bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relation of the frequency and functional molecules expression on plasmacytoid dendritic cells to postpartum hepatitis in women with HBeAg-positive chronic hepatitis B virus infection
Authors: Wang Fuchuan , Song Meiying , Hu Yuhong , Yang Liu , Bi Xiaoyue , Lin Yanjie , Jiang Tingting , Deng Wen , Wang Shiyu , Sun Fangfang , Zeng Zhan , Lu Yao , Shen Ge , Liu Ruyu , Chang Min , Wu Shuling , Gao Yuanjiao , Hao Hongxiao , Xu Mengjiao , Chen Xiaoxue , Hu Leiping , Wan Gang , Zhang Lu , Li Minghui , Xie Yao 
Published: November 2022

ObjectiveTo explore the correlation between postpartum hepatitis and changes of plasmacytoid dendritic cells’ (pDC) function and frequency in hepatitis B e antigen (HBeAg)-positive pregnant women with chronic hepatitis B virus (HBV) infection.MethodsPregnant women with chronic HBV infection receiving antiviral treatment (treated group) or not receiving antiviral treatment (untreated group) were enrolled and demographic information was collected before delivery. Clinical biochemical, virological serology, pDC frequency and functional molecular expression were tested before delivery and at 6, 12, 24 weeks after delivery.Results90 eligible pregnant women were enrolled, 36 in the untreated group and 54 in the treated group. 36 patients developed postpartum hepatitis, including 17 (17/36, 47.2%) in the untreated group and 19 (19/54, 35.2%) in the treated group (χ2 = 1.304 p=0.253), and 22 cases of hepatitis occurred at 6 weeks postpartum, 12 at 12 weeks postpartum, and 2 at 24 weeks postpartum. The alanine transaminase (ALT) levels at any time postpartum were significantly higher than that of the antepartum, especially at 6 weeks and 12 weeks postpartum. However, the frequencies of pDCs, CD83+ pDCs and CD86+ pDCs antepartum had no significant difference from any time postpartum. The frequencies of CD83+ pDCs, CD86+ pDCs in the treated group antepartum were significantly higher than those in the untreated group [12.70 (9.46, 15.08) vs. 10.20 (7.96, 11.85), p=0.007; 22.05 (19.28, 33.03) vs. 18.05 (14.33, 22.95), p=0.011], and the same at 12 weeks postpartum [12.80 (10.50, 15.50) vs. 9.38 (7.73, 12.60), p=0.017; 22.50 (16.80, 31.20) vs. 16.50 (12.65, 20.80), p=0.001]. The frequency of CD86+ pDCs in the treated group was significantly higher than that in the untreated group at 24 weeks postpartum [22.10 (16.70, 30.00) vs. 17.10 (13.70, 20.05), p=0.006].ConclusionsPostpartum hepatitis in HBV infected women mainly occurs at 6-12 weeks postpartum. Antiviral treatment during pregnancy can significantly increase the frequencies of CD83+ pDCs and CD86+ pDCs in pregnant women with chronic HBV infection.
Chromomycin A5 induces bona fide immunogenic cell death in melanoma
Authors: Florêncio Katharine Gurgel Dias , Edson Evelline Araújo , Fernandes Keilla Santana da Silva , Luiz João Paulo Mesquita , Pinto Francisco das Chagas Lima , Pessoa Otília Deusdênia Loiola , Cunha Fernando de Queiroz , Machado-Neto João Agostinho , Wilke Diego Veras 
Published: November 2022

PurposeSome first-line cytotoxic chemotherapics, e.g. doxorubicin, paclitaxel and oxaliplatin, induce activation of the immune system through immunogenic cell death (ICD). Tumor cells undergoing ICD function as a vaccine, releasing damage-associated molecular patterns (DAMPs), which act as adjuvants, and neoantigens of the tumor are recognized as antigens. ICD induction is rare, however it yields better and long-lasting antitumor responses to chemotherapy. Advanced metastatic melanoma (AMM) is incurable for more than half of patients. The discovery of ICD inducers against AMM is an interesting drug discovery strategy with high translational potential. Here we evaluated ICD induction of four highly cytotoxic chromomycins A (CA5-8).MethodsICD features and DAMPs were evaluated using several in vitro techniques with metastatic melanoma cell line (B16-F10) exposed to chromomcins A5-8 such as flow cytometry, western blot, RT-PCR and luminescence. Additionally in vivo vaccination assays with CA5-treated cells in a syngeneic murine model (C57Bl/6) were performed to confirm ICD evaluating the immune cells activation and their antitumor activity.ResultsB16-F10 treated with CA5-8 and doxorubicin exhibited ICD features such as autophagy and apoptosis, externalization of calreticulin, and releasing of HMGB1. However, CA5-treated cells had the best profile, also inducing ATP release, ERp57 externalization, phosphorylation of eIF2α and altering expression of transcription of genes related to autophagy, endoplasmic reticulum stress, and apoptosis. Bona fide ICD induction by CA5 was confirmed by vaccination of C57BL/6 mice with CA5-treated cells which activated antigen-presenting cells and T lymphocytes and stimulated antitumor activity.ConclusionCA5 induces bona fide immunogenic cell death on melanoma.
Fertility preferences and unmet need for family planning in women with multiple sclerosis
Authors: López-Reyes Lorena , Guío-Sánchez Claudia , González-Uribe Catalina , Cárdenas-Robledo Simón 
Published: November 2022

