bluuebunny/crossref_metadata_2025_split huggingface dataset:
GAP-43 closely interacts with BDNF in hippocampal neurons and is associated with Alzheimer's disease progression
Authors: Lee Ye Ji , Jeong Ye Ji , Kang Eun Ji , Kang Beom Seok , Lee Song Hee , Kim You Jin , Kang Seong Su , Suh Sang Won , Ahn Eun Hee 
Published: April 2023

IntroductionGrowth-associated protein 43 (GAP-43) is known as a neuronal plasticity protein because it is widely expressed at high levels in neuronal growth cones during axonal regeneration. GAP-43 expressed in mature adult neurons is functionally important for the neuronal communication of synapses in learning and memory. Brain-derived neurotrophic factor (BDNF) is closely related to neurodegeneration and synaptic plasticity during the aging process. However, the molecular mechanisms regulating neurodegeneration and synaptic plasticity underlying the pathogenesis and progression of Alzheimer's disease (AD) still remain incompletely understood.MethodsRemarkably, the expressions of GAP-43 and BDNF perfectly match in various neurons in the Human Brain Atlas database. Moreover, GAP-43 and BDNF are highly expressed in a healthy adults' hippocampus brain region and are inversely correlated with the amyloid beta (Aβ), which is the pathological peptide of amyloid plaques found in the brains of patients with AD.ResultsThese data led us to investigate the impact of the direct molecular interaction between GAP-43 and BDNF in hippocampal neuron fate. In this study, we show that GAP-43 and BDNF are inversely associated with pathological molecules for AD (Tau and Aβ). In addition, we define the three-dimensional protein structure for GAP-43 and BDNF, including the predictive direct binding sites via analysis using ClusPro 2.0, and demonstrate that the deprivation of GAP-43 and BDNF triggers hippocampal neuronal death and memory dysfunction, employing the GAP-43 or BDNF knock-down cellular models and 5XFAD mice.ConclusionThese results show that GAP-43 and BDNF are direct binding partners in hippocampal neurons and that their molecular signaling might be potential therapeutic targets for AD.
Effects of Niacin on Resistance to Enterotoxigenic Escherichia coli Infection in Weaned Piglets
Authors: Zhen Rui , Feng Junsen , He Dongsheng , Chen Yibo , Chen Tianbao , Cai Weiyou , Xiong Yunxia , Qiu Yueqin , Jiang Zongyong , Wang Li , Yi Hongbo 
Published: April 2023

Graphical AbstractNicotinic acid could improve intestinal antimicrobial peptides to enhance resistance of weaned piglets to E. coli infection by regulating intestinal microflora and its metabolites, histone deacetylase SIRT1 and HDAC7, modification sites such as acH3K9, acH3K27, and pH3S10 in the promoter region.
An 8-step approach for the systematic development of an evidence-based exercise program for patients undergoing hematopoietic stem cell transplantation
Authors: An Ki-Yong , Yu Mi-Seong , Cho Wonhee , Choi Meeok , Courneya Kerry S. , Cheong June-Won , Jeon Justin Y. 
Published: April 2023

BackgroundA tailored and reliable intervention program developed based on evidence is necessary for patients with serious health conditions.ObjectiveWe describe the development of an exercise program for HSCT patients based on evidence from a systematic process.MethodsWe developed the exercise program for HSCT patients using eight systematic steps: (1) a literature review, (2) understanding patient characteristics, (3) first expert group discussion, (4) development of the first draft of the exercise program, (5) a pre-test, (6) second expert group discussion, (7) a pilot randomized controlled trial (n=21), and (8) a focus group interview.ResultsThe developed exercise program was unsupervised and consisted of different exercises and intensities according to the patients’ hospital room and health condition. Participants were provided with instructions for the exercise program, exercise videos via smartphone, and prior education sessions. In the pilot trial, the adherence to the exercise program was only 44.7%, however, some changes in physical functioning and body composition favored the exercise group despite the small sample size.ConclusionStrategies to improve adherence to this exercise program and larger sample sizes are needed to adequately test if the developed exercise program may help patients improve physical and hematologic recovery after HSCT. This study may help researchers develop a safe and effective evidence-based exercise program for their intervention studies. Moreover, the developed program may benefit the physical and hematological recovery in patients undergoing HSCT in larger trials, if exercise adherence is improved.Clinical trial registrationhttps://cris.nih.go.kr/cris/search/detailSearch.do?seq=24233&amp;search_page=L, identifier KCT 0008269.
Combined treatment of disulfiram with PARP inhibitors suppresses ovarian cancer
Authors: Tang Bin , Wu Min , Zhang Lin , Jian Shuyi , Lv Shiyi , Lin Tongyuan , Zhu Shuangshuang , Liu Layang , Wang Yixue , Yi Zhengfang , Jiang Feiyun 
Published: April 2023

