bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generate-Boost: study protocol for a prospective, multicenter, randomized controlled, double-blinded phase II trial to evaluate efficacy and safety of bortezomib in patients with severe autoimmune encephalitis
Authors: Wickel Jonathan , Chung Ha-Yeun , Platzer Stephanie , Lehmann Thomas , Prüss Harald , Leypoldt Frank , Günther Albrecht , Scherag André , Geis Christian 
Published: May 2020

Abstract
Background: Autoimmune encephalitis is a new spectrum of autoimmune disorders of the central nervous system (CNS), which are characterized by pathogenic autoantibodies against neuronal surface antigens. Clinical presentations range from acute to subacute encephalopathy with neurological and psychiatric symptoms, and life-threatening autonomic dysfunction in severe cases. There exist no approved therapies nor is data available from controlled clinical trials. Patients are usually treated with diverse combinations of immunotherapy. However, effect of immunotherapy on antibody-producing cells and thus on levels of pathogenic autoantibodies is insufficient. Therefore, therapeutic response is sometimes prolonged with necessity of long-time intensive care treatment and also irreversible deficits occur in severe cases. This trial will investigate the efficacy and safety of bortezomib, a proteasome inhibitor known to selectively deplete plasma cells, in patients with severe autoimmune encephalitis who have been treated with rituximab with insufficient response.Methods: Generate-Boost is an investigator-initiated, multicenter, double-blinded, randomized controlled phase II trial which will be conducted in specialized neurological hospitals within the GENERATE (GErman NEtwork for Research on AuToimmune Encephalitis) network in Germany. Adult patients with severe autoimmune encephalitis (modified Rankin scale, mRS ≥ 3), autoantibodies against neuronal surface antigens, and pretreatment with rituximab are eligible for study participation. 50 patients will be randomized 1:1 and undergo up to 3 cycles (each 21 days with 4 s. c. applications) of bortezomib or placebo. All patients will receive concomitant medication with dexamethasone, acyclovir and co-trimoxazole. The primary efficacy endpoint is the mRS score 17 weeks after first treatment application. Secondary endpoints are neurocognitive function, antibody titers, markers of neuronal cell damage, length of ICU/hospital stay as well as mRS and Glasgow coma scale scores throughout the trial up to week 17. General and bortezomib-specific adverse events are monitored continuously. Discussion: The expected outcome of the study is to obtain first reliable data on a hypothesis-driven therapeutic option in severe and difficult-to-treat autoimmune encephalitis. If treatment with bortezomib is beneficial in these cases, this will be the basis for implementation in the current guidelines. Trial registration: Clinicaltrials.gov, NCT03993262. Registered June 20, 2019;https://www.clinicaltrials.gov/ct2/show/NCT03993262German Clinical Trials Register, DRKS00017497
A N-propionylsulfonamide prodrug of K-5a2 provided improved aqueous solubility and hERG inhibition
Authors: Zuo Xiaofang , Huo Zhipeng , Kang Dongwei , Zhao Tong , Clercq Erik De , Pannecouque Christophe , Chen Chin Ho , Lee Kuo-Hsiung , Liu Xinyong , Zhan Peng 
Published: May 2020

