bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction of a Non-Mutually Exclusive Decision Tree for Medication Recommendation of Chronic Heart Failure
Authors: Bai Yongyi , Yao Haishen , Jiang Xuehan , Bian Suyan , Zhou Jinghui , Sun Xingzhi , Hu Gang , Sun Lan , Xie Guotong , He Kunlun 
Published: February 2022

Objective: Although guidelines have recommended standardized drug treatment for heart failure (HF), there are still many challenges in making the correct clinical decisions due to the complicated clinical situations of HF patients. Each patient would satisfy several recommendations, meaning the decision tree of HF treatment should be nonmutually exclusive, and the same patient would be allocated to several leaf nodes in the decision tree. In the current study, we aim to propose a way to ensemble a nonmutually exclusive decision tree for recommendation system for complicated diseases, such as HF.Methods: The nonmutually exclusive decision tree was constructed via knowledge rules summarized from the HF clinical guidelines. Then similar patients were defined as those who followed the same pattern of leaf node allocation according to the decision tree. The frequent medication patterns for each similar patient were mined using the Apriori algorithms, and we also carried out the outcome prognosis analyses to show the capability for the evidence-based medication recommendations of our nonmutually exclusive decision tree.Results: Based on a large database that included 29,689 patients with 84,705 admissions, we tested the framework for HF treatment recommendation. In the constructed decision tree, the HF treatment recommendations were grouped into two independent parts. The first part was recommendations for new cases, and the second part was recommendations when patients had different historical medication. There are 14 leaf nodes in our decision tree, and most of the leaf nodes had a guideline adherence of around 90%. We reported the top 10 popular similar patients, which accounted for 32.84% of the whole population. In addition, the multiple outcome prognosis analyses were carried out to assess the medications for one of the subgroups of similar patients. Our results showed even for the subgroup of the same similar patients that no one medication pattern would benefit all outcomes.Conclusion: In the present study, the methodology to construct a nonmutually exclusive decision tree for medication recommendations for HF and its application in CDSS was proposed. Our framework is universal for most diseases and could be generally applied in developing the CDSS for treatment.
Adverse Drug Reactions with Drugs Used in Multiple Sclerosis: An Analysis from the Italian Pharmacovigilance Database
Authors: Barbieri Maria Antonietta , Sorbara Emanuela Elisa , Battaglia Alessandro , Cicala Giuseppe , Rizzo Vincenzo , Spina Edoardo , Cutroneo Paola Maria 
Published: February 2022

Given the importance of inflammation at the onset of multiple sclerosis (MS), therapy is mainly based on the use of anti-inflammatory drugs including disease modifying therapies (DMTs). Considering the recent approval of some DMTs, pharmacovigilance becomes a fundamental tool for the acquisition of new safety data. The aim of the study was to analyze adverse drug reactions (ADRs) related to the use of drugs approved for MS. All national publicly-available aggregated ADR reports recorded from 2002 to 2020 into the Reports of Adverse Reactions of Medicines (RAM) system and all complete Sicilian data reported into the Italian spontaneous reporting system (SRS) database having as suspected drugs interferon β-1a (IFN β-1a), interferon β-1b (IFN β-1b), peginterferon β-1a (PEG-IFN β-1a), glatiramer acetate (GA), natalizumab (NTZ), fingolimod (FNG), teriflunomide (TRF), dimethyl fumarate (DMF), alemtuzumab (Alem), ocrelizumab (OCZ), or cladribine (Cladr), were collected. Descriptive analyses of national, publicly-available aggregated data and full-access regional data were performed to assess demographic characteristics and drug-related variables followed by a more in-depth analysis of all Sicilian ADRs with a case-by-case assessment and a disproportionality analysis of unexpected ADRs. A total of 13,880 national reports have been collected from 2002 to 2020: they were mainly not serious ADRs (67.9% vs. 26.1%) and related to females (71.7% vs. 26.3%) in the age group 18–65 years (76.5%). The most reported ADRs were general and administration site conditions (n = 6,565; 47.3%), followed by nervous (n = 3,090; 22.3%), skin (n = 2,763; 19.9%) and blood disorders (n = 2,180; 15.7%). Some unexpected Sicilian ADRs were shown, including dyslipidemia for FNG (n = 10; ROR 28.5, CI 14.3–59.6), NTZ (n = 5; 10.3, 4.1–25.8), and IFN β-1a (n = 4; 8.7, 3.1–24.1), abortion and alopecia for NTZ (n = 9; 208.1, 73.4–590.1; n = 3; 4.9, 1.5–15.7), and vitamin D deficiency for GA (n = 3; 121.2, 30.9–475.3). Moreover, breast cancer with DMF (n = 4, 62.8, 20.5–191.9) and hypothyroidism with Cladr (n = 3; 89.2, 25.9–307.5) were also unexpected. The reporting of drugs-related ADRs in MS were mostly reported in the literature, but some unknown ADRs were also found. However, further studies are necessary to increase the awareness about the safety profiles of new drugs on the market.
Ca2+-Permeable Channels/Ca2+ Signaling in the Regulation of Ileal Na+/Gln Co-Transport in Mice
Authors: Chu Fenglan , Wan Hanxing , Xiao Weidong , Dong Hui , Lü Muhan 
Published: February 2022

