bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case report: NUDT15 polymorphism and severe azathioprine-induced myelosuppression in a young Chinese female with systematic lupus erythematosus: a case analysis and literature review
Authors: Gu Juan , Lin Yupei , Wang Yuhe 
Published: May 2023

Azathioprine is clinically used as an immunosuppressant for treating autoimmune diseases. However it has narrow therapeutic indices due to frequent myelosuppression. Polymorphic variants of genes coding for thiopurine S-methyltransferase (TPMT) and nucleoside diphosphate-linked moiety X motif 15 (NUDT15) are critical determinants of AZA intolerance, and the differences in frequencies of the two genetic variants exist among people of different ethnicities. Most reports regarding NUDT15 variant, AZA-induced myelosuppression occurred in patients with inflammatory bowel disease and acute lymphoblastic leukemia. Moreover, detailed clinical characteristics were not frequently reported. Here we present the case of a young Chinese female with the NUDT15 c.415C&gt;T (rs116855232, TT) homozygous variant and wild-type TPMT*2 (rs1800462), TPMT*3B (rs1800460), and TPMT*3C (rs1142345) who received high doses of AZA (2.3 mg/kg/d) for systematic lupus erythematosus and had not been told to undergo routine blood cell counts during AZA ingestion. The patient had suffered from severe AZA-induced myelosuppression and alopecia. Moreover, dynamic changes in blood cell counts and responses to treatment were observed. We also conducted a systematic review of published case reports of patients exclusively with NUDT15 c.415C&gt;T homozygous or heterozygous variants to review the characteristics of dynamic changes in blood cells so as to provide reference information for clinical treatment.
Modulation of gut microbiota alleviates cerebral ischemia/reperfusion injury in rats by inhibiting M1 polarization of microglia
Authors: Li Hai-Jun , Li Dan-Qing , Zhang Yu-Liang , Ding Xiao-Fei , Gao Hai-Tao , Zhu Ya , Liu Jun , Zhang Li-Xia , Chen Jie , Chen Guang , Yu Ying 
Published: May 2023

Gut microbiota affects the gut–brain axis; hence, the modulation of the microbiota has been proposed as a potential therapeutic strategy for cerebral ischemia/reperfusion injury (CIRI). However, the role and mechanism of the gut microbiota in regulating microglial polarization during CIRI remain poorly understood. Herein, using a middle cerebral artery occlusion and reperfusion (MCAO/R) rat model, we evaluated changes in the gut microbiota after CIRI and the potential effects of fecal microbiota transplant (FMT) on the brain. Rats underwent either MCAO/R or sham surgery, and then they received FMT (started 3 days later; continued for 10 days). 2,3,5-Triphenyltetrazolium chloride staining, neurological outcome scale, and Fluoro-Jade C staining showed that MCAO/R induced cerebral infarction, neurological deficits, and neuronal degeneration. In addition, immunohistochemistry or real-time PCR assay showed increased expression levels of M1-macrophage markers—TNF-α, IL-1β, IL-6, and iNOS—in the rats following MCAO/R. Our finding suggests that microglial M1 polarization is involved in CIRI. 16 S ribosomal RNA gene sequencing data revealed an imbalance in the gut microbiota of MCAO/R animals. In contrast, FMT reversed this MCAO/R-induced imbalance in the gut microbiota and ameliorated nerve injury. In addition, FMT prevented the upregulation in the ERK and NF-κB pathways, which reversed the M2-to-M1 microglial shift 10 days after MCAO/R injury in rats. Our primary data showed that the modulation of the gut microbiota can attenuate CIRI in rats by inhibiting microglial M1 polarization through the ERK and NF-κB pathways. However, an understanding of the underlying mechanism requires further study.
Identification of afatinib-associated ADH1B and potential small-molecule drugs targeting ADH1B for hepatocellular carcinoma
Authors: Zhou Yongxu , Yu Liang , Huang Peng , Zhao Xudong , He Risheng , Cui Yunfu , Pan Bo , Liu Chang 
Published: May 2023

