, monobenzyl phthalate (MBzP), and monomethyl phthalate (MMP), respectively. Compared with those who had exposed at the first tertile, cord-blood follicle-stimulating hormone (FSH) decreased among male newborns exposed at higher levels of MMP, mono-n-butyl phthalate (MnBP), MBzP and DEHP, and among female newborns exposed at higher levels of MMP, MBzP and mono(2-ethyl-5-hydroxyhexyl) phthalate. However, we did not observe significant correlations of maternal or cord-blood sex steroid hormones with newborns' AGDs., Conclusions: Alterations in cord-blood sex steroid hormone levels were associated with prenatal phthalate exposures, particularly in male newborns. Women aspiring to be pregnant should be alerted of the need of reducing phthalate exposure., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lu 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.)

In neurosurgery, accurately identifying brain tumor tissue is vital for reducing recurrence. Current imaging techniques have limitations, prompting the exploration of alternative methods. This study validated a binary hierarchical classification of brain tissues: normal tissue, primary central nervous system lymphoma (PCNSL), high-grade glioma (HGG), and low-grade glioma (LGG) using transfer learning. Tumor specimens were measured with optical coherence tomography (OCT), and a MobileNetV2 pre-trained model was employed for classification. Surgeons could optimize predictions based on experience. The model showed robust classification and promising clinical value. A dynamic t-SNE visualized its performance, offering a new approach to neurosurgical decision-making regarding brain tumors., Competing Interests: The authors declare no conflicts of interest., (© 2024 Optica Publishing Group.)

Patients with mild cognitive impairment (MCI) are at a high risk of developing future dementia. However, early identification and active intervention could potentially reduce its morbidity and the incidence of dementia. Functional near-infrared spectroscopy (fNIRS) has been proposed as a noninvasive modality for detecting oxygenation changes in the time-varying hemodynamics of the prefrontal cortex. This study sought to provide an effective method for detecting patients with MCI using fNIRS and the Wisconsin card sorting test (WCST) to evaluate changes in blood oxygenation. The results revealed that all groups with a lower mini-mental state examination grade had a higher increase in HHb concentration during a modified WCST (MCST). The increase in the change in oxygenated hemoglobin concentration in the stroke group was smaller than that in the normal group due to weak cerebrovascular reactivity., (© 2023 Wiley-VCH GmbH.)

Extracorporeal membrane oxygenation (ECMO) is a vital emergency procedure providing respiratory and circulatory support to critically ill patients, especially those with compromised cardiopulmonary function. Its use has grown due to technological advances and clinical demand. Prolonged ECMO usage can lead to complications, necessitating the timely assessment of peripheral microcirculation for an accurate physiological evaluation. This study utilizes non-invasive near-infrared spectroscopy (NIRS) to monitor knee-level microcirculation in ECMO patients. After processing oxygenation data, machine learning distinguishes high and low disease severity in the veno-venous (VV-ECMO) and veno-arterial (VA-ECMO) groups, with two clinical parameters enhancing the model performance. Both ECMO modes show promise in the clinical severity diagnosis. The research further explores statistical correlations between the oxygenation data and disease severity in diverse physiological conditions, revealing moderate correlations with the acute physiologic and chronic health evaluation (APACHE II) scores in the VV-ECMO and VA-ECMO groups. NIRS holds the potential for assessing patient condition improvements.

Cardinal features of lupus include elevated B cell activation and autoantibody production with a female sex preponderance. We quantified interactions of sex and genetic variation on the development of autoimmune B-cell phenotypes and autoantibodies in the BXD2 murine model of lupus using a cohort of backcrossed progeny (BXD2 x C57BL/6J) x BXD2. Sex was the key factor leading to increased total IgG, IgG2b, and autoantibodies. The percentage of T-bet + CD11c + IgD + activated naive B cells (aNAV) was higher in females and was associated with increased T-bet + CD11c + IgD - age-related B cells, Fas + GL7 + germinal center B cells, Cxcr5 - Icos + peripheral T-helper cells, and Cxcr5 + Icos + follicular T-helper cells. IFN-β was elevated in females. Variation in aNAV cells was mapped to Chr 7 in a locus that shows significant interactions between the female sex and heterozygous B/D variant. Our results suggest that activation of naive B cells forms the basis for the female-predominant development of autoantibodies in lupus-susceptible BXD2 mice., Competing Interests: Declaration of Competing Interest The Authors declare that there is no conflict of interest., (Published by Elsevier Inc.)

The determination of resection extent traditionally relies on the microscopic invasiveness of frozen sections (FSs) and is crucial for surgery of early lung cancer with preoperatively unknown histology. While previous research has shown the value of optical coherence tomography (OCT) for instant lung cancer diagnosis, tumor grading through OCT remains challenging. Therefore, this study proposes an interactive human-machine interface (HMI) that integrates a mobile OCT system, deep learning algorithms, and attention mechanisms. The system is designed to mark the lesion's location on the image smartly and perform tumor grading in real time, potentially facilitating clinical decision making. Twelve patients with a preoperatively unknown tumor but a final diagnosis of adenocarcinoma underwent thoracoscopic resection, and the artificial intelligence (AI)-designed system mentioned above was used to measure fresh specimens. Results were compared to FSs benchmarked on permanent pathologic reports. Current results show better differentiating power among minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma (IA), and normal tissue, with an overall accuracy of 84.9%, compared to 20% for FSs. Additionally, the sensitivity and specificity, the sensitivity and specificity were 89% and 82.7% for MIA and 94% and 80.6% for IA, respectively. The results suggest that this AI system can potentially produce rapid and efficient diagnoses and ultimately improve patient outcomes.

The land surface temperature (LST) of volcanoes detected from satellite sensors reflects the thermal status of heat sources in the subsurface. Volcanic earthquakes occur as magma and volcanic fluids transport to the surface from depth. Thus, both LST and earthquake magnitude are key parameters to the study of active volcanoes. Here we investigate the volcanic status of Tatun Volcanic Group (TVG) based on LST and seismic observations. The Earth-observing satellites onboard thermal sensor derived land surface temperature, and the seismic records retrieved volcanic earthquake magnitude are used to delineate the past and current pattern of volcanic activity plus the future trend of the TVG. The spatiotemporal distribution of LST and volcanic earthquake magnitude in TVG are analyzed. The high-similarity trends of the 4-decade LST time series and 3-decade earthquake magnitude time series are inspected. The retrieved surface thermal pattern shows the non-steady-state nature of the subsurface thermal sources at this volcanic complex. The LST trend exhibits a rather positive correlation with the energy released from volcanic earthquakes and consequently, the presumption on the connection between LSTs and earthquakes is validated., (© 2023. The Author(s).)