Oral glutamine (Gln) has been widely used in gastrointestinal (GI) clinical practice, but it is unclear if Ca2+ regulates intestinal Gln transport, although both of them are essential nutrients for mammals. Chambers were used to determine Gln (25 mM)-induced Isc through Na+/Gln co-transporters in the small intestine in the absence or the presence of selective activators or blockers of ion channels and transporters. Luminal but not serosal application of Gln induced marked intestinal Isc, especially in the distal ileum. Lowering luminal Na+ almost abolished the Gln-induced ileal Isc, in which the calcium-sensitive receptor (CaSR) activation were not involved. Ca2+ removal from both luminal and serosal sides of the ileum significantly reduced Gln- Isc. Blocking either luminal Ca2+ entry via the voltage-gated calcium channels (VGCC) or endoplasmic reticulum (ER) release via inositol 1,4,5-triphosphate receptor (IP3R) and ryanodine receptor (RyR) attenuated the Gln-induced ileal Isc, Likewise, blocking serosal Ca2+ entry via the store-operated Ca2+ entry (SOCE), TRPV1/2 channels, and Na+/Ca2+ exchangers (NCX) attenuated the Gln-induced ileal Isc. In contrast, activating TRPV1/2 channels enhanced the Gln-induced ileal Isc. We concluded that Ca2+ signaling is critical for intestinal Gln transport, and multiple plasma membrane Ca2+-permeable channels and transporters play roles in this process. The Ca2+ regulation of ileal Na+/Gln transport expands our understanding of intestinal nutrient uptake and may be significant in GI health and disease.
Impact of Fluoxetine Treatment and Folic Acid Supplementation on the Mammary Gland Transcriptome During Peak Lactation
Authors: Sheftel Celeste M. , Liu Lihe , Field Sena L. , Weaver Samantha R. , Vezina Chad M. , Peñagaricano Francisco , Hernandez Laura L. 
Published: February 2022