BackgroundMost women with multiple sclerosis (MS) have childbearing potential. Although fertility and pregnancy are not affected by MS, the fertility preferences of women with MS can change due to the risk of complications for the mother and/or adverse pregnancy outcomes resulting from the disease or its treatment.ObjectivesTo describe fertility preferences (FPs) and their associated factors, to estimate the Unmet Need for Family Planning (UNFP), use of contraceptives, and history of exposure to disease-modifying therapies (DMTs) during pregnancy in women with MS.MethodsIn a cross-sectional observational study, a random sample of women with MS were surveyed with the FP subset of the Demographic and Health Survey of Colombia. Factors associated with FP were evaluated through bivariate and logistic regression analysis. The proportion of pregnancies exposed to DMTs, UNFP, and use of contraceptives was estimated.ResultsOf the 141 women interviewed, 101 women had childbearing potential, of whom 49 did not want to have children, 38 were sterilized, 33 wanted to have more children, 19 were undecided, and 2 stated they were unable to bear children (menopause or hysterectomy). No MS-related variables were associated with the preference to have more children. Age (OR 0.91; 95% CI 0.84–0.98) and the number of children (OR 0.23; 95% CI 0.09–0.58) decreased the likelihood of desire for children. Of 116 sexually active women, 87.06 % (101) were using contraceptives, and among them, four were using fertility awareness methods and withdrawal. The UNFP was estimated at 6.03% and was not significantly different from the general population. Eighty-two pregnancies were identified, of which 48 occurred after diagnosis, and 25 were exposed to DMTs.ConclusionFertility preference in women with MS is not associated with clinical variables. A large proportion of women choose not to have children and prefer to use permanent contraceptive methods. Although the frequency of contraceptive use was high, some women have the UNFP and use low-efficacy contraceptive methods, which may result in unplanned pregnancies.
Characteristics and predictors of breast milk iodine in exclusively breastfed infants: Results from a repeated-measures study of iodine metabolism
Authors: Guo Wenxing , Wu Wen , Gao Min , Yang Ying , Pearce Elizabeth N. , Li Shaohan , Ren Zhiyuan , Zhang Naifan , Zhang Kexin , Pan Ziyun , Zhang Wanqi 
Published: November 2022

BackgroundThe iodine supply of exclusively breastfed infants entirely depends upon breast milk. Changes in breast milk iodine affect infants’ iodine nutritional status. This study aimed to comprehensively assess the characteristics and predictors of breast milk iodine concentration (BMIC).Materials and methodsThis 7-day iodine metabolism experiment was conducted in 25 exclusively breastfed mother-infant pairs. The duplicate portion method was used to measure the mother’s daily iodine intake from foods and water, and maternal 24-h urine excretion was assessed. We recorded the number of breastfeeds per mother per day and collected breast milk samples before and after each feeding.ResultsThe median [quartile (Q)1–Q3 range] of BMIC was 115 (86.7, 172) μg/L. The BMIC before breastfeeding was generally higher than that after breastfeeding. Time-sequential analysis found that morning BMIC was most highly correlated with the prior day’s iodine intake. Breast milk samples taken in the afternoon or after midnight are closer to the median level of BMIC throughout the day. The number of breast milk samples needed to estimate the iodine level with 95% CI within precision ranges of ± 20% was 83 for a population, 9 for an individual, and 2 for an individual’s single day. Maternal total iodine intake (TII) and urine iodine were significantly associated with BMIC. 24-h urinary iodine excretion (24-h UIE) was found to be the best predictive indicator for the BMIC (β = 0.71, 95% CI: 0.64, 0.79).ConclusionBMIC is a constantly changing indicator and trended downward during each breastfeeding. Breast milk samples taken in the afternoon or after midnight are most representative. BMIC was significantly associated with recent iodine intake. Maternal 24-h UIE was the best predictor of BMIC.
Prospective population pharmacokinetic study of tacrolimus in adult recipients early after liver transplantation: A comparison of Michaelis-Menten and theory-based pharmacokinetic models
Authors: Cai Xiao-Jun , Li Rui-Dong , Li Jian-Hua , Tao Yi-Feng , Zhang Quan-Bao , Shen Cong-Huan , Zhang Xiao-Fei , Wang Zheng-Xin , Jiao Zheng 
Published: November 2022

