bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Internet Delivered Cognitive Behaviour Therapy for Anxiety and Depression in People with Bipolar Disorder
Authors: Nielssen Olav , Staples Lauren , Karin Eyal , Kayrouz Rony , Dear Blake , Titov Nicholai
Published: October 2020

BackgroundMindSpot is a national digital mental health service providing free assessment and treatment for anxiety and depression. Mindspot services have been accessed by people with a broad range of psychiatric conditions, including people who report a diagnosis of bipolar disorder (BD). There is comparatively little research reporting the outcome of internet delivered cognitive behaviour therapy (iCBT) for the depressed phase of BD (BDd), including as part of routine care. MethodDemographic characteristics, baseline scores and treatment outcomes were examined for patients who reported taking Lithium and had entries in their clinic records confirming the diagnosis of BD. Results were compared to the clinic benchmarks. Outcomes were completion rates, patient satisfaction and changes in measures of psychological distress, depression and anxiety as measured by the Kessler-10 item (K-10), Patient Health Questionnaire 9 Item (PHQ-9), and Generalized Anxiety Disorder Scale 7 Item (GAD-7), respectively. ResultsA total of 21,745 people completed a MindSpot assessment between January 2013 and December 2019 and enrolled in a MindSpot treatment course. Of these, 124 reported that they were currently taking Lithium, of whom 83 had entries in their clinic records confirming a diagnosis of BD. Mean age of patients with confirmed BD was 43.8 years, compared to the clinic mean of 39.8 years. Their baseline symptom scores were higher than the benchmark. However, reductions in symptoms on the K-10, PHQ-9, and GAD-7 were large (effect sizes > 1.0 on all measures, percentage change between 32.4% and 40%), and lesson completion and satisfaction with the course were also high. ConclusionsMindSpot treatments were effective in treating anxiety and depression in people diagnosed with BD, and the outcomes were comparable to clinic benchmarks. Results suggest that the routine provision of iCBT can help overcome the under-use of evidence based psychological treatments of people with BDd.
Carers’ Experiences of Assistive Technology Use in Dementia Care: A Cross Sectional Survey
Authors: Sri Vimal , Jenkinson Crispin , Peters Michele
Published: October 2020

BackgroundAssistive Technology (AT) supports persons with dementia and their carers (family, friends and neighbours), yet little is known about experiences and the impact of AT on carers. We report on an exploratory survey that examined the types, uses, costs and impact of AT on carers as well as their quality of life.MethodsA cross-sectional survey using the Carers Assistive Technology Experience Questionnaire collected data from carers in the UK, who used at least one AT in the previous year and provided more than 10 hours of care for a person with dementia, living at home. Carers completed the questionnaire online or on paper and information on AT, socio-demographic details, and Short-Form Health Survey (SF-12) data were collected. Descriptive and inferential statistics were used to report results and draw conclusions. ResultsData from 201 carers was analysed. Smartphones and tablet computers were the most frequently used AT. AT were used predominantly for safety, communication, and reminders. Carers usually make decisions on buying and continued use of AT. Multiple AT devices were used in the care of persons with dementia and number of AT used was associated with perceived satisfaction. Satisfaction with AT was not related to age, living arrangements and relationship of carers. From the SF-12, Mean Physical Component Score was 49.19 (95%CI- 47.75 to 50.63) and Mental Component Score was 45.37 (95%CI- 43.93 to 46.80). Women, carers in the 46-65 age group and carers who were not extremely satisfied with AT had lower MCS scores. Carers who lived with the person with dementia and older carers had lower PCS scores. ConclusionsCarers report that AT has a beneficial impact. Carers use multiple ATs, perceive AT to be satisfactory and recommend AT use to others. To support carers, we recommend establishment of centrally funded information sources and a loan store for AT. Further research on incremental addition of AT and changes to formal/paid care because of using AT should be undertaken. Practitioners, academics, manufactures and policy makers should consider the experiences of carers in research, development and use of AT to facilitate improved community living of people with dementia.
Beliefs, Knowledge and the Impact of COVID-19 on Menopause Therapies in Spanish Women: Comem-treatment Study
Authors: Baquedano Laura , Espiau Andrea , Fasero Maria , Ortega Silvia , Ramirez Isabel , Mendoza Nicolás
Published: October 2020

ObjectiveTo study what women think about menopause treatments and assess their knowledge about them. To analyze adherence to treatment during COVID-19 confinement as a secondary objective.MethodsA multi-center cross-sectional observational study was conducted using a survey of 2500 women between January and June 2019. This was administered following a non-probability sampling procedure including women between 35 and 75 years. An extension study was conducted during the coronavirus pandemic, between March and June 2020. ResultsThe responses of 2355 surveyed women were analyzed. Of this sample, 42% knew about menopause hormone therapy (MHT). The most frequently identified indication was the treatment of hot flashes (65.6%). The MHT risks most frequently perceived were weight gain (24.2%) and breast cancer (21.7%); the main reason for rejecting MHT was a lack of information (96.1%). Comparative analyses were conducted according to age, menopausal status, type of menopause, place of residence, type of health care and level of education. During the coronavirus confinement period, 85 women using MHT were located, of which 84.7% continued it. ConclusionsWomen hold certain false beliefs about menopause, and their knowledge of the available treatments is somewhat limited. Adherence to MHT during the COVID-19 confinement in Spain has been high.
Improved Production of Germacrene A, a Direct Precursor of ß-elemene, in Engineered Saccharomyces Cerevisiae by Expressing a Cyanobacterial Germacrene A Synthase 
Authors: Zhang Weixin , Guo Junqi , Wang Zheng , Li Yanwei , Meng Xiangfeng , Shen Yu , Liu Weifeng
Published: October 2020