Serotonin is a key regulator of mammary gland homeostasis during lactation. Selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat peripartum depression, but also modulates mammary gland serotonin concentrations and signaling in part through DNA methylation. The objective of this study was to determine mouse mammary transcriptome changes in response to the SSRI fluoxetine and how methyl donor supplementation, achieved by folic acid supplementation, affected the transcriptome. Female C57BL/6J mice were fed either breeder diet (containing 4 mg/kg folic acid) or supplemented diet (containing 24 mg/kg folic acid) beginning 2 weeks prior to mating, then on embryonic day 13 mice were injected daily with either saline or 20 mg/kg fluoxetine. Mammary glands were harvested at peak lactation, lactation day 10, for transcriptomic analysis. Fluoxetine but not folic acid altered circulating serotonin and calcium concentrations, and folic acid reduced mammary serotonin concentrations, however only fluoxetine altered genes in the mammary transcriptome. Fluoxetine treatment altered fifty-six genes. Elovl6 was the most significantly altered gene by fluoxetine treatment along with gene pathways involving fatty acid homeostasis, PPARγ, and adipogenesis, which are critical for milk fat synthesis. Enriched pathways in the mammary gland by fluoxetine revealed pathways including calcium signaling, serotonin receptors, milk proteins, and cellular response to cytokine stimulus which are important for lactation. Although folic acid did not impact specific genes, a less stringent pathway analysis revealed more diffuse effects where folic acid enriched pathways involving negative regulation of gene expression as expected, but additionally enriched pathways involving serotonin, glycolysis, and lactalbumin which are critical for lactation. In conclusion, peripartal SSRI use and folic acid supplementation altered critical genes related to milk synthesis and mammary gland function that are important to a successful lactation. However, folic acid supplementation did not reverse changes in the mammary gland transcriptome altered by peripartal SSRI treatment.
Canagliflozin Prevents Lipid Accumulation, Mitochondrial Dysfunction, and Gut Microbiota Dysbiosis in Mice With Diabetic Cardiovascular Disease
Authors: Wang Xueliang , Wang Zhe , Liu Di , Jiang Hao , Cai Chao , Li Guoyun , Yu Guangli 
Published: February 2022

Type 2 diabetes mellitus (T2DM) is associated with cardiovascular disease (CVD) and sodium glucose cotransporter 2 inhibitors, as oral medications for T2DM treatment have shown the potential to improve vascular dysfunction. The aim of this study was to evaluate the ability of canagliflozin (Cana) to relieve CVD in T2DM mice and its possible action mechanism. Mice with diabetic CVD was conducted by a high-fat diet for 24 weeks, followed by oral gavaging with metformin (200 mg/kg/day) or Cana (50 mg/kg/day) for 6 weeks. The result demonstrated that Cana reduced serum lipid accumulation, and decreased the arteriosclerosis index and atherogenic index of plasma. In addition, Cana treatment reduced the circulating markers of inflammation. More importantly, Cana improved cardiac mitochondrial homeostasis and relieved oxidative stress. Moreover, Cana treatment alleviated the myocardial injury with decreasing levels of serous soluble cluster of differentiation 40 ligand and cardiac troponin I. Thus, cardiovascular abnormality was relieved by suppressing fibrosis and basement membrane thickening, while elevating the cluster of differentiation 31 expression level. Importantly, Cana increased the ratio of gut bacteria Firmicutes/Bacteroidetes and the relative abundance of Alistipes, Olsenella, and Alloprevotella, while it decreased the abundance of Mucispirillum, Helicobacter, and Proteobacteria at various taxonomic levels in mice with diabetic CVD. In short, Cana treatment altered the colonic microbiota composition close to the normal level, which was related with blood lipid, inflammation, and oxidative stress, and might play a vital role in CVD. In general, the improvements in the gut microbiota and myocardial mitochondrial homeostasis may represent the mechanism of Cana on CVD treatment.
A Comparative Study of the Antihypertensive and Cardioprotective Potentials of Hot and Cold Aqueous Extracts of Hibiscus sabdariffa L. in Relation to Their Metabolic Profiles
Authors: Salem Mohamed A. , Ezzat Shahira M. , Ahmed Kawkab A. , Alseekh Saleh , Fernie Alisdair R. , Essam Reham M. 
Published: February 2022

