bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of engineered ferredoxin reductase systems for the efficient hydroxylation of steroidal substrates
Authors: Zhu Zhangliang , Gao Xin , Song Zhan , Li Chao , Lu Fuping , Tanokura Masaru , Qin Hui-Min 
Published: June 2020

Abstract
Background
9α-hydroxy-4-androstene-3,17-dione (9OHAD), catalyzed by 3-ketosteroid-9-hydroxylase (KSH) using 4-androstene-3,17-dione (AD) as a substrate, is an important precursor for the synthesis of adrenocortical hormones. Whole-cell catalyst in microorganisms with this KSH system for desirable hydroxylated steroids in high purity and productivity have rarely been successful.
Results
The rate-limiting step for the biosynthesis of 9OHAD is catalyzed by the reductase KshB, which is an important component of electrons donor. A sufficient supply system of the cofactor NADH was constructed on KshB by introducing the formate dehydrogenase (FDH) gene. Several reductases were then screened to find a TDO reductase containing a ferredoxin, which showed a maximal NADH activity with a catalytic efficiency (kcat/Km) of 0.43 s− 1 µM− 1 and 54.8% of 9OHAD yield via multienzyme cascade catalysis in vitro. TDO mutagenesis was further performed via a protein engineering strategy, resulting in a 2.25-fold improvement in activity and a 74.8% 9OHAD yield. The modification of a Rieske [2Fe-2S] cluster in KshB and TDO showed 9OHAD yields of 56.1% and 74.5% higher than wild-type ones, which implied Rieske [2Fe-2S] ferredoxin strengthening for electrons transferring. The biosynthesis of 9OHAD was further optimized in a whole-cell catalysis system with FDH, KshA, and TDO_M9 mutant with the Rieske [2Fe-2S] ferredoxin (BLKA-RMT-F), resulting in a final production of 5.24 g/L 9OHAD, a considerable yield of 99.3% of theoretical without by-products.
Conclusion
An efficient whole-cell catalyst was constructed with considerable production and yield by modification of a Rieske [2Fe-2S] cluster in TDO with increased the efficiency of electron transfer. This research provided comprehensive insight into the electron transfer system for these steroid hydroxylation reactions and NADH regeneration systems.
pH-responsive and hyaluronic acid-functionalized metal-organic frameworks for therapy of osteoarthritis
Authors: Xiong Feng , Qin Zainen , chen haimin , Lan Qiumei , Wang Zetao , Lan Nihan , Yang Yuan , Zheng Li , Zhao Jinmin , Kai Dan 
Published: June 2020

Abstract
Drug therapy of osteoarthritis (OA) is limited by the short retention and lacking of stimulus-responsiveness after intra-articular (IA) injection. The weak acid microenvironment in joint provides a potential trigger for controlled drug release systems in the treatment of OA. Herein, we developed an pH-responsive metal−organic frameworks (MOFs) system modified by hyaluronic acid (HA) and loaded with an anti-inflammatory protocatechuic acid (PCA), designated as MOF@HA@PCA, for the therapy of OA. Results demonstrated that MOF@HA@PCA could smartly respond to acidic conditions in OA microenvironment and gradually release PCA, which could remarkably reduce synovial inflammation in both IL-1β induced chondrocytes and the OA joints. MOF@HA@PCA also down-regulated the expression of inflammatory markers of OA and promoted the expression of cartilage-specific makers. This work may provide a new insight for the design of efficient nanoprobes for precision theranostics of OA.
Snapshot of narcotic drugs and psychoactive substances in Kuwait: a qualitative analysis of illicit drugs and their associated mortality in Kuwait from 2015 to 2018
Authors: Al-Matrouk Abdullah , Al-Hasan Mohammed , Al-Abkal Neamat , Mohammed Hanan , Haider Meshaal , Al-Shammeri Dalal , Bojbarah Haider 
Published: June 2020