Abstract
Background Having the potential disadvantages and safety risk of the use of anti-HIV-1 drug candidate K-5a2 in the longterm treatment of HIV patients in mind, we set out with the goal of finding a second-generation backup compound of K-5a2 with the appropriate anti-HIV potency, significantly reduced hERG activity, decreased induction of the CYP enzyme, and improved aqueous solubility. Herein, using a N-propionylsulfonamide prodrug strategy, we report the discovery of compound HM-1Methods In vitro assay of anti-HIV activities in TZM-bl and MT-4 cells, metabolic stability in HLM and human plasma, measurements of water solubility and Log P, assay procedures for hERG activity, acute and subacute toxicity experiment and cytochrome P450 inhibition assay were carried out for HM-1.Results HM-1 can be rapidly hydrolyzed to parent drug K-5a2 and exhibited high potency against HIV-1NL4 − 3 strain (EC50 = 7.99 nM) in TZM-bl cells, HIV-1IIIB strain (EC50 = 2.9 nM) and HIV-1Y181C strain (EC50 = 5.5 nM) in MT-4 cells. And it also showed a > 70-fold improvement in aqueous solubility and presented a low acute toxicity in mice (LD50 > 2 g•kg− 1); no obvious organ damage was detected in the assessment of subacute toxicity. Meanwhile, HM-1 also showed 50 times lower hERG inhibition (IC50 = 6.39 µM) than K-5a2 (IC50 = 0.13 µM).Conclusions It was HM-1 appeared to be free of most of the drawbacks associated with K-5a2 and has been selected for further development as an oral anti-HIV-infection agent.
Moxibustion versus diclofenac sodium gel for the treatment of knee osteoarthritis: a double-blinded, double-placebo, randomized controlled trial
Authors: Luo Ling , Liao Mo , Zhou Jian-Ying , Peng Jia-Xi , Wang Xiang , Zhang Cai-Rong , Guo Ling-Ling , Liu Min , Wang Jia-Ping , Han Xiao-Xia , Lu Sheng-Feng , Hou Tian-Shu , Du Ping , Zhao Jing-Jing , Zuo Jia , Chen Jing-Zhu , Huang Bi-Qing , Peng Jia , Ran Guo-Ping , Zhu Lin-Lin , Yin Hai-Yan , Wu Qiao-Feng , Zhang Cheng-Shun , Lv Peng , Tang Yong , Yu Shu-Guang 
Published: May 2020

Abstract
ObjectiveThe purpose of this study was to evaluate the difference of efficacy between moxibustion (experimental group) and local diclofenac sodium gel (control group) in the treatment of knee osteoarthritis (KOA).MethodsA multicenter, double-blinded, double-placebo, randomized controlled clinical trial was conducted in this research. 144 participants with knee osteoarthritis were randomly divided into two groups according to 1:1 ratio. The participants in the experimental group were treated with active Moxibustion plus placebo gel, whereas the control group was given diclofenac sodium gel plus placebo moxibustion. Moxibustion treatment was administrated at 3 acupoints (EX-LE4, ST35, ST36) for 4 weeks in 12 sessions. The entire trial cycle lasted 13 weeks, including 1 week at baseline, 4 weeks at treatment and 8 weeks at follow-up. Diclofenac sodium gel or placebo gel at a dose of 4 g per knee were applied three times per day for 4 weeks. The primary outcome measures were the changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcome measures included changes in other subscales of WOMAC (pain, stiffness and function), visual analogue scale (VAS) and participant overall assessment (PGA).ResultsThe analysis showed that both the experimental group and the control group at 2 weeks, 4weeks, 8weeks and 12 weeks were statistically significant compared with baseline (P <0.05). There was no significant difference between the two groups in the first four weeks (P > 0.05). At 8 weeks, WOMAC total score (95% CI, 4.3 [0.5 to 8.1], P=0.03), pain score (95% CI, 1.0 [0.2 to 1.9], P=0.02) and functional score (95% CI, 3.0 [0.1 to 5.8], P=0.04) the control group are better than the experimental group (P < 0.05). At 12 weeks, there were no significant difference between the two groups (P > 0.05). ConclusionsDuring the treatment, moxibustion has the same therapeutic effect as local diclofenac sodium gel, which can alleviate the pain of KOA participants to different degrees, rigidity and dysfunction. The therapeutic effect of it can basically maintained until 2 months after treatment. Local diclofenac sodium gel was superior to moxibustion in relieving knee pain and knee dysfunction at 8 weeks.Trial registration number Clinical Trials.gov, NCT02769572.Date of trial registration May 2016＃These authors contributed equally to this work.
Adverse birth outcomes among women who gave births at Eastern Ethiopian Hospitals: a cross sectional study
Authors: Dibisa Teshale Mulatu , Kebede Adera Debela , Gelano Tilaye Feto , Bacha Yadeta Dessie , Jemal Kemal 
Published: May 2020

Abstract
Background

Adverse births outcomes (ABO) such as preterm birth, low birth weight (LBW) and stillbirth are important determining of neonatal morbidity and mortality. It is the major public health problem in low resourced countries. Despite many efforts to reduce neonatal morbidity and mortality, adverse birth outcomes in hospitals has remained high. Therefore, this study aimed to assess the prevalence and factors associated with adverse birth outcomes among women who gave birth at selected public hospitals in Eastern Ethiopia.
Methods

Facility based cross-sectional study design was conducted in February 2017. Data were collected using a pretested and structured face to face interviewer-administered questionnaire. Binary logistic regression was used to analyze the association between the dependent and independent variables.
Results

