bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunopathology in schistosomiasis is regulated by TLR2,4- and IFN-γ-activated MSC through modulating Th1/Th2 responses
Authors: Liu Chao , Zhang Yi-shu , Chen Fang , Wu Xiao-ying , Zhang Bei-bei , Wu Zhong-dao , Lei Jun-xia 
Published: June 2020

Abstract
Background and aims
A marked egg-induced CD4+ T cell programmed inflammation and subsequent hepatic fibrosis characterize the pathogenesis of schistosomiasis. Mesenchymal stem cell (MSC) has been extensively studied for the treatment of schistosomiasis. However, the mechanism by which MSCs modulate the pathogenesis of schistosomiasis has not been clarified. Furthermore, the local inflammatory milieu may greatly influence the immunoregulatory properties of MSCs, and our early experiments demonstrated that Toll-like receptor (TLR)2/TLR4 agonist effected immune modulation of MSC. Here, we further investigated their modulation on the pathogenesis of schistosomiasis.

Methods
Adult BALB/c male mice were percutaneously infected with 16 ± 2 pairs S. japonicum cercariae and received intravenously pretreated MSC at 1 week and 3 weeks post-infection, respectively. At 8 weeks post-infection, effects of MSC on liver histology were shown by hematoxylin and eosin (H&E) staining and Masson staining and quantitatively compared by the hepatic hydroxyproline content; α-smooth muscle actin (α-SMA), collagen type I(Col-1), transforming growth factor β (TGF-β), and tumor necrosis factor-α (TNF-α) gene expression in the liver were assessed by semi-quantitative polymerase chain reaction (PCR); the Th1/Th2 dominance among different groups was compared by analyzing CD4+ interferon-γ (IFN-γ)+ and CD4+interleukin-4 (IL-4)+T cells in the liver by flow cytometry and serum level of IFN-γ and IL-5 using enzyme-linked immunosorbent assay (ELISA). Effects of different kinds of MSC were further evaluated in vitro by the coculture system.

Results
Results showed TLR4- and IFN-γ-activated MSC alleviated liver fibrosis in infected mice, without a significant increase of mortality, and unpretreated MSC showed no clear improvement; however, TLR2- and IFN-γ-activated MSC displayed aggravated immunopathology. In accord with the pathological results, TLR4- and IFN-γ-activated MSC groups showed moderate enhancement of Th1 response in vitro and clear Th1 dominance in vivo without leading to extreme inflammation, whereas TLR2- and IFN-γ-activated MSC not only induced Th1 response, but also triggered excessive inflammation as evidenced by atrophy of the thymus and higher TNF level in the coculture system.

Conclusions
This study demonstrates that TLR4 combined with IFN-γ can activate the MSC group with positive effects on the pathology of schistosomiasis by modulating Th subsets at some degree. This result suggests that when MSC is being used to treat different immuno-disturbance complications, subtle pretreatment methods should be seriously considered.
Sex differences in pharmacokinetics predict adverse drug reactions in women
Authors: Zucker Irving , Prendergast Brian J. 
Published: June 2020