We established a methodology using machine learning algorithms for determining the pathogenic factors for premenstrual dysphoric disorder (PMDD). PMDD is a disease characterized by emotional and physical symptoms that occurs before menstruation in women of childbearing age. Owing to the diverse manifestations and various pathogenic factors associated with this disease, the diagnosis of PMDD is time-consuming and challenging. In the present study, we aimed to establish a methodology for diagnosing PMDD. Using an unsupervised machine-learning algorithm, we divided pseudopregnant rats into three clusters (C1 to C3), depending on the level of anxiety- and depression-like behaviors. From the results of RNA-seq and subsequent qPCR of the hippocampus in each cluster, we identified 17 key genes for building a PMDD diagnostic model using our original two-step feature selection with supervised machine learning. By inputting the expression levels of these 17 genes into the machine learning classifier, the PMDD symptoms of another group of rats were successfully classified as C1-C3 with an accuracy of 96%, corresponding to the classification by behavior. The present methodology would be applicable for the clinical diagnosis of PMDD using blood samples instead of samples from the hippocampus in the future., Competing Interests: Declaration of competing interest None of the authors have any commercial or financial involvements in connection with this study that represent or appear to represent any conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Clot retraction results from retractions of platelet filopodia and fibrin fibers and requires the functional platelet α IIb β 3 integrin. This assay is widely used to test the functions of platelets and fibrinogen as well as the efficacy of fibrinolysis. Changes in clot retraction have been found in a variety of hemostatic abnormalities and, more recently, in arterial thrombosis. Despite its broad clinical use and low cost, many aspects of clot retraction are poorly understood. In the present study, we performed two clinical standard clot retraction assays using whole-blood and platelet-rich plasma (PRP) samples to determine how clot retraction correlates with platelet counts and mean volume, the density of α IIb β 3 integrin and PLA genotypes, and plasma fibrinogen levels. We found that clot retraction was affected by platelet counts, but not mean platelet volume. It correlated with the surface density of the integrin α Iib β 3 , but not PLA genotypes. These results indicate that clot retraction measures a unique aspect of platelet function and can serve as an additional means to detect functional changes in platelets.

Ovarian cancer is a complex disease associated with multiple genetic and epigenetic alterations. The emergence of treatment resistance in most patients causes ovarian cancer to become incurable, and novel therapies remain necessary. We identified epigenetic regulator ATPase family AAA domain-containing 2 (ATAD2) is overexpressed in ovarian cancer and is associated with increased incidences of metastasis and recurrence. Genetic knockdown of ATAD2 or its pharmacological inhibition via ATAD2 inhibitor BAY-850 suppressed ovarian cancer growth and metastasis in both in vitro and in vivo models. Transcriptome-wide mRNA expression profiling of ovarian cancer cells treated with BAY-850 revealed that ATAD2 inhibition predominantly alters the expression of centromere regulatory genes, particularly centromere protein E (CENPE). In ovarian cancer cells, changes in CENPE expression following ATAD2 inhibition resulted in cell-cycle arrest and apoptosis induction, which led to the suppression of ovarian cancer growth. Pharmacological CENPE inhibition phenotypically recapitulated the cellular changes induced by ATAD2 inhibition, and combined pharmacological inhibition of both ATAD2 and CENPE inhibited ovarian cancer cell growth more potently than inhibition of either alone. Thus, our study identified ATAD2 as regulators of ovarian cancer growth and metastasis that can be targeted either alone or in combination with CENPE inhibitors for effective ovarian cancer therapy., (© 2023. The Author(s).)

Competing Interests: The authors declare no conflict of interest.

Phthalates have become a matter of public health concern due to their extensive use worldwide and negative health effects. The evaluation of potential sources of phthalate exposure is crucial to design prevention strategies, especially for vulnerable populations. This study included 528 mother-child pairs in the Taiwan Mother Infant Cohort Study who were followed up at ages 3-6 years between 2016 and 2020. Each mother was interviewed by using a structured questionnaire containing questions on demographic characteristics and household environment factors, such as the use of plastic food packaging, residential visible mold, insecticide sprays, and electric mosquito repellents. Eleven phthalate metabolites were analyzed in urine samples simultaneously collected from the mother-child pairs. The phthalate metabolite urinary concentrations were higher among the children than among their mothers, except those of mono-ethyl phthalate (MEP) and mono-2-ethylhexyl phthalate (MEHP). Multiple linear regression analyses showed that urine samples collected during the summer showed higher concentrations of phthalate metabolites than those collected during the winter. Family income levels had negative associations with the concentrations of MnBP and metabolites of di-2-ethylhexyl phthalate (DEHP) in children. The use of plastic food packaging was positively associated with mono-n-butyl phthalate (MnBP) and metabolites of DEHP in mothers. Residential visible mold or mold stains were significantly associated with higher MnBP and DEHP metabolite concentrations in children. The use of insecticide sprays was positively associated with MnBP concentrations in children. Significant associations between household environmental factors and phthalate exposure were mostly found in children, potentially indicating different exposure pathways between mothers and their children. Findings from this study provide additional information for the design of prevention strategies to protect the health of children and women., 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

On-site instant determination of benign or malignant tumors for deciding the types of resection is crucial during pulmonary surgery. We designed a portable spectral-domain optical coherence tomography (SD-OCT) system to do real-time scanning intraoperatively for the distinction of fresh tumor specimens in the lung. A total of 12 ex vivo lung specimens from six patients were enrolled. Three patients were diagnosed with invasive adenocarcinoma (IA), while the others were benign. After OCT-imaged reconstruction, we compared the qualitative morphology of OCT and histology among malignant, benign, and normal tissues. In addition, through analysis of the quantitative data, a discrete difference in optical attenuation coefficients around the junctional surface was shown by our data processing. This study demonstrated a feasible OCT-assisted resection guide by a rapid on-site tumor diagnosis. The results indicate that future deep learning of OCT-captured image systems able to improve diagnostic and therapeutic efficiency is warranted., (© 2023 The Authors. Journal of Biophotonics published by Wiley-VCH GmbH.)