Background: Afatinib is an irreversible epidermal growth factor receptor tyrosine kinase inhibitor, and it plays a role in hepatocellular carcinoma (LIHC). This study aimed to screen a key gene associated with afatinib and identify its potential candidate drugs.Methods: We screened afatinib-associated differential expressed genes based on transcriptomic data of LIHC patients from The Cancer Genome Atlas, Gene Expression Omnibus, and the Hepatocellular Carcinoma Database (HCCDB). By using the Genomics of Drug Sensitivity in Cancer 2 database, we determined candidate genes using analysis of the correlation between differential genes and half-maximal inhibitory concentration. Survival analysis of candidate genes was performed in the TCGA dataset and validated in HCCDB18 and GSE14520 datasets. Immune characteristic analysis identified a key gene, and we found potential candidate drugs using CellMiner. We also evaluated the correlation between the expression of ADH1B and its methylation level. Furthermore, Western blot analysis was performed to validate the expression of ADH1B in normal hepatocytes LO2 and LIHC cell line HepG2.Results: We screened eight potential candidate genes (ASPM, CDK4, PTMA, TAT, ADH1B, ANXA10, OGDHL, and PON1) associated with afatinib. Patients with higher ASPM, CDK4, PTMA, and TAT exhibited poor prognosis, while those with lower ADH1B, ANXA10, OGDHL, and PON1 had unfavorable prognosis. Next, ADH1B was identified as a key gene negatively correlated with the immune score. The expression of ADH1B was distinctly downregulated in tumor tissues of pan-cancer. The expression of ADH1B was negatively correlated with ADH1B methylation. Small-molecule drugs panobinostat, oxaliplatin, ixabepilone, and seliciclib were significantly associated with ADH1B. The protein level of ADH1B was significantly downregulated in HepG2 cells compared with LO2 cells.Conclusion: Our study provides ADH1B as a key afatinib-related gene, which is associated with the immune microenvironment and can be used to predict the prognosis of LIHC. It is also a potential target of candidate drugs, sharing a promising approach to the development of novel drugs for the treatment of LIHC.
A comprehensive comparison of the in vitro hemocompatibility of extracorporeal centrifugal blood pumps
Authors: Li Ping , Mei Xu , Ge Wanning , Wu Tingting , Zhong Min , Huan Nana , Jiang Qiubo , Hsu Po-Lin , Steinseifer Ulrich , Dong Nianguo , Zhang Liudi 
Published: May 2023

Purpose: Blood damage has been associated with patients under temporary continuous-flow mechanical circulatory support. To evaluate the side effects caused by transit blood pumping, in vitro hemocompatibility testing for blood damage in pumps is considered a necessary reference before clinical trials.Methods: The hemocompatibility of five extracorporeal centrifugal blood pumps was investigated comprehensively, including four commercial pumps (the Abbott CentriMag, the Terumo Capiox, the Medos DP3, and the Medtronic BPX-80) and a pump in development (the magAssist MoyoAssist®). In vitro, hemolysis was tested with heparinized porcine blood at nominal operating conditions (5 L/min, 160 mmHg) and extreme operating conditions (1 L/min, 290 mmHg) using a circulation flow loop. Hematology analyses concerning the blood cell counts and the degradation of high-molecular-weight von Willebrand factor (VWF) during 6-h circulation were also evaluated.Results: Comparing the in vitro hemocompatibility of blood pumps at different operations, the blood damage was significantly more severe at extreme operating conditions than that at nominal operating conditions. The performance of the five blood pumps was arranged in different orders at these two operating conditions. The results also demonstrated superior hemocompatibility of CentriMag and MoyoAssist® at two operating conditions, with overall low blood damage at hemolysis level, blood cell counts, and degradation of high-molecular-weight VWF. It suggested that magnetic bearings have an advantage in hemocompatibility compared to the mechanical bearing of blood pumps.Conclusion: Involving multiple operating conditions of blood pumps in in vitro hemocompatibility evaluation will be helpful for clinical application. In addition, the magnetically levitated centrifugal blood pump MoyoAssist® shows great potential in the future as it demonstrated good in vitro hemocompatibility.
An in-field heat treatment to reduce Cercospora beticola survival in plant residue and improve Cercospora leaf spot management in sugarbeet
Authors: Hernandez Alexandra P. , Bublitz Daniel M. , Wenzel Thomas J. , Ruth Sarah K. , Bloomingdale Chris , Mettler David C. , Bloomquist Mark W. , Hanson Linda E. , Willbur Jaime F. 
Published: May 2023