A total of 555 women who give births were involved from four hospitals in Eastern Ethiopia. The prevalence of low birth weight, stillbirth and preterm births were 40(7.2%), 37(6.7%) and 28(5%) respectively. The overall prevalence of adverse birth outcomes was 76(13.7%). Four-ninth 247(44.5%) of mothers had high-risk pregnancies. Hypertension [AOR = 7.25; 95%, CI= (1.71, 30.64)], history of adverse birth outcome [AOR = 12.12; 95%, CI= (6.5, 22.6)], multiple pregnancy [AOR = 6.94; 95%, CI= (2.74, 17.53)] and spontaneous vaginal delivery [AOR = 0.11; 95%, CI= (0.44, 0.16)] were associated with adverse birth outcome.
Conclusion

In this study adverse birth outcomes were still found as public health problems. Hypertension, history of adverse birth outcome, multiple pregnancy and spontaneous vaginal delivery were significantly associated with ABO. Thus, developing strategies to prevent and treat complications during pregnancy and increasing maternal health utilization at ANC clinics are warranted.
Exploring anti-nonalcoholic fatty liver disease mechanism of Gardeniae Fructus by combining an animal model with network pharmacology and molecular docking
Authors: Li Lin , Lu Lihua , Tang Zhong-yan , Xia Zhengxiang 
Published: May 2020

Abstract
Background

Gardeniae Fructus (GF), a traditional Chinese medicine in clinic for the treatment of nonalcoholic fatty liver disease (NAFLD). However, the mechanisms of action of GF was still margin. To explore the efficacy and mechanism of action of GF for the treatment of NAFLD, we proposed a strategy combined in vivo efficacy verification, network pharmacology analysis, molecular docking, and validity assay of target protein.
Methods

Firstly, an animal model induced by the high fat diet feed was established, then orally administrated with GF, the mRNA expression levels of lipogenesis was performed by RT-PCR, the liver tissue specimens were stained by hematoxylin and eosin (H&E), then observed by light microscopy. Secondly, network pharmacology studies clarified the relationship among the active constituents, target protein, and pathways, and then explored by the molecular docking. Finally, validity assay of target protein was performed in surface plasmon resonance (SPR) test.
Results

GF protected against NAFLD in rats. Network pharmacology showed that quercetin, oleanolic acid, and geniposide, targeted on PPARα, PPARγ, and CA2 genes, through regulating PPAR, AMPK, and cGMP-PKG signal pathways, to protect against NAFLD. And the
Conclusion

GF could alleviate NAFLD through the molecular mechanisms explored by network pharmacology, molecular docking, and surface plasmon resonance, those method can be effective tools to clarify the mechanisms of actions of traditional Chinese medicine from a holistic perspective.
Assessment of changes in blood urea and creatinine levels in patients with coronavirus disease 2019 (COVID-19)
Authors: Mahmoudi Hassan , Alikhani Mohammad Yousef , Taheri Narges Mofrad , Behzadi Alireza 
Published: May 2020

Abstract
Background Coronavirus disease 2019 (COVID-19) is new respiratory tract infections disease with an evolving understanding of its epidemiology and clinical appearances. Kidney defect seems to be common in patients with Covid-19. Urea and creatinine level often occurs at the beginning or during the infection. This evidence shows that Covid-19 also attacks the kidneys. The aim of this study was to evaluate changes in biochemical parameters associated with kidney function, including urea and creatinine in patients with COVID-19.Methods We conducted a retrospective analysis of the plasma creatinine and urea levels of the 100 COVID-19 patients with normal plasma creatinine and urea at first clinical presentation of COVID-19.Results Among these 100 patients with COVID 19, total of 35 (35%) patients, increased BUN and creatinine levels occurred at duration of 2–4 days after the onset of viral infection. The mean serum urea level in first clinical presentation and at duration of 2, 3 and 4 days after the onset of viral infection were 34.75 ± 0.10 and 37.64 ± 0.32, 39.81 ± 0.10, 42.56 ± 0.35 mg/dl, respectively. The mean of creatinine concentration in first clinical presentation and at duration of 2, 3 and 4 days after the onset of viral infection were 1.50 ± 0.026 and 1.51 ± 0.016, 1.99 ± 0.012, 2.58 ± 0.020 mg/dl, respectively.
The Natural Course of Hereditary Angioedema in a Chinese Cohort
Authors: Cao Yang , Liu Shuang , Zhi Yuxiang 
Published: May 2020

Abstract
Background
Hereditary angioedema (HAE) is a rare disease with potential life-threatening risks. Until now, few studies have focused on the natural course of HAE, which is essential for practitioners and patients to predict disease progression and avoid possible risk factors.
Objectives
Describe the natural course of HAE and explore possible risk factors, providing new clues for guiding clinical prevention and treatment.
Methods
A web-based survey was conducted in 103 Chinese patients with type 1 HAE. Disease progression under therapy-free conditions was collected at different age stages. The demographic characteristics, lifestyles, disease severity and family history were also provided by each participant.
Results
Among 103 patients, 14 (13.6%) had their first HAE attack before ten years old and 51 (49.5%) between 10 and 19. The disease worsened in 83.3% of the patients in their twenties. The proportion of patients with symptoms alleviated increased after the age of 30 years old, but the disease maintained relatively severe in most cases before 50. The participants also reported 233 members shared similar symptoms of angioedema in their family and 30 had died of laryngeal edema with the median death age of 46 years old. The disease severity was not observed to be affected significantly by gender, BMI, alcohol or smoking.
Conclusions
We summarized HAE progression patterns in therapy-free conditions, showing the natural course of disease development along with aging. Long-term prophylaxis and symptomatic treatment are recommended for all HAE patients, especially young and middle-aged and might be adjusted depending on the disease progression.
Mutation screening and burden analysis of GLT8D1 in Chinese patients with ALS
Authors: Cao Bei , Gu Xiaojing , Wei Qianqian , Li Chunyu , Chen Yongping , Ou Ruwei , Hou Yanbing , Zhang Lingyu , Li Tao , Song Wei , Zhao Bi , Wu Ying , Chen Xueping , Shang Huifang 
Published: May 2020

Abstract
Objective Glycosyltransfersase 8 domain containing 1 ( GLT8D1 ) gene was identified to be an amyotrophic lateral sclerosis (ALS) causative gene via pedigree co-segregation and burden analysis. However, validations based on large cohort of ALS among different ethnic population are essential. We aimed to systematically screen all exons of GLT8D1 in a large cohort of Chinese ALS patients, study the genotype-phenotype correlation and explore the role of rare variants of GLT8D1 in ALS.Methods A total of 977 sporadic ALS (sALS) and 47 familial ALS (fALS) cases underwent whole exome sequencing. Rare variants with MAF<0.1% in GLT8D1 were analyzed. Moreover, by using the controls from gnomAD database, rare variants were included in the burden analysis via 5 different algorithms.Results We identified 1 likely pathogenic variant in the exon 4 of GLT8D1 in a fALS case and validated within the pedigree. Moreover, 3 variant of uncertain significance (VUS) in 4 patients among the 977 sALS cases 1 VUS in 1 case among the 47 fALS cases were also identified. Furthermore, in the burden analysis, there were no significant enrichment of rare variants of GLT8D1 in the whole gene level or exon 4 exclusively among Chinese patients with sALS.Conclusion Cosegregation findings in our study further supported the pathogenic role of GLT8D1 in fALS. However, no pathogenic mutation was identified in the sALS patients, and rare variants were not enriched in the whole gene level or exon 4 of GLT8D1 among sALS patients, both of which suggested that the GLT8D1 may not play a role in Chinese patients with sALS.
Clinical presentation and visual outcome of broomstick ocular injury in 120 eyes of children at a tertiary eye care in India
Authors: Gupta Abhishek , Singh Prabhakar , Gupta Richa , Bhushan Vidya , Sinha Shivani , Sinha Bibhuti Prasann 
Published: May 2020

Abstract
Background

Eye injuries are a serious health problem globally. Ocular trauma accounts for 5% of blindness cases. In India broomstick injury is very common. But only few studies are published regarding the nature and outcome of broomstick ocular injuries. The aim of this study is to determine the frequency, mode of presentation, complications and surgical results with a view to offering solutions to reduce this trend.
Methods

This retrospective study was conducted at Regional Institute of Ophthalmology, Patna. The records of all patients presenting to the Eye OPD and Emergency clinic with ocular trauma from broomstick injury between March2017 and April 2020 were reviewed. A total of 120 cases were identified. Patient’s age, gender, interval between injury and presentation to eye OPD, mechanism of injury, activity at time of injury, visual acuity at presentation, anterior and posterior segment findings, diagnosis, complications, treatments offered and follow-up events were documented. Data were analysed statistically.
Results

