bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential drug–drug interactions associated with adverse clinical outcomes and abnormal laboratory findings in patients with malaria
Authors: Noor Sidra , Ismail Mohammad , Khadim Faiza 
Published: August 2020

Abstract
Background
Hospitalized patients with malaria often present with comorbidities or associated complications for which a variety of drugs are prescribed. Multiple drug therapy often leads to drug–drug interactions (DDIs). Therefore, the current study investigated the prevalence, levels, risk factors, clinical relevance, and monitoring parameters/management guidelines of potential DDIs (pDDIs) among inpatients with malaria.

Methods
A retrospective cohort study was carried out at two tertiary care hospitals. A total of 398 patients’ profiles were evaluated for pDDIs using the Micromedex Drug-Reax®. Odds ratios were calculated to identify the strength of association between presence of DDIs and potential risk factors via logistic regression analysis. Further, the clinical relevance of frequent pDDIs was investigated.

Results
Of 398 patients, pDDIs were observed in 37.2% patients, while major-pDDIs in 19.3% patients. A total of 325 interactions were found, of which 45.5% were of major- and 34.5% moderate-severity. Patients with the most common pDDIs were found with signs/symptoms and abnormalities in laboratory findings representing nephrotoxicity, hepatotoxicity, QT interval prolongation, and reduced therapeutic efficacy. The following drug pairs reported the highest frequency of adverse events associated with the interactions; calcium containing products-ceftriaxone, isoniazid–rifampin, pyrazinamide–rifampin, isoniazid–acetaminophen, and ciprofloxacin–metronidazole. The adverse events were more common in patients prescribed with the higher doses of interacting drugs. Multivariate regression analysis showed statistically significant association of pDDIs with 5–6 prescribed medicines (p = 0.01), > 6 prescribed medicines (p < 0.001), > 5 days of hospital stay (p = 0.03), and diabetes mellitus (p = 0.04).

Conclusions
PDDIs are commonly observed in patients with malaria. Healthcare professional’s knowledge about the most common pDDIs could help in preventing pDDIs and their associated negative effects. Pertinent clinical parameters, such as laboratory findings and signs/symptoms need to be checked, particularly in patients with polypharmacy, longer hospital stay, and diabetes mellitus.
Modeling the neuro-mechanics of human balance when recovering from a fall: a continuous-time approach
Authors: Cerda-Lugo Angel , González Alejandro , Cardenas Antonio , Piovesan Davide 
Published: August 2020

Abstract
Background
Balance control deteriorates with age and nearly 30% of the elderly population in the United States reports stability problems. Postural stability is an integral task to daily living reliant upon the control of the ankle and hip. To this end, the estimation of joint parameters can be a useful tool when analyzing compensatory actions aimed at maintaining postural stability.

Methods
Using an analytical approach, this study expands on previous work and analyzes a two degrees of freedom human model. The first two modes of vibration of the system are represented by the neuro-mechanical parameters of a second-order, time-varying Kelvin–Voigt model actuated at the ankle and hip. The model is tested using a custom double inverted pendulum and healthy volunteers who were subjected to a positional step-like perturbation during quiet standing. An in silico sensitivity analysis of the influence of inertial parameters was also performed.

Results
The proposed method is able to correctly identify the time-varying visco-elastic parameters of of a double inverted pendulum. We show that that the parameter estimation method can be applied to standing humans. These results appear to identify a subject-independent strategy to control quiet standing that combines both the modulation of stiffness, and the use of an intermittent control.

Conclusions
This paper presents the analysis of the non-linear system of differential equations representing the control of lumped muscle–tendon units. It utilizes motion capture measurements to obtain the estimates of the system’s control parameters by constructing a simple time-dependent regressor for estimating the time-varying parameters of the control with a single perturbation. This work is a step forward into the understanding of the neuro-mechanical control parameters of human recovering from a fall. In previous literature, the analysis is either restricted to the first vibrational mode of an inverted-pendulum model or assumed to be time-invariant. The proposed method allows for the analysis of hip related movement for stability control and highlights the importance of core training.
Perinatal oral exposure to low doses of bisphenol A, S or F impairs immune functions at intestinal and systemic levels in female offspring mice
Authors: Malaisé Yann , Lencina Corinne , Cartier Christel , Olier Maïwenn , Ménard Sandrine , Guzylack-Piriou Laurence 
Published: August 2020

Abstract
Background
Bisphenol A (BPA), one of the highest-volume chemicals produced worldwide, has been identified as an endocrine disruptor. Many peer-reviewing studies have reported adverse effects of low dose BPA exposure, particularly during perinatal period (gestation and/or lactation). We previously demonstrated that perinatal oral exposure to BPA (via gavage of mothers during gestation and lactation) has long-term consequences on immune response and intestinal barrier functions. Due to its adverse effects on several developmental and physiological processes, BPA was removed from consumer products and replaced by chemical substitutes such as BPS or BPF, that are structurally similar and not well studied compare to BPA. Here, we aimed to compare perinatal oral exposure to these bisphenols (BPs) at two doses (5 and 50 μg/kg of body weight (BW)/day (d)) on immune response at intestinal and systemic levels in female offspring mice at adulthood (Post Natal Day PND70).

Methods
Pregnant female mice were orally exposed to BPA, BPS or BPF at 5 or 50 μg/kg BW/d from 15th day of gravidity to weaning of pups at Post-Natal Day (PND) 21. Humoral and cellular immune responses of adult offspring (PND70) were analysed at intestinal and systemic levels.

Results
In female offspring, perinatal oral BP exposure led to adverse effects on intestinal and systemic immune response that were dependant of the BP nature (A, S or F) and dose of exposure. Stronger impacts were observed with BPS at the dose of 5 μg/kg BW/d on inflammatory markers in feces associated with an increase of anti-E. coli IgG in plasma. BPA and BPF exposure induced prominent changes at low dose in offspring mice, in term of intestinal and systemic immune responses, provoking an intestinal and systemic Th1/Th17 inflammation.

Conclusion
These findings provide, for the first time, results of long-time consequences of BPA, S and F perinatal exposure by oral route on immune response in offspring mice. This work warns that it is mandatory to consider immune markers and dose exposure in risk assessment associated to new BPA’s alternatives.
Concentrations of perfluoroalkyl and polyfluoroalkyl substances and blood glucose in pregnant women
Authors: Ren Yanfeng , Jin Longmei , Yang Fen , Liang Hong , Zhang Zhaofeng , Du Jing , Song Xiuxia , Miao Maohua , Yuan Wei 
Published: August 2020

Abstract
Background
Evidence on the association between exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) and blood glucose concentrations in pregnant women is inconsistent. This study aimed to examine the association between PFAS exposure and the concentrations of fasting plasma glucose (FPG) and one-hour plasma glucose (1 h-PG) after a 50-g oral glucose tolerance test in pregnant women.

Methods
The study was based on the Shanghai-Minhang Birth Cohort, in which 1292 pregnant women were recruited. Among them, 981 women provided blood samples (at 12–16 gestational weeks) for PFAS measurement. FPG data collected from 856 women at 12–20 GW and 1 h-PG data collected from 705 women at 20–28 GW were obtained through medical records from the routine prenatal care system. High FPG or 1 h-PG was defined as ≥90th percentile of FPG or 1 h-PG. The analysis of eight PFASs was conducted in this study: perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUdA), perfluorododecanoic acid (PFDoA), and perfluorotridecanoic acid (PFTrDA). The odds ratios (ORs) and associated 95% confidence intervals (CIs) were estimated to determine the associations of each PFAS compound with high FPG and 1 h-PG from a logistic regression model.

Results
After adjustment for potential confounders, most PFASs were positively associated with high 1 h-PG concentrations. The OR for high 1 h-PG concentrations was 1.87 (95% CI: 1.15–3.05) with a one log unit increase of PFOS; similar associations were observed for PFNA (OR: 2.15, 95% CI: 1.24–3.74), PFDA (OR: 1.61, 95% CI: 1.10–2.44), PFUdA (OR: 1.71, 95% CI: 1.12–2.62), and PFDoA (OR: 1.34, 95% CI: 1.00–1.81). When the PFAS concentrations were categorized into three groups by tertiles, the highest tertiles of PFOS, PFOA, PFNA, PFDA, PFDoA, and PFTrDA had a statistically significant increase in the risk of high 1 h-PG concentrations compared with the lowest tertiles. No statistically significant association was observed between PFAS exposure and high FPG.