Abstract
Background
The misuse of illicit substances is associated with increased morbidity and mortality; thus, substance abuse is a global health concern. However, a lack of laboratory-based research has limited the scientific assessment of drug misuse in the Arabian Gulf region. Thus, the primary aim of this study was to assess the problem of illicit drugs in Kuwait using laboratory-based analyses.
Methods
We investigated the type and quantity of detained narcotic drugs and psychotropic substances from 2015 to 2018, number of abusers, and mortality among abusers. In total, 6220 cases from the Narcotic and Psychotropic Laboratory and 17,755 cases from the Forensic Toxicology Laboratory were reviewed and analyzed. Substances were identified and documented using gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry.
Results
Cannabis, including marijuana, was the most seized substance, followed by heroin, opium, and cocaine. Amphetamines, including methamphetamine, in the form of powder or pills, were seized in larger quantities than other psychoactive substances. Benzodiazepines, tramadol, Khat, synthetic cannabinoids, and psilocin were also seized. The most consumed substances were, in order, amphetamines (including methamphetamine), benzodiazepines, cannabis, and heroin. Drug misuse was considerably higher among men than among women. We report the death rate associated with the abuse of various illegal drugs according to sex. The mortality rate associated with single-drug use was the highest among abusers of heroin, benzodiazepines, and methamphetamine. The mortality rate asscoaited with multiple-drug use was the highest among abusers of heroin–benzodiazepines, cannabis–benzodiazepines, and cannabis–amphetamines.
Conclusions
Our study shows the changing trends in quantity and variety of substances illegally abused and marketed in Kuwait. Additionally, we report a direct gender-based association between mortality and consumption of certain substances. These findings suggest that there is a growing need to conduct larger scale studies to implement new strategies, policies, and interventions in populations affected by illicit drugs.
Initial symptoms of patients with coronavirus disease 2019 in Japan.
Authors: Komagamine Junpei , Yabuki Taku 
Published: June 2020

Abstract
Background: Fever, cough, malaise, and throat pain are the most common initial symptoms of coronavirus disease 2019 (COVID-19). However, no studies have ever been conducted to investigate the initial symptoms of COVID-19 in Japan. Methods: We investigated 707 consecutive COVID-19 patients who were diagnosed in ten prefectures of Japan until May 16, 2020 by using publicly available data. The primary outcome was initial symptoms on the day of symptom onset. The proportion of patients with individual symptoms among symptomatic patients was calculated.Results: Of all the patients, 79 (11.2%) were asymptomatic. Among the 628 symptomatic patients, the most common initial symptom was fever (65.9%), followed by cough (23.5%), malaise (23.5%), and throat pain (12.9%). At least one of these four symptoms was reported in 88.2% of all symptomatic patients. Nineteen patients (3.0%) reported gastrointestinal symptoms without respiratory symptoms, while six patients (1.0%) reported only loss of smell or taste as the initial symptom. Conclusions: Like other countries, the most common initial symptoms of COVID-19 patients in Japan are fever, cough, malaise, or throat pain. Gastrointestinal symptoms without respiratory symptoms and loss of smell and taste are uncommon initial symptoms in Japan.
Gender dimensions of the impact of HIV/AIDS on stunting in children under five years in Zimbabwe
Authors: Macheka Lesley , Kembo George , Kairiza Terrence 
Published: June 2020