Functional optical coherence tomography (fOCT) detects activity-dependent light scattering changes in micro-structures of neural tissue, drawing attention as in vivo volumetric functional imaging technique at a sub-columnar level. There are 2 plausible origins for the light scattering changes: (i) hemodynamic responses such as changes in blood volume and in density of blood cells and (ii) reorientation of dipoles in cellular membrane. However, it has not been clarified which is the major contributor to fOCT signals. Furthermore, previous studies showed both increase and decrease of reflectivity as fOCT signals, making interpretation more difficult. We proposed combination of fOCT with Fourier imaging and adaptive statistics to the rat barrel cortex. Active voxels revealed barrels elongating throughout layers with mini-columns in superficial layers consistent with physiological studies, suggesting that active voxels revealed by fOCT reflect spatial patterns of activated neurons. These voxels included voxels with negative changes in reflectivity and those with positive changes in reflectivity. However, they were temporally mirror-symmetric, suggesting that they share common sources. It is hard to explain that hemodynamic responses elicit positive signals in some voxels and negative signals in the other. On the other hand, considering membrane dipoles, polarities of OCT signals can be positive and negative depending on orientations of scattering particles relative to the incident light. Therefore, the present study suggests that fOCT signals are induced by the reorientation of membrane dipoles., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background/purpose: This study aims to establish reference intervals for important biochemical parameters in cord blood of newborn male and female infants in Taiwan and to investigate their sex difference. We also examined the correlation of the same markers between maternal blood levels and neonatal cord blood levels., Methods: 2,136 pregnant women receiving regular routine prenatal health assessments in their third trimester (weeks 29-40) were recruited from nine hospitals in Taiwan between 2012 and 2015. After exclusion, we were left with 580 cord blood samples to include in this study., Results: Cord blood thyroid-stimulating hormone was higher in males than females (p < 0.05). Males also had significantly higher sex hormone levels (estradiol, follicle-stimulating hormone, and sex hormone-binding globulin), while females had higher levels of luteinizing hormone. Male newborns had higher cord blood immunoglobulin E (IgE), while females had higher insulin-like growth factor-1 (IGF-1) levels. We found a slight positive link between maternal blood and cord blood in thyroid hormones and sex hormones., Conclusion: This study found sex differences in cord blood thyroid hormone, sex hormone, IGF-1, and IgE levels and a link between maternal blood levels of thyroid and sex hormones and those in the cord blood of their infants., 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 © 2023 Elsevier B.V. All rights reserved.)

Previous studies have shown associations between prenatal phthalate exposure and neurobehavioral changes in children. However, few studies have focused on neonatal neurobehavioral development. This study aimed to examine the associations between prenatal phthalate exposure and neonatal neurobehavioral development in the early days of life after birth. This cohort study included 283 mother-infant pairs who participated in the Taiwan Mother Infant Cohort Study during 2012-2015. Each mother was interviewed, and urine samples were collected during the third trimester of pregnancy (weeks 29-40). Eleven common phthalate metabolites in maternal urine were analyzed. The Chinese version of the Neonatal Neurobehavioral Examination was used to evaluate early infant neurobehavioral development within five days of birth. We performed multiple linear regressions to explore the associations between phthalate exposure and neonatal neurobehavioral development. Sex differences in the association between phthalate metabolites and neonatal neurobehaviors were noted. Among girls, tertiles of phthalate metabolite concentrations were associated with worse behavioral responses and tone and motor patterns in the high-molecular-weight phthalate (HMW) and low-molecular-weight phthalate (LMW) groups. Girls in the highest tertile of di-2-ethylhexyl phthalate (DEHP) and mono-isobutyl phthalate (MiBP) had a negative association with tone and motor patterns. Girls in the highest tertile of mono-n-butyl phthalate (MnBP) and MiBP showed a negative association with behavioral responses. In contrast, tertiles of phthalate metabolite exposure were associated with improved neurobehaviors in mono-methyl phthalate (MMP) among boys. The highest tertile of MMP was positively associated with behavioral responses, primitive reflexes, and tone and motor patterns. Our findings suggest that maternal phthalate exposure affects neonatal neurobehavioral development in a sex-specific manner. Despite the relatively small sample size, our findings add to the existing research linking maternal phthalate exposure to neonatal neurobehavioral development. Additional research is needed to determine the potential long-term effects of prenatal phthalate exposure on children., 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 © 2022 Elsevier Ltd. All rights reserved.)

Objective: To understand the basic characteristics of previously reported patients with hepatitis C and analyze the related factors affecting their antiviral treatment. Methods: A convenient sampling method was adopted. Patients who had been previously diagnosed with hepatitis C in the Wenshan Prefecture of Yunnan Province and Xuzhou City of Jiangsu Province were contacted by telephone for an interview study. The Andersen health service utilization behavior model and related literature were used to design the research framework for antiviral treatment in previously reported hepatitis C patients. A step-by-step multivariate regression analysis was used in previously reported hepatitis C patients treated with antiviral therapy. Results: A total of 483 hepatitis C patients, aged 51.73 ± 12.06 years, were investigated. The proportion of male, agricultural occupants who were registered permanent residents, farmers and migrant workers was 65.24%, 67.49%, and 58.18%, respectively. Han ethnicity (70.81%), married (77.02%), and junior high school and below educational level (82.61%) were the main ones. Multivariate logistic regression analysis results showed that married patients with hepatitis C ( OR = 3.19, 95% CI : 1.93-5.25, compared with unmarried, divorced, and widowed patients) with high school education or above ( OR = 2.54, 95% CI : 1.54-4.20, compared with patients with junior high school education or below) were more likely to receive antiviral treatment in the predisposition module. Patients with severe self-perceived hepatitis C in the need factor module (compared with patients with mild self-perceived disease, OR = 3.36, 95% CI : 2.09-5.40) were more likely to receive treatment. In the competency module, the family's per capita monthly income was more than 1,000 yuan (compared with patients with per capita monthly income below 1,000 yuan, OR = 1.59, 95% CI : 1.02-2.47), and the patients had a high level of awareness of hepatitis C knowledge (compared with patients with a low level of knowledge, OR = 1.54, 95% CI : 1.01-2.35), and the family members who knew the patient's infection status (compared with patients with an unknown infection status, OR = 4.59, 95% CI : 2.24-9.39) were more likely to receive antiviral treatment. Conclusion: Different income, educational, and marital statuses are related to antiviral treatment behavior in hepatitis C patients. Family support of hepatitis C patients receiving hepatitis C-related knowledge and their families knowing the infection status is more important in promoting the antiviral treatment of patients, suggesting that in the future, we should further strengthen the hepatitis C knowledge of hepatitis C patients, especially the family support of hepatitis C patients' families in treatment.

Background: Nickel, the fifth most common element on Earth, is the leading inducer of contact allergies in humans, with potent immunological effects. Nickel-induced contact allergies predominantly affect females. Maternal exposure to nickel has been associated with several developmental abnormalities. However, how a maternal nickel exposure affects the development of atopic diathesis and immune abnormalities in children has never been addressed., Objectives: We aimed to determine whether maternal nickel exposure affects the development of atopic dermatitis and immune abnormalities in their children., Methods: Using a birth cohort study, we analysed 140 mother-child pairs recruited in 2012-2015 from central Taiwan. Maternal exposure to nickel was estimated using urinary nickel levels measured by inductively coupled plasma mass spectrometry (ICP-MS). The serum levels of 65 analytes and IgE in 3-year-old children were profiled with a multiplex ELISA. The correlation between the maternal urinary nickel concentration and serum analyte levels was assessed using Spearmen's correlation. Multivariant regression analysis was performed to evaluate the association between maternal urinary nickel levels and serum analyte concentrations in their children., Results: The geometric means of the maternal urinary nickel and the children's serum IgE levels were 2.27 μg/L and 69.71 IU/mL, respectively. The maternal nickel exposure was associated with increased serum levels of IL-1β, IL-2, TNF-α, and leukaemia inhibitory factor (LIF) but with decreased serum levels of matrix metalloproteinase-1 (MMP-1), IL-2R, and eotaxin-1 in the children. In addition, the development of childhood atopic dermatitis at 3 years old was significantly associated with the child's serum levels of IgE and IL-2R, but it was negatively associated with the maternal nickel exposure., Conclusions: This is the first study showing the potential immunological effects of maternal nickel exposure in their children at an early developmental stage., (© 2022 European Academy of Dermatology and Venereology.)