AbstractBackgroundWomen experience adverse drug reactions, ADRs, nearly twice as often as men, yet the role of sex as a biological factor in the generation of ADRs is poorly understood. Most drugs currently in use were approved based on clinical trials conducted on men, so women may be overmedicated. We determined whether sex differences in drug pharmacokinetics, PKs, predict sex differences in ADRs.MethodsSearches of the ISI Web of Science and PubMed databases were conducted with combinations of the terms: drugs, sex or gender, pharmacokinetics, pharmacodynamics, drug safety, drug dose, and adverse drug reaction, which yielded over 5000 articles with considerable overlap. We obtained information from each relevant article on significant sex differences in PK measures, predominantly area under the curve, peak/maximum concentrations, and clearance/elimination rates. ADRs were identified from every relevant article and recorded categorically as female-biased, male-biased, or not sex-biased.ResultsFor most of the FDA-approved drugs examined, elevated blood concentrations and longer elimination times were manifested by women, and these PKs were strongly linked to sex differences in ADRs. Of the 86 drugs evaluated, 76 had higher PK values in women; for 59 drugs with clinically identifiable ADRs, sex-biased PKs predicted the direction of sex-biased ADRs in 88% of cases. Ninety-six percent of drugs with female-biased PK values were associated with a higher incidence of ADRs in women than men, but only 29% of male-biased PKs predicted male-biased ADRs. Accessible PK information is available for only a small fraction of all drugsConclusionsSex differences in pharmacokinetics strongly predict sex-specific ADRs for women but not men. This sex difference was not explained by sex differences in body weight. The absence of sex-stratified PK information in public records for hundreds of drugs raises the concern that sex differences in PK values are widespread and of clinical significance. The common practice of prescribing equal drug doses to women and men neglects sex differences in pharmacokinetics and dimorphisms in body weight, risks overmedication of women, and contributes to female-biased adverse drug reactions. We recommend evidence-based dose reductions for women to counteract this sex bias.
Efficacy and acceptability of pharmacological and non-pharmacological interventions for non-specific chronic low back pain: a protocol for a systematic review and network meta-analysis
Authors: Thompson Trevor , Dias Sofia , Poulter Damian , Weldon Sharon , Marsh Lucy , Rossato Claire , Shin Jae Il , Firth Joseph , Veronese Nicola , Dragioti Elena , Stubbs Brendon , Solmi Marco , Maher Christopher G. , Cipriani Andrea , Ioannidis John P. A. 
Published: June 2020

Abstract
Background
Despite the enormous financial and humanistic burden of chronic low back pain (CLBP), there is little consensus on what constitutes the best treatment options from a multitude of competing interventions. The objective of this network meta-analysis (NMA) is to determine the relative efficacy and acceptability of primary care treatments for non-specific CLBP, with the overarching aim of providing a comprehensive evidence base for informing treatment decisions.

Methods
We will perform a systematic search to identify randomised controlled trials of interventions endorsed in primary care guidelines for the treatment of non-specific CLBP in adults. Information sources searched will include major bibliographic databases (MEDLINE, Embase, CENTRAL, CINAHL, PsycINFO and LILACS) and clinical trial registries. Our primary outcomes will be patient-reported pain ratings and treatment acceptability (all-cause discontinuation), and secondary outcomes will be functional ability, quality of life and patient/physician ratings of overall improvement. A hierarchical Bayesian class-based NMA will be performed to determine the relative effects of different classes of pharmacological (NSAIDs, opioids, paracetamol, anti-depressants, muscle relaxants) and non-pharmacological (exercise, patient education, manual therapies, psychological therapy, multidisciplinary approaches, massage, acupuncture, mindfulness) interventions and individual treatments within a class (e.g. NSAIDs: diclofenac, ibuprofen, naproxen). We will conduct risk of bias assessments and threshold analysis to assess the robustness of the findings to potential bias. We will compute the effect of different interventions relative to placebo/no treatment for both short- and long-term efficacy and acceptability.

Discussion
While many factors are important in selecting an appropriate intervention for an individual patient, evidence for the analgesic effects and acceptability of a treatment are key factors in guiding this selection. Thus, this NMA will provide an important source of evidence to inform treatment decisions and future clinical guidelines.

Systematic review registration
PROSPERO registry number: CRD42019138115
Dynamic linkages between poverty, inequality, crime, and social expenditures in a panel of 16 countries: two-step GMM estimates
Authors: Anser Muhammad Khalid , Yousaf Zahid , Nassani Abdelmohsen A. , Alotaibi Saad M. , Kabbani Ahmad , Zaman Khalid 
Published: June 2020

AbstractThe study examines the relationship between growth–inequality–poverty (GIP) triangle and crime rate under the premises of inverted U-shaped Kuznets curve and pro-poor growth scenario in a panel of 16 diversified countries, over a period of 1990–2014. The study employed panel Generalized Method of Moments (GMM) estimator for robust inferences. The results show that there is (i) no/flat relationship between per capita income and crime rate; (ii) U-shaped relationship between poverty headcount and per capita income and (iii) inverted U-shaped relationship between income inequality and economic growth in a panel of selected countries. Income inequality and unemployment rate increases crime rate while trade openness supports to decrease crime rate. Crime rate substantially increases income inequality while health expenditures decrease poverty headcount ratio. Per capita income is influenced by high poverty incidence, whereas health expenditures and trade factor both amplify per capita income across countries. The results of pro-poor growth analysis show that though the crime rate decreases in the years 2000–2004 and 2010–2014, while the growth phase was anti-poor due to unequal distribution of income. Pro-poor education and health trickle down to the lower income strata group for the years 2010–2014, as education and health reforms considerably reduce crime rate during the time period.
Effects of supplementation of green tea extract on the milk performance of peripartal dairy cows and the expression of stress response genes in the liver
Authors: Gessner Denise K. , Brock Corinna , Hof Lena M. , Most Erika , Koch Christian , Eder Klaus 
Published: June 2020