Abstract
Background: HIV/AIDS can have a disastrous effect on household food and nutrition security, an example includes stunting in children. However, stunting and HIV/AIDS are highly gendered phenomena that need to be explored in order to get an in-depth understanding of the interrelationship. This study was therefore aimed at investigating gender dimensions of the impact of HIV/AIDS on stunting in children under five years from HIV/AIDS affected households in Zimbabwe. Methods: The study uses a large scale nationally representative cross-sectional dataset of 13 854 Zimbabwean households for the year 2019. To test hypothesis 1, the study employs binary choice models (Probit and Logit) since the outcome variable household HIV/AIDS status is dichotomous. To test hypothesis 2 and 3, the study employs the Propensity Score Matching (PSM) approach to circumvent the self selection problem in the creation of treatment and control groups for households affected by HIV/AIDS and those that are not. Results: The results revealed that household HIV/AIDS status is independent of the gender of household head. On the other hand, the results for the PSM estimates show that the probability of the household having a stunted child under five years is higher for households with an HIV positive member compared to those without. In addition, female headed households with an HIV positive member are more likely to have a stunted child under five years compared to male headed households under similar circumstances. Conclusion: Overall, the results provide evidence of a higher risk of stunting among children from households affected by HIV/AIDS. The study offers three major findings. Firstly, the study finds no significant association between gender of the household head and household HIV/AIDS status. Secondly, households that have at least one HIV positive member are more likely to have a stunted child under five years. Lastly, female headed households with at least one HIV positive member are more likely to have a stunted child under five years compared to male headed household with similar HIV/AIDS status. The findings have important policy implications towards improved integration of HIV/AIDS status, household head gender and child nutrition services in affected households.
Egr-1 mediates low dose Arecoline induced human oral mucosa fibroblasts proliferation by transaction the expression of Wnt5a
Authors: Chen Qiang , Jiao Jiuyang , Wang Youyuan , Mai Zhihui , Ren Jing , He Sijie , Li Xiaolan , Chen Zheng 
Published: June 2020

Abstract
Background
Arecoline is the main carcinogens in Areca nut that induce oral submucous fibrosis to develop into cancer. However, many previous studies have showed that Arecoline may inhibit proliferation and prevent collagen synthesis of fibroblasts.
Results
High dose Arecoline (> 32 µg/ml) could inhibit but low dose Arecoline (< 16 µg/ml) could promote the proliferation of human oral fibroblasts. Wnt5a was both sufficient and necessary for the promotion of fibrobasts proliferation. Egr-1, but not NF-κB, FOXO1, Smad2 or Smad3, mediated the expression of Wnt5a in fibrobasts. The specific siRNAs of Egr-1, Egr inhibitors or Wnt5a antibodies treatment blocked Arecoline induced Wnt5a upregulation and fibroblasts proliferation.
Conclusions
Egr-1 mediates low dose Arecoline induced human oral mucosa fibroblasts proliferation by transaction the expression of Wnt5a, and Egr inhibitors or Wnt5a antibodies are potential therapeutic drugs of oral submucosal fibrosis and oral cancer.
Blood Coagulation Parameters in Patients with Severe COVID-19
Authors: Sayad Babak , Rahimi Zohreh 
Published: June 2020

Abstract
Background: Infection with coronavirus disease 2019 (COVID-19) could be complicated with coagulopathy and high risk of thromboembolic events. Methods: Coagulation parameters were analyzed in 74 confirmed severe COVID-19 patients admitted to the intensive care unit of Farabi University Hospital, Kermanshah, Western Iran.Results: Around 42% of patients had abnormal prothrombin time (PT) and international normalized ratio (INR). The rate of abnormal coagulation parameters in the mean age 76.6±7.7 and 46.6±10.3 years were 62 and 38%, respectively. Patients with comorbidities had significantly longer PT and higher INR that increased the rate of mortality to around 77% in these individuals. The abnormal pattern of coagulation parameters was highly associated with comorbidities and poor prognosis. Conclusions: Our study demonstrated abnormal coagulation parameters and a high rate of coagulopathy in hospitalized patients with COVID-19 that was associated with age, comorbidities and mortality which should be considered in management of these patients.
The Added Value of CA125 Normalization Before Interval Debulking Surgery to the Chemotherapy Response Score for the Prognostication of Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy for Advanced Disease
Authors: Liang Wei-feng , Wang Li-juan , Wu Jie-ying , Liu Chang-hao , Wu Miao-fang , Li Jing 
Published: June 2020