Here, we report a case of atopic dermatitis (AD) in a patient who received biweekly doses of dupilumab, an antibody against the IL-4 receptor α chain (IL-4Rα). Single cell RNA-sequencing showed that naïve B cells expressed the highest levels of IL4R compared to other B cell subpopulations. Compared to controls, the dupilumab-treated patient exhibited diminished percentages of IL4R+IGHD+ naïve B cells and down-regulation of IL4R, FCER2 (CD23), and IGHD. Dupilumab treatment resulted in upregulation of genes associated with apoptosis and inhibition of B cell receptor signaling and down-regulation of class-switch and memory B cell development genes. The dupilumab-treated patient exhibited a rapid decline in COVID-19 anti-spike and anti-receptor binding domain antibodies between 4 and 8 and 11 months post COVID-19 vaccination. Our data suggest that intact and persistent IL-4 signaling is necessary for maintaining robust survival and development of naïve B cells, and maintaining a long term vaccine response., Competing Interests: Declaration of Competing Interest All Authors report no conflicts of interest that are relevant to the content of this article., (Published by Elsevier Inc.)

Background: Depressed individuals experience deficits in emotional reactivity. One well-established theory is the Emotion Context Insensitivity (ECI) theory. To better understand impairments in emotional reactivity, we investigated whether the ECI theory is applicable to anticipatory, consummatory, and remembered affect, in both clinical and subclinical depression., Methods: Participants were divided into four groups: Major Depressive Disorder Group (MDD, N = 60), Control Group for MDD (Control MDD , N = 50), Subclinical Depression Group (SD, N = 56), and Control Group for SD (Control SD , N = 56). The Hamilton Depression Rating Scale and the Beck Depression Inventory were used to assess the severity of depression and anhedonia symptoms. The Monetary Incentive Delay Task evaluated participants' affective responses towards monetary stimuli., Results: The MDD group was more insensitive to both monetary reward and loss across most types of affect than was the control group. Compared with the controls, the SD group exhibited lower reactivity in anticipatory positive affect but enhanced reactivity in consummatory positive, anticipatory, and remembered negative affect., Limitations: Emotional affect was evaluated by subjective ratings, which may lack objectivity. Additionally, laboratory settings and monetary rewards used in this study may cause the results less generalized to daily life and to other types of rewards., Conclusion: The pattern of emotional reactivity in the MDD group was partly consistent with the ECI theory, whereas the SD group showed greater arousal and instability of emotional reactions. These different patterns could facilitate the understanding of emotional reactivity and develop further treatments across the course of depression., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Migraine is a common and complex neurovascular disorder. Clinically, the diagnosis of migraine mainly relies on scales, but the degree of pain is too subjective to be a reliable indicator. It is even more difficult to diagnose the medication-overuse headache, which can only be evaluated by whether the symptom is improved after the medication adjustment. Therefore, an objective migraine classification system to assist doctors in making a more accurate diagnosis is needed. In this research, 13 healthy subjects (HC), 9 chronic migraine subjects (CM), and 12 medication-overuse headache subjects (MOH) were measured by functional near-infrared spectroscopy (fNIRS) to observe the change of the hemoglobin in the prefrontal cortex (PFC) during the mental arithmetic task (MAT). Our model shows the sensitivity and specificity of CM are 100% and 75%, and that of MOH is 75% and 100%.The results of the classification of the three groups prove that fNIRS combines with machine learning is feasible for the migraine classification., (© 2022. The Author(s).)

The knowledge of high-pressure behavior of LiH is significant for the validation of fundamental theoretical models and applications in thermonuclear materials and potential energy supplies. The compressibility of 7 LiH under isentropic compression at high pressure was investigated experimentally and theoretically. The experimental technique for quasi-isentropic compression with low-density materials was developed using the magnetocumulative generator CJ-100 and x-ray flash radiography. The x-ray images and extracted interface of the sample target in dynamic flash radiography experiments were obtained. According to each interface size of the target both before and after compression, the compression ratio of 7 LiH and reference material aluminum was obtained. The density of the reference and using its known isentropic curve provide the pressure in the reference. The pressure in 7 LiH was deduced from the pressure in the reference and using the calculated gradient correction factor. The quasi-isentropic data point at 438 GPa was obtained experimentally. A semiempirical three-term complete equation of state was constructed and validated for 7 LiH using the theory of Mie-Grüneisen-Debye with experimental data from the literature. The quasi-isentrope data point is reasonably consistent with the theoretical results. The quasi-isentropic experimental techniques and results broaden the existing research scope and are practical and helpful to further validate theoretical models in the future.

The therapeutic effect of antidepressants has been demonstrated for anhedonia in patients with depression. However, antidepressants may cause side-effects, such as cardiovascular dysfunction. Although physical activity has minor side-effects, it may serve as an alternative for improving anhedonia and depression. We sought to investigate whether physical activity reduces the level of anhedonia in individuals with depression. Fifty-six university students with moderate depressive symptoms (Beck Depression Inventory total score > 16) were divided into three training groups: the Running Group (RG, n = 19), the Stretching Group (SG, n = 19), and the Control Group (n = 18). We employed the Monetary Incentive Delay (MID) task and the Temporal Experience of Pleasure Scale (TEPS) to evaluate hedonic capacity. All participants in the RG and SG received 8 weeks of jogging and stretching training, respectively. The RG experienced an increase in the level of arousal during anticipation of a future reward and recalled less negativity towards the loss condition. The SG exhibited enhanced scores on the Anticipatory and Consummatory Pleasure subscales of the TEPS after training. Moreover, in the RG, greater improvements in anticipatory arousal ratings for pleasure and remembered valence ratings for negative affect were associated with longer training duration, lower maximum heart rate, and higher consumed calories during training. To conclude, physical activity is effective in improving anticipatory anhedonia in individuals with depressive symptoms., (© 2021 Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

