bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide CRISPR Screening Reveals Pyrimidine Metabolic Reprogramming in 5-FU Chronochemotherapy of Colorectal Cancer
Authors: Niu Ya , Fan Xinyi , Wang Yaping , Lin Jiaxin , Hua Luchun , Li Xiaobo , Qian Ruizhe , Lu Chao 
Published: July 2022

ObjectiveDisruption of the circadian rhythm is associated with cancer occurrence, response to chemotherapy, and poor prognosis. Thus, using internal clock-based chronotherapy to optimize the administration time may improve the therapeutic effects of anticancer drugs while reducing the side effects. Chronotherapy with 5-fluorouracil (5-FU) has been observed in colorectal cancer (CRC) for a long time, but its effect is under controversial and the mechanism remains unclear.MethodsGenome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screening and RNA-sequencing were combined to identify the potential genes or pathways involved in 5-FU chronochemotherapy. Genetic deletion or overexpression of pyrimidine metabolic pathway genes were conducted to examine cellular viability with or without 5-FU via flow cytometry. Western blotting, qPCR, chromatin immunoprecipitation, gain-of-function and loss-of-function assays of several CRC cell lines in vitro and in vivo were used to elaborate and validate the mechanism of 5-FU chronotherapeutic effects.ResultsChronochemotherapeutic effects of 5-FU on CRC in vivo were verified. Furthermore, 5-FU chronochemotherapy related genes such as UPP2, UCK2 and UMPS in the pyrimidine metabolic pathway were identified. Disturbance in these genes, especially UMPS, perturbs 5-FU treatment outcomes in CRC cells. Mechanistically, the core circadian gene, brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 (BMAL1), extensively regulate gene expression in pyrimidine metabolic pathway by binding to E-box element in the promoter region of key genes such as UMPS and perturb their enzymatic activities, thereby maintain diurnal efficacy of 5-FU in CRC cells.ConclusionThis study uncovered a new mechanism by which a core circadian gene BMAL1 increases the effectiveness of 5-FU by enhancing the expression and enzymatic activities of key genes in the pyrimidine metabolic pathway in CRC cells. The findings suggest a novel strategy for CRC chemotherapy by targeting chrono-modulated genes of the 5-FU metabolic pathway.
The Combination of AFP and “Up-To-Seven” Criteria May Be a Better Strategy for Liver Transplantation in Chinese Cirrhotic HCC Patients
Authors: Zhang Da-li , Feng Dan-ni , He Xi , Zhang Xiao-feng , Li Li-xin , Li Zhi-jie , Niu Xiao-feng , Zhuang Yun-long , Liu Zhen-wen , Gao Xu-dong , Wang Hong-bo 
Published: July 2022

BackgroundOrthotopic liver transplantation (OLT) is a life-saving option for patients with hepatocellular carcinoma (HCC), but the expanded OLT criteria remain controversial.ObjectiveThe study aimed to explore whether expanded OLT criteria can be applied to Chinese cirrhotic patients with HCC.MethodsThis retrospective study analyzed risk factors for HCC recurrence and death and compared patients’ tumor characteristics and outcomes in groups of Milan, “Up-to-seven,” and Hangzhou criteria, and groups between met and unmet the combinative criteria of “Up-to-seven” and AFP of &lt; 1000 ng/mL.ResultsAmong 153 patients who underwent OLT for HCC from January 2015 to February 2019 in 4 years of follow-up, 20 (13.1%) patients had HCC recurrence, and 11 (7.2%) had HCC-related death. Multivariate Cox regression analysis showed that preoperative alpha-fetoprotein (AFP) of &gt; 1000 ng/mL (hazard ratio [HR]: 10.05, 95% confidence interval [CI]: 2.45–41.13, P = 0.001) was an independent risk factor for HCC recurrence and HCC-related death (HR: 6.63, 95%CI: 1.31–33.52, P = 0.022). Patients who did not meet Milan criteria but satisfied the “Up-to-seven” criteria had no differences in overall survival (OS) (P = 0.69) and disease-free survival (DFS) (P = 0.35) than patients who met the Milan criteria. The combination of “Up-to-seven” criteria and AFP of &lt; 1000 ng/mL differed significantly (HR: 18.9; 95% CI: 4.0–89.2; P &lt; 0.001). Patients with HCC who met the “Up-to-seven” criteria and AFP of &lt; 1000 ng/mL (n = 121) had excellent survival with 4-year OS of 91.6% (P &lt; 0.001) and DFS of 90.8% (P &lt; 0.001), which is significantly better compared to the other group (n = 32) (OS of 67.5% and DFS of 46.5%) and patients who met the Milan criteria (n = 108, OS of 89.8%, DFS of 89.6%), allowing 28.9% (13/45) of patients who did not meet the Milan criteria to benefit from OLT.ConclusionChinese cirrhotic patients with HCC who met the combinative criteria of “Up-to-seven” and AFP of &lt; 1000 ng/mL had better survival than those who met the Milan criteria, and these combinative criteria benefited more patients and may become a better option for OLT.
Mortality of Hemato-Oncologic Patients Admitted to a Pediatric Intensive Care Unit: A Single-Center Experience
Authors: Pechlaner Agnes , Kropshofer Gabriele , Crazzolara Roman , Hetzer Benjamin , Pechlaner Raimund , Cortina Gerard 
Published: July 2022