Abstract
Objective: To investigate whether CA125 normalization following neoadjuvant chemotherapy (NACT) can complement the chemotherapy response system (CRS) in the prognostication of patients with tubo-ovarian high-grade serous carcinoma (HGSC).Methods: In total, 106 HGSC patients who received NACT followed by interval debulking surgery (IDS) for FIGO stage IIIC-IV disease were included, and their clinical data were retrospectively reviewed. The primary endpoint was progression-free survival (PFS). Cox regression analysis was performed to identify predictors of PFS.Results: Following NACT, CRS3 was noted in 24 patients (22.6%), and CA125 normalization (≤ 35 U/ml) was noted in 54 patients (50.9%). Both CRS3 and CA125 normalization were identified as independent prognosticators of PFS. Combining these two factors, we stratified the 106 patients into three groups with different risks of recurrence: low-risk group (CRS3 + post-NACT CA125≤ 35 U/ml; n = 17, 16.0%), intermediate-risk group (CRS3 + post-NACT CA125 > 35 U/ml; n = 7, 6.6%) and high-risk group (CRS1-2; n= 82, 77.4%). The differences in PFS between the three groups were significant (log-rank test, P < 0.0001). In Cox regression analyses, the new stratification method was found to have an independent prognostic effect.Conclusion: Both the CRS system and the normalization of CA125 following NACT could reliably predict the risk of recurrence following primary treatment. The combination of the two factors refined the prognostic stratification of HGSC patients who were treated with NACT and IDS.
Evaluation of the first experience with COVID-19: An observational study on the screening policy among employees and patients of a Dutch teaching hospital
Authors: Weterings Veronica , Rijen Miranda van , Tinga Mark , Meijs Job , Bijllaardt Wouter van den , Kluytmans Jan 
Published: June 2020

Abstract
BackgroundIn the beginning of March 2020, the Amphia hospital in Breda was one of the first hospitals in the Netherlands that received patients with COVID-19. Within ten days after the first COVID-19 positive patient, the number of (suspected) COVID-19 cases among patients and employees increased rapidly and thus the number of requests for SARS-CoV-2 PCR tests. From mid-March, we changed to a non-test-based strategy for employees whereby a work ban was implemented, based on the presence or absence of respiratory symptoms without the use of a diagnostic test. The objective of our study was to evaluate the safety of the non-test-based strategy. MethodsThe study period was March 1 to May 22, 2020. For all patients in whom the SARS-CoV-2 PCR test was positive > 2 days after admission, the medical record was reviewed by infection control staff for (respiratory) symptoms, laboratory results and lung CT/X-ray images to assess possible hospital-onset COVID-19. For employees, the number of sick reports per week were extracted from the department of Human Resources. Reason for reporting sick was not registered. ResultsTen of the 374 patients (2.7%) developed symptoms suspected for COVID-19 ≥3 days after admission and were tested positive for SARS-CoV-2, of which nosocomial transmission is the most likely cause in three patients. In the period in which the employees were still actively tested for SARS-CoV-2, there was a temporary increase in the number of sick reports (week 10-11). After this two-week period, the number of sick reports decreased rapidly. The total number of sick reports in the first 20 weeks of 2020 is comparable or lower than the total number of sick reports in the same period in previous years.ConclusionWith this non-test-based strategy for employees combined with a restriction of visitors to the patients and strict isolation of COVID-19 (suspected) patients, there was no excessive absenteeism of work due to illness and there were only few patients with indications of COVID-19 acquisition in the hospital.
Pregnancy in GNE Myopathy Patients: A Nationwide Repository Survey in Japan
Authors: Yoshioka Wakako , Miyasaka Naoyuki , Okubo Ryo , Shimizu Reiko , Takahashi Yuji , Oda Yuriko , Nishino Ichizo , Nakamura Harumasa , Mori-Yoshimura Madoka 
Published: June 2020

Abstract
Background: GNE myopathy is an autosomal recessive adult-onset distal myopathy. While a few case reports have described the progression of GNE myopathy during pregnancy, none have examined progression after delivery or obstetric complications. Objective: This study aimed to reveal maternal complications, newborn complications, and the impact of pregnancy on disease progression in GNE myopathy patients. Methods: We conducted a questionnaire survey on pregnancy, delivery, and newborns involving female GNE myopathy patients who are currently registered in a national registry in Japan.Results: The response rate for the questionnaire survey was 60.0% (72/120). Of the 72 respondents, 44 (61.1%) had pregnancy experience (average, 1.8 pregnancies; 53 pregnancies before onset and 28 after onset). The incidence of threatened abortion was 26.9% among post-onset pregnancies, which was higher compared to those of the general Japanese population (p=0.03). No other maternal or infant complications were commonly observed. Over 80% were unaware of changes in disease progression during pregnancy or after delivery, while 19.0% experienced disease exacerbation within a year after delivery. Six patients developed myopathy within a year after delivery, while none developed myopathy during pregnancy.Conclusions: There were no serious maternal or newborn complications, and subjective progression did not differ during or after delivery in the majority of GNE myopathy patients. However, our findings suggest the importance of considering the possibility of threatened abortion and disease progression after delivery.
Flexible Thermoplastic Starch Films Functionalized With Copper Particles for Packaging of Food Products
Authors: López Olivia , Villanueva María E. , Copello Guillermo J. , Villar Marcelo A 
Published: June 2020