Background and Objective: Tacrolimus, a calcineurin inhibitor widely used as a potent immunosuppressant to prevent graft rejection, exhibits nonlinear kinetics in patients with kidney transplantation and nephrotic syndrome. However, whether nonlinear drug metabolism occurs in adult patients undergoing liver transplantation remains unclear, as do the main underlying mechanisms. Therefore, here we aimed to further confirm the characteristics of nonlinearity through a large sample size, and determine the potential influence of nonlinearity and its possible mechanisms.Methods: In total, 906 trough concentrations from 176 adult patients (150 men/26 women; average age: 50.68 ± 9.71 years, average weight: 64.54 ± 11.85 kg after first liver transplantation) were included in this study. Population pharmacokinetic analysis was performed using NONMEM®. Two modeling strategies, theory-based linear compartmental and nonlinear Michaelis–Menten (MM) models, were evaluated and compared. Potential covariates were screened using a stepwise approach. Bootstrap, prediction-, and simulation-based diagnostics (prediction-corrected visual predictive checks) were performed to determine model stability and predictive performance. Finally, Monte Carlo simulations based on the superior model were conducted to design dosing regimens.Results: Postoperative days (POD), Aspartate aminotransferase (AST), daily tacrolimus dose, triazole antifungal agent (TAF) co-therapy, and recipient CYP3A5*3 genotype constituted the main factors in the theory-based compartmental final model, whereas POD, Total serum bilirubin (TBIL), Haematocrit (HCT), TAF co-therapy, and recipient CYP3A5*3 genotype were important in the nonlinear MM model. The theory-based final model exhibited 234 L h−1 apparent plasma clearance and 11,000 L plasma distribution volume. The maximum dose rate (Vmax) of the nonlinear MM model was 6.62 mg day−1; the average concentration at steady state at half-Vmax (Km) was 6.46 ng ml−1. The nonlinear MM final model was superior to the theory-based final model and used to propose dosing regimens based on simulations.Conclusion: Our findings demonstrate that saturated tacrolimus concentration-dependent binding to erythrocytes and the influence of daily tacrolimus dose on metabolism may partly contribute to nonlinearity. Further investigation is needed is need to explore the causes of nonlinear pharmacokinetic of tacrolimus. The nonlinear MM model can provide reliable support for tacrolimus dosing optimization and adjustment in adult patients undergoing liver transplantation.
Ameliorative effect of Berberidis radix polysaccharide selenium nanoparticles against carbon tetrachloride induced oxidative stress and inflammation
Authors: Gao Fei , Liu Huimin , Han Hao , Wang Xin , Qu Lihua , Liu Congmin , Tian Xuemei , Hou Ranran 
Published: November 2022