The mean age of presentation was 8.10 ± 4.93 years. All were children < 15 years old. 80% patients sustained trauma from broomstick shot as an arrow. 70% had presenting vision < Hand movement. 90% of the cases were open globe injuries. Most of them had multiple complications such as corneal perforation (80%), traumatic cataract (27%), endophthalmitis (68%), retinal detachment (12.5%), panophthalmitis 8 (7%) and orbital cellulitis (6%). Culture was positive in 20%. Pseudomonas aeuroginosa was the most common organism isolated. Therapeutic vitrectomy was performed in 67% eyes. Only 12% eyes gained ambulatory vision (VA > 3/60) after vitrectomy.
Conclusion

Broomstick shot as an arrow causes devastating and multiple complications resulting in rapid and immediate loss of vision. Overall prognosis is bad and early presentation to the hospital does not appear to improve the prognosis. Such injuries often affect younger, male children. Primary prevention is the only way to control blindness occurring from such injuries. Primary health education should be given in school to highlight these risk factors.
Alcohol Drinking as a Mediator of the Influence of Smoking Prevalence on Second-Hand Smoke Exposure in Workplaces: A Mediation Analysis
Authors: LIN Haoxiang , Chang Chun , LIU Zhao 
Published: May 2020

Abstract
Objective: Both alcohol drinking and second-hand smoke (SHS) exposure have shown a strong association with smoking behaviour. This study uses mediation analysis to clarify the process underlying the relationship between smoking prevalence and SHS exposure and the extent to which this relationship is mediated by alcohol use in the workplace.Method: A total of 14195 employees from 81 companies in China participated in this survey. Mediation analysis was used to establish the mediation effect of alcohol drinking. Structural equation modelling（SEM） was used to evaluate the role of alcohol drinking when a smoke-free (SF) workplace policy was imposed.Results: For males, approximately 6.3% of the effects on SHS exposure were mediated through the channel of alcohol use. For females, this channel mediated 14.1% of the total effects. SF policy was negatively associated with smoking prevalence and SHS exposure. The indirect effect of the SF policy on reducing SHS exposure by controlling smoking behaviour was significant. For smokers, worksite smoking bans were negatively associated with the smoking amount and drinking behaviour, and the indirect effect of this policy on promoting smokers’ intention to quit by reducing the smoking amount and controlling drinking behaviour was significant.Conclusion: This study confirmed that alcohol drinking is among the channels that mediate the association between smoking prevalence and SHS exposure in workplaces. Our results also find a spillover effect of SF workplace policy and call for effective interventions for alcohol use, which may influence the outcomes of SF policy implementation.
Activated microglia-induced neuroinflammatory cytokines lead to photoreceptor apoptosis in age-related macular degeneration-like mice model
Authors: Wu Jing , Gao Ge , Shi Fanjun , Zhang Chaoyang , Xie Hai , Yang Qian , Liu Dandan , Qu Sichang , Qin Haifeng , Xu Guo-Tong , Liu Fang , Zhang Jingfa 
Published: May 2020

Abstract
Background

Age-related macular degeneration (AMD) is mainly characterized by progressive deposits of drusen and photoreceptor apoptosis. Due to amyloid β (Aβ) is the main component of drusen, there is a great possibility that Aβ-induced activated microglia leads to inflammation, and plays a critical role in the pathogenesis of AMD. However, the relationship between activated microglia-mediated neuroinflammatory cytokines and photoreceptor apoptosis still remains unclarified.
Results

In this study, we demonstrated that subretinal injection of Aβ1−42 induced the microglia activation and increased inflammatory cytokines, gave rise to photoreceptor apoptosis in mice. Our results were verified in vitro by co-culture of Aβ1−42 activated primary microglia and photoreceptor cell line 661W, and we also performed that p38 MAPK signaling pathway was involved in Aβ1−42 induced microglia activation and inflammatory cytokines release.
Conclusions

Overall, our findings indicated that activated microglia-mediated neuroinflammatory cytokines contributed to photoreceptor apoptosis under the stimulation of Aβ1−42. Moreover, this study will provide a potential preventive and therapeutic approach for AMD treatment.