Objective: To determine if both gestational diabetes mellitus (GDM) and maternal overweight/obesity are independently associated with delivery of large-for-gestational-age (LGA) babies in Taiwan., Materials and Methods: Anthropometric parameters were measured and 75-g oral glucose-tolerance tests were administered to a cohort of 1428 pregnant women at 24-28 weeks gestation at nine hospitals in Taiwan. GDM was diagnosed based on the International Association of Diabetes and Pregnancy Study Groups criteria. Reported pre-pregnancy BMI and measured BMI during pregnancy were recorded at the late stage of the second trimester and the third trimester. Neonatal anthropometrics were measured at delivery. Primary outcome was LGA, defined in this study as having a birth weight ≥90th percentile for gestational age defined by WHO or a Chinese growth reference, taking into consideration the racial/ethnic and environmental differences in growth around the world. Multiple logistic regression was used to examine associations of GDM and maternal overweight/obesity with outcomes., Results: Based on WHO growth reference definition of LGA, subjects with pre-pregnancy BMI ≥24 and pregnancy BMI >28.4 were found to be 2.46 times (0.76-7.97) and 3.28 times (1.01-10.60), respectively, more likely to deliver LGA babies than subjects with normal pre-pregnancy and pregnancy BMIs. Compared to those without GDM, subjects with GDM were 7.55 (1.62-35.25) times more likely to deliver LGA babies. The odds ratios for delivering a baby with a birth weight ≥90th percentile were 11.40 (1.65-78.75) for those with GDM alone, 4.10 (1.07-15.65) for those with overweight/obesity alone and 15.75 (1.30-190.40) for those with both GDM and overweight/obesity, compared to those with no GDM and no overweightness. Women with both pre-pregnancy and pregnancy overweightness/obesity were 3.64 (1.07-12.34) times more likely to deliver LGA. The above results remained similar when analyzing data based on Chinese growth reference definition of LGA., Conclusion: Maternal overweightness/obesity and GDM are independently associated with LGA. Their combination had a greater impact than either one alone., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022. Published by Elsevier B.V.)

Background: The Mullen Scales of Early Learning (MSEL) is a standardized comprehensive developmental assessment tool for children aged 0-68 months. However, few Asia-based studies have explored cultural and linguistic adaptations of the MSEL or investigated its psychometric properties in populations with autism spectrum disorder (ASD)., Aims: This study evaluated the reliability and validity of the MSEL-Taiwan version (MSEL-T) for Taiwanese children with ASD, global developmental delay (GDD), and typical development (TD)., Methods and Procedures: The MSEL items were translated and modified according to the language and culture in Taiwan. In total, 191 children (ASD, 69; GDD, 36; and TD, 86) aged 19-68 months were assessed using the MSEL-T and Peabody Developmental Motor Scales 2 (PDMS-2) at enrollment, followed by the assessments of Vineland Adaptive Behavior Scale-Chinese version (VABS-C) at the age of 36 months or later., Outcomes and Results: All subscales were verified to have good interrater reliability and internal consistency, and subscale scores indicated moderate to high correlations with PDMS-2 and VABS-C scores. Significant differences in MSEL-T scores were observed between same-aged pairs of children with TD and GDD and between pairs of children with TD and ASD., Conclusions and Implications: The findings provide evidence of validity and reliability of the MSEL-T. And it is suggested that the culturally and linguistically adapted MSEL-T is a good tool for the clinical assessment of children with and without ASD., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Arabidopsis CHLOROPLAST IMPORT APPARATUS 2 (CIA2) and its paralogous protein CIA2-LIKE (CIL) are nuclear transcription factors containing a C-terminal CCT motif. CIA2 promotes the expression of nuclear genes encoding chloroplast-localized translocons and ribosomal proteins, thereby increasing the efficiency of protein import and synthesis in chloroplasts. We have previously reported that CIA2 and CIL form a homodimer or heterodimer through their C-terminal sequences and interact with other nuclear proteins, such as CONSTANS (CO), via their N-terminal sequences, but the function of CIL had remained unclear. In this study, we verified through transgenic cia2 mutant plants expressing the CIL coding sequence that CIL is partially functionally redundant to CIA2 during vegetative growth. We also compared phenotypes and gene expression profiles of wildtype Col-0, cia2 , cil , and cia2/cil mutants. Our results indicate that CIA2 and CIL coordinate chloroplast biogenesis and function mainly by upregulating the expression of the nuclear factor GOLDEN2-LIKE 1 ( GLK1 ) and chloroplast transcription-, translation-, protein import-, and photosynthesis-related genes, with CIA2 playing a more crucial role. Furthermore, we compared flowering phenotypes in single, double, and triple mutant plants of co , cia2 , and cil . We found that CIA2 and CIL participate in modulating long-day floral development. Notably, CIA2 increases flower number and height of the inflorescence main axis, whereas CIL promotes flowering., Competing Interests: The Authors did not report any conflict of interest., (© 2022 The Authors. Plant Direct published by American Society of Plant Biologists and the Society for Experimental Biology and John Wiley & Sons Ltd.)

Significance: Differentiation of primary central nervous system lymphoma from glioblastoma is clinically crucial to minimize the risk of treatments, but current imaging modalities often misclassify glioblastoma and lymphoma. Therefore, there is a need for methods to achieve high differentiation power intraoperatively. Aim: The aim is to develop and corroborate a method of classifying normal brain tissue, glioblastoma, and lymphoma using optical coherence tomography with deep learning algorithm in an ex vivo experimental design. Approach: We collected tumor specimens from ordinal surgical operations and measured them with optical coherence tomography. An attention ResNet deep learning model was utilized to differentiate glioblastoma and lymphoma from normal brain tissues. Results: Our model demonstrated a robust classification power of detecting tumoral tissues from normal tissues and moderate discrimination between lymphoma and glioblastoma. Moreover, our results showed good consistency with the previous histological findings in the pathological manifestation of lymphoma, and this could be important from the aspect of future clinical practice. Conclusion: We proposed and demonstrated a quantitative approach to distinguish different brain tumor types. Using our method, both neoplasms can be identified and classified with high accuracy. Hopefully, the proposed method can finally assist surgeons with decision-making intraoperatively., (© 2022 The Authors.)

Human connectome describes the complicated connection matrix of nervous system among human brain. It also possesses high potential of assisting doctors to monitor the brain injuries and recoveries in patients. In order to unravel the enigma of neuron connections and functions, previous research has strived to dig out the relations between neurons and brain regions. Verbal fluency test (VFT) is a general neuropsychological test, which has been used in functional connectivity investigations. In this study, we employed convolutional neural network (CNN) on a brain hemoglobin concentration changes (ΔHB) map obtained during VFT to investigate the connections of activated brain areas and different mental status. Our results show that feature of functional connectivity can be identified accurately with the employment of CNN on ΔHB mapping, which is beneficial to improve the understanding of brain functional connections., (© 2021 Wiley-VCH GmbH.)