BackgroundThe sesquiterpene germacrene A is a direct precursor of ß-elemene that is a major component of the Chinese medicinal herb Curcuma wenyujin with prominent antitumor activity. The microbial platform for germacrene A production was previously established in Saccharomyces cerevisiae using the germacrene A synthase (LTC2) of Lactuca sativa. ResultsWe evaluated the performance of LTC2 as well as nine other identified or putative germacrene A synthases from different sources for the production of germacrene A. AvGAS, a synthase of Anabaena variabilis, was found to be the most efficient in germacrene A production in yeast. AvGAS expression alone in S. cerevisiae CEN.PK2-1D already resulted in a substantial production of germacrene A while LTC2 expression did not. Further metabolic engineering the yeast using known strategies including overexpression of tHMGR1, repression of squalene synthesis pathway and decreasing farnesol synthesis, led to an 11-fold increase in germacrene A production. Site-directed mutagenesis of AvGAS revealed that while changes of several residues located within the active site cavity severely compromised germacrene A production , substitution of Phe23 located on the lateral surface with tryptophan or valine led to a 35.2% and 21.8% increase in germacrene A production, respectively. Finally, the highest production titer of germacrene A reached 309.8 mg/L in shake-flask batch culture. ConclusionsOur study highlights the potential of applying bacterial sesquiterpene synthases with improved performance by mutagenesis engineering in producing germacrene A.
The association of food insecurity with diabetes control and self-care in diabetes type 2 patients: A cross-sectional study
Authors: Mohammadi Marjan , Djazayeri Seyyed Abolghasem , Jafari Asal Ataie
Published: October 2020

Background

Food insecurity can increase risks of health and nutritional problems, leading to difficulties in self-care and poor glycemic control in diabetic patients. This study assessed food insecurity and its association with diabetes control and self-care in type 2 diabetes patients.
Methods

In this cross sectional study, 148 adults with type 2 diabetes participated. Food insecurity and self-care were determined using the 18-item USDA household food security status questionnaire and self-care (SDSCA) questionnaire. Data were analyzed using logistic and linear regression tests (SPSS 20 software).
Results

Thirty-seven percent of the participants were food-insecure and significantly more likely than food-secure participants to have poor glycemic control (OR = 3.02; CI: 1.45–2.65). No significant association was found between food-insecurity and overall self-care score.
Conclusion

Food-insecurity was directly associated with poor glycemic control in type 2 diabetes patients. Since economic status was significantly better in the food-secure group, it can be postulated that financial problems will eventually lead to poor glycemic control. Policy strategies to increase access to diabetes-appropriate foods may reduce socioeconomic inequalities in glycemic control.
An Unusual Case of Myasthenia-Like Presentation in Erdheim-Chester Disease
Authors: Lauricella Eleonora , d'Amati Antonio , Ingravallo Giuseppe , Foresio Maurizio , Ribatti Domenico , de Tommaso Marina , Cives Mauro , Girolamo Francesco
Published: October 2020

Background: Erdheim-Chester disease (ECD), a rare disorder of monocyte/macrophage lineage, has been related to cerebellar dysfunction. To increase the awareness of this rare, protean disease, an unusual, myasthenia-like onset of ECD is reported.Case presentation: A 42-year-old man presented with a 6-year history of mild evening fatigability in his four limbs followed by motor and cognitive symptoms associated with cerebellar atrophy, dentate nuclei and dentato-thalamic pathway degeneration. Magnetic resonance imaging revealed hyperintense signals in T2 and fluid-attenuated inversion recovery sequences within the pons, cerebellar white matter, dentate nuclei and globi pallidi in the absence of any contrast enhancement. Whole-body bone scintigraphy with 99Technetium - methylene diphosphonate and fluorodeoxyglucose-positron emission tomography both revealed symmetric uptake in the lower extremities a finding suggestive of a diagnosis of ECD. Histological examination revealed diffuse infiltration of CD 68+ histiocytes with foamy cytoplasms in the presence of B-type of Rapidly Accelerated Fibrosarcoma protein kinase (BRAF)V600E activating mutation in tumor cells.Conclusion: In patients with myasthenia-like symptoms who test negatively for myasthenia gravis, neurodegenerative diseases, and disorders of the hypothalamus, a diagnosis of ECD should be taken into consideration.
A Newly Generated DOCK8-expressing T Follicular Helper Cell Type, aiCD4 T Cell, Causes Systemic Lupus Erythematosus: Self-Organized Criticality Theory
Authors: Shiozawa Shunichi , Tsumiyama Ken , Sakurai Keiichi , Horiuchi Takahiko , Matsubara Tsukasa , Oribe Motohiro , Yamane Takashi , Kagawa Hidetoshi , Li Quan-Zhen , Mukai Yohei , Miyazawa Masaaki
Published: October 2020