Berberidis radix polysaccharide (BRP) extracted as capping agents was applied to prepare BRP-selenium nanoparticles (BRP-SeNPs) in the redox reaction system of sodium selenite and ascorbic acid. The stability and characterization of BRP-SeNPs were investigated by physical analysis method. The results revealed that BRP were tightly wrapped on the surface of SeNPs by forming C-O⋯Se bonds or hydrogen bonding interaction (O-H⋯Se). BRP-SeNPs presented irregular, fragmented and smooth surface morphology and polycrystalline nanoring structure, and its particle size was 89.4 nm in the optimal preparation condition. The pharmacologic functions of BRP-SeNPs were explored in vitro and in vivo. The results showed that BRP-SeNPs could heighten the cell viabilities and the enzyme activity of GSH-Px and decrease the content of MDA on H2O2-induced AML-12 cells injury model. In vivo tests, the results displayed that BRP-SeNPs could increase the body weight of mice, promote the enzyme activity like SOD and GSH-Px, decrease the liver organ index and the hepatic function index such as ALT, AST, CYP2E1, reduce the content of MDA, and relieve the proinflammation factors of NO, IL-1β and TNF-α in CCl4-induced mice injury model. Liver tissue histopathological studies corroborated the improvement of BRP-SeNPs on liver of CCl4-induced mice. The results of Western blot showed that BRP-SeNPs could attenuate oxidant stress by the Nrf2/Keap1/MKP1/JNK pathways, and downregulate the proinflammatory factors by TLR4/MAPK pathway. These findings suggested that BRP-SeNPs possess the hepatoprotection and have the potential to be a green liver-protecting and auxiliary liver inflammation drugs.
A PDE10A inhibitor CPL500036 is a novel agent modulating striatal function devoid of most neuroleptic side-effects
Authors: Matloka Mikolaj , Janowska Sylwia , Pankiewicz Piotr , Kokhanovska Sofiya , Kos Tomasz , Hołuj Małgorzata , Rutkowska-Wlodarczyk Izabela , Abramski Krzysztof , Janicka Monika , Jakubowski Piotr , Świątkiewicz Maciej , Welniak-Kaminska Marlena , Hucz-Kalitowska Joanna , Dera Paulina , Bojarski Lukasz , Grieb Paweł , Popik Piotr , Wieczorek Maciej , Pieczykolan Jerzy 
Published: November 2022

Background: Phosphodiesterase 10A (PDE10A) is expressed almost exclusively in the striatum and its inhibition is suggested to offer potential treatment in disorders associated with basal ganglia. We evaluated the selectivity, cytotoxicity, genotoxicity, pharmacokinetics and potential adverse effects of a novel PDE10A inhibitor, CPL500036, in vivo.Methods: The potency of CPL500036 was demonstrated by microfluidic technology, and selectivity was investigated in a radioligand binding assay against 44 targets. Cardiotoxicity in vitro was evaluated in human ether-a-go-go related gene (hERG)-potassium channel-overexpressing cells by the patch-clamp method and by assessing key parameters in 3D cardiac spheroids. Cytotoxicity was determined in H1299, HepG2 and SH-SY5Y cell lines. The Ames test was used for genotoxicity analyses. During in vivo studies, CPL500036 was administered by oral gavage. CPL500036 exposure were determined by liquid chromatography–tandem mass spectrometry and plasma protein binding was assessed. The bar test was employed to assess catalepsy. Prolactin and glucose levels in rat blood were measured by ELISAs and glucometers, respectively. Cardiovascular safety in vivo was investigated in dogs using a telemetry method.Results: CPL500036 inhibited PDE10A at an IC50 of 1 nM, and interacted only with the muscarinic M2 receptor as a negative allosteric modulator with an IC50 of 9.2 µM. Despite inhibiting hERG tail current at an IC25 of 3.2 μM, cardiovascular adverse effects were not observed in human cardiac 3D spheroids or in vivo. Cytotoxicity in vitro was observed only at &gt; 60 μM and genotoxicity was not recorded during the Ames test. CPL500036 presented good bioavailability and penetration into the brain. CPL500036 elicited catalepsy at 0.6 mg/kg, but hyperprolactinemia or hyperglycemic effects were not observed in doses up to 3 mg/kg.Conclusion: CPL500036 is a potent, selective and orally bioavailable PDE10A inhibitor with a good safety profile distinct from marketed antipsychotics. CPL500036 may be a compelling drug candidate.
Streamlined single-molecule RNA-FISH of core clock mRNAs in clock neurons in whole mount Drosophila brains
Authors: Yuan Ye , Padilla Marc-Antonio , Clark Dunham , Yadlapalli Swathi 
Published: November 2022

Circadian clocks are ∼24-h timekeepers that control rhythms in almost all aspects of our behavior and physiology. While it is well known that subcellular localization of core clock proteins plays a critical role in circadian regulation, very little is known about the spatiotemporal organization of core clock mRNAs and its role in generating ∼24-h circadian rhythms. Here we describe a streamlined single molecule Fluorescence In Situ Hybridization (smFISH) protocol and a fully automated analysis pipeline to precisely quantify the number and subcellular location of mRNAs of Clock, a core circadian transcription factor, in individual clock neurons in whole mount Drosophila adult brains. Specifically, we used ∼48 fluorescent oligonucleotide probes that can bind to an individual Clock mRNA molecule, which can then be detected as a diffraction-limited spot. Further, we developed a machine learning-based approach for 3-D cell segmentation, based on a pretrained encoder-decoder convolutional neural network, to automatically identify the cytoplasm and nuclei of clock neurons. We combined our segmentation model with a spot counting algorithm to detect Clock mRNA spots in individual clock neurons. Our results demonstrate that the number of Clock mRNA molecules cycle in large ventral lateral clock neurons (lLNvs) with peak levels at ZT4 (4 h after lights are turned on) with ∼80 molecules/neuron and trough levels at ZT16 with ∼30 molecules/neuron. Our streamlined smFISH protocol and deep learning-based analysis pipeline can be employed to quantify the number and subcellular location of any mRNA in individual clock neurons in Drosophila brains. Further, this method can open mechanistic and functional studies into how spatiotemporal localization of clock mRNAs affect circadian rhythms.
The effectiveness and associated factors of online psychotherapy on COVID-19 related distress: A systematic review and meta-analysis
Authors: Chi Danni , Zhang Yuanyuan , Zhou Dongsheng , Xu Guozhang , Bian Guolin 
Published: November 2022