Survival prediction is highly valued in end-of-life care clinical practice, and patient performance status evaluation stands as a predominant component in survival prognostication. While current performance status evaluation tools are limited to their subjective nature, the advent of wearable technology enables continual recordings of patients' activity and has the potential to measure performance status objectively. We hypothesize that wristband actigraphy monitoring devices can predict in-hospital death of end-stage cancer patients during the time of their hospital admissions. The objective of this study was to train and validate a long short-term memory (LSTM) deep-learning prediction model based on activity data of wearable actigraphy devices. The study recruited 60 end-stage cancer patients in a hospice care unit, with 28 deaths and 32 discharged in stable condition at the end of their hospital stay. The standard Karnofsky Performance Status score had an overall prognostic accuracy of 0.83. The LSTM prediction model based on patients' continual actigraphy monitoring had an overall prognostic accuracy of 0.83. Furthermore, the model performance improved with longer input data length up to 48 h. In conclusion, our research suggests the potential feasibility of wristband actigraphy to predict end-of-life admission outcomes in palliative care for end-stage cancer patients. Clinical Trial Registration: The study protocol was registered on ClinicalTrials.gov (ID: NCT04883879)., 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 © 2021 Yang, Kuo, Huang, Lin, Malwade, Lu, Tsai, Syed-Abdul, Sun and Chiou.)

Background: Phthalates esters are widely used commercially and can leach from a food container or food packaging. Few studies have been conducted in Asia regarding food processed to varying levels and human phthalate exposure. This study aimed to evaluate the association between unprocessed and ultra-processed food intake and urinary phthalate metabolite levels in the Taiwanese adult population. Methods: A total of 516 participant data were extracted from the cross-sectional 1993-1996 and 2005-2008 Nutrition and Health Survey in Taiwan of those aged over 18 years, where urinary measures and one 24-h dietary recall were collected. Urinary concentrations of dimethyl phthalate, diethyl phthalate, dibutyl phthalate, butyl benzyl phthalate, and di-(2-ethylhexyl) phthalate metabolites including monomethyl phthalate, monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate, mono-(2-ethylhexyl) phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, and mono-(2-ethyl-5-oxohexyl) phthalate were measured in spot urine samples. The NOVA food processing classification system was applied to divide all consumed foods into four mutually exclusive groups including unprocessed or minimally processed, processed culinary ingredients, processed and ultra-processed food. Generalized linear models were employed to examine the associations between the percentage quartiles (Qs) of unprocessed and ultra-processed foods in the total weight of food and the urinary phthalate metabolites. Results: Compared with participants in the lowest quartiles (Q1) of ultra-processed food intake, highest ultra-processed food intake (Q4) had 65.7% (95% confidence interval [CI]: 4.83, 162) higher urinary concentrations of MEP after adjusted for covariates. In contrast, the higher unprocessed food consumption was inversely associated with urinary concentrations of MEP and MBP ( P for trend = 0.03). When compared to the lowest unprocessed food consumers (Q1), higher consumers (Q4) presented 38.6% (95% CI: -61.3, -2.59) lower MEP concentrations and 23.1% (95% CI: -38.5, -3.71) lower MBP concentrations. Conclusion: Ultra-processed food consumption was associated with increased concentrations of urinary MEP. Conversely, consuming unprocessed food was associated with lower concentrations of MEP and MBP in the Asian Taiwanese adult population., 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 © 2021 Huang, Huang, Lo, Sun, Pan, Wang and Huang.)

Importance: The prevalence of atopic dermatitis has substantially increased in recent decades, and atopic dermatitis could lead to allergic airway inflammation later in life. A previous study found that inorganic arsenic exposure was associated with allergic airway inflammation in children aged 8 to 14 years. However, the association between prenatal exposure to arsenic and other metals and the risk of atopic dermatitis among young children remains unknown., Objective: To assess the association between prenatal exposure to arsenic and other metals and the occurrence of atopic dermatitis in children at age 4 years., Design, Setting, and Participants: In total, 1152 pregnant women were enrolled in the original Taiwan Maternal and Infant Cohort Study (TMICS), a multicenter birth cohort study conducted at 9 hospitals in northern, central, southern, and eastern Taiwan from October 2012 to May 2015. Of those, 586 mothers and children aged 4 years participated in follow-up questionnaire interviews from August 2016 to January 2019. After excluding 216 participants with missing data, the final statistical analysis of follow-up data included 370 mother and child pairs from the central and eastern regions of Taiwan. Data were analyzed from February 2 to August 12, 2021., Exposures: Arsenic, cadmium, lead, cobalt, copper, nickel, thallium, and zinc during pregnancy., Main Outcomes and Measures: The outcome was parent-reported atopic dermatitis history among children aged 4 years. The presence of atopic dermatitis was defined as a positive response to the question, "Has your child ever had atopic dermatitis diagnosed by a physician?" During the initial TMICS study period, concentrations of arsenic, cadmium, lead, cobalt, copper, nickel, thallium, and zinc were measured in maternal urine during the third trimester of pregnancy using an inductively coupled plasma mass spectrometer. Estimated total inorganic arsenic exposure was calculated using a model that included data on both total arsenic and arsenic species (arsenite, arsenate, monomethylarsonate, and dimethylarsenate) obtained from a previous TMICS cohort., Results: Among 370 children included in the analysis, the mean (SD) age was 3.94 (0.59) years; 208 children (56.2%) were male, and 267 children (72.2%) were from the central region of Taiwan. A total of 110 children (29.7%) had atopic dermatitis at age 4 years. Maternal estimated total inorganic arsenic exposure during pregnancy was associated with increased odds of atopic dermatitis among children at age 4 years (odds ratio [OR], 2.42 [95% CI, 1.33-4.39] for every doubled increase of total inorganic arsenic) after adjusting for parental allergies, child's sex, geographic area, maternal educational level, and exposure to tobacco smoke. Every increased unit in the weighted quantile sum index of maternal metal exposure was significantly associated with atopic dermatitis (OR, 1.63; 95% CI, 1.28-2.07). Arsenic (40.1%) and cadmium (20.5%) accounted for most of the metal mixture index., Conclusions and Relevance: This cohort study found that prenatal exposure to inorganic arsenic and coexposure to inorganic arsenic and cadmium were associated with a higher risk of atopic dermatitis in young children. These findings suggest that prevention of exposure to inorganic arsenic and cadmium during pregnancy may be helpful for the control of atopic dermatitis and other potential allergies in children.