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease of unknown cause. We show here that a novel T follicular helper cell type expressing the guanine nucleotide exchange factor DOCK8 on the cell surface causes SLE. These cells, which we have designated autoantibody-inducing CD4 T (aiCD4 T) cells, are generated after resuscitation from anergy following strong TCR stimulation by antigen. When mice normally not prone to autoimmune disease were repeatedly immunized with an antigen such as OVA, they generated DOCK8+ CD4 T cells. These DOCK8+ CD4 T cells, in vivo and also upon transfer to naïve mice, induced a variety of autoantibodies and lesions characteristic of SLE. TCR repertoire analyses showed that a substantial number of novel TCR repertoires were generated in the DOCK8+ CD4 T cells, which induced novel autoantibodies upon transfer to naïve mice. DOCK8+ CD4 T cells are localized in splenic red pulp, the space immunoreactive against a variety of antigens, and specifically increased in the peripheral blood of SLE patients in association with disease activity. Anti-DOCK8 antibody treatment ameliorated the lesions induced by DOCK8+ CD4 T cells and in lupus model (NZB x W) F1 mice. Thus, when CD4 T cells are overstimulated by an external disturbance, i.e., repeatedly stimulated with antigen, to levels that surpass the system’s self-organized criticality, these cells express DOCK8 on the cell surface and acquire autoreactivity via TCR re-revision at the periphery. These DOCK8+ CD4 T cells subsequently induce a variety of autoantibodies and SLE.
The Clinical Significance and Biological Function of PCDH7 in Cervical Cancer
Authors: Zhang Shitong , Fu Xianhu
Published: October 2020

Background: Cervical cancer is a common malignant tumor in women that is prone to recurrence and metastasis. Recently, many people have explored the role of protocadherin 7 (PCDH7) in cancer, and found that PCDH7 is abnormally expressed in many cancers. The purpose of this study is to investigate the expression and mechanism of PCDH7 in cervical cancer and evaluate its clinical prognostic significance.Methods: The expression of PCDH7 in cervical cancer and cells was detected by qRT-PCR. The relationship between PCDH7 expression and clinical prognosis was calculated by the Kaplan-Meier method and Cox regression analyses. The effects of PCDH7 on cancer cell proliferation, migration, and invasion were studied by MTT assay and transwell assays.Results: The expression of PCDH7 in cervical cancer tissues and cell lines was significantly down-regulated compared with the control. Low PCDH7 expression was associated with low survival rate. PCDH7 expression was significantly correlated with lymph node metastasis, cell differentiation, and FIGO staging. PCDH7 can be used as an independent prognostic factor for cervical cancer. Up-regulation of PCDH7 significantly inhibited the proliferation, migration, and invasion of cancer cells.Conclusions: PCDH7 may be used as a biomarker for the prognosis of cervical cancer.
An assessment of recently released high-degree global geopotential models based on heterogeneous geodetic and ocean data
Authors: Wu Yihao , Abulaitijiang Adili , He Xiufeng , Luo Zhicai , Wang Haihong , Zhou Boyang
Published: October 2020

The development of the state-of-the-art global geopotential model (GGM) broadens its applications in ocean science, which emphasizes the importance for model assessment. We validate the recently released high-degree GGMs over the South China Sea using geodetic observations and synthetic/ocean reanalysis data. The assessment against a recently conducted high resolution (~ 3 km) airborne gravimetric survey over the Paracel Islands shows that XGM2019e_2159 has the highest accuracy (~ 3.1 mGal). However, the comparison with airborne/shipborne data hardly discriminate the qualities of other GGMs that have or truncated to same degree and order. Whereas, the validation results of GGMs against synthetic/ocean data are not identical. XGM2019e_2159/XGM2019 has the best quality, and the accuracy of associated mean dynamic topography (MDT) is 2.5 cm, and this value changes to 7.1 cm/s (6.8 cm/s) when the zonal (meridian) geostrophic currents are assessed. In contrast, the assessments of other GGMs show that they have deteriorated accuracies compared to XGM2019e_2159/XGM2019; in particular, the widely used EGM2008 has the worst performance, and the accuracies of associated MDT and zonal (meridian) currents are reduced by 3.9 cm and 4.0 cm/s (5.5 cm/s), respectively, compared to results derived from XGM2019e_2159/XGM2019. These results suggest that the choice of GGM in oceanographic research is crucial, especially in coastal zones and regions that only fill-in data were used for GGM development. Moreover, the existing synthetic/ocean data may be served as an additional data source for global/regional gravity field assessment, which is especially useful in regions that lack of control data.
Cardiovascular Disease Risk Prevention Services by Pharmacists in Saudi Arabia: What Do Policymakers and Opinion Leaders Think?
Authors: Almansour Hadi A. , Aloudah Nouf M. , Alhawassi Tariq M. , Chaar Betty , Krass Ines , Saini Bandana
Published: October 2020