IntroductionMortality in children with hemato-oncologic disease admitted to a pediatric intensive care unit (PICU) is higher compared to the general population. The reasons for this fact remain unexplored. The aim of this study was to assess outcomes and trends in hemato-oncologic patients admitted to a PICU, with analytical emphasis on emergency admissions.MethodsPatients with a hemato-oncologic diagnosis admitted to a tertiary care university hospital PICU between 1 January 2009 and 31 December 2019 were retrospectively analyzed. Additionally, patient mortality 6 months after PICU admission and follow-up mortality until 31 December 2020 were recorded.Measurements and Main ResultsWe reviewed a total of 701 PICU admissions of 338 children with hemato-oncologic disease, of which 28.5% were emergency admissions with 200 admissions of 122 patients. Of these, 22 patients died, representing a patient mortality of 18.0% and an admission mortality of 11.0% in this group. Follow-up patient mortality was 25.4% in emergency-admitted children. Multivariable analysis revealed severe neutropenia at admission and invasive mechanical ventilation (IMV) as independent risk factors for PICU death (p = 0.029 and p = 0.002). The total number of PICU admissions of hemato-oncologic patients rose notably over time, from 44 in 2009 to 125 in 2019.ConclusionAlthough a high proportion of emergency PICU admissions of hemato-oncologic patients required intensive organ support, mortality seemed to be lower than previously reported. Moreover, in this study, total PICU admissions of the respective children rose notably over time.
How Well Are Socioeconomic Factors Associated With Improved Outcomes for Infants Diagnosed With Early Childhood Developmental Delay? An Observational Study
Authors: Ji Fang , Sun Yao , Xu Yi , Tang Jian , Hu Jing 
Published: July 2022

PurposeEarly childhood developmental delay remains problematic worldwide in terms of weight and the five domains of child development, including gross motor, fine motor, cognition, language, and social domains. Based on the World Health Organization (WHO) guideline and the theoretical domain framework, this study identified five key socioeconomic factors, such as parenting time during hospitalization, parental educational level, medical spending, distance to hospital, and medical insurance coverage, to describe how these five factors are associated with improved outcomes of developmental quotient (DQ) values and the weight of infants in a tertiary hospital.MethodsIn this prospective observational study, clinical and socioeconomic data were collected. Clinical data included the weight and DQ values of infants and other data relevant to the birth of infants. A National Developmental Scale was used to observe infants in five domains and calculate the DQ values of infants. These five domains include gross motor, fine motor, cognition, language, and social domains. Parenting time during hospitalizations was observed by a research nurse. Other socioeconomic factors were reported by parents and verified with system information.ResultsA total of 75 infants' parents were approached, of which 60 were recruited. The age of infants ranged from 75 to 274 days at the first admission. Increments of their weight and DQ values improved from −0.5 to 2.5 kg and from −13 to 63, respectively. More than half of the parents (54.1%) were at the level of minimum secondary education although the results were not statistically significant. However, there was a positive correlation between weight improvement and parenting time during hospitalization (r(58) = 0.258, p &lt; 0.05), medical spending (r(58) = 0.327, p &lt; 0.05), distance to hospital (r(58) = 0.340, p &lt; 0.01), but there was a negative association with medical insurance coverage (r(58) =-0.256, p &lt; 0.05). There was also a significant relationship between the improved DQ value and distance to hospital (r(58)= 0.424, p &lt; 0.01).ConclusionParenting time during hospitalization, medical spending, distance to hospital, and medical insurance coverage are important factors for early childhood developmental delay in relation to possible hospital intervention and improved accessibility to health services for families in rural areas. Therefore, changes in the current medical scheme are needed because a universal medical subsidy among regions will reduce the financial burden of families and provide families with more access to the necessary health services that their children need.
Case Report: Novel TRPM6 Mutations Cause Hereditary Hypomagnesemia With Secondary Hypocalcemia in a Chinese Family and a Literature Review
Authors: Han Yiran , Zhao Yajuan , Wang Hua , Huo Liang 
Published: July 2022