Split-spectrum amplitude-decorrelation angiography (SSADA) is a noninvasive and three-dimensional angiographic technique with a microscale spatial resolution based on optical coherence tomography. The SSADA signal is known to be correlated with the blood flow velocity and the quantitative velocimetry with SSADA has been expected; however, the signal properties of SSADA are not completely understood due to lack of comprehensive investigations of parameters related to SSADA signals. In this study, phantom experiments were performed to comprehensively investigate the relation of SSADA signals with flow velocities, time separations, particle concentrations, signal-to-noise ratios, beam spot sizes, and viscosities, and revealed that SSADA signals reflect the spatial commonality within a coherence volume between adjacent A-scans., Competing Interests: The authors declare that there are no conflicts of interest related to this article., (© 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

Objective: To investigate the clinical features and prognostic influencing factors of toxic epidermal necrolysis (TEN). Methods: A retrospective observational study was conducted. From January 2008 to March 2019, a total of 46 TEN patients who met the inclusion criteria were admitted to Guangdong Provincial People's Hospital. The gender, age, and hospital admission diagnosis of the 46 patients, the category of department admitted of patients complicated with sepsis, death ratio of the sepsis patients with or without treatment history in intensive care unit (ICU)/department of burns and wound repair, and the cause of death of the deceased patients were recorded. Depending on whether complicated with sepsis, the patients were divided into sepsis group (32 cases) and non-sepsis group (14 cases). According to whether died or not, the patients were divided into death group (9 cases) and survival group (37 cases). The specific conditions of suspected pathogenic agents and combined underlying diseases, the abnormality of transaminase/bilirubin, creatinine, and platelet count in blood on admission, and the detection of pathogenic microorganisms and drug resistance during the course of disease of patients were recorded in both sepsis group and non-sepsis group. The gender, age, lesion area, severity of illness score for TEN (SCORTEN) system score, combined underlying diseases on admission, and blood microbial culture positivity, hormone use, and gamma globulin use during the course of disease of patients between sepsis group and non-sepsis group, death group and survival group were compared respectively. Data were statistically analyzed with chi-square test, Fisher's exact probability test, and Mann-Whitney U test. The factors with statistically significant differences between sepsis group and non-sepsis group, death group and survival group were selected for binary multivariate logistic regression analysis, so as to screen the independent risk factors affecting sepsis and death in TEN patients. Results: Of the 46 TEN patients, 30 were male and 16 were female, aged from 8 months to 92.0 years, with 11 cases (23.91%) of epidermolysis bullosa, 9 cases (19.57%) of exfoliative dermatitis, 9 cases (19.57%) of TEN, 7 cases (15.22%) of epidermolysis bullosa, 6 cases (13.04%) of Stevens-Johnson syndrome, and 4 cases (8.70%) of severe drug rash for hospital admission diagnosis. The patients complicated with sepsis were admitted to 11 departments, and the death ratio of patients with treatment history in ICU/department of burns and wound repair was similar to that of patients without such department treatment history ( P >0.05). All the deceased patients were complicated with sepsis, which was also the main cause of death. On admission, the suspected pathogenic agents of patients in sepsis group were mainly allopurinol (8 cases) and non-steroidal anti-inflammatory drugs (4 cases), while those in non-sepsis group were allopurinol (3 cases) and psychotropic drugs (3 cases). Patients in sepsis group combined as many as 10 underlying diseases, while those in non-sepsis group combined only 4 underlying diseases. The proportions of patients with increased creatinine ( χ 2 =13.349, P <0.01) and decreased platelet count ( P <0.01) in sepsis group were significantly higher than those in non-sepsis group, while the transaminase/bilirubin abnormality was similar to that in non-sepsis group ( P >0.05). A wide variety of pathogens were detected in the blood, respiratory tract secretions, and skin secretions of 21 patients in sepsis group, and 14 patients were infected with drug-resistant bacteria; among the 9 strains cultured from the blood samples, 8 were drug-resistant bacteria and 6 were Gram-positive bacteria. In non-sepsis group, pathogens were detected in blood, respiratory tract secretions, and skin secretions of 8 patients, with fewer species, and 6 patients were infected with drug-resistant bacteria. The gender, age, lesion area, blood microbial culture positivity, hormone use, and gamma globulin use of patients in sepsis group were similar to those in non-sepsis group ( P >0.05). The proportion of patients combined with underlying diseases ( χ 2 =4.493, P <0.05) and the proportion of patients with SCORTEN system score of 4-6 points ( P <0.01) of patients in sepsis group were significantly higher than those in non-sepsis group. The gender, combined underlying diseases, lesion area, blood microbial culture positivity, hormone use, and gamma globulin use of patients were similar between survival group and death group ( P >0.05). The proportion of patients with age≥60 years and the proportion of patients with SCORTEN system score of 4-6 points of patients in death group were significantly higher than those in survival group ( χ 2 =4.412, 11.627, P <0.05 or P <0.01). The SCORTEN system score was an independent risk factor affecting sepsis and death in TEN patients (odds ratio=3.025, 2.757, 95% confidence interval=1.352-6.769, 1.244-6.110, P <0.05 or P <0.01). Conclusions: The diagnosis of TEN is difficult on admission. Male population is susceptible to TEN, and allopurinol is the common pathogenic agent. The proportion of patients combined with underlying diseases is high in TEN patients complicated with sepsis, with mainly drug-resistant bacteria and mostly Gram-positive bacteria in blood-borne infections. The deceased patients are older than the survived, and the main cause of death is sepsis. The SCORTEN system score is an independent risk factor affecting sepsis and death in TEN patients.

Mitogen-activated protein kinases (MAPKs) are inactivated by dual-specificity phosphatases (DUSPs), the activities of which are tightly regulated during cell differentiation. Using knockdown screening and single-cell transcriptional analysis, we demonstrate that DUSP4 is the phosphatase that specifically inactivates p38 kinase to promote megakaryocyte (Mk) differentiation. Mechanistically, PRMT1-mediated methylation of DUSP4 triggers its ubiquitinylation by an E3 ligase HUWE1. Interestingly, the mechanistic axis of the DUSP4 degradation and p38 activation is also associated with a transcriptional signature of immune activation in Mk cells. In the context of thrombocytopenia observed in myelodysplastic syndrome (MDS), we demonstrate that high levels of p38 MAPK and PRMT1 are associated with low platelet counts and adverse prognosis, while pharmacological inhibition of p38 MAPK or PRMT1 stimulates megakaryopoiesis. These findings provide mechanistic insights into the role of the PRMT1-DUSP4-p38 axis on Mk differentiation and present a strategy for treatment of thrombocytopenia associated with MDS., Competing Interests: Declaration of interests M.L. has served on the Scientific Advisory Board for Epi One. A.V. has received research funding from GlaxoSmithKline, Incyte, MedPacto, Novartis, Curis, and Eli Lilly and Company; has received compensation as a scientific advisor to Novartis, Stelexis Therapeutics, Acceleron Pharma, and Celgene; and has equity ownership in Stelexis Therapeutics. The remaining authors declare no competing interests. Array BioPharma provided the p38 inhibitor pexmetinib (ARRY614) and participated in its phase I study (ClinicalTrials.gov: NCT01496495)., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

We report the generation of frequency-uncorrelated photon pairs from counter-propagating spontaneous parametric down-conversion in a periodically-poled KTP waveguide. The joint spectral intensity of photon pairs is characterized by measuring the corresponding stimulated process, namely, the difference frequency generation process. The experimental result shows a clear uncorrelated joint spectrum, where the backward-propagating photon has a narrow bandwidth of 7.46 GHz and the forward-propagating one has a bandwidth of 0.23 THz like the pump light. The heralded single-photon purity estimated through Schmidt decomposition is as high as 0.996, showing a perspective for ultra-purity and narrow-band single-photon generation. Such unique feature results from the backward-wave quasi-phase-matching condition and does not has a strict limitation on the material and working wavelength, thus fascinating its application in photonic quantum technologies.