Background: Cardiovascular disease (CVD) is an emerging contributor to national morbidity and mortality in Saudi Arabia. CVD risk prevention services are limited, particularly with an over-utilised public health sector and an under-utilised and under-resourced primary care sector. Globally, there is evidence that community pharmacists can play a key role in CVD prevention within primary care. However, the perspectives of policymakers and opinion leaders are critical to successful translation of evidence into practice. Thus, the aim was to engage policymakers and professional leaders in discussions about implementing high-quality CVD risk prevention services in community pharmacy. Methods: Qualitative semi-structured interviews were conducted, audio-recorded and transcribed verbatim. All transcripts were thematically analysed. Results: A total of 23 participants (87% male) from government and non-government sectors were interviewed. Of these, almost 65% had pharmacy qualifications. Limited provision of CVD risks preventative services in primary care was acknowledged. However, most participants favoured the concept of utilising community pharmacist’s capacity to assist in preventive health services. The data yielded four key themes: 1) Future pharmacy CVD health service models, 2) Demonstrable outcomes, 3) Professional engagement and advocacy and 4) Implementability. CVD health services roles (health screening, primary and secondary prevention services), pragmatic factors and tiered models of care (minimal, medium and comprehensive pharmacist involvement) were discussed. The need for humanistic, clinical and cost effectiveness outcomes and activation of professional bodies were deemed important. Professional pharmacy governance to develop pharmacy careers and workforce, pharmacy curricular reform and ongoing education were posed as key success factors for pharmacy roles. Practice policies, standards and guidelines were seen as required to adhere to stringent quality control for future pharmacy services provision. Participants implementation vision for such services included scalability, affordability, access, adoption and health system reform. Most discussion focused on the need for structural improvement with limited input regarding processes or outcomes required to establish such models. Conclusions: Most participants favoured pharmacy-based CVD risk prevention services, despite the variability in proposed service models. However, prior to developing such services, support structures at the health system and health professional level are needed as well as building public support and acceptability for pharmacy services.
De novo Propagation of Alfalfa Under Hydroponics
Authors: Yang Liu , Wenyu Zhang , Shuai Li , Yao Wu , Xiaohui Sun , Siyu Li , Zongyu Wang , Lichao Ma , Juan Sun , Cong Lili , Guofeng Yang
Published: October 2020

Background: The legume plant alfalfa (Medicago sativa L.) is a widely cultivated perennial forage due to its high protein levels, palatability, and strong adaptability to diverse soil types and agro-ecological zones. This forage plant is a self-incompatible, cross-pollinated autotetraploid with tetrasomic inheritance. Therefore, maintaining excellent traits through seed reproduction is challenging in alfalfa. However, the cutting propagation technology could enable consistent multiplication of quality plants that are genetically identical to the parent plant, for use in breeding and other research applications. Most of previous alfalfa omics researches used varieties as material on omics and gene mining experiment due to poor growth consistency of cuttings by existing cutting methods, which generate genetically un-identical cuttings and thus compromise on the reliability of the results. Therefore, this study aimed to develop a simple, cost-effective, reproducible, and efficient hydroponic cutting method for the preservation of alfalfa plants and molecular research applications such as genomic, transcriptomic, and proteomic analyses. Results: Alfalfa cultivar ‘Wudi’ grown under hydroponics for 30 days was used as source material for cuttings. The top, middle and bottom sections of its stem were used as cuttings. The rooting rate, root length, and stem height of the different stem sections were compared to determine the best segment for alfalfa propagation in four nutrient solutions (HM, HM+1/500H, HM+1/1000H and d HM+1/2000H). After 21 days of culture, the rooting rates of all the three stem types under four cutting nutrient solutions were above 78%, The rooting rate of the middle and bottom parts in HM +1/1000 H and HM +1/2000 H nutrient solutions reached more than 93% with higher health survey score (>4.70). Besides, root length and stem height in these two sections was exemplary. Conclusions: This study developed a de novo cutting propagation method that can be used to conserve and propagate germplasm in breeding programs and research. This article is the first report on the cutting propagation of alfalfa by hydroponics, which could supplement the existing cutting propagation methods.
Continuous Infusion Compared with Intermittent Intravenous Infusion of Beta-Lactam Antibiotics for Critically Ill Patients: A Systematic Review and Meta-Analysis of Randomized Trials
Authors: Huang Chien-Huei , Shih Ching-Yao , Tsay Meng Keng , Hsuan Shen-Pei , Tseng Yung-Hsin , Tsai Wen-Shan , Cheng Ching-Lan
Published: October 2020

Background: The pathophysiologic changes during critical illness and high minimal inhibitory concentration (MIC) pathogens are important risk factors of mortality and bacterial eradication in critical care. Beta-lactam antibiotics have a time-dependent effect on bactericidal activity. The continuous infusion (CIF) of beta-lactam antibiotics achieves sufficient drug concentration above the MIC, especially for critically ill patients. However, the superiority of CIF over intermittent infusion (IIF) of beta-lactam antibiotics is yet to be clearly established. Thus, we aimed to investigate the effects on mortality of CIF of beta-lactams antibiotics in comparison to those of IIF of beta-lactams antibiotics in patients with sepsis admitted to the intensive care unit (ICU).Methods: We systematically searched PUBMED, MEDLINE, Cochrane Library, EMBASE, Web of Science, and ICTRP for randomized controlled trials (RCTs) comparing CIF with IIF of beta-lactam antibiotics in critically ill populations. All RCTs published until October 2019 were eligible. The primary outcome measure was the relative risk (RR) of mortality, while the secondary outcome measures were bacterial eradication rate, length of ICU stay, and length of admission. Results: In total, 6 RCTs comprising 974 patients were analyzed. We found a significantly lower mortality for critically ill patients on CIF (RR: 0.79; 95% CI: 0.63, 0.98) compared with those on IIF of beta-lactam antibiotics. The pooled RR for the bacterial eradication rate was 1.16 (95% CI: 1.03, 1.29) for CIF compared with IIF administration. Conclusion: CIF of beta-lactam antibiotics for critically ill patients significantly reduces mortality and yields a better bacterial eradication rate than IIF. These findings support the clinical and bacterial eradication benefits in adult critically ill patients, and may guide clinical discussions and decisions.
Interpretable Machine Learning Model for Mortality Prediction in ICU: A Multicenter Study
Authors: Fong Ka Man , Au Shek Yin , Ng George Wing Yiu , Leung Anne Kit Hung
Published: October 2020

Background: Researchers have long been struggling to improve the disease severity score in mortality prediction in ICU. The digitalization of medical health records and advancement of computation power have promoted the use of machine learning in critical care. This study aimed to develop an interpretable machine learning model using datasets from multicenters, and to compare with the APACHE IV, in predicting hospital mortality of patients admitted to ICU.Method: The datasets were assembled from the eICU database including 136145 patients across 208 hospitals throughout the U.S. and 5 ICUs in Hong Kong, including 10909 patients. The two datasets were first combined into one large dataset before 80:20 stratified split into the training set and the test set. The XGBoost machine algorithm was chosen to predict the hospital mortality. The variables in the model were the same as those included in the APACHE IV score. The discrimination and calibration of the model were assessed. The model would be interpreted using the Shapley Additive explanations values.Results: Of the 147054 patients in the whole cohort, the hospital mortality was 9.3%. The area under the precision-recall curve for the XGBoost algorithm was 0.57, and 0.49 for APACHE IV. Similarly, the XGBoost reached an area under the receiving operating curve (AUROC) of 0.90, while APACHE IV had an AUROC of 0.87. Additionally, the XGBoost algorithm showed better calibration than the APACHE IV. The three most important variables were age, heart rate, and whether the patient was on ventilator.Conclusions: The severity score developed by machine learning model using mutlicenter datasets outperformed the APACHE IV in predicting hospital mortality for patients admitted to ICU.
Strategies to Maximize the Wood Production in Amazon Forest
Authors: Canetti Aline , Braz Evaldo Muñoz , Mattos Patricia , Basso Renato Olivir , Filho Afonso Figueiredo
Published: October 2020

BackgroundThis study aimed to develop a procedure to determine which logging diameter would achieve optimal wood production by species, aiming to support sustainable management of the Amazon forest. Two main methodologies of analysis by species were combined: probability density function (PDF) and growth modeling. The growth models were used to derive the volume increment curves at the individual tree level. To detect the points of maximum annual increment in volume at the population tree level we used PDF with adjusted growth equations.ResultsThe population maximum annual volumetric increments occurred in smaller diameters compared to that of the individual-level. When combining shorter cutting cycles with the population biological rotation point considered as the minimum cutting diameter (MCD), we observed higher annual increments in volume than that achieved using the Brazilian law criteria (MCD = 50 cm) or other MCD tested.Conclusion﻿The procedure proposed may be used by forest managers and forest law-makers, aiming to maximize sustainable wood production in the Amazon forest.
Conjoint analysis of m6A regulators and copy number variations in thyroid carcinoma
Authors: Han Hui , Yu Jian-Yi , Fu Xiao-Dan , Ni Ye-Qin , Luo Ding-Cun , Zhang Xian-Feng
Published: October 2020

Background: Most patients with thyroid carcinoma have a good prognosis, but some thyroid carcinomas are aggressive and prone to recurrence and metastasis. Further, concomitant overdiagnosis and overtreatment are important issues. This study aimed to investigate the relationship between mutations and copy number variations in m6A regulatory genes and the clinicopathological features of thyroid carcinoma.Results: Advanced pathological stage and T stage were significantly correlated with changes in m6A regulatory genes (p<0.05). Patients with abnormal copy numbers of m6A regulatory genes had a significantly shorter progression-free interval than patients with normal copy numbers. Mutations and copy number variations in m6A regulatory genes were significantly correlated with advanced pathological stage and T stage. Conclusions: Copy number variations were a poor prognostic factor for thyroid carcinoma as evidenced by the significantly short progression-free interval in patients with copy number variations in m6A regulatory genes. Further, the ZC3H13 gene may be involved in the occurrence and development of thyroid carcinoma by regulating cancer-associated signaling pathways and biological processes. These findings may help distinguish patients with poor prognoses who may need more aggressive treatment from patients who have better prognoses.
Atypical fungal thoracic vertebral osteomylitis resembling metastatic tumor and literature review of fungal vertebral osteomylitis
Authors: Wu Xifa , Sun Jian , Li Yanyan , Wu Xueqiong , Wang Zhen , Li Tao , Zou Dexin
Published: October 2020

Case DescriptionFungal vertebral osteomylitis is a rare disease that difficult to diagnosis and cure. Because the early specific clinical manifestations of this disease are few and atypical, it is often missed or misdiagnosed, resulting in treatment delay and aggravation of the disease.ObjectiveTo report a rare case of cryptococcal osteomyelitis that resembles metastatic tumor happened in an immunecompromised patient with a history of mantle cell lymphoma and to review cases reported in literature.Study DesignBased on imaging studies, metastatic tumor was highly suspected. For a further examination and therapy, the patient was referred to our spine clinic. After admission to our clinical, chest and abdominal CT were checked to evaluate the disease status.TreatmentsAfter general anesthesia, posterior thoracic pedicle screw fixation (T2.3.5.6) were performed, followed by posterior laminectomy and decompression of T4 vertebral body. The right facet joint of T3/4, costal transverse joint, right pedicle and transverse process of T4 vertebra were fully removed and curetted. After careful hemostasis, posterolateral bone grafting was performed. The nail-rod connection is fixed.OutcomesThe postoperative intercostal neuralgia and chest pain were significantly relieved, without complications. The postoperative pathological results were suppurative inflammation with focal granuloma formation, dead bone formation and fungal (cryptococcal) infection. ConclusionsWhen complicated with vertebral fungal spondylitis, no obvious abnormality and fever can be found. When pain or nerve dysfunction caused by spinal cord compression or nerve root compression occurs, surgical treatment can effectively relieve clinical symptoms.
Pharmacokinetic of linezolid dose adjustment for creatinine clearance in critically ill patients: a multicenter, prospective, open-label, observational study
Authors: Wang Xipei , Wang Yifan , Yao Fen , Chen Shenglong , Zheng Zhijie , Luo Jinbiao , Qiu Binghui , Li Zhanfu , Wang Yirong , Wu Zheng , Lan Jinghua , Chen Chunbo
Published: October 2020