AbstractBackgroundWe hypothesised that supplementation of green tea extract (GTE) in dairy cows during the transition period can attenuate proinflammatory conditions and prevent endoplasmic reticulum (ER) stress in the liver of these cows. Thirty Holstein cows with an average parity of 3.06 (± 1.31, SD) were divided into a control group and a group that received a daily amount of 10 g of GTE from d 7 before the calving day and a daily amount of 20 g of GTE from the day of calving until d 7 of lactation.ResultsCows supplemented with GTE did not show differences in energy intake or milk yield in weeks 2–7 of lactation. However, these cows had a lower milk fat concentration and a lower energy corrected milk yield than the control cows and showed a trend of improved energy balance. The relative mRNA concentrations of proinflammatory genes, genes involved in the acute phase reaction and antioxidant genes in the liver in weeks 1, 4 and 7 of lactation were not different between the two groups of cows. The concentrations of α-tocopherol and the Trolox equivalent antioxidant capacity in plasma were not different between the two groups. However, the group supplemented with GTE showed significant reductions of some genes of the unfolded protein response (UPR) in week 1 and a trend of lower liver triacylglycerol (TAG) concentrations in the liver compared to the control group.ConclusionsThis study shows that supplementation of GTE in dairy cows lowers the fat concentration in the milk but overall has no effect on the expression of inflammatory genes and the antioxidative status in dairy cows during early lactation. The finding of reduced mRNA levels of genes involved in the UPR at week 1, however, supports other results showing that supplementation of polyphenols could prevent the development of ER stress in the liver of cows during early lactation. The finding of a tendency towards a reduced TAG concentration in the liver of cows supplemented with GTE might be due to an improved energy balance in these cows.
Skin microbiota analysis-inspired development of novel anti-infectives
Authors: Liu Yao , Liu Yuanzhen , Du Zixiu , Zhang Lidan , Chen Juan , Shen Zhen , Liu Qian , Qin Juanxiu , Lv Huiying , Wang Hua , He Lei , Liu Junlan , Huang Qian , Sun Yuhui , Otto Michael , Li Min 
Published: June 2020

Abstract
Background
The alarming spread of antimicrobial resistance requires the development of novel anti-infective drugs. Despite the recent research focus on the human microbiome and its likely value to understand and exploit inter-bacterial inhibitory phenomena as a source for antimicrobial strategies, the human microbiota has barely been investigated for the purpose of drug development.

Results
We performed a large screen analyzing over 3000 human skin isolates to evaluate bacterial competition within the human skin microbiota as a basis for the development of anti-infective therapeutics. We discovered a Staphylococcus hominis strain with strong and broad activity against Gram-positive pathogens that was mediated by the bacteriocin micrococcin P1 (MP1). In “probiotic” approaches, this strain led to reduced Staphylococcus aureus infection and accelerated closure of S. aureus-infected wounds. Furthermore, we used a nanoparticle strategy to overcome the physico-chemical limitations often encountered with natural substances such as MP1 and demonstrate a significant reduction of S. aureus infection by MP1-loaded nanoparticles.

Conclusions
Our study gives examples of how analysis of bacterial interactions in the human microbiota can be explored for the development of novel, effective anti-infective strategies.
Clinical performance of non-invasive prenatal served as a first-tier screening test for trisomy 21, 18, 13 and sex chromosome aneuploidy in a pilot city in China
Authors: Liu Yanhui , Liu Hailiang , He Yi , Xu Wanfang , Ma Qiulin , He Yuzhen , Lei Wei , Chen Guoquan , He Zheng , Huang Jiayi , Liu Jianan , Liu Yuanru , Huang Quanfei , Yu Fubing 
Published: June 2020