Background: Exposure to either melamine or phthalate, two common toxicants, during pregnancy may cause adverse health effects, including kidney damage., Objectives: We investigated the independent and interactive effect of exposure to melamine and phthalates, particularly di-(2-ethylhexyl) phthalate (DEHP), on markers of early renal injury in women their third trimester of pregnancy in one nationwide birth cohort, the Taiwan Maternal and Infant Cohort Study (TMICS)., Methods: Between October, 2012 and May, 2015, participants were administered questionnaires, physical examinations, and blood and urine tests during their third trimester. One-spot overnight urine specimens were used to simultaneously measure melamine, 11 phthalate metabolites, and two markers of renal injury, microalbumin and N-acetyl-beta-D-glucosaminidas (NAG). Estimated daily DEHP intake was calculated based on measurement of three urinary DEHP metabolites. Microalbuminuria was defined as having a urinary albumin/creatinine ratio (ACR) higher than 3.5 mg/mmol., Results: Total 1433 pregnant women were analyzed. The median value for urinary melamine was 0.63 μg/mmol Cr and estimated DEHP intake was 1.84 μg/kg/day. We found subjects in the highest quartile of estimated DEHP intake to have significantly higher urinary ACR (β = 0.095, p = 0.043) and the prevalence of microalbuminuria (adjusted OR = 1.752, 95% confidence interval = 1.118-2.746), compared to those in the lowest quartile. In addition, there was a significant interactive effect between urinary melamine and estimated DEHP intake on urinary ACR and NAG., Conclusion: Our results suggest these two ubiquitous chemicals together may be associated with markers of early kidney injury in pregnant women., 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 © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Room-temperature superconductivity has always been an area of intensive research. Recent findings of clathrate metal hydrides structures have opened up the doors for achieving room-temperature superconductivity in these materials. Here, we report first-principles calculations for stable H-rich clathrate structures of uranium hydrides at high pressures. The clathrate uranium hydrides contain H cages with stoichiometries of H 24 , H 29 , and H 32 , in which H atoms are bonded covalently to other H atoms, and U atoms occupy the centers of the cages. Especially, a UH 10 clathrate structure containing H 32 cages is predicted to have an estimated T c higher than 77 K at high pressures., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Background: Because there are no published biochemical reference intervals (RI) for pregnant Taiwanese women, we used an established islandwide birth cohort, the Taiwan Maternal and Infant Cohort Study, to establish RIs for important biochemical parameters in women during their 3rd trimester in Taiwan. Additionally, we compared the differences in these biochemical parameters between early third trimester (weeks 28 to 31) and late third trimester (weeks 37 to 40) of pregnant women as well as the differences in them between the third trimester and after delivery., Methods: Between 2012 and 2015, we recruited a total of 2,136 pregnant women from nine hospitals located in northern (n = 3), central (n = 3), southern (n = 2), and eastern Taiwan (n = 1) to receive regular prenatal health examinations during their third trimester (weeks 28 to 40). After exclusion, samples obtained from 993 eligible pregnant women were analyzed., Results: There were increases in both lower and upper normal limits for blood neutrophil, thyroid profile (triiodothyronine (T3) and thyroxine (T4)), testosterone, estradiol, and progesterone and decreases for RBC, hemoglobin (Hb), alanine aminotransferase (ALT) and creatinine (Cr) during their third trimesters. Women in their late third trimester (n = 378) had higher median RBC, Hb, aspartate aminotransferase (AST), Cr, thyroid-stimulating hormone (TSH), testosterone, estradiol, and progesterone and lower median platelet and insulin, compared with those in their early third trimester (n = 490). Twenty-three of the women had both third trimester and post-pregnancy data. After delivery, the women had lower median AST, ALT, insulin, T3, T4, testosterone, estradiol, and progesterone and higher median Cr, free T4, FSH, and luteinizing hormone (LH), compared to their third trimesters., Conclusions: Gestation-related changes in important biochemical parameters should be considered when evaluating clinical laboratory values in pregnant women., Competing Interests: The authors have declared that no competing interests exist.

Central centrifugal cicatricial alopecia (CCCA) and lichen planopilaris (LPP) can look identical on histopathology. Both entities demonstrate perifollicular fibrosis, peri- infundibular lymphocytic infiltrates, and reduced follicular density. Presence of normal follicular units and preservation of sebaceous glands favor CCCA. An elastin stain, that is, Verhoeff-Van Gieson stain, can differentiate the tree trunk fibrosis of CCCA from the narrow wedge-shaped fibrosis of LPP. Look for important clues such as patient race and pattern of alopecia for diagnosis and treatment instead of relying solely on the pathology report.

Phthalic acid esters (PAE) are widely used during chemical synthesis and do not form covalent linkages with products. It has been reported that exposure to PAE affects the immune response. However, their effect on antibody concentrations in children is still under investigation. We aimed to examine the association between early-life phthalate exposure and antibody concentrations in children in a longitudinal birth cohort established in 2000-2001. We recruited 398 neonates in central Taiwan and followed them up every 2-3 years, with various antibody-related studies at 11- and 14-year follow-ups. Seven urinary phthalate metabolites were quantified in mothers during pregnancy and children aged 11 years. Four antibody concentrations were analyzed in children aged 11 and 14 years. The percent change in antibody concentrations from ages 11 to 14 years was calculated and its association with phthalate exposure was evaluated via multivariate regression analysis. Eighty-one followed-up children were with sufficient data. After adjusting for prenatal exposure and other confounders, double concentrations of the urinary sum of di-2-ethylhexyl phthalate (ΣDEHPm) and mono-n-butyl phthalate (MnBP) were associated with a 18.06% (95% CI = 3.34%, 32.78%) and 22.53% decrease (95% CI = 3.39%, 41.66%) in antibody concentration against hepatitis B, respectively. Phthalate exposure was found to be related to decreased antibody concentrations against hepatitis B (DEHP, DBnP) in the early teens. This exposure is suggested to be considered for clinical re-booster vaccines among junior high school students. Further verification with additional cohorts and studies on the underlying mechanisms of phthalate exposure are warranted., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)