Abstract
Biodegradable films based on thermoplastic corn starch (TPS) and copper particles with antimicrobial capacity were developed. Copper nanoparticles (Cu) and silica coated copper microparticles (Si-Cu) in the range of 0.25 to 5 % were used. Composite films were obtained by melt-mixing and subsequent thermo-compression. Particles distribution within TPS matrix and the presence of some pores and cracks, induced by Si-Cu particles, was evaluated by SEM. The presence of both fillers gave to composite films a brown pigmentation and decreased their transparency; these effects were more pronounced at higher particles concentrations. Regarding mechanical properties, copper particles at 1 and 5 % acted as reinforcing agents increasing the maximum tensile strength but their presence lead to a decrease in elongation at break, affecting films ductility. Composites inhibited the growth of Gram+ and Gram- bacteria, demonstrating their antimicrobial capacity. Copper effectively migrated to a simulant of aqueous foods and naked particles concentration in the simulant medium resulted higher than the minimum inhibitory concentration for bacteria.The characteristics and properties of developed composite films make them an interesting material for food primary packaging, mainly for meat fresh products.
Management Protocol for Emergency Aneurysm Craniotomy Clipping in Non-Major COVID-19 Epidemic Areas in Beijing, China
Authors: Chen Yu , Chen Xiaolin , Ma Li , Deng Xiaofeng , Li Zelin , Ye Xun , Wang Hao , Kang Shuai , Zhang Yan , Wang Rong , Zhang Dong , Cao Yong , Zhao Yuanli , Wang Shuo , Zhao Jizong 
Published: June 2020

Abstract
Background: An epidemic of COVID-19 outbroke in Wuhan, China since December 2019. The ordinary medical service were hindered, however, the emergency cases including aneurysmal subarachnoid hemorrhage (aSAH) still required timely intervention and provoked challenges to the management protocol. In this study, we summarized our experience in the emergency management of aSAH (Beijing Tiantan Protocol, BTP) in Beijing, China.Methods: Demographic, clinical and imaging data of consecutive emergency aSAH patients who underwent craniotomy clipping during the COVID-19 epidemic season were reviewed and compared with the retrospective period last year. Subgroup analysis was further performed to assess the outcomes of different screening results and different detail protocols. Neurological outcome was assessed with the modified Rankin Scale (mRS).Results: A total of 127 aSAH referred to our emergency department and 42 (33.1%) underwent craniotomy clipping between January 20, 2020 and March 25, 2020. Compared with the retrospective period last year, the incidence of preoperative hospitalized adverse events and postoperative outcomes were similar (0.1, 95% CI 1.0 to 0.8, P = 0.779). In the subgroup analysis, 8 (19.0%) were initially screened as preliminary undetermined COVID-19 and 2 of them underwent craniotomy clipping in the negative pressure operating room (OR), the prognosis of patients with varied COVID-19 screening results was similar (F(2, 39) = 0.393, P = 0.678). Since February 28, 12 cases (28.6%) received COVID-19 nucleic acid testing (NAT) upon admission and all showed negative, the false negative rate was 0.0%. The preoperative hospitalized adverse events and postoperative prognosis were still similar between patients with and without COVID-19 NAT (-0.3, 95% CI -1.4 to 0.9, P = 0.653).Conclusions: Our emergency surgery management protocol (BTP) is reliable for scheduling emergency aneurysm craniotomy clipping in non-major epidemic areas.