BackgroundLinezolid (LNZ) is a common antibiotic used to treat bacterial infections. But there is a lack of evaluation of pharmacokinetics (PK) of LNZ dose adjustment for creatinine clearance (CrCL) in highly heterogeneous critically ill patients. By using a population PK approach, we aimed to determine the optimal dosing strategy for LNZ in critically ill patients, especially those along with renal dysfunction. MethodsThis multicenter, prospective, open-label, observational study was conducted in intensive care units of 4 tertiary hospitals. Of the 152 eligible patients, 117 were included for establishing the PK model. Besides internal validation, external validation was conducted using another 35 patients as a validation group. The area under curve from 0 to 24h at steady-state divided by the minimum inhibitory concentration (AUC24/MIC) >80 and trough concentration of LNZ <10 mg/L was used as the target pharmacodynamic index. Dosing regimens for MIC of 0.5 to 4 mg/L were evaluated based on low, normal, and high creatinine clearance using Monte Carlo simulation.ResultsA one-compartment model was chosen as the base model. The PK parameter estimates were clearance of 5.60 L/h and the volume of the central compartment of 43.4 L. CrCL had a significant influence on clearance of LNZ, with an adjusting factor of 0.386. The standard dosing regimen [600 mg every 12 hour (q12h)] achieved adequate exposure in patients with severe renal impairment (CrCL, 40 mL/min). A daily dose of 1200 mg could provide sufficient exposure for MIC less than 2 mg/L in patients with normal renal functions (CrCL, 80 mL/min). For augmented renal clearance (ARC), a daily dose of 1200 mg could provide sufficient exposure for MIC less than 2 mg/L. Continuous infusion obtained a similar clinical response.ConclusionsFor critically ill patients, the standard dose of 600 mg LNZ q12h was adequate for MIC<1 mg/L. With ARC, a 1200 or 1800 mg/day 24h continuous infusion was recommended.
Influence of hydrogenation conditions on the structural, optical, and magnetic properties of degenerated Ni/Al co-doped anatase nanocomposite
Authors: Dakhel A. A.
Published: October 2020

In the present work, pristine and Ni2+/Al3+- codoped anatase (TiO2) nanocomposite powders were synthesized by the thermal co-precipitation method. The samples were characterized by several techniques. The X‐Ray diffraction (XRD) was used for structural characterization and the optical absorption spectroscopy was used for the optical characterization. The structural/optical studies proved the formation of a substitutional solid solution (SSS). The magnetization measurements were performed to investigate the magnetic properties of the synthesized samples. In the present work, nickel (Ni2+) dopant ions were used to introduce stable ferromagnetic (FM) properties into the synthesized anatase, while Al3+ dopant ions were utilized to supply itinerant electrons necessary to support and boost the created FM properties. The roadmap of the present work was to establish the hydrogenation conditions necessary to create ferromagnetic (FM) properties in the host codoped samples and study the effect of hydrogenation temperature on the parameters of the created FM properties, especially the magnetic energy (Umag) and saturation magnetization (Msat). It was found that the created FM properties in Ni/Al-doped TiO2 nanocomposite powder by using the hydrogenation effect could be enhanced and controlled via the temperature of the hydrogenation (TH). The experimental results revealed that Umag of TiO2:Ni:Al system increased by ~241% and the saturation magnetization by ~140% with increasing of TH by 100 oC (from 400 oC to 500oC). The obtained saturation magnetization (Msat) of 1.09 emu/g and magnetic energy (Umag) of 42.6 erg/g were higher than the previously obtained values for created Ni-doped TiO2 by ~50 times. Such great novel results were obtained due to dealing with two factors; the Al3+ ions as co-dopant, which can supply an excess of itinerant electrons that boost the S.S Heisenberg interactions in addition to choosing a suitable temperature of hydrogenation.
Novel Controlled and Targeted Releasing Hydrogen Sulfide System Exerts Combinational Cerebral and Myocardial Protection after Cardiac Arrest
Authors: Sun Xiaotian , Wang Yiqing , Wen Shuyan , Huang Kai , Huang Jiechun , Chun Xianglin , Wang Fangrui , Pang Liewen
Published: October 2020

Background : Cardiac arrest (CA) is a leading cause of death worldwide. Even after successful cardiopulmonary resuscitation (CPR), the majorities of survivals are companied with permanent myocardial and cerebral injury. Hydrogen sulfide (H 2 S) has been recognized as a novel gasotransmitter exerting multiple organ protection; however, the lacks of ideal H 2 S donors which can controlled release H 2 S to targeted organs such as heart and brain limits its application.