IntroductionDue to the difficulty of early diagnosis, nearly 70% of ovarian cancer patients are first diagnosed at an advanced stage. Thus, improving current treatment strategies is of great significance for ovarian cancer patients. Fast-developing poly (ADP-ribose) polymerases inhibitors (PARPis) have been beneficial in the treatment of ovarian cancer at different stages of the disease, but PARPis have serious side effects and can result in drug resistance. Using PARPis in combination with other drug therapies could improve the efficacy of PRAPis.In this study, we identified Disulfiram as a potential therapeutic candidate through drug screening and tested its use in combination with PARPis.MethodsCytotoxicity tests and colony formation experiments showed that the combination of Disulfiram and PARPis decreased the viability of ovarian cancer cellsResultsThe combination of PARPis with Disulfiram also significantly increased the expression of DNA damage index gH2AX and induced more PARP cleavage. In addition, Disulfiram inhibited the expression of genes associated with the DNA damage repair pathway, indicating that Disulfiram functions through the DNA repair pathway.DiscussionBased on these findings, we propose that Disulfiram reinforces PARPis activity in ovarian cancer cells by improving drug sensitivity. The combined use of Disulfiram and PARPis provides a novel treatment strategy for patients with ovarian cancer.
Development and validation of a clinical survival model for young-onset colorectal cancer with synchronous liver-only metastases: a SEER population-based study and external validation
Authors: Li Tao , Liang Yahang , Wang Daqiang , Zhou Zhen , Shi Haoran , Li Mingming , Liao Hualin , Li Taiyuan , Lei Xiong 
Published: April 2023

BackgroundThe morbidity and mortality of young-onset colorectal cancer (YO-CRC) patients have been increasing in recent years. Moreover, YO-CRC patients with synchronous liver-only metastases (YO-CRCSLM) have various survival outcomes. Therefore, the purpose of this study was to construct and validate a prognostic nomogram for patients with YO-CRCSLM.MethodsThe YO-CRCSLM patients were rigorously screened from the Surveillance, Epidemiology, and End Results (SEER) database in January 2010 and December 2018 and then assigned to a training and validation cohort randomly (1488 and 639 patients, respectively). Moreover, the 122 YO-CRCSLM patients who were enrolled in The First Affiliated Hospital of Nanchang University were served as a testing cohort. The variables were selected using the multivariable Cox model based on the training cohort and then developed a nomogram. The validation and testing cohort were used to validate the model’s predictive accuracy. The calibration plots were used to determine the Nomogram’s discriminative capabilities and precision, and the decision analysis (DCA) was performed to evaluate the Nomogram’s net benefit. Finally, the Kaplan-Meier survival analyses were performed for the stratified patients based on total nomogram scores classified by the X-tile software.ResultsThe Nomogram was constructed including ten variables: marital status, primary site, grade, metastatic lymph nodes ratio (LNR), T stage, N stage, carcinoembryonic antigen (CEA), Surgery, and chemotherapy. The Nomogram performed admirably in the validation and testing group according to the calibration curves. The DCA analyses showed good clinical utility values. Low-risk patients (score&lt;234) had significantly better survival outcomes than middle-risk (234–318) and high-risk (&gt;318) patients (P &lt; 0.001).ConclusionA nomogram predicting the survival outcomes for patients with YO-CRCSLM was developed. In addition to facilitating personalized survival prediction, this nomogram may assist in developing clinical treatment strategies for patients with YO-CRCSLM who are undergoing treatment.
Surgical treatment for recurrent cholangiocarcinoma: a single-center series
Authors: Fernández Laura , Gastaca Mikel , Alonso Eva , Prieto Mikel , Ruiz Patricia , Ventoso Alberto , Palomares Ibone , Perfecto Arkaitz , Valdivieso Andrés 
Published: April 2023

PurposeThe present study aims to assess the results obtained after surgical treatment of cholangiocarcinoma (CC) recurrences.MethodsWe carried out a single-center retrospective study, including all patients with recurrence of CC. The primary outcome was patient survival after surgical treatment compared with chemotherapy or best supportive care. A multivariate analysis of variables affecting mortality after CC recurrence was performed.ResultsEighteen patients were indicated surgery to treat CC recurrence. Severe postoperative complication rate was 27.8% with a 30-day mortality rate of 16.7%. Median survival after surgery was 15 months (range 0-50) with 1- and 3-year patient survival rates of 55.6% and 16.6%, respectively. Patient survival after surgery or CHT alone, was significantly better than receiving supportive care (p&lt; 0.001). We found no significant difference in survival when comparing CHT alone and surgical treatment (p=0.113). Time to recurrence of &lt;1 year, adjuvant CHT after resection of the primary tumor and undergoing surgery or CHT alone versus best supportive care were independent factors affecting mortality after CC recurrence in the multivariate analysis.ConclusionSurgery or CHT alone improved patient survival after CC recurrence compared to best supportive care. Surgical treatment did not improve patient survival compared to CHT alone.
Prevalence and determinants of anemia among children aged from 6 to 59 months in Liberia: a multilevel analysis of the 2019/20 Liberia demographic and health survey data
Authors: Adugna Dagnew Getnet , Kibret Anteneh Ayelign , Aragie Hailu , Enyew Engidaw Fentahun , Dessie Gashaw , Melese Mihret , Simegn Wudneh , Abebe Endeshaw Chekol , Admasu Fitalew Tadele , Dejenie Tadesse Asmamaw 
Published: April 2023

BackgroundAnemia is a serious worldwide public health issue that happens at any stage of life but primarily affects young kids and pregnant mothers. Although anemia has a significant impact on child health, its magnitude and associated factors in children aged 6–59 months have not been yet studied in Liberia. Therefore, the aim of this study was to identify the prevalence and determinants of anemia in children aged 6–59 months in Liberia.MethodsThe data was extracted from Liberia Demographic and Health Survey, conducted from October 2019 to February 2020. The sample was obtained using a stratified two-stage cluster sampling technique. An overall weighted sample of 2,524 kids aged 6–59 months was involved in the final analysis. We used Stata version 14 software for data extraction and analysis. A multilevel logistic regression model was employed to identify factors associated with anemia. Variables with aP-value of &lt;0.2 in the bivariable logistic regression analysis were selected as candidates for multivariable analysis. In multivariable analysis, the adjusted odds ratios (AOR) with the 95% confidence interval (CI) were declared as the determinants of anemia.ResultsThe prevalence of anemia in children aged 6–59 months in Liberia was 70.8% [95% CI: 68.9%, 72.5%]. Of these, 3.4% were severe anemia, 38.3% were moderate anemia and 29.1% were mild anemia. Children aged 6–23 and 24–42 months, being stunted, children from households with unimproved toilet facilities, children from households with unimproved water sources, and lack of media (television) exposure were significantly associated with higher odds of anemia. However, using mosquito bed nets, living in the Northwestern and Northcentral region were significantly associated with lower odds of anemia among children 6–59 months.ConclusionIn this study, anemia in kids aged 6–59 months in Liberia was a main public health issue. Age of the child, stunting, toilet facility, water source, exposure to television, mosquito bed net use, and region were significant determinants of anemia. Therefore, it is better to provide intervention for the early detection and management of stunted children. Similarly, interventions should be strengthened to address unimproved water sources, unimproved toilet facilities, and lack of media exposure.
Associations of maternal pre-pregnancy body mass index and gestational weight gain with risk of offspring neurodevelopment at 2 years: A Chinese birth cohort study
Authors: Dong Xiaohan , Zhou Aifen 
Published: April 2023