Conclusion
PFAS exposure was associated with an increased risk of high 1 h-PG among pregnant women, but no such association was observed for FPG.
Synergistic co-delivery of diacid metabolite of norcantharidin and ABT-737 based on folate-modified lipid bilayer-coated mesoporous silica nanoparticle against hepatic carcinoma
Authors: Liu Minchen , Tu Jue , Feng Yi , Zhang Jiquan , Wu Jing 
Published: August 2020

AbstractDiacid metabolite as the stable form of norcantharidin (DM-NCTD) derived from Chinese blister beetle (Mylabris spp.). The previous studies reported that DM-NCTD could enhance ABT-737-triggered cell viability inhibition and apoptosis in hepatocellular carcinoma (HCC) cell lines. To translate this synergistic therapy into in vivo anticancer treatment, a folate receptor-targeted lipid bilayer-supported chlorodimethyloctadecylsilane-modified mesoporous silica nanoparticle (FA-LB-CHMSN) with DM-NCTD loaded in CHMSN and ABT-737 in lipid bilayer was prepared, which could promote the cancer cell uptake of the drugs through folate receptor-mediated endocytosis. The structure and the properties of the nanoparticle were evaluated. FA-LB-CHMSN with DM-NCTD/ABT-737 loaded induced apparent tumor cell apoptosis and showed remarkably tumor inhibition in H22 tumor-bearing mice model, with significant cellular apoptosis in the tumor and no obvious toxicity to the tissues. We expect that this nanoparticle could be of interest in both biomaterial investigations for HCC treatment and the combination of chemotherapeutic drugs for synergistic therapies.
Effects of oral contraceptives on the quality of life of women with polycystic ovary syndrome: a crossover randomized controlled trial
Authors: Amiri Mina , Nahidi Fatemeh , Yarandi Razieh Bidhendi , Khalili Davood , Tohidi Maryam , Tehrani Fahimeh Ramezani 
Published: August 2020

AbstractBackground and objectiveA limited number of studies have evaluated the effects of oral contraceptives (OCs) on the quality of life (QOL) of polycystic ovary syndrome (PCOS) patients. This study aimed to compare the effects of using OCs containing levonorgestrel (LNG) and those containing desogestrel (DSG), cyproterone acetate (CPA) or drospirenone (DRSP) for 6 months on the QOL with PCOS.MethodsIn this crossover randomized controlled 6-arm trial, 200 eligible patients with PCOS scheduled for OC therapy were randomly assigned to one of the 6 study arms. All 6 arms include two 6-month treatment periods, one period with OCs containing LNG, and the other with each of the 3 OCs containing DSG, CPA, or DRSP. Outcomes of interest were the total score of QOL and its domains, which were assessed using a specific and valid health-related quality of life questionnaire for PCOS, which is consisted of six domains, including psychosocial–emotional, self-image, fertility, sexual function, hirsutism, and obesity– menstrual disorders.ResultsFinally, a total of 88 patients were analyzed for this study. The results showed that use of OCs containing DSG, CPA, and DRSP for 3 months was not associated with significant differences in the total scores of QOL compared to those OCs containing LNG, whereas, after 6 months of treatment, patients treated with OCs containing CPA had more improvements in their total scores of QOL, in comparison to OCs containing LNG (P < 0.042). We found no significant differences in QoL domains, including psychosocial–emotional, self-image, fertility, sexual function, hirsutism, and obesity-menstrual disorders after 3–6 months of treatment with DSG, CPA, or DRSP, compared to LNG. The sequence and period effects were not significant in any of the analyses at 3 and 6 months of treatment. The carry-over effect was not significant for most outcomes assessed.ConclusionsThis crossover study demonstrated non-inferiority of OCs with newer generation progestins on different domains of QOL, in comparison with older compounds, although usage of products containing CPA was significantly associated with more improvement in total QOL of PCOS patients, compared to those containing LNG after 6-month of treatment.Trial registrationIRCT201702071281N2.
Early gastric cancer with three gastric gastrointestinal stromal tumors combined with synchronous colon cancer: a case report
Authors: Lee Sung Chul , Nam Kwangwoo , Nam Dajeong , Kwon Min A , Kim Dong-Wook 
Published: August 2020

Abstract
Background
There have been very few reports of patients with early gastric cancer (EGC) and colorectal cancer combined with gastric gastrointestinal stromal tumors (GISTs).