IntroductionSugarbeets account for 55 to 60% of U.S. sugar production. Cercospora leaf spot (CLS), primarily caused by the fungal pathogen Cercospora beticola, is a major foliar disease of sugarbeet. Since leaf tissue is a primary site of pathogen survival between growing seasons, this study evaluated management strategies to reduce this source of inoculum.MethodsFall- and spring-applied treatments were evaluated over three years at two study sites. Treatments included standard plowing or tilling immediately post-harvest, as well as the following alternatives to tillage: a propane-fueled heat treatment either in the fall immediately pre-harvest or in the spring prior to planting, and a desiccant (saflufenacil) application seven days pre-harvest. After fall treatments, leaf samples were evaluated to determine C. beticola viability. The following season, inoculum pressure was measured by monitoring CLS severity in a susceptible beet variety planted into the same plots and by counting lesions on highly susceptible sentinel beets placed into the field at weekly intervals (fall treatments only).ResultsNo significant reductions in C. beticola survival or CLS were observed following fall-applied desiccant. The fall heat treatment, however, significantly reduced lesion sporulation (2019-20 and 2020-21, P &lt; 0.0001; 2021-22, P &lt; 0.05) and C. beticola isolation (2019-20, P &lt; 0.05) in at-harvest samples. Fall heat treatments also significantly reduced detectable sporulation for up to 70- (2021-22, P &lt; 0.01) or 90-days post-harvest (2020-21, P &lt; 0.05). Reduced numbers of CLS lesions were observed on sentinel beets in heat-treated plots from May 26-June 2 (P &lt; 0.05) and June 2-9 (P &lt; 0.01) in 2019, as well as June 15-22 (P &lt; 0.01) in 2020. Both fall- and spring-applied heat treatments also reduced the area under the disease progress curve for CLS assessed the season after treatments were applied (Michigan 2020 and 2021, P &lt; 0.05; Minnesota 2019, P &lt; 0.05; 2021, P &lt; 0.0001).DiscussionOverall, heat treatments resulted in CLS reductions at levels comparable to standard tillage, with more consistent reductions across year and location. Based on these results, heat treatment of fresh or overwintered leaf tissue could be used as an integrated tillage-alternative practice to aid in CLS management.
Mixed legume–grass seeding and nitrogen fertilizer input enhance forage yield and nutritional quality by improving the soil enzyme activities in Sichuan, China
Authors: Tahir Muhammad , Wei Xiao , Liu Haiping , Li Jiayi , Zhou Jiqiong , Kang Bo , Jiang Dongmei , Yan Yanhong 
Published: May 2023

Information regarding relationships between forage yield and soil enzymes of legume–grass mixtures under nitrogen (N) fertilization can guide the decision-making during sustainable forage production. The objective was to evaluate the responses of forage yield, nutritional quality, soil nutrients, and soil enzyme activities of different cropping systems under various N inputs. Alfalfa (Medicago sativa L.), white clover (Trifolium repens L.), orchardgrass (Dactylis glomerata L.), and tall fescue (Festuca arundinacea Schreb.) were grown in monocultures and mixtures (A1: alfalfa, orchardgrass, and tall fescue; A2: alfalfa, white clover, orchardgrass, and tall fescue) under three N inputs (N1: 150 kg ha−1; N2, 300 kg ha−1; and N3: 450 kg ha−1) in a split plot arrangement. The results highlight that A1 mixture under N2 input had a greater forage yield of 13.88 t ha−1 year−1 than the other N inputs, whereas A2 mixture under N3 input had a greater forage of 14.39 t ha−1 year−1 than N1 input, but it was not substantially greater than N2 input (13.80 t ha−1 year−1). The crude protein (CP) content of grass monocultures and mixtures significantly (P &lt; 0.05) increased with an increase in the rate of N input, and A1 and A2 mixtures under N3 input had a greater CP content of 18.91% and 18.94% dry matter, respectively, than those of grass monocultures under various N inputs. The A1 mixture under N2 and N3 inputs had a substantially greater (P &lt; 0.05) ammonium N content of 16.01 and 16.75 mg kg−1, respectively, whereas A2 mixture under N3 had a greater nitrate N content of 4.20 mg kg−1 than the other cropping systems under various N inputs. The A1 and A2 mixtures under N2 input had a substantial higher (P &lt; 0.05) urease enzyme activity of 0.39 and 0.39 mg g−1 24 h−1 and hydroxylamine oxidoreductase enzyme activity of 0.45 and 0.46 mg g−1 5 h−1, respectively, than the other cropping systems under various N inputs. Taken together, growing legume–grass mixtures under N2 input is cost-effective, sustainable, and eco-friendly, which provide greater forage yield and improved nutritional quality by the better utilization of resources.
Navigating cultural transitions during resettlement: the case of unaccompanied refugee minors
Authors: Andersson Elin Sofia , Øverlien Carolina 
Published: May 2023

