bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and efficacy profile of mogamulizumab (Poteligeo) in the treatment of cancers: An update evidence from 14 studies&nbsp;
Authors: Zhang Ting , Sun Jing , Li Jinying , Zhao Yunuo , Zhang Tao , Yang Ruoning , Ma Xuelei 
Published: November 2020

Abstract
Background: CC chemokine receptor 4 (CCR4), the receptor for CCL22 and CCL17, is expressed on the surface of effector Tregs that have the highest suppressive effects on antitumor immune response. CCR4 is also widely expressed on the surface of tumor cells from patients with adult T-cell leukemia/lymphoma (ATL), peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL). Mogamulizumab is a humanized, IgG1 kappa monoclonal antibody that is directed against CCR4. By reducing the number of CCR4-positive Tregs and tumor cells, the mogamulizumab can reduce tumor burden and boost antitumor immunity to achieve antitumor effects.Methods: We examined the PubMed and ClinicalTrials.gov until 1 February 2020. Considering variability in different studies, we selected the adverse events (AEs), overall survival (OS), progression‐free survival (PFS), objective responses rate (ORR) and Hazard Ratio (HR) for PFS to evaluate the safety and efficacy profile of mogamulizumab. Results: When patients were treated with mogamulizumab monotherapy, the most common all-grade AEs were lymphopenia, infusion reaction, fever, rash and chills while the most common grade ≥3 AEs were lymphopenia, neutropenia and rash. When patients were treated with combined therapy of mogamulizumab and other drugs, the most common all-grade AEs were neutropenia, anaemia, lymphopenia and gastrointestinal disorder, while the most common grade ≥3 AEs was lymphopenia. For patients treated with mogamulizumab monotherapy, the pooled ORR and mean PFS were 0.430 (95% CI: 0.393-0.469) and 1.060 months (95% CI: 1.043-1.077), respectively. For patients treated with combined therapy of mogamulizumab and other drugs, the pooled ORR was 0.203 (95% CI: 0.022-0.746) while the pooled PFS and OS were 2.093 months (95% CI: 1.602-2.584) and 6.591 months (95% CI: 6.014-7.167), respectively.Conclusions: Based on present evidence, we believed that mogamulizumab had clinically meaningful antitumor activity with acceptable toxicity which is a novel therapy in treating patients with cancers.
Population Genetic Analysis of&nbsp;Plasmodium falciparum&nbsp;Circumsporozoite Protein in Two Distinct Ecological Regions in Ghana
Authors: Amegashie Elikplim A , Amenga-Etego Lucas , Adobor Courage , Ogoti Peter , Mbogo Kevin , Amambua-Ngwa Alfred , Ghansah Anita 
Published: November 2020

Abstract
Background Extensive genetic diversity in the Plasmodium falciparum circumsporozoite protein (PfCSP) is a major contributing factor to the moderate efficacy of the RTS,S/AS01 vaccine. The transmission intensity and rates of recombination within and between populations influence the extent of its genetic diversity. Understanding the extent and dynamics of PfCSP genetic diversity in different transmission settings will help to interpret the results of current RTS,S efficacy and Phase IV implementation trials conducted within and between populations in malaria-endemic areas such as Ghana. Methods Pfcsp sequences were retrieved from the Illumina-generated paired-end short-read sequences of 101 and 131 malaria samples from children aged 6-59 months presenting with clinical malaria at health facilities in Cape Coast (in the coastal belt) and Navrongo (Guinea savannah region), respectively, in Ghana. The sequences were mapped onto the 3D7 reference strain genome to yield high-quality genome-wide coding sequence data. Following data filtering and quality checks to remove missing data, 220 sequences were retained and analysed for the allele frequency spectrum, genetic diversity both within the host and between populations and signatures of selection. Population genetics tools were used to determine the extent and dynamics of Pfcsp diversity in P. falciparum from the two geographically distinct locations in Ghana. Results Pfcsp showed extensive diversity at the two sites, with the higher transmission site, Navrongo, exhibiting higher within-host and population-level diversity. The vaccine strain C-terminal epitope of Pfcsp was found in only 5.9% and 45.7% of the Navrongo and Cape Coast sequences, respectively. Between 1 and 6 amino acid variations were observed in the TH2R and TH3R epitope regions of PfCSP. Tajima’s D was negatively skewed, especially for the population from Cape Coast, given the expected historical population expansion. In contrast, a positive Tajima’s D was observed for the Navrongo P. falciparum population, consistent with balancing selection acting on the immuno-dominant TH2R and TH3R vaccine epitopes. Conclusion The low frequencies of the Pfcsp vaccine haplotype in the analysed populations indicate a need for additional molecular and immuno-epidemiological studies with broader temporal and geographic sampling in endemic populations targeted for RTS,S application. These results have implications for the efficacy of the vaccine in Ghana and will inform the choice of alleles to be included in future multivalent or chimeric vaccines.
Biochemical and genetic analysis of Ecm14, a conserved fungal pseudopeptidase
Authors: McDonald R Christian , Schott Matthew J , Idowu Temitope A , Lyons Peter J 
Published: November 2020