Case presentation
We report the case of a patient with multiple tumors that were found at the same time in the abdomen. The patient was a 77-year-old man who was referred for a gastric GIST. Esophagogastroduodenoscopy showed the known lesion (a gastric GIST) on the lesser curvature of the upper body and a new lesion on the lesser curvature of the lower body of the stomach with suspicion of EGC. Computed tomography findings confirmed the presence of a GIST in the stomach and revealed two new lesions. One of these lesions was suspected to be a 4-cm submucosal tumor on the anterior wall of the upper body of the stomach. The other was a wall thickening of the descending colon that demonstrated the possibility of malignancy. Synchronous colon cancer was confirmed on colonoscopy. Laparoscopic near-total gastrectomy with D1+ lymph node dissection and left hemicolectomy were performed sequentially without significant events. The patient was discharged without any postoperative complications.

Conclusions
We reported a rare case of EGC with multiple gastric GISTs combined with synchronous colon cancer.
TRPP2 and STIM1 form a microdomain to regulate store-operated Ca2+ entry and blood vessel tone
Authors: Guo Jizheng , Zhao Ren , Zhou Muyao , Li Jie , Yao Xiaoqiang , Du Juan , Chen Jiexia , Shen Bing 
Published: August 2020

Abstract
Background
Polycystin-2 (TRPP2) is a Ca2+ permeable nonselective cationic channel essential for maintaining physiological function in live cells. Stromal interaction molecule 1 (STIM1) is an important Ca2+ sensor in store-operated Ca2+ entry (SOCE). Both TRPP2 and STIM1 are expressed in endoplasmic reticular membrane and participate in Ca2+ signaling, suggesting a physical interaction and functional synergism.

Methods
We performed co-localization, co-immunoprecipitation, and fluorescence resonance energy transfer assay to identify the interactions of TRPP2 and STIM1 in transfected HEK293 cells and native vascular smooth muscle cells (VSMCs). The function of the TRPP2-STIM1 complex in thapsigargin (TG) or adenosine triphosphate (ATP)-induced SOCE was explored using specific small interfering RNA (siRNA). Further, we created TRPP2 conditional knockout (CKO) mouse to investigate the functional role of TRPP2 in agonist-induced vessel contraction.

Results
TRPP2 and STIM1 form a complex in transfected HEK293 cells and native VSMCs. Genetic manipulations with TRPP2 siRNA, dominant negative TRPP2 or STIM1 siRNA significantly suppressed ATP and TG-induced intracellular Ca2+ release and SOCE in HEK293 cells. Inositol triphosphate receptor inhibitor 2-aminoethyl diphenylborinate (2APB) abolished ATP-induced Ca2+ release and SOCE in HEK293 cells. In addition, TRPP2 and STIM1 knockdown significantly inhibited ATP- and TG-induced STIM1 puncta formation and SOCE in VSMCs. Importantly, knockdown of TRPP2 and STIM1 or conditional knockout TRPP2 markedly suppressed agonist-induced mouse aorta contraction.

Conclusions
Our data indicate that TRPP2 and STIM1 are physically associated and form a functional complex to regulate agonist-induced intracellular Ca2+ mobilization, SOCE and blood vessel tone.
FGF21 alleviates neuroinflammation following ischemic stroke by modulating the temporal and spatial dynamics of microglia/macrophages
Authors: Wang Dongxue , Liu Fei , Zhu Liyun , Lin Ping , Han Fanyi , Wang Xue , Tan Xianxi , Lin Li , Xiong Ye 
Published: August 2020

Abstract
Background
Resident microglia and macrophages are the predominant contributors to neuroinflammation and immune reactions, which play a critical role in the pathogenesis of ischemic brain injury. Controlling inflammatory responses is considered a promising therapeutic approach for stroke. Recombinant human fibroblast growth factor 21 (rhFGF21) presents anti-inflammatory properties by modulating microglia and macrophages; however, our knowledge of the inflammatory modulation of rhFGF21 in focal cerebral ischemia is lacking. Therefore, we investigated whether rhFGF21 improves ischemic outcomes in experimental stroke by targeting microglia and macrophages.