ObjectiveA quantitative synthesis of online psychotherapies' effectiveness in managing COVID-19 related distress is lacking. This study aimed to estimate online psychological interventions' effectiveness and associated factors on COVID-19 related psychological distress.MethodsMulti-databases including PubMed, EBSCO, ProQuest, and Cochrane were searched repeatedly till the end of June 2022. Hand-picking was also utilized for relevant papers. Depression, anxiety, stress, and quality of sleep were evaluated as outcomes. The risk of bias was evaluated using the Cochrane tool. Data analyses were conducted through Review Manager (version 5.4.1).ResultsA total of 13 studies involving 1,897 participants were included for meta-analysis. Results showed that online psychotherapy significantly reduced the levels of depression [standard mean difference, SMD = −0.45, 95% CI (−0.69, −0.20)], anxiety [SMD = −0.67, 95% CI (−0.99, −0.36)], and stress [SMD = −0.73, 95% CI (−1.11, −0.34)], but not quality of sleep [SMD = −0.53, 95% CI (−1.23, 0.17)]. In addition, guided therapies were more effective than self-help ones on reducing levels of anxiety (χ2 = 5.58, p = 0.02, and I2 = 82.1%), and ≤ 2 weeks' daily interventions were more effective on treating depression than 2-month weekly interventions (χ2 = 7.97, p = 0.005, I2 = 87.5%).ConclusionOnline psychological interventions effectively reduced COVID-19 related depression, anxiety, and stress levels, and the effectiveness was influenced by settings like guidance and duration and frequency.Systematic review registrationhttps://inplasy.com/inplasy-2022-7-0081/, identifier: INPLASY202270081.
Use of central nervous system drugs in combination with selective serotonin reuptake inhibitor treatment: A Bayesian screening study for risk of suicidal behavior
Authors: Lagerberg Tyra , Sjölander Arvid , Gibbons Robert D. , Quinn Patrick D. , D’Onofrio Brian M. , Hellner Clara , Lichtenstein Paul , Fazel Seena , Chang Zheng 
Published: November 2022

BackgroundUsing other central nervous system (CNS) medications in combination with selective serotonin reuptake inhibitor (SSRI) treatment is common. Despite this, there is limited evidence on the impact on suicidal behavior of combining specific medications. We aim to provide evidence on signals for suicidal behavior risk when initiating CNS drugs during and outside of SSRI treatment.Materials and methodsUsing a linkage of Swedish national registers, we identified a national cohort of SSRI users aged 6–59 years residing in Sweden 2006–2013. We used a two-stage Bayesian Poisson model to estimate the incidence rate ratio (IRR) of suicidal behavior in periods up to 90 days before and after a CNS drug initiation during SSRI treatment, while accounting for multiple testing. For comparison, and to assess whether there were interactions between SSRIs and other CNS drugs, we also estimated the IRR of initiating the CNS drug without SSRI treatment.ResultsWe identified 53 common CNS drugs initiated during SSRI treatment, dispensed to 262,721 individuals. We found 20 CNS drugs with statistically significant IRRs. Of these, two showed a greater risk of suicidal behavior after versus before initiating the CNS drug (alprazolam, IRR = 1.39; flunitrazepam, IRR = 1.83). We found several novel signals of drugs that were statistically significantly associated with a reduction in the suicidal behavior risk. We did not find evidence of harmful interactions between SSRIs and the selected CNS drugs.ConclusionSeveral of the detected signals for reduced risk correspond to drugs where there is previous evidence of benefit for antidepressant augmentation (e.g., olanzapine, quetiapine, lithium, buspirone, and mirtazapine). Novel signals of reduced suicidal behavior risk, including for lamotrigine, valproic acid, risperidone, and melatonin, warrant further investigation.