Ethnopharmacological relevance: Since ancient times, Hibiscus sabdariffa L. calyces have been used as a folk remedy for the treatment of hypertension. However, it is questionable as to whether there is a difference in the antihypertensive activity of the hot or cold aqueous extracts.Aim of the study: We designed this study to specify the best method for water extraction of the antihypertensive metabolites of H. sabdariffa and to confirm their in vivo antihypertensive capabilities.Materials and methods: The powdered dried calyces of H. sabdariffa were independently extracted with cold and hot water. A comparative study was performed between the cold and hot aqueous extracts of H. sabdariffa based on evaluation of the in vitro renin and angiotensin-converting enzyme (ACE) inhibition activities. Additionally, both extracts were subjected to an in vivo study for the evaluation of their antihypertensive activities in L-Nw-Nitro arginine methyl ester (L-NAME)–induced hypertensive rats. Further, a metabolomics study was also performed for both extracts to identify their chemical constituents.Results: The cold and hot extracts significantly reduced the angiotensin II, ACE, and aldosterone levels in the plasma. Furthermore, in the myocardium and aorta, decreased iNOS (inducible nitric oxide synthase) levels and elevated eNOS (endothelial nitric oxide synthase), as well as the rise in plasma NO levels, were reported with both extracts, but better results were displayed with the hot extract, leading to a potential antihypertensive effect. Additionally, the cold and hot Hibiscus extracts induced a cardioprotective effect through reducing necrosis, inflammation, and vacuolization that results from the induction of hypertension, an effect that was more prominent with the hot extract. Moreover, a comprehensive metabolomics approach using ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC–MS/MS) was able to trace the metabolites in each extraction.Conclusion: The extracts showed different anthocyanin and phenolic compounds, but the hot extract showed higher contents of specific phenolics to which the superior antihypertensive and cardioprotective activities could be related.
Unraveling the Proteomic Landscape of Intestinal Epithelial Cell-Derived Exosomes in Mice
Authors: Ding Zhenyu , Zhang Cuiyu , Zhang Baokun , Li Qin 
Published: February 2022

PurposeThis study aimed to identify the biological functions of small intestine intestinal epithelial cell derived exosomes (IEC-Exos) and further distinguished the difference proteins in IEC-Exos between ileum and jejunum related to function of the digestive system and occurrence of several diseases.Materials and MethodsIECs of Male C57BL/6J mice were isolated. IEC-Exos were extracted from jejunum and ileum epithelial cell culture fluid by ultracentrifugation. In addition, isobaric tags for relative and absolute quantitation (iTRAQ) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to detect IEC-Exo proteins and conduct biological information analysis.ResultsThe results showed that compared with jejunum IEC-Exos from ileum IEC-Exos, there were 393 up-regulated proteins and 346 down-regulated proteins. IECs-Exos, especially derived from jejunum, were rich in angiotensin-converting enzyme 2 (ACE2). The highly expressed proteins from ileum IEC-Exos were mostly enriched in genetic information processing pathways, which mainly mediate the processes of bile acid transport, protein synthesis and processing modification. In contrast, the highly expressed proteins from jejunum IEC-Exos were mainly enriched in metabolic pathways involved in sugar, fatty acid, amino acid, drug, and bone metabolism, etc. The differentially expressed proteins between ileum and jejunum IEC-Exos were not only related to the function of the digestive system but also closely related to the occurrence of infectious diseases, endocrine diseases and osteoarthritis, etc.ConclusionIEC-Exos there were many differentially expressed proteins between ileum and jejunum, which played different roles in regulating intestinal biological functions. ACE2, the main host cell receptor of SARS-CoV-2, was highly expressed in IEC-Exos, which indicated that IEC-Exos may be a potential route of SARS-CoV-2 infection.
Quality of Life and Depressive Symptoms Among Peruvian University Students During the COVID-19 Pandemic
Authors: Figueroa-Quiñones Joel , Cjuno Julio , Machay-Pak Daniel , Ipanaqué-Zapata Miguel 
Published: February 2022

ObjectiveTo determine the factors associated with quality of life and depressive symptoms in Peruvian university students during the COVID-19 pandemic.MethodsMulticentre study in 1,634 students recruited by convenience sampling. The quality of life (QoL) was assessed with the European Quality of Life-5 Dimensions at three levels (EQ-5D-3L) and depressive symptoms with the Patient Health Questionnaire-9 (PHQ-9). To assess factors associated with QoL and depressive symptoms, linear regressions and fitted regressions were used, with robust coefficients of variance information (β).ResultsA 345 (21.1%) reported problems in performing daily activities, 544 (33.3%) reported pain and discomfort, 772 (47.2%) were moderately/very anxious or depressed. Furthermore, 207 (12.7%) had moderate-severe and severe depressive symptoms. Men reported better QoL than women (β: 3.2; 95% CI: 1.1, 5.4; p = 0.004) and fewer depressive symptoms (β: −0.7; 95% CI: −1.3, −0.2; p = 0.011). Ayacucho’s residents had more depressive symptoms than Ancash’s residents (β: 0.8; 95% CI: 0.1, 1.5; p = 0.022) and Piura’s residents had fewer depressive symptoms than Ancash’s residents (β: −1.195% CI: −1.8, −0.3, p = 0.005). Students who left home during quarantine reported more depressive symptoms (β: 0.7, 95% CI: 0.2, 1.2, p = 0.006).ConclusionProblems performing daily activities, pain and discomfort, as well as mild to severe depressive symptoms were found in more than three-quarters of the sample. Authorities could consider depression care to improve quality of life in regions where high rates of infection occurred during the pandemic.
Evidence of Psychological Manipulation in the Process of Violent Radicalization: An Investigation of the 17-A Cell
Authors: González Irene , Moyano Manuel , Lobato Roberto M. , Trujillo Humberto M. 
Published: February 2022