Results : This work utilized mesoporous iron oxide nanoparticle (MION) as the carriers of diallyl trisulfide (DATS), with polyethylene glycol (PEG) and lactoferrin (LF) modified to MIONs to acquire the prolonged circulation time and brain-targeting effects, and a novel targeted H 2 S releasing system was constructed ( DATS@MION-PEG-LF ), which exhibited excellent biocompatibility, controlled-releasing H 2 S pattern, heart and brain targeting features, and the ability to be non-invasive traced by magnetic resonance imaging. DATS@MION-PEG-LF presented potent protective effects against cerebral and cardiac ischemic injury after CA in both in vitro hypoxia/reoxygenation models and in vivo CA/CPR models, which mainly involves anti-apoptosis, anti-inflammatory and anti-oxidant mechanisms. Accordingly, the cardiac and cerebral functions were obviously improved after CA/CPR, with potentially improved survival.

Conclusions : The present work provides a unique platform for targeted controlled release of H 2 S based on MIONs, and offers a new method for combinational myocardial and cerebral protection from ischemic injury, bringing considerable benefits for CA patients.
Das (Un-) Wahre der Bildung
Authors: Leineweber Christian
Published: October 2020

Fake News beeinflussen die Aneignung politischer Informationen in Social Media und Internet sowie damit die Art und Weise der Konstruktion von Wirklichkeit und Erfahrung von Wahrheit. Der vorliegende Beitrag setzt sich mit dieser Beeinflussung auf Basis einer bildungstheoretischen Perspektive auseinander, die die Autonomie der Subjekte fokussiert. Ausgehend von der These, dass Autonomie auf sozialen Praktiken beruht, die Subjekte als Legitimation ihres eigenen Handelns anerkennen, wird das Phänomen der Fake News zunächst skizziert und mithin als Problemgegenstand beschrieben. Auf diese Weise kann ein medienpädagogisches Handlungsfeld abgesteckt werden. Innerhalb dieses Feldes werden auf der einen Seite Prinzipien der Autonomie unterlaufen, wodurch auf der anderen Seite neuartige Anforderungen an den Bildungsbegriff entstehen. Diese Anforderungen erwecken die Notwendigkeit eines sowohl affirmierenden als auch negierenden Welt- und Selbstbezugs der Subjekte, welches es anhand des Verhältnisses zwischen ‹Wahrheit› und ‹Unwahrheit› zu explorieren gilt.
Potential Therapeutic Benefits of Dipyridamole in COVID-19 Patients
Authors: Aliter Kholoud F. , Al-Horani Rami A.
Published: October 2020

Background:

COVID-19 pandemic is caused by coronavirus also known as severe acute respiratory
syndrome coronavirus-2 (SARS-CoV-2). The viral infection continues to impact the globe with no vaccine to
prevent the infection or highly effective therapeutics to treat the millions of infected people around the world.
The disease starts as a respiratory infection, yet it may also be associated with a hypercoagulable state, severe
inflammation owing to excessive cytokines production, and a potentially significant oxidative stress. The disease
may progress to multiorgan failure and eventually death.

Objective:

In this article, we summarize the potential of dipyridamole as an adjunct therapy for COVID-19.

Methods:

We reviewed the literature describing the biological activities of dipyridamole in various settings of
testing. Data were retrieved from PubMed, SciFinder-CAS, and Web of Science. The review concisely covered
relevant studies starting from 1977.

Results:

Dipyridamole is an approved antiplatelet drug, that has been used to prevent stroke, among other indications.
Besides its antithrombotic activity, the literature indicates that dipyridamole also promotes a host of
other biological activities including antiviral, anti-inflammatory, and antioxidant ones.

Conclusion:

Dipyridamole may substantially help improve the clinical outcomes of COVID-19 treatment. The
pharmacokinetics profile of the drug is well established which makes it easier to design an appropriate therapeutic
course. The drug is also generally safe, affordable, and available worldwide. Initial clinical trials have
shown a substantial promise for dipyridamole in treating critically ill COVID-19 patients, yet larger randomized
and controlled trials are needed to confirm this promise.
The Functional Impact of Alternative Splicing and Single Nucleotide Polymorphisms in Rheumatoid Arthritis
Authors: Aravilli R. Kowshik , Vikram S. Laveen , Kohila V.
Published: October 2020

Advances in genomics and proteomics aid the identification of genes associated with various
diseases. Genome-Wide Association Studies (GWAS) have identified multiple loci as risk alleles
for susceptibility to Rheumatoid Arthritis (RA). A bisection of RA risk can be attributed to genetic factors.
Over 100 associated genetic loci that encompass immune regulatory factors have been found to be
linked with RA. Aberrant Single Nucleotide Polymorphisms (SNPs) and alternative splicing mechanisms
in such loci induce RA. These aberrations are viewed as potential therapeutic targets due to their
association with a multitude of diseases. This review presents a few imperious genes whose alterations
can cause severe bone deformities culminating in RA.
Recent Update on the Anti-infective Potential of β-carboline Analogs
Authors: Faheem  , Kumar Banoth Karan , Sekhar Kondapalli Venkata Gowri Chandra , Kunjiappan Selvaraj , Jamalis Joazaizulfazli , Balaña-Fouce Rafael , Sankaranarayanan Murugesan
Published: October 2020