IntroductionRefugees face the process of cross-cultural transitions upon arrival in their host country. This process is commonly referred to as acculturation and can be particularly challenging for asylum-seeking children and adolescent unaccompanied by a caregiver. To more effectively facilitate unaccompanied refugee minors (URMs) resettlement, this study sought to obtain an enhanced understanding of the acculturation processes of these youth’.MethodsThus, interviews with 48 URMs, all of whom arrived before the age of 16 years, were analyzed in two steps. First, how the youth described their host country’s society and culture, followed by how they navigated within this societal and cultural landscape during resettlement.ResultsThe youth described how they navigated the Norwegian cultural and societal landscape by gaining cultural competence, adapting and finding ways to contribute, which made it easier for the youth to gain access to the society, to succeed as well as enhance their sense of agency. However, the youths also reported having to navigate between the expectations of their original and host country cultures, struggling with finding a balance between the two cultures.DiscussionThe youth’ acculturation processes seemed to be the result of both their own needs, wishes and behavior as well as specific features in their host country culture, which supports the notion that acculturation processes to some degree are context- and culture-dependent. Knowledge regarding the cultural and societal framework that these youth face and how they navigate within it during resettlement is critical for identifying possible cross-cultural challenges and promoting positive developmental tracks. To understand more about acculturation and integration processes, future research should include specific cultural and societal features as well as immigrants’ own perspectives and experiences during resettlement.
TMS reveals a two-stage priming circuit of gesture-speech integration
Authors: Zhao Wanying 
Published: May 2023

IntroductionNaturalistically, multisensory information of gesture and speech is intrinsically integrated to enable coherent comprehension. Such cross-modal semantic integration is temporally misaligned, with the onset of gesture preceding the relevant speech segment. It has been proposed that gestures prime subsequent speech. However, there are unresolved questions regarding the roles and time courses that the two sources of information play in integration.MethodsIn two between-subject experiments of healthy college students, we segmented the gesture-speech integration period into 40-ms time windows (TWs) based on two separately division criteria, while interrupting the activity of the integration node of the left posterior middle temporal gyrus (pMTG) and the left inferior frontal gyrus (IFG) with double-pulse transcranial magnetic stimulation (TMS). In Experiment 1, we created fixed time-advances of gesture over speech and divided the TWs from the onset of speech. In Experiment 2, we differentiated the processing stages of gesture and speech and segmented the TWs in reference to the speech lexical identification point (IP), while speech onset occurred at the gesture semantic discrimination point (DP).ResultsThe results showed a TW-selective interruption of the pMTG and IFG only in Experiment 2, with the pMTG involved in TW1 (−120 ~ −80 ms of speech IP), TW2 (−80 ~ −40 ms), TW6 (80 ~ 120 ms) and TW7 (120 ~ 160 ms) and the IFG involved in TW3 (−40 ~ 0 ms) and TW6. Meanwhile no significant disruption of gesture-speech integration was reported in Experiment 1.DiscussionWe determined that after the representation of gesture has been established, gesture-speech integration occurs such that speech is first primed in a phonological processing stage before gestures are unified with speech to form a coherent meaning. Our findings provide new insights into multisensory speech and co-speech gesture integration by tracking the causal contributions of the two sources of information.
Mean platelet volume, platelet count, and neutrophil/lymphocyte ratio in drug-naïve patients with schizophrenia: a cross-sectional study
Authors: Cabello-Rangel Héctor , Basurto-Morales Marisol , Botello-Aceves Elizabeth , Pazarán-Galicia Osiris 
Published: May 2023

IntroductionMean platelet volume (MPV), platelet count, and neutrophil/lymphocyte ratio (NLR) have been proposed to be biomarkers of the chronic inflammatory process in schizophrenia and indicative of increased cardiovascular risk.ObjectiveTo describe MPV, total platelet count (PLT), and NLR between healthy controls and patients with schizophrenia to determine the correlation between these parameters and the duration of untreated psychosis (DUP).MethodsIn a retrospective cross-sectional study, we included 175 patients with schizophrenia who had never received psychiatric treatment, and who had undergone blood biometry and blood chemistry within 24 h of admission. Laboratory studies were determined by the impedance method on Coulter ac-T 5 diff hematological equipment.ResultsMean platelet volume levels in patients with schizophrenia were higher than in healthy controls but not statistically significant. The receiver operating characteristic curve for this parameter shows that the optimal cutoff point of agreement was 8.95 fL, with sensitivity and specificity for schizophrenia of 52% and 67%, respectively, and the area under the curve (AUC) was 0.580 (p = 0.079). DUP had no significant correlation with the blood parameters analyzed.ConclusionThe results partially support the hypothesis that MPV, platelet count, and NLR is related to schizophrenia, and further research is needed to establish whether there is an underlying chronic inflammatory process.
Improvement of personality functioning among people treated within personality disorder mental health services. A longitudinal, observational study
Authors: Kvarstein Elfrida H. , Frøyhaug Mathias , Pettersen Mona S. , Carlsen Sara , Ekberg Andreas , Fjermestad-Noll Jane , Ulvestad Dag A. , Gikling Elisabeth L. , Hjermann Eirik , Lindberget Kenneth , Omvik Siri , Eikenæs Ingeborg U-M. , Hummelen Benjamin , Morken Katharina T. E. , Wilberg Theresa , Pedersen Geir A. F. 
Published: May 2023