Abstract
Background. Like most major enzyme families, the M14 family of metallocarboxypeptidases (MCPs) contains a number of pseudoenzymes predicted to lack enzyme activity and with poorly characterized molecular function. The genome of the yeast Saccharomyces cerevisiae encodes one member of the M14 MCP family, a pseudoenzyme named Ecm14 proposed to function in the extracellular matrix. In order to better understand the function of such pseudoenzymes, we studied the structure and function of Ecm14 in S. cerevisiae. Results. A phylogenetic analysis of Ecm14 in fungi found it to be conserved throughout the ascomycete phylum, with a group of related pseudoenzymes found in basidiomycetes. To investigate the structure and function of this conserved protein, His6-tagged Ecm14 was overexpressed in Sf9 cells and purified. The prodomain of Ecm14 was cleaved in vivo and in vitro by endopeptidases, suggesting an activation mechanism; however, no activity was detectable using standard carboxypeptidase substrates. In order to determine the function of Ecm14 using an unbiased screen, we undertook a synthetic lethal assay. Upon screening approximately 27,000 yeast colonies, twenty-two putative synthetic lethal clones were identified. Further analysis showed many to be synthetic lethal with auxotrophic marker genes and requiring multiple mutations, suggesting that there are few, if any, single S. cerevisiae genes that present synthetic lethal interactions with ecm14Δ. Conclusions. We show in this study that Ecm14, although lacking detectable enzyme activity, is a conserved carboxypeptidase-like protein that is secreted from cells and is processed to a mature form by the action of an endopeptidase. Our study and datasets from other recent large-scale screens suggest a role for Ecm14 in processes such as vesicle-mediated transport and aggregate invasion, a fungal process that has been selected against in modern laboratory strains of S. cerevisiae.
A retrospective survey of strabismus surgery in a tertiary eye center in northern China, 2014-2019
Authors: wan xiaomei , wan luqin , jiang mingming , ding yichao , wang yuan , Zhang Jing 
Published: November 2020

Abstract
Background: To evaluate the distribution pattern and changes of strabismus surgery in northern China. Methods: The records of strabismus patients at Qingdao Eye Hospital from January 2014 to December 2019 were reviewed retrospectively. The characteristics analysed included gender, regional distribution, constituent ratio of age and type of strabismus. Changes during the periods 2014–2016 and 2017–2019 were compared and analysed. Results: A total of 5746 strabismus patients were recruited. The number of strabismus patients was relatively stable each year from 2014 to 2016 but gradually increased each year from 2017 to 2019. Of these, 51.7% (2868/5746) were male, and 48.3% (2778/5746) were female. The majority (89.8%, 5159/5746) of the patients were from Shandong Province. The statistical results of the constituent ratio of age showed that 32.4% (1860/5746) were 7–12 years old(primary school level). Patients under 12 years of age (preschool and primary school level) accounted for 60.0% (3447/5746) of all the patients. In terms of the types of strabismus, exotropia accounted for 63.5% (3650/5746), followed by esotropia and vertical rotational strabismus at 13.2% (758/5746) and 9.7% (555/5746), respectively. Intermittent exotropia was the most common type among the exotropia patients, accounting for 71.3% (2604/3650). Among the patients with intermittent exotropia, 62.5% (1627/2604) were children aged 4–12 years, and the basic type of intermittent exotropia was the main type. Four percent (231/5746) of the patients, of which adult patients comprised the main population, required reoperation. Conclusion: Patients with strabismus at primary school level comprised the largest group of strabismus patients in north China. Exotropia was the most common type of strabismus, and intermittent exotropia was the most common type of exotropia. The rate of exotropia to esotropia was 5:1.
Chinese SLE Treatment and Research Group (CSTAR) Registry: prevalence and risk factors for chronic scarring alopecia in patients with systemic lupus erythematosus
Authors: Xiang Yirong , Li Mengtao , Luo Hui , Wang Yanhong , Duan Xinwang , Zhao Cheng , Zhan Feng , Wu Zhenbiao , Li Hongbin , Yang Min , Xu Jian , Wei Wei , Wu Lijun , You Hanxiao , Qian Junyan , Yang Xiaoxi , Huang Can , Zhao Jiuliang , Wang Qian , Leng Xiaomei , Tian Xinping , Zhao Yan , Zeng Xiaofeng 
Published: November 2020