β-Carboline, a naturally occurring indole alkaloid, holds a momentous spot in the field of
medicinal chemistry due to its myriad of pharmacological actions like anticancer, antiviral, antibacterial,
antifungal, antileishmanial, antimalarial, neuropharmacological, anti-inflammatory and antithrombotic
among others. β-Carbolines exhibit their pharmacological activity via diverse mechanisms.
This review provides a recent update (2015-2020) on the anti-infective potential of natural and synthetic
β-carboline analogs focusing on its antibacterial, antifungal, antiviral, antimalarial, antileishmanial
and antitrypanosomal properties. In cases where enough details are available, a note on its mechanism
of action is also added.
Chalcones and Bis-Chalcones Analogs as DPPH and ABTS Radical Scavengers
Authors: Bale Adebayo Tajudeen , Salar Uzma , Khan Khalid Mohammed , Chigurupati Sridevi , Fasina Tolulope , Ali Farman , Ali Muhammad , Nanda Sitansu Sekhar , Taha Muhammad , Perveen Shahnaz
Published: October 2020

Background:

A number of synthetic scaffolds, along with natural products, have been identified as potent antioxidants. The present study deals with the evaluation of varyingly substituted, medicinally distinct class of compounds “chalcones and bis-chalcones” for their antioxidant potential.

Methods:

In vitro radical scavenging activities were performed on a series of synthetic chalcones 1- 13 and bis-chalcones 14-18.

Results:

All molecules 1-18 revealed a pronounced 2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2ʹ- azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radicals scavenging potential in the ranges of IC50s= 0.58 ± 0.14 - 1.72 ± 0.03 and 0.49 ± 0.3 - 1.48 ± 0.06 μM, respectively. Ascorbic acid (IC50s= 0.5 ± 0.1 and 0.46 ± 0.17 μM for DPPH and ABTS, respectively) was used as a standard radical scavenger.

Conclusion:

Structure-activity relationship (SAR) revealed an active participation of various groups, including -SMe and -OMe in scavenging activity.
Voltage-Dependent Sodium Channel Blocker Anticonvulsants: An Approach to the Structure-Activity Relationship
Authors: del Carmen Salazar-López María , Guevara-Salazar Juan Alberto , Arellano-Mendoza Mónica Griselda , Jiménez-Vázquez Hugo Alejandro , Benavides Adriana , Quintana-Zavala Delia
Published: October 2020

Background:

Anticonvulsants are drugs used in the treatment of seizures; their pharmacology
includes promoters of brain inhibition and inhibitors of brain activity. Of the latter, voltagedependent
sodium channel blockers (VGSCB) are the most widely used in therapeutics.

Objective:

The study aimed at proposing the structural requirements of VGSC blockers through a
quantitative structure-activity relationship analysis of drugs with proven activity.

Methods:

IC50 values of anticonvulsant drugs on VGSCs were considered under similar experimental
conditions; some physicochemical properties of the molecules that were correlated with their biological
activity were determined in silico.

Results:

Relationships were observed between the dipole moment, pKa, EHOMO, and MR with the
biological activity, which infers that between greater polarity and basicity of the drugs, their activity
as blockers will increase. Subsequently, the structural subclassification of the drugs was carried out,
based on the urea derivation, the groups of which were: Group 1 (direct and bioisostere derivatives)
and Group 2 (homologue and vinylogue derivatives of urea).

Conclusion:

The biological activity depends on the polarity, basicity, and electronic density of the
drugs. The derivation of urea is essential, which is present in its original substituted form or a bioisosteric
form. Urea can be in the form of a homologue or a vinylogue at the ends of the molecule. Aromatic
substitution to the urea portion is necessary.
Simultaneous Analysis of Ipratropium Bromide and its Related Substances Using HPLC
Authors: Li Jiankun , Li Guoxin , Zhao Lili , Wang Hairong , Sun Chujun
Published: October 2020

Background:

The main goal of process-related substances investigations is to understand
how impurities should be controlled during the synthetic or purification process to produce a
high-quality drug substance. The simultaneous determination of related substances is a very important
factor in the quality control of API and pharmaceutical dosage forms.

Methods:

A new HPLC method was developed for the simultaneous analysis of Ipratropium bromide
and its seven related substances. The separation was performed on a waters HPLC ZORBAX
Eclipse XDB- C8 column (150 × 4.6 mm, 3.5 μm). The gradient method used mobile phases containing
methanol, acetonitrile, trifluoroacetic acid (TFA), water: A: (methanol, acetonitrile, TFA,
500:500:0.3 v/v/v) and B (0.3% TFA in water v/v). The gradient elution conditions were as follows:
0-32.0 min, linear from 10% A to 35% A; 32.0-36.0 min isocratic 35% A; 36.0-42.0 min linear
from 35% to 10%A. The wavelength by UV detector was 220 nm and the flow rate was 1.2
mL/min. The injection volume of sample was 20 μL, and the column temperature was 30 ºC. The
proposed RP-HPLC method was applied for the determination of seven related substances.

Results:

All standard curves obtained exhibited good linear regression (r > 0.9939) within the tested
range. The average recovery rates were in the range of 98.2-102.0% and RSD was less than
2.9% (n = 3). The process-related impurities were not observed in different batches (<0.025% purity).

Conclusion:

The method was applied to determine 7 process-related substances in ipratropium bromide
and proved to be robust, linear, repeatable, sensitive, selective and easy to perform. The results
are valuable for quality control in the manufacturing of ipratropium bromide.