BackgroundHereditary hypomagnesemia with secondary hypocalcemia (HSH) is a rare autosomal recessive disease due to biallelic TRPM6 mutations. Although the reports of HSH caused by TRPM6 mutations are not very rare, the age of onset in previously reported HSH cases were &lt;1 year.MethodsWe collected and analyzed the clinical data of twin brothers with onset age over 1 year old and performed whole exome sequencing in the patients and their parents. Confirmed by Sanger sequencing, missense mutation was analyzed in silico. We also searched Pubmed, and extracted clinical data from case reports and case series with full text in English, reporting original data of patients with TRPM6 mutations.ResultsThe twin patients had canonical HSH phenotype with compound novel TRPM6 mutations, p.T87K and c.705dupT, inherited from their father and mother, respectively. T87 is a highly conserved site and T87K is predicted to cause hydrogen bond disruption. We identified 26 articles published between May 28, 2002 to December 31, 2021 which reported a total of 88 patients with TRPM6 mutation. We found that the most common clinical phenotypes were hypomagnesemia, hypocalcemia, and convulsions. However, the age of onset in HSH patients almost always occurred under 12 months old, the twin patients of our study were 18 and 26 months old at onset.ConclusionWe identified two novel TRPM6 mutations in a Chinses family with HSH, and showed that the age of onset with c.704c-c.705(exon7)insT and c.260(exon4)C&gt;A mutation in TRPM6 was much later than other mutations and would be much less serious.
Case Report: Successful Treatment of a Child With COVID-19 Reinfection-Induced Fulminant Myocarditis by Cytokine-Adsorbing oXiris® Hemofilter Continuous Veno-Venous Hemofiltration and Extracorporeal Membrane Oxygenation
Authors: Phan Phuc H. , Nguyen Dung T. , Dao Nam H. , Nguyen Ha T. T. , Vu An V. , Hoang Son T. , Nguyen Lam V. , Cao Tung V. , Tran Dien M. 
Published: July 2022

BackgroundIndirect cardiomyocyte damage-related hyperinflammatory response is one of the key mechanisms in COVID-19-induced fulminant myocarditis. In addition to the clinical benefit of using cytokines absorption hemofiltration, the effectiveness of instituting veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support for cardiac compromise has been reported. However, current literature enunciates a paucity of available data on the effectiveness of these novel modalities.Case PresentationWe reported a 9-year-old boy with recurrent COVID-19 infection-causing fulminant myocarditis, who was treated successfully by using novel modalities of oXiris® hemofilter continuous venovenous hemofiltration (CVVH) and VA-ECMO. The patient made a full recovery without any sequelae.ConclusionWe conclude that the novel highly-absorptive hemofilter CVVH and VA-ECMO may be effective treatment modalities in managing SARS-CoV-2-induced fulminant myocarditis. Our report highlights the need for further well-designed investigations to confirm this extrapolation.
Analysis of the Anti-Tumour Effect of Xuefu Zhuyu Decoction Based on Network Pharmacology and Experimental Verification in Drosophila
Authors: Wang Sitong , Wu Chenxi , Li Yinghong , Ye Bin , Wang Shuai , Li Guowang , Wu Jiawei , Liu Shengnan , Zhang Menglong , Jia Yongsen , Cao Huijuan , Jiang Chunhua , Wu Fanwu 
Published: July 2022