IntroductionIn recent decades, there has been a surge in both obesity and developmental impairments. Only a few research have looked at the relationship between gestational weight growth and pre-pregnancy BMI in mothers and the neurobehavioral development of their infants. The current research investigates the associations among maternal pre-pregnancy BMI, GWG, and the risk of child neural development at 2 years of age depending on a Chinese birth prospective study.MethodsThe study population was 3,115 mother-infant pairs were registered in the Wuhan Health Baby cohort between September 2013 and October 2018, and data from this cohort was used in this investigation. The Chinese classification was used to group maternal BMI before conception. Based on the 2019 Life Cycle Project-Maternal Obesity and Childhood Outcomes Study Group, categories for GWG were created. The outcome was an assessment of child neural development at age 2 which was measured by employing a Chinese translation of the Bayley scales (BSID-CR). The multivariate regression models were used to calculate the beta (β) coefficients and 95% confidence intervals (CIs) for estimating the associations between continuous Bayley scores and maternal pre-pregnancy BMI categories, as same as in GWG categories.ResultsInfants of overweight and obese moms exhibited lower MDI scores than those of mothers with normal pre-pregnancy BMI (β = −2.510, 95%CI = −4.821 to −0.200) in the entire sample. Meanwhile, we find among the normal pre-pregnancy BMI mothers, infants of inadequate GWG mothers had lower MDI scores (β = −3.952, 95%CI = −7.809 to −0.094) compared with the referenced adequate GWG mothers, as well as the infants of excessive GWG mothers among the underweight pre-pregnancy BMI mothers (β = −5.173, 95%CI = −9.803 to −0.543). The PDI scores of the infants were not affected by the maternal pre-pregnancy BMI or GWG.ConclusionFor Chinese babies aged 2 in this nationally representative sample, aberrant pre-pregnancy BMI and GWG can impair infants’ mental development, but not psychomotor development. Such results are significant given the incidence of overweight and obesity as well as the long-term effects of early brain development. In this study we found optimal GWG recommendations proposed by 2019 Life Cycle Project-Maternal Obesity and Childhood Outcomes Study Group were more suitable for Chinese women than 2009 Institute of Medicine(IOM) guidelines. Additionally, women should be given general advice on how to achieve their ideal pre-pregnancy BMI and GWG.
LC–MS/MS-based multiplex antibacterial platform for therapeutic drug monitoring in intensive care unit patients
Authors: Liu Liang , Zhang Liu , Zheng Xiangyi , Liu Xing , Liu Wei , Wu Jianhua 
Published: April 2023

Empirically prescribed standard dosing regimens of antibacterial agents may result in insufficient or excess plasma concentrations with persistently poor clinical outcomes, especially for patients in intensive care units (ICUs). Therapeutic drug monitoring (TDM) of antibacterial agents can guide dose adjustments to benefit patients. In this study, we developed a robust, sensitive, and simple liquid chromatography-tandem mass spectrometry (LC–MS/MS) platform for the quantification of 14 antibacterial and antifungal agents (beta-lactams piperacillin, cefoperazone, and meropenem; beta-lactamase inhibitors tazobactam and sulbactam; antifungal agents fluconazole, caspofungin, posaconazole, and voriconazole; and daptomycin, vancomycin, teicoplanin, linezolid, and tigecycline) that can be used for patients with severe infection. This assay requires only 100 µL of serum with rapid protein precipitation. Chromatographic analysis was performed using a Waters Acquity UPLC C8 column. Three stable isotope-labeled antibacterial agents and one analogue were used as internal standards. Calibration curves ranged from 0.1–100 μg/mL, 0.1–50 μg/mL, and 0.3–100 μg/mL for different drugs, and all correlation coefficients were greater than 0.9085. Intra- and inter-day imprecision and inaccuracy values were below 15%. After validation, this new method was successfully employed for TDM in routine practice.
Neuroprotective effects of açaí (Euterpe oleracea Mart.) against diabetic retinopathy
Authors: de Oliveira Edwiges de Fátima , Brasil Alódia , Herculano Anderson Manoel , Rosa Matheus A. , Gomes Bruno Duarte , Rocha Fernando Allan de Farias 
Published: April 2023