Methods
C57BL/6 mice were subjected to middle cerebral artery occlusion (MCAO) and randomly divided into groups that received intraperitoneal rhFGF21 or vehicle daily starting at 6 h after reperfusion. Behavior assessments were monitored for 14 days after MCAO, and the gene expression levels of inflammatory cytokines were analyzed via qRT-PCR. The phenotypic variation of microglia/macrophages and the presence of infiltrated immune cells were examined by flow cytometry and immunostaining. Additionally, magnetic cell sorting (MACS) in combination with fluorescence-activated cell sorting (FACS) was used to purify microglia and macrophages.

Results
rhFGF21 administration ameliorated neurological deficits in behavioral tests by regulating the secretion of pro-inflammatory and anti-inflammatory cytokines. rhFGF21 also attenuated the polarization of microglia/macrophages toward the M1 phenotype and the accumulation of peripheral immune cells after stroke, accompanied by a temporal evolution of the phenotype of microglia/macrophages and infiltration of peripheral immune cells. Furthermore, rhFGF21 treatment inhibited M1 polarization of microglia and pro-inflammatory cytokine expression through its actions on FGF receptor 1 (FGFR1) by suppressing nuclear factor-kappa B (NF-κB) and upregulating peroxisome proliferator-activated receptor-γ (PPAR-γ).

Conclusions
rhFGF21 treatment promoted functional recovery in experimental stroke by modulating microglia/macrophage-mediated neuroinflammation via the NF-κB and PPAR-γ signaling pathways, making it a potential anti-inflammatory agent for stroke treatment.
Benzo(a)pyrene exposure induced neuronal loss, plaque deposition, and cognitive decline in APP/PS1 mice
Authors: Liu Dan , Zhao Yujia , Qi Yuze , Gao Yun , Tu Dezhen , Wang Yinxi , Gao Hui-Ming , Zhou Hui 
Published: August 2020

Abstract
Background
Exposure to benzo(a)pyrene (BaP) was associated with cognitive impairments and some Alzheimer’s disease (AD)-like pathological changes. However, it is largely unknown whether BaP exposure participates in the disease progression of AD.

Objectives
To investigate the effect of BaP exposure on AD progression and its underlying mechanisms.

Methods
BaP or vehicle was administered to 4-month-old APPswe/PS1dE9 transgenic (APP/PS1) mice and wildtype (WT) mice for 2 months. Learning and memory ability and exploratory behaviors were evaluated 1 month after the initiation/termination of BaP exposure. AD-like pathological and biochemical alterations were examined 1 month after 2-month BaP exposure. Levels of soluble beta-amyloid (Aβ) oligomers and the number of Aβ plaques in the cortex and the hippocampus were quantified. Gene expression profiling was used to evaluate alternation of genes/pathways associated with AD onset and progression. Immunohistochemistry and Western blot were used to demonstrate neuronal loss and neuroinflammation in the cortex and the hippocampus. Treatment of primary neuron-glia cultures with aged Aβ (a mixture of monomers, oligomers, and fibrils) and/or BaP was used to investigate mechanisms by which BaP enhanced Aβ-induced neurodegeneration.

Results
BaP exposure induced progressive decline in spatial learning/memory and exploratory behaviors in APP/PS1 mice and WT mice, and APP/PS1 mice showed severer behavioral deficits than WT mice. Moreover, BaP exposure promoted neuronal loss, Aβ burden and Aβ plaque formation in APP/PS1 mice, but not in WT mice. Gene expression profiling showed most robust alteration in genes and pathways related to inflammation and immunoregulatory process, Aβ secretion and degradation, and synaptic formation in WT and APP/PS1 mice after BaP exposure. Consistently, the cortex and the hippocampus of WT and APP/PS1 mice displayed activation of microglia and astroglia and upregulation of inducible nitric oxide synthase (iNOS), glial fibrillary acidic protein (GFAP), and NADPH oxidase (three widely used neuroinflammatory markers) after BaP exposure. Furthermore, BaP exposure aggravated neurodegeneration induced by aged Aβ peptide in primary neuron-glia cultures through enhancing NADPH oxidase-derived oxidative stress.

Conclusion
Our study showed that chronic exposure to environmental pollutant BaP induced, accelerated, and exacerbated the progression of AD, in which elevated neuroinflammation and NADPH oxidase-derived oxidative insults were key pathogenic events.