Background: Tumours are among the most lethal diseases that heavily endanger human health globally. Xuefu Zhuyu Decoction (XFZYD) is a prescription used to treat blood-activating stasis. Although XFZYD has been shown to suppress migration and invasion of tumour cells, the active ingredients, potential targets, and underlying mechanism remain largely elusive.Purpose: To identify the prospective ingredients and major targets of XFZYD against tumours, and evaluate the efficacy and potential molecular mechanisms of XFZYD extract on tumour growth and invasion.Methods: We predicted that XFZYD might act on 80 targets through 128 active components using the network pharmacology analysis method. In addition, we prepared an XFZYD aqueous extract and employed the RasV12/lgl−/−-induced Drosophila tumour model to carry out experimental verification.Results: XFZYD did not exhibit any side effects on development, viability, and fertility. Furthermore, XFZYD significantly impeded tumour size and invasion at moderate concentrations and suppressed the increased phosphorylation of JNK but strongly enhanced the expression of Caspase 3 in the RasV12/lgl−/− model. Finally, the mRNA level of the transcription complex AP-1 component c-FOS was remarkably reduced. In contrast, the transcription of three pro-apoptotic genes was significantly increased when XFZYD was used to treat the tumour model.Conclusion: The study findings suggest that XFZYD may promote tumour cell apoptosis by activating caspase signalling to control primary growth and hinder tumour cell invasion by suppressing JNK/AP-1 signalling activity, thus providing a potential therapeutic strategy for XFZYD in the clinical treatment of cancer and other related diseases.
Comparative Pharmacokinetics of Three Bioactive Diterpenoids of Rabdosia serra Extract in Normal and Con A-Induced Liver Injury Rats Using UPLC-MS/MS
Authors: Liu Fangle , Zeng Yun , Dai Pengyu , Huang Kaiwen , Zhang Kaihui , Tao Tao , Wang Meiqi , Zhu Chenchen , Lin Chaozhan 
Published: July 2022

Rabdosia serra (Maxim.) Hara (R. serra), one of the source plants of “Xihuangcao”, has been widely used as a Chinese folk herb with the concomitant function of both medicine and foodstuff for the prevention and treatment of liver disease. Diterpenoids were considered as the major bioactive components in R. serra, responsible for their effect on hepatoprotection in previous phytochemical and pharmacological studies, while few comparative pharmacokinetic studies have been conducted under the physiological and pathological conditions. To reveal the difference in the pharmacokinetics process of R. serra extract (RSE) in normal and Con A-induced liver injury rats, a rapid ultra-high-pressure liquid chromatography–tandem mass spectrometry method (total running time: 5 min) was established to simultaneously determine three bioactive diterpenoids (enmein, epinodosin, and isodocarpin) in rat plasma. The results showed significant differences in the pharmacokinetic properties of three analytes between the physiological and pathological states. Compared with normal rats, the AUC of the three analytes was remarkably higher in liver injury rats, while the Tmax, T1/2, and MRT were shortened. It indicated that RSE has higher exposure and quicker elimination in liver injury rats than that in normal rats. Our results suggested that the pharmacokinetics of hepatoprotective medications was affected by liver injury, which prospected to provide essential information for guiding the healthcare and clinical application of R. serra in pathological states.
Alcohol Use Among Young Adults in Northern California During the COVID-19 Pandemic—An Electronic Health Records-Based Study
Authors: Metz Verena E. , Palzes Vanessa A. , Chi Felicia W. , Campbell Cynthia I. , Sterling Stacy A. 
Published: July 2022

BackgroundIndividuals globally were affected by the COVID-19 pandemic in myriad of ways, including social isolation and economic hardship, resulting in negative impacts on mental health and substance use. Young adults have been subjected to extraordinary challenges such as job loss, virtual school, or childcare issues, but have received limited attention from research so far.MethodsUsing electronic health record data from a large integrated healthcare system in Northern California, this longitudinal observational study examined changes in the prevalence of unhealthy alcohol use (identified via systematic alcohol screening in adult primary care) from pre- (3/1/2019–12/31/2019) to post-COVID onset (3/1/2020–12/31/2020) among young adults (18–34 years). Among the 663,111 and 627,095 young adults who utilized primary care in the pre- and post-COVID onset periods, 342,889 (51.9%) and 186,711 (29.8%) received alcohol screening, respectively. We fit generalized estimating equation Poisson models to estimate the change in prevalence of unhealthy alcohol use from pre- to post-COVID onset among those who were screened, while using inverse probability weighting to account for potential selection bias of receiving alcohol screening. Heterogeneity in the change of prevalence by patient characteristics was also examined.ResultsOverall, the unadjusted prevalence of unhealthy alcohol use slightly decreased from 9.2% pre-COVID to 9.0% post-COVID onset. After adjusting for patient covariates, the prevalence of unhealthy alcohol use decreased by about 2% [adjusted prevalence ratio (aPR) = 0.98, 95% CI = 0.96, 1.00]. The prevalence of unhealthy alcohol use increased among women by 8% (aPR = 1.08, 95% CI = 1.06, 1.11), patients 18–20 years by 7% (aPR = 1.07, 95% CI = 1.00, 1.15), and Latino/Hispanic patients by 7% (aPR = 1.07, 95% CI = 1.03, 1.11). While the prevalence of unhealthy alcohol use decreased among men by 12% (aPR = 0.88, 95% CI = 0.86, 0.90), patients 21–34 years by 2% (aPR = 0.98, 95% CI = 0.96, 0.99), White patients by 3% (95% CI = 0.95, 1.00), and patients living in neighborhoods with the lowest deprivation indices by 9% (aPR = 0.91, 95% CI = 0.88, 0.94), their unadjusted prevalence remained higher than their counterparts post-COVID onset. There was no variation in the change of prevalence by comorbid mental health conditions or drug use disorders.ConclusionsWhile changes in unhealthy alcohol use prevalence among young adults were small, findings raise concerns over increased drinking among women, those younger than the U.S. legal drinking age, and Latino/Hispanic patients.
Cortisol, Depression, and Anxiety Levels Before and After Short-Term Intensive Nutritional Stabilization in Patients With Severe Anorexia Nervosa
Authors: Hemmingsen Simone Daugaard , Jensen Nikolai Arndal , Larsen Pia Veldt , Sjögren Jan Magnus , Lichtenstein Mia Beck , Støving René Klinkby 
Published: July 2022