Introduction: Diabetes mellitus describes a metabolic disorder of multiple etiologies, characterized by chronic hyperglycemia, which induces a series of molecular events capable of leading to microvascular damage, affecting the blood vessels of the retina, causing diabetic retinopathy. Studies indicate that oxidative stress plays a central role in complications involving diabetes. Açaí (Euterpe oleracea) has attracted much attention given its antioxidant capacity and potential associated health benefits in preventing oxidative stress, one of the causes of diabetic retinopathy. The objective of this work was to evaluate the possible protective effect of açaí (E. oleracea) on the retinal function of mice with induced diabetes, based on full field electroretinogram (ffERG).Methods: We opted for mouse models with induced diabetes by administration of a 2% alloxan aqueous solution and treatment with feed enriched with açaí pulp. The animals were divided into 4 groups: CTR (received commercial ration), DM (received commercial ration), DM + açaí (E. oleracea-enriched ration) and CTR + açaí (E. oleracea-enriched ration). The ffERG was recorded three times, 30, 45 and 60 days after diabetes induction, under scotopic and photopic conditions to access rod, mixed and cone responses, in addition to monitoring the weight and blood glucose of the animals during the study period. Statistical analysis was performed using the two-way ANOVA test with Tukey’s post-test.Results: Our work obtained satisfactory results with the ffERG responses in diabetic animals treated with açaí, where it was observed that there was no significant decrease in the b wave ffERG amplitude of this group over time when compared to the results of the Diabetic group not treated with açaí, which showed a significant reduction of this ffERG component.Discussion: The results of the present study show, for the first time, that treatment with an açaí-enriched diet is effective against the decrease in the amplitude of visual electrophysiological responses in animals with induced diabetes, which opens a new horizon for the prevention of retinal damage in diabetic individuals from treatment with açaí base. However, it is worth mentioning that our findings consist of a preliminary study and further researches and clinical trials are needed to examine açaí potential as an alternative therapy for diabetic retinopathy.
Unveiling behavioral and molecular neuroadaptations related to the antidepressant action of cannabidiol in the unpredictable chronic mild stress model
Authors: García-Gutiérrez María Salud , Navarro Daniela , Austrich-Olivares Amaya , Manzanares Jorge 
Published: April 2023

Introduction: This study aims to further characterize cannabidiol’s pharmacological and molecular profile as an antidepressant.Methods: Effects of cannabidiol (CBD), alone or combined with sertraline (STR), were evaluated in male CD1 mice (n = 48) exposed to an unpredictable chronic mild stress (UCMS) procedure. Once the model was established (4 weeks), mice received CBD (20 mg·kg-1, i.p.), STR (10 mg·kg-1, p.o.) or its combination for 28 days. The efficacy of CBD was evaluated using the light-dark box (LDB), elevated plus maze (EPM), tail suspension (TS), sucrose consumption (SC) and novel object recognition (NOR) tests. Gene expression changes in the serotonin transporter, 5-HT1A and 5-HT2A receptors, BDNF, VGlut1 and PPARdelta, were evaluated in the dorsal raphe, hippocampus (Hipp) and amygdala by real-time PCR. Besides, BDNF, NeuN and caspase-3 immunoreactivity were assessed in the Hipp.Results: CBD exerted anxiolytic and antidepressant-like effects at 4 and 7 days of treatment in the LDB and TS tests, respectively. In contrast, STR required 14 days of treatment to show efficacy. CBD improved cognitive impairment and anhedonia more significantly than STR. CBD plus STR showed a similar effect than CBD in the LBD, TST and EPM. However, a worse outcome was observed in the NOR and SI tests. CBD modulates all molecular disturbances induced by UCMS, whereas STR and the combination could not restore 5-HT1A, BDNF and PPARdelta in the Hipp.Discussion: These results pointed out CBD as a potential new antidepressant with faster action and efficiency than STR. Particular attention should be given to the combination of CBD with current SSRI since it appears to produce a negative impact on treatment.