ObjectiveEvidence-based personality disorder (PD) treatments are dominated by interventions targeting Borderline PD, although clinical populations characteristically include different PD features and severity. Personality functioning is a new concept intended to capture common features across PDs. This study aimed to investigate longitudinal improvement of personality functioning in a clinical sample assigned to PD treatment.MethodAn observational, large, longitudinal study of patients in PD treatments on specialist mental health service levels (N = 1,051). DSM-5 PDs were systematically assessed on referral. Personality functioning was repeatedly assessed (LPFS-BF-2.0), supplemented by symptom distress (anxiety: PHQ-GAD-7, depression: PHQ-9), and social/occupational activity (WSAS, work/study activity). Statistics were linear mixed models.ResultsThirty per cent had personality difficulties below PD threshold. Among PDs, 31% had Borderline (BPD), 39% Avoidant (AvPD), 15% not otherwise specified, 15% other PDs, and 24% &gt; one PD. More severe initial LPFS-BF was associated with younger age, presence of PD and increasing number of total PD criteria. Across PD conditions, LPFS-BF, PHQ-9 and GAD-7 improved significantly (overall effect size 0.9). Mean duration of PD treatment was 15 (SD 9) months. Drop-out rates were low (12%). LPFS-BF improvement-rates were higher for BPD. Younger age was moderately associated with slower PHQ-9 improvement. Work/study activity was initially poor, poorer levels associated with AvPD and younger age, and improvement was non-significant across PD conditions. AvPD was associated with slower WSAS improvement-rates.ConclusionPersonality functioning improved across PD conditions. The results highlight BPD improvements. The study points to challenges concerning AvPD treatment, poor occupational activity and age-related differences.
Effectiveness of a blended learning intervention in cardiac physiotherapy. A randomized controlled trial
Authors: Marques-Sule Elena , Sánchez-González Juan Luis , Carrasco Juan J. , Pérez-Alenda Sofía , Sentandreu-Mañó Trinidad , Moreno-Segura Noemí , Cezón-Serrano Natalia , Ruiz de Viñaspre-Hernández Regina , Juárez-Vela Raúl , Muñoz-Gómez Elena 
Published: May 2023

BackgroundBlended learning (BL) combines both face-to-face learning (FL) and online learning. This study aims to compare the effectiveness of a BL intervention vs. a FL intervention in relation to the knowledge, competencies, satisfaction, perceptions, usability, and BL acceptance of physiotherapy students.MethodsAn assessor-blinded randomized trial was performed. A total of 100 students were randomly allocated to either the BL group (BLG, n = 48) or FL group (FLG, n = 52). The BLG received face-to-face classes plus access to online resources (online syllabus, Moodle, scientific-based videos and websites, activities, glossary, and apps). The FLG received face-to-face classes and hardcopy resources (hardcopy syllabus, scientific-based information, activities, and a glossary). Knowledge, ethical and gender competencies, satisfaction, perceptions, usability, and BL acceptance were assessed.ResultsThe BLG showed higher scores than the FLG for knowledge (p = 0.011), three ethical/gender competencies (p &lt; 0.05), increased motivation to prepare themselves before class (p = 0.005), increased motivation and ability of thinking (p = 0.005), improved understanding of important topics (p = 0.015), course organization (p = 0.017), educational material (p = 0.001), easiness of understanding (p = 0.007), comprehensive coverage of the subject (p = 0.001), and clarity of instructions (p = 0.004), while usability was acceptable.ConclusionThe BL intervention can be used for improving the knowledge, competencies, perceptions, and satisfaction of the students. In addition, BL acceptance was positive, and usability was found to be acceptable. This study supports the use of BL as a pedagogical approach to foster innovative learning.