IntroductionDepression and anxiety are well-known comorbid conditions in patients with anorexia nervosa (AN). Hypercortisolemia in patients with AN may be pathogenic and contribute to depression and anxiety symptomatology.ObjectiveThe aim of this study was to investigate short-term changes in cortisol levels and depression and anxiety symptomatology following intensive re-nutrition in patients with severe AN and hospitalized in a specialized unit. Furthermore, we investigated the potential association between cortisol levels and psychometric parameters.MethodsA total of 36 patients with AN were enrolled in the study. Nine dropped out before follow-up. Patients underwent paraclinical and psychometric examinations at admission and discharge. Measurements included plasma cortisol, cortisol binding globulin (CBG), 24-h urine cortisol, and self-report questionnaires regarding eating disorder, depression, anxiety, and stress symptoms. Patients were hospitalized in the unit for somatic stabilization and intensive re-nutrition. Mean admission length was 41 days. The study was registered at ClinicalTrials.gov (NCT02502617).ResultsCortisol levels in blood and urine did not change from admission to discharge in patients with severe AN. Symptoms of depression, anxiety, stress, and eating disorder remained elevated at discharge. There were no associations between changes in cortisol levels and changes in psychometrics.DiscussionOur results suggest that short-term intensive re-nutrition did not alter hypothalamic-pituitary-adrenal axis activity or mental health in patients with severe AN. Long-term stabilization and longer follow-up after hospital discharge may be needed to detect changes in cortisol levels and whether these changes are associated with depression and anxiety symptomatology. Greater knowledge about cortisol levels and mental health in patients with severe AN may help in the development of new treatment choices for the chronically ill patients. Future studies could investigate whether cortisol-lowering drugs have a therapeutic effect on mental health in AN.
Mental Health Status of Medical Staff Exposed to Hospital Workplace Violence: A Prospective Cohort Study
Authors: Wang Licheng , Ni Xin , Li Zhe , Ma Yuanshuo , Zhang Yafeng , Zhang Zhong , Gao Lei , Liu Xinyan , Yan Wenxin , Fan Lihua , Shi Lei 
Published: July 2022

ObjectiveHospital workplace violence is one of the most frequently reported types of workplace violence in the world, and it harms the mental and physical health of medical staff. Existing research on workplace violence focused more on cross-sectional studies, than longitudinal studies. Therefore, this study examined the dynamic impact of hospital workplace violence on the mental health of medical staff, with the aim of providing appropriate countermeasures and suggestions for hospitals to develop targeted psychological intervention measures in time for medical staff who experience workplace violence.DesignA prospective cohort study.ParticipantsA total of 112 medical staff who had experienced workplace violence in the hospital for the first time were chosen.SettingAn unconditional latent variable growth curve model was established based on the average value of the general health scale scores of medical staff, and gender and violence types (intimidation threats, physical violence) as control variables. Each medical staff was assessed for depression and anxiety at 4 different time points and the changes in the trajectories was observed.ResultsThere were significant differences in the incidence of mental health and anxiety among medical staff at different observation times. There were significant individual differences in the initial mental health status, growth rate of anxiety and depression of medical staff.ConclusionsHospitals should undertake various psychological intervention strategies based on the staff's mental health to safeguard those who have experienced workplace violence.