Abstract
Background: Scarring alopecia in systemic lupus erythematosus (SLE) patients caused reduced life quality and prolonged disease course. This case control study aims to survey the prevalence of scarring alopecia during the disease course of SLE and evaluate the risk factors for scarring alopecia in Chinese SLE patients. Methods: SLE patients in Chinese SLE treatment and Research group (CSTAR) were recruited. Scarring alopecia was defined according to SLICC/ACR-DI which was collected during follow-up visits or via self-reported questionnaires. We collected demographic characteristics, common comorbidities, autoantibody profiles, disease activity status, major organ involvements and treatment strategies of these patients at registry. Univariate and multivariate logistic regression analyses were used to investigate the risk factors for scarring alopecia. Results: We recruited 4792 SLE patients, and 374 (7.80%) patients had scarring alopecia. Mucocutaneous lesions (OR 2.062, p<0.001), high SLICC/ACR-DI (OR 1.409, p<0.001) and positive anti-Sm (OR 1.374, p=0.029) were risk factors for scarring alopecia, while renal (OR 0.714, p=0.028) and cardio-respiratory involvements (OR 0.347, p=0.044), and immunosuppressants treatment (OR 0.675, p<0.001) were significantly negative associated with it. Conclusions: The prevalence of scarring alopecia in SLE patients is 7.80%. Active treatment strategies should be adopted to prevent scarring alopecia occurring.
Development of the Labor Pain Relief Attitude Questionnaire for Pregnant Women (LPRAQ-p)
Authors: Hulsbosch Lianne P , Nyklíček Ivan , Potharst Eva S , Boekhorst Myrthe GBM , Pop Victor JM 
Published: November 2020

Abstract
Background: Receiving epidural analgesia during labor can possibly have negative consequences for mother and child. Yet, the use of epidural analgesia rapidly increased in the Netherlands over the last decade. Since antenatal plans for labor pain relief have been related to epidural analgesia use during labor, the aim of the current study was to develop a Labor Pain Relief Attitude Questionnaire for pregnant women (LPRAQ-p).Methods: Three focus group interviews were conducted with pregnant women, new mothers and caregivers and 13 candidate items were derived. Psychometric properties were tested with explorative factor analysis in sample I (N = 429) and a subsequent confirmatory factor analysis in a different sample II (N = 432).Results: The explorative factor analysis suggested a two-factor seven-item solution: a ‘women’s perception’ and ‘social environment’ subscale. The confirmatory factor analysis confirmed an excellent six-item model fit with appropriate internal consistency. Higher scores on the six-item LPRAQ-p indicate greater willingness for request of pain relief medication during labor. Two-tailed t-tests showed that women with elevated levels of depression and pregnancy-specific distress symptoms, nulliparous women and multiparous women with complications during previous delivery had greater willingness for request of pain relief medication during labor. Linear regression showed that the most important association with higher scores on the LPRAQ-p were high pregnancy-specific distress symptoms.Conclusions: This study showed the LPRAQ-p to be a valid instrument to evaluate attitude towards labor pain relief in pregnant women. High scores on this questionnaire are associated with high levels of pregnancy-specific distress symptoms.
Bathing and Toileting Difficulties of Older Adults in Rural China: The Role of Environment
Authors: Liu Changxi , Fong Joelle H. , Hoh Jasmon W. T. , Wu Hailin , Dong Yunsheng , Gu Danan , Qiushi FENG 
Published: November 2020

Abstract
Background: For older adults, difficulties in bathing and toileting are often the most prevalent in the index of Activities of daily living (ADL). This study aims to examine how environmental factors are associated with difficulty of bathing and toileting among older adults in rural China. Method: The data are from the 2014 Thousand-Village Survey (TVS), a national survey of Chinese rural residents of old age. The sample consists of 10,689 subjects, 55 years or older, from 536 villages across all provinces of China. Logistic regressions were applied to examine how difficulty in bathing and toileting was related to environmental factors such as geographic location, neighbourhood amenity, and related facility of bathing and toileting. Results: Older adults living in the southern regions of China had lesser difficulty in bathing and toileting than those living in Northern China, controlling on other confounders. Better neighbourhood conditions also reduced the likelihood of having such disabilities. Persons who bathed indoors without shower facilities, in public facility, and outdoors were significantly more likely to have bathing disability than those who showered indoors. Rural older adults who used pedestal pan and indoor bucket for toileting were more likely to have toileting disability than those who used indoor squatting facilities. Conclusion: Environmental barriers were associated with functional disability among older adults in rural China, but these individuals may also change their environment to adapt to their functioning. Our findings suggest it is imperative to promote the use of showering facilities and pedestal pans for toileting in rural China
Metabolic Syndrome in patients with type 2 diabetes and atherosclerotic cardiovascular disease: A post hoc analyses of the EMPA-REG OUTCOME trial
Authors: Ferreira João Pedro , Verma Subodh , Fitchett David , Ofstad Anne Pernille , Lauer Sabine , Zwiener Isabella , George Jyothis , Wanner Christoph , Zinman Bernard , Inzucchi Silvio 
Published: November 2020

Abstract
Background: Patients with type 2 diabetes (T2D) and metabolic syndrome (MetS) are at greater cardiovascular risk than those with T2D without MetS. In the current report we aim to study the characteristics, cardio-renal outcomes and the effect of empagliflozin in patients with MetS enrolled in the EMPA-REG OUTCOME trial. Methods: A total of 7020 patients with T2D and atherosclerotic cardiovascular disease were treated with empagliflozin (10mg or 25mg) or placebo for a median of 3.1 years. The World Health Organization MetS criteria could be determined for 6985 (99.5%) patients. We assessed the association between baseline MetS and multiple cardio-renal endpoints using Cox regression models, and we studