bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome of Severe Bacterial Pneumonia in the Era of Pneumococcal Vaccination
Authors: del Rosal Teresa , Caminoa María Belén , González-Guerrero Alba , Falces-Romero Iker , Romero-Gómez María Pilar , Baquero-Artigao Fernando , Sainz Talía , Méndez-Echevarría Ana , Escosa-García Luis , Aracil Francisco Javier , Calvo Cristina 
Published: January 2021

Introduction: After the introduction of pneumococcal conjugate vaccines, community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae has decreased whereas Staphylococcus aureus and Streptococcus pyogenes could be increasing. These bacteria have been associated with high rates of complications.Aims: (1) To describe the characteristics of pediatric bacterial CAP requiring hospitalization. (2) To compare outcomes according to causative microorganisms. (3) To analyze changes in bacterial CAP rate and etiology over time.Patients and Methods: Retrospective single-center study of inpatients aged 1 month-16 years with culture-confirmed bacterial CAP in 2010-2018 in Madrid, Spain.Results: We included 64 cases (42 S. pneumoniae, 13 S. pyogenes and 9 S. aureus). Culture-confirmed CAP represented 1.48-2.33/1,000 all-cause pediatric hospital admissions, and its rate did not vary over time. However, there was a significant decrease in pneumococcal CAP in the last 3 years of the study (78% of CAP in 2010–2015 vs. 48% in 2016-18, p = 0.017). Median hospital stay was 10.5 days (interquartile range 5-19.5), 38 patients (59%) developed complications and 28 (44%) were admitted to the intensive care unit. Outcomes were similar among children with S. pneumoniae and S. aureus CAP, whereas S. pyogenes was associated with a higher risk for complications (OR 8 [95%CI 1.1-57.2]) and ICU admission (OR 7.1 [95%CI 1.7-29.1]) compared with pneumococcal CAP.Conclusion: In a setting with high PCV coverage, culture-confirmed bacterial CAP did not decrease over time and there was a relative increase of S. pyogenes and S. aureus. Children with CAP caused by S. pyogenes were more likely to develop complications.
Anisodamine Maintains the Stability of Intervertebral Disc Tissue by Inhibiting the Senescence of Nucleus Pulposus Cells and Degradation of Extracellular Matrix via Interleukin-6/Janus Kinases/Signal Transducer and Activator of Transcription 3 Pathway
Authors: Tang Ning , Dong Yulei , Chen Chong , Zhao Hong 
Published: January 2021

Objectives: Anisodamine (ANI) has been used to treat a variety of diseases. However, the study of ANI in intervertebral disc degeneration (IVDD) is unclear. This study investigated the effects of ANI on degenerative nucleus pulposus cells (NPCs) and IVDD rats, and its possible mechanisms.Methods: Human nucleus pulposus cells (HNPCs) were treated with IL-1β (20 ng/ml) to simulate IVDD, and an IVDD rat model was constructed. IL-1β-induced HNPCs were treated with different concentrations (10, 20, or 40 μM) of ANI, and IVDD rats were also treated with ANI (1 mg/kg).Results: ANI treatment significantly reduced the apoptosis, caspase-3 and SA-β-gal activities, and p53 and p21 proteins expression, while promoted telomerase activity and aggrecan and collagen II synthesis in IL-1β-induced HNPCs. Moreover, the introduction of ANI inhibited the expression of IL-6, phosphorylation of JAK and STAT3, and nuclear translocation of p-STAT3 in Degenerated HNPCs. Additionally, the application of ANI abolished the effects of IL-6 on apoptosis, SA-β-gal and telomerase activity, and the expression of p53, p21, aggrecan and collagen II proteins in degenerated HNPCs. Simultaneously, ANI treatment enhanced the effects of AG490 (inhibitor of JAK/STAT3 pathway) on IL-1β-induced apoptosis, senescence and ECM degradation in HNPCs. Furthermore, ANI treatment markedly inhibited the apoptosis and senescence in the nucleus pulposus of IVDD rats, while promoted the synthesis of aggrecan and collagen II. ANI treatment obviously inhibited JAK and STAT3 phosphorylation and inhibited nuclear translocation of p-STAT3 in IVDD rats.Conclusion: ANI inhibited the senescence and ECM degradation of NPCs by regulating the IL-6/JAK/STAT3 pathway to improve the function of NPCs in IVDD, which may provide new ideas for the treatment of IVDD.
Frequency and Severity of Adverse Drug Reactions to Medications Prescribed for Alzheimer’s Disease in a Brazilian City: Cross-Sectional Study
Authors: Ferreira Tânia Regina , Lopes Luciane Cruz , Bergamaschi Cristiane de Càssia 
Published: January 2021

Background:There is lack of national studies that assess the risks associated with the drugs provided under the Brazilian public health system for treating Alzheimer’s disease. Then, this study determined the prevalence and severity of self-reported adverse drug reactions (ADRs) prescribed to patients with Alzheimer’s disease in the Brazilian public health system.Methods:A cross-sectional study was carried out based on public data from the MEDEX system (information on dispensing data, known as exceptional dispensing medications) and interviews with patients and/or caregivers who get access to Alzheimer’s drugs at a public pharmacy in a large Brazilian city, between July and September 2017, inquiring about ADRs and serious adverse events (SAEs).Results:The subjects were asked about ADRs and SAEs related to the use of donepezil, galantamine, rivastigmine and memantine. Out of 285 patients enrolled on the database, 250 participated in the study (87.7%). Among the participants, approximately 63.0% were female, 70.3% aged ≥75 years and 70.3% had comorbidities. Overall, 209 patients (83.6%) reported at least one ADR (total 1,149 ADRs) and rivastigmine was associated with the largest number of ADRs per patient (7.9 ADRs/patient). The predominant adverse effects were psychiatric disorders with common frequency (57.1%) and mild severity (89.0%). Six patients (2.4%) had SAEs that required hospitalization. The use of antipsychotics was the variable associated with ADR (OR = 4.95; 95% CI: 1.45–16.93;p= 0.011).Conclusion:There was a large number of reported ADRs and most of them were of common frequency and mild severity, being mainly related to psychiatric disorders. Considering the fragility of these patients, it is important to improve safety-related care in the use of drugs for treating this disease.
Escitalopram Ameliorates Cardiomyopathy in Type 2 Diabetic Rats via Modulation of Receptor for Advanced Glycation End Products and Its Downstream Signaling Cascades
Authors: Ahmed Lamiaa A. , Shiha Nesma A. , Attia Amina S. 
Published: January 2021

Type 2 diabetes mellitus (T2DM) has been recognized as a known risk factor for cardiovascular diseases. Additionally, studies have shown the prevalence of depression among people with diabetes. Thus, the current study aimed to investigate the possible beneficial effects of escitalopram, a selective serotonin reuptake inhibitor, on metabolic changes and cardiac complications in type 2 diabetic rats. Diabetes was induced by feeding the rats high fat-high fructose diet (HFFD) for 8 weeks followed by a subdiabetogenic dose of streptozotocin (STZ) (35 mg/kg, i. p.). Treatment with escitalopram (10 mg/kg/day; p. o.) was then initiated for 4 weeks. At the end of the experiment, electrocardiography was performed and blood samples were collected for determination of glycemic and lipid profiles. Animals were then euthanized and heart samples were collected for biochemical and histopathological examinations. Escitalopram alleviated the HFFD/STZ-induced metabolic and cardiac derangements as evident by improvement of oxidative stress, inflammatory, fibrogenic and apoptotic markers in addition to hypertrophy and impaired conduction. These results could be secondary to its beneficial effects on the glycemic control and hence the reduction of receptor for advanced glycation end products content as revealed in the present study. In conclusion, escitalopram could be considered a favorable antidepressant medication in diabetic patients as it seems to positively impact the glycemic control in diabetes in addition to prevention of its associated cardiovascular complications.
In Vitro, In Vivo and In Silico Effectiveness of LASSBio-1386, an N-Acyl Hydrazone Derivative Phosphodiesterase-4 Inhibitor, Against Leishmania amazonensis
Authors: Silva Dahara Keyse Carvalho , Teixeira Jessicada Silva , Moreira Diogo Rodrigo Magalhães , da Silva Tiago Fernandes , Barreiro Eliezer Jesus de Lacerda , Freitas Humberto Fonseca de , Pita Samuel Silva da Rocha , Teles André Lacerda Braga , Guimarães Elisalva Teixeira , Soares Milena Botelho Pereira 
Published: January 2021

Leishmaniasis are group of neglected diseases with worldwide distribution that affect about 12 million people. The current treatment is limited and may cause severe adverse effects, and thus, the search for new drugs more effective and less toxic is relevant. We have previously investigated the immunomodulatory effects of LASSBio-1386, an N-acylhydrazone derivative. Here we investigated the in vitro and in vivo activity of LASSBio-1386 against L. amazonensis. LASSBio-1386 inhibited the proliferation of promastigotes of L. amazonensis (EC50 = 2.4 ± 0.48 µM), while presenting low cytotoxicity to macrophages (CC50 = 74.1 ± 2.9 µM). In vitro incubation with LASSBio-1386 reduced the percentage of Leishmania-infected macrophages and the number of intracellular parasites (EC50 = 9.42 ± 0.64 µM). Also, in vivo treatment of BALB/c mice infected with L. amazonensis resulted in a decrease of lesion size, parasitic load and caused histopathological alterations, when compared to vehicle-treated control. Moreover, LASSBio-1386 caused ultrastructural changes, arrested cell cycle in G0/G1 phase and did not alter the membrane mitochondrial potential of L. amazonensis. Aiming to its possible molecular interactions, we performed docking and molecular dynamics studies on Leishmania phosphodiesterase B1 (PDB code: 2R8Q) and LASSBio-1386. The computational analyses suggest that LASSBio-1386 acts against Leishmania through the modulation of leishmanial PDE activity. In conclusion, our results indicate that LASSBio-1386 is a promising candidate for the development of new leishmaniasis treatment.
Carnosine Stimulates Macrophage-Mediated Clearance of Senescent Skin Cells Through Activation of the AKT2 Signaling Pathway by CD36 and RAGE
Authors: Li Xuenan , Yang Kaiye , Gao Shuang , Zhao Jungang , Liu Guangrong , Chen Yu , Lin Haojie , Zhao Wengang , Hu Zhenlin , Xu Nuo 
Published: January 2021

Background:Macrophages can selectively recognize and eliminate senescent cells, but this function is impaired with age, resulting in excessive accumulation of senescent cells in the skin, which ultimately causes skin aging. Therefore, enhancing the immune surveillance ability of macrophages to clear senescent keratinocytes and fibroblasts from aging skin may be an effective skin rejuvenation strategy.Methods:In this study, a macrophage and senescent skin cell co-culture model was established whereby THP-1-derived macrophages and tert-butyl hydroxide-induced senescent skin cells (HaCaT and HFF-1) were grown in the same culture. Senescent skin cells were detected by the SPiDER-βgal assay, and the expression of secretory phenotype factors related to senescence was assayed by qPCR. The effect of carnosine on the number of SA-β-gal positive skin cells in the macrophage-senescent skin cell co-culture was evaluated and compared with that in the senescent skin cell monoculture.Results:Carnosine promoted macrophage-mediated elimination of senescent skin cells in the co-culture. Through the AKT2 signaling pathway, carnosine upregulated the expression of CD36 and receptors for advanced glycation end products and elevated the phagocytic capacity of the macrophages, thereby promoting the ability of the macrophages to eliminate the senescent skin cells.Conclusions:Carnosine could boost the immune surveillance ability of macrophages to clear senescent keratinocytes and fibroblasts in the macrophage-senescent skin cell co-culture by activating the AKT2 signaling pathway, suggesting the possibility of using carnosine as an agent to reverse skin aging.
H3 Relaxin Alleviates Migration, Apoptosis and Pyroptosis Through P2X7R-Mediated Nucleotide Binding Oligomerization Domain-Like Receptor Protein 3 Inflammasome Activation in Retinopathy Induced by Hyperglycemia
Authors: Yang Kelaier , Liu Jiannan , Zhang Xiaohui , Ren Ziqi , Gao Lei , Wang Ying , Lin Wenjian , Ma Xuefei , Hao Ming , Kuang Hongyu 
Published: January 2021

Introduction: P2X7R excitation-interrelated NLRP3 inflammasome activation induced by high glucose contributes to the pathogenesis of diabetic retinopathy (DR). Relaxin-3 is a bioactive peptide with a structure similar to insulin, which has been reported to be effective in diabetic cardiomyopathy models in vivo and in vitro. However, it is not known whether relaxin-3 has a beneficial impact on DR, and the underlying mechanisms of the effect are also remain unknown.Methods and Results: The retinas of male streptozotocin (STZ)-induced diabetic Sprague-Dawley (SD) rats were characterized. Human retinal microvascular endothelial cells (HRMECs) were used to evaluate the anti-inflammatory, antiapoptotic, antipyroptotic and anti-migration effects of H3 relaxin by transmission electron microscopy, wound-healing assay, transwell assay, flow cytometry, cytokine assays and western-blot analysis. After H3 relaxin treatment, changes of the ultrastructure and expression of NLRP3 inflammasome related proteins in the retinas of rats were compared with those in the diabetic group. In vitro, H3 relaxin played a beneficial role that decreased cell inflammation, apoptosis, pyroptosis and migration stimulated by advanced glycation end products (AGEs). Moreover, inhibition of P2X7R and NLRP3 inflammasome activation decreased NLRP3 inflammasome-mediated injury that similar to the effects of H3 relaxin. H3 relaxin suppressed the stimulation of apoptosis, pyroptosis and migration of HRMECs in response to AGEs mediated by P2X7R activation of the NLRP3 inflammasome.Conclusion: Our findings provide new insights into the mechanisms of the inhibitory effect of H3 relaxin on AGE-induced retinal injury, including migration, apoptosis and pyroptosis, mediated by P2X7R-dependent activation of the NLRP3 inflammasome in HRMECs.
Nestin Promotes Peritoneal Fibrosis by Protecting HIF1-α From Proteasomal Degradation
Authors: Shentu Yangping , Jiang Huanchang , Liu Xiaoyuan , Chen Hao , Yang Dicheng , Zhang Jinqi , Cheng Chen , Zheng Yulin , Zhang Yang , Chen Chaosheng , Zheng Chenfei , Zhou Ying 
Published: January 2021

BackgroundPeritoneal dialysis (PD) is a treatment for end stage renal disease patients, but it can also cause peritoneal fibrosis. Nestin is known as a neural stem cell marker and it has many functions. The hypoxia induced factor (HIF) signaling pathway can be activated under hypoxia conditions, leading to the overexpression of some angiogenesis related genes. The aim of our study is to demonstrate Nestin’s role in the development of peritoneal fibrosis (PF), and to provide a new target (Nestin) to treat PF.MethodsPD mice models were constructed by an intraperitoneal administration of PDS at 10 ml/100g/d for 4 weeks. Nestin-positive cells were isolated from peritonea of Nestin-GFP mice by flow cytometry. The relationship of Nestin and HIF1-α-VEGFA pathway was detected by Nestin knockdown, Co-immunoprecipitation and immunofluorescence. Also, proteasomal activity was demonstrated by CHX and MG132 application, followed by Western blotting and Co-immunoprecipitation.ResultsIn our experiments, we found that Nestin expression resulted in PF. Also, HIF1-α/VEGFA pathway was activated in PF. Nestin knockdown reduced the level of HIF1-α. Nestin directly bound to HIF1-α and protected HIF1-α from proteasomal degradation. Overexpression of HIF1-α reverts the fibrosis levels in Nestin-knockdown cells. In brief, Nestin inhibited the degradation of HIF1-α by mitigating its ubiquitination level, leading to the activation of HIF1-α signaling pathway, and eventually promoted PF.ConclusionWe found a novel mechanism of PF that Nestin promotes by protecting HIF1-α from proteasomal degradation. Taken together, our key findings highlight a novel mechanism by which the silencing of Nestin hinders HIF1- α -induced PF.
The Relationship Between Simple Renal Cysts and Renal Function in Patients With Type 2 Diabetes
Authors: Wei Ling , Xiao Ying , Xiong Xiaofen , Li Li , Yang Yuan , Han Yachun , Zhao Hao , Yang Ming , Sun Lin 
Published: January 2021

Introduction: Simple renal cysts (SRCs) are the most common acquired cystic kidney disease, but the relationship between SRCs and renal function has not been clarified in patients with type 2 diabetes mellitus (T2DM).Methods: A retrospective study was conducted to analyze the clinical features of renal cysts and ultrasound data of the kidney in 4,304 patients with T2DM.Results: The prevalence of SRCs in patients with T2DM was 21.1%. Compared to patients with no SRCs, patients with SRCs had worse renal function (estimated glomerular filtration rate: 108.65 ± 40.93 vs. 92.38 ± 42.1 ml/min/1.73 m2, p &lt; 0.05). After adjusting the confounders, SRC was related to estimated glomerular filtration rate in patients with T2DM [odds ratio = 1.49, 95% confidence interval (1.24, 1.79), p &lt; 0.01]. Age, gout, proteinuria, cerebrovascular disease (CVD), and increased serum phosphorus levels were associated with SRCs in patients with T2DM.Conclusion: SRCs are associated with worse renal function in patients with T2DM. More attention should be paid to gout, proteinuria, CVD, serum phosphorus levels, and renal function in T2DM patients with SRCs.
The Psychological Pressures of Breast Cancer Patients During the COVID-19 Outbreak in China—A Comparison With Frontline Female Nurses
Authors: Cui Qin , Cai Zhongxiang , Li Juanjuan , Liu Zhongchun , Sun Shengrong , Chen Chuang , Wang Gaohua 
Published: January 2021

Objective: During the outbreak of the COVID-19 epidemic in China, breast cancer (BC) patients and healthcare workers faced several challenges, resulting in great psychological stress. We measured the psychological status of BC patients and female nurses and compared the severity within the two groups at the peak time-point of the COVID-19 outbreak.Methods: A total of 207 BC patients and 684 female nurses were recruited from Wuhan. They completed an anonymous questionnaire online using the most popular social media software in China, WeChat. The psychological status of BC patients and of female nurses was measured using the Chinese versions of the 9-item Patient Health Questionnaire (PHQ-9), the 7-item Generalized Anxiety Disorder scale (GAD-7), the 7-item Insomnia Severity Index (ISI), and the 22-item Impact of Event Scale-Revised (IES-R) for evaluation of post-traumatic stress disorder (PTSD). The differences between the two groups were analyzed.Results: The scores of BC patients and frontline female nurses for the four scales were significantly higher than those of non-frontline female nurses (P &lt; 0.001). There were similar scores between BC patients and frontline female nurses for PHQ-9, GAD-7, and IES-R (P = 0.789, P = 0.101, P = 0.158, respectively). Notably, the scores of BC patients for ISI were significantly higher than those of the frontline female nurses (P = 0.016). A considerable proportion of BC patients reported symptoms of depression (106/207, 51.2%), anxiety (130/207, 62.8%), insomnia (106/207, 51.2%), and PTSD (73/207, 35.5%), which was more severe than that of female nurses.Conclusions: BC patients experienced great psychological pressure during the COVID-19 outbreak. The incidents of symptomatic anxiety, depression, sleep disorders, and PTSD were significantly comparable to that of frontline female nurses, and episodes of insomnia among BC participants were more serious than for frontline female nurses.
Assessment of Current Mental Health Status in a Population-Based Sample of Canadian Men With and Without a History of Prostate Cancer Diagnosis: An Analysis of the Canadian Longitudinal Study on Aging (CLSA)
Authors: Moodie Louise , Ilie Gabriela , Rutledge Robert , Andreou Pantelis , Kirkland Susan 
Published: January 2021

Background: Small-scale studies indicate an increase in mental health disorders among prostate cancer survivors compared to the general population, but large population-based data assessing this relationship are scarce. The present study examined the prevalence of lifetime history of prostate cancer in a cross-sectional sample of Canadian men and assessed the contribution of lifetime history of a prostate cancer diagnosis, multimorbidity, and current alcohol and smoking status to the association with current mental health outcomes in this population.Methods: The analytical sample included 25,183 men (aged 45 to 85 years old), who completed a survey as part of the Canadian Longitudinal Study on Aging (CLSA). The Center for Epidemiological Studies Depression Scale (CES-D10), Kessler's Psychological Distress Scale (K10), and self-reported mental health were mental health outcomes. Multiple logistic regression analyses, and controlling for the complexity of the design and covariates, evaluated the association between prostate cancer survivorship, multimorbidity, alcohol and smoking status, and current mental health outcomes.Results: The prevalence of lifetime history of prostate cancer diagnosis in this population-based sample of men was 4% (95% CI: 3.7, 4.4). Our results indicate statistically significantly higher odds of current psychological distress (aOR = 1.52, 95% CI: 1.09, 2.11) and screening positive for depression (aOR = 1.24; 95% CI: 1.02, 1.51) among survivors of prostate cancer, compared to men without a history of prostate cancer diagnosis in demographics controlled analyses. After addition of multimorbidity and substance use, the odds of screening positive for depression among survivors of prostate cancer are 1.32 (95% CI: 1.06, 1.64) higher compared to men who never had a history of prostate cancer diagnosis.Interpretation: Patient education and empowerment programs aimed at addressing concerns during the diagnosis and treatment and enhancing survivorship care plans by adding routine screening for mental distress to help survivors overcome poor mental health during the cancer survivorship journey, are warranted.