IntroductionRadicalization leading to violence is a complex social process that frequently targets young people. In this study, we examine the 17-A cell, which carried out terrorist attacks in the Spanish cities of Barcelona and Cambrils on August 17, 2017. We focus on the psychological manipulation techniques used to radicalized members of the cell.MethodsUsing deductive content analysis, we examined the judicial order of the National High Court related to “Operation Ramblas” and the police proceedings of Cuerpo de Mossos d'Esquadra (CME) associated with the Barcelona and Cambrils attacks. Our goal was to determine whether psychological manipulation was used on the cell members and, if so, how frequently.ResultsOur results suggest that different psychological manipulation techniques were used on the 17-A cell members to facilitate their use of ideological violence. The most frequent strategies were cognitive control (control of attention, group identification, and denigration of critical thinking), environmental control (control of information), and emotional control (authoritarian leadership).ConclusionsThis study provides evidence that psychological manipulation techniques were used in the radicalization of 17-A cell members. The results are discussed in the context of previous research on the psychology of violent extremism and terrorism. We highlight the need for prevention and psychosocial interventions to steer young people away from violent extremism.
Families With Violence Exposure and the Intergenerational Transmission of Somatization
Authors: Glaus Jennifer , Moser Dominik A. , Rusconi Serpa Sandra , Jouabli Sondes , Turri Fiorella , Plessen Kerstin J. , Schechter Daniel S. 
Published: February 2022

Introduction:Adults who have histories of childhood trauma have been noted to display greater somatization, dissociative symptoms and affect dysregulation. What happens in the parent-child relationship when those traumatized children become parents? A potential link to somatization in the child has been suggested by several prior studies. Children who have early attachment disturbances had more physical complaints if their mothers displayed less maternal sensitivity during observed parent-child interactions. Yet, the intergenerational link between maternal and child somatization has not been sufficiently explored in a longitudinal study in order to understand the potential impact of maternal trauma history and related psychopathology on subsequent child somatization and psychopathology.MethodsThis paper examined prospective, longitudinal data of 64 mother-toddler dyads (mean age = 2.4 years, SD = 0.7) who were later studied when children had a mean age of 7 years. Mothers with and without histories of interpersonal violence (IPV; physical/sexual abuse and/or family violence exposure) were included. Mothers with IPV histories were oversampled. Linear and Poisson regression models were used to test the associations between maternal IPV-related post-traumatic stress disorder (PTSD) with maternal somatization severity when children were toddlers, and between maternal somatization and maternal interactive behaviors with child somatization by maternal report and clinician-rated assessment at school-age.ResultsMaternal PTSD severity was significantly associated with increased maternal somatization severity (p = 0.031). Maternal somatization severity during the child's early childhood predicted both maternal report of child somatization (p = 0.011) as well as child thought problems (p = 0.007) when children were school-aged. No association was found between maternal somatization and child-reported psychopathology. The study did not find that maternal alexithymia, caregiving behaviors or child exposure to violence contributed significantly to the model examining the association between maternal and child somatization.ConclusionThe results are in line with the hypothesis of intergenerational transmission of somatization in the context of IPV and related maternal PTSD during formative early development. We interpret this as an expression of psychological distress from mother to child, as maternal trauma and pathology affect the caregiving environment and, thus, the parent–child relationship. The authors conclude with a discussion of implications for parent–infant and early childhood intervention.