AbstractBackgroundCell-free fetal DNA (cffDNA) has opened up new approaches for non-invasive prenatal testing (NIPT), and it is often used as the second-tier test for high-risk pregnant women in detecting trisomy (T) 21, T18, and T13 after serum biochemistry screening. This study aims to discuss the clinical performance of NIPT as an alternative first-tier screening test for pregnant women in detecting T21, T18, T13, and sex chromosome aneuploidies (SCAs) in China.MethodsA total of 42,924 samples were recruited. The cell-free plasma DNA was directly sequenced. Each of the chromosome aneuploidies of PPV was analyzed. A total of 22 placental samples were acquired, including 14 FP and 8 TP samples. The placental verification of FP NIPT results was performed.ResultsAmong 42,924 samples, 281 (0.65%) positive cases, including 87 of T21, 31 of T18, 22 of T13, and 141 of SCAs were detected. For the detection of T21, the positive predictive value (PPV) was 78.46%, for trisomy 18, 62.96%, for trisomy 13, 10.00%, for SCAs, 47.22% in the total samples. For trisomy 21, the PPV was 86.67%, for trisomy 18, 80.00%, for trisomy 13, 20.00%, for SCAs, 56.52% in advanced maternal age (AMA) women. The PPV of T21 increased with age. For T18, the PPV showed an overall upward trend. For T13 and SCAs, PPV was raised first and then lowered. Placental verification of false positive (FP) NIPT results confirmed confined placental mosaicism(CPM) was the reason for false positives.ConclusionsThis study represents the first time that NIPT has been used as a first-tier screening test for fetal aneuploidies in a pilot city with large clinical samples in China. We propose that NIPT could replace serum biochemistry screening as a first-tier test.
Impact of a community-based intervention on Aedes aegypti and its spatial distribution in Ouagadougou, Burkina Faso
Authors: Bonnet Emmanuel , Fournet Florence , Benmarhnia Tarik , Ouedraogo Samiratou , Dabiré Roch , Ridde Valéry 
Published: June 2020

Abstract
Background
Several studies highlighted the impact of community-based interventions whose purpose was to reduce the vectors’ breeding sites. These strategies are particularly interesting in low-and-middle-income countries which may find it difficult to sustainably assume the cost of insecticide-based interventions. In this case study we determine the spatial distribution of a community-based intervention for dengue vector control using different entomological indices. The objective was to evaluate locally where the intervention was most effective, using spatial analysis methods that are too often neglected in impact assessments.

Methods
Two neighbourhoods, Tampouy and Juvenat in Ouagadougou, Burkina Faso, were chosen among five after a survey was conducted, as part of an assessment related to the burden of dengue. As part of the community-based intervention conducted in Tampouy between August and early October 2016, an entomological survey was implemented in two phases. The first phase consisted of a baseline entomological characterization of potential breeding sites in the neighbourhood of Tampouy as well as in Juvenat, the control area. This phase was conducted in October 2015 at the end of the rainy season. The mosquito breeding sites were screened in randomly selected houses: 206 in Tampouy and 203 in Juvenat. A second phase took place after the intervention, in October 2016. The mosquito breeding sites were investigated in the same yards as during the baseline phase. We performed several entomological analyses to measure site productivity as well as before and after analysis using multilevel linear regression. We used Local Indicators of Spatial Association (LISAs) to analyse spatial concentrations of larvae.

Results
After the intervention, it is noted that LISAs at Tampouy reveal few aggregates of all types and the suppression of those existing before the intervention. The analysis therefore reveals that the intervention made it possible to reduce the number of concentration areas of high and low values of pupae.

Conclusions
The contribution of spatial methods for assessing community-based intervention are relevant for monitoring at local levels as a complement to epidemiological analyses conducted within neighbourhoods. They are useful, therefore, not only for assessment but also for establishing interventions. This study shows that spatial analyses also have their place in population health intervention research.
Osteomalacia and renal failure due to Fanconi syndrome caused by long-term low-dose Adefovir Dipivoxil: a case report
Authors: Xiang Qian , Liu Zhiyan , Yu Yanyan , Zhang Hanxu , Xie Qiufen , Mu Guangyan , Zhang Jianhua , Cen Xinan , Cui Yimin 
Published: June 2020

Abstract
Background
Progressive bone pain and fracture and abnormal positron emission tomography combined with a computed tomography are main reasons for the oncologists suspecting bone tumor. During the patient’s medical treatment, the oncologists’ unfamiliarity with adverse reactions to anti-HBV drugs were main reason for the long-term exposure to the drug and the adverse reaction (ADR) experienced by the patient.

Case presentation
A 63-year-old Chinese man had a 27-month history of progressive generalized bone pain combined with spontaneous fractures. Positron emission tomography combined with a computed tomography, revealed an abnormal increase in ribose metabolism and low positron serum inorganic phosphorus concentration (0.7; 0.78–1.65 mmol/L). Serum creatinine level was 252 μmol/L (53–97) μmol/L, and glomerular filtration rate was 22.79 mL/min/1.73 m2. The patient was referred to a multidisciplinary clinic to clarify the diagnosis of myeloma or bone tumor for further treatment in 2017. His medical history revealed that he had a 30-year history of chronic hepatitis B infection. He had received lamivudine at a daily dose of 100 mg for 19 years (1990 to 2009), which had been changed to adefovir (10 mg/day) owing to lamivudine resistance in 2009. Based on the changes in the patient’s laboratory markers and the results of emission computed tomography and other radiographic findings, adefovir-induced hypophosphatemic osteomalacia due to acquired renal Fanconi syndrome was suspected by the clinical pharmacist. Considerable clinical improvement was observed after adefovir discontinuation and the administration of entecavir (1.0 mg, every other day).

Conclusion
Fanconi syndrome with osteomalacia can develop in patients with chronic hepatitis B infection being treated with adefovir at a conventional low dosage of 10 mg/day. This case highlights the importance of ADR as a differential diagnosis and the need of pharmacists with drug safety expertise expert in the patient management.
Characterization of the TNF and IL-1 systems in human brain and blood after ischemic stroke
Authors: Clausen Bettina H. , Wirenfeldt Martin , Høgedal Sofie S. , Frich Lars H. , Nielsen Helle H. , Schrøder Henrik D. , Østergaard Kamilla , Finsen Bente , Kristensen Bjarne W. , Lambertsen Kate L. 
Published: June 2020

AbstractPreclinical and clinical proof-of-concept studies have suggested the effectiveness of pharmacological modulation of inflammatory cytokines in ischemic stroke. Experimental evidence shows that targeting tumor necrosis factor (TNF) and interleukin (IL)-1 holds promise, and these cytokines are considered prime targets in the development of new stroke therapies. So far, however, information on the cellular expression of TNF and IL-1 in the human ischemic brain is sparse.We studied 14 cases of human post-mortem ischemic stroke, representing 21 specimens of infarcts aged 1 to > 8 days. We characterized glial and leukocyte reactions in the infarct/peri-infarct (I/PI) and normal-appearing tissue (NAT) and the cellular location of TNF, TNF receptor (TNFR)1 and TNFR2, IL-1α, IL-1β, and IL-1 receptor antagonist (IL-1Ra). The immunohistochemically stained tissue sections received a score reflecting the number of immunoreactive cells and the intensity of the immunoreactivity (IR) in individual cells where 0 = no immunoreactive cells, 1 = many intermediately to strongly immunoreactive cells, and 2 = numerous and intensively immunoreactive cells. Additionally, we measured blood TNF, TNFR, and IL-1 levels in surviving ischemic stroke patients within the first 8 h and again at 72 h after symptom onset and compared levels to healthy controls.We observed IL-1α and IL-1β IR in neurons, glia, and macrophages in all specimens. IL-1Ra IR was found in glia, in addition to macrophages. TNF IR was initially found in neurons located in I/PI and NAT but increased in glia in older infarcts. TNF IR increased in macrophages in all specimens. TNFR1 IR was found in neurons and glia and macrophages, while TNFR2 was expressed only by glia in I/PI and NAT, and by macrophages in I/PI. Our results suggest that TNF and IL-1 are expressed by subsets of cells and that TNFR2 is expressed in areas with increased astrocytic reactivity. In ischemic stroke patients, we demonstrate that plasma TNFR1 and TNFR2 levels increased in the acute phase after symptom onset compared to healthy controls, whereas TNF, IL-1α, IL-1β, and IL-1Ra did not change.Our findings of increased brain cytokines and plasma TNFR1 and TNFR2 support the hypothesis that targeting post-stroke inflammation could be a promising add-on therapy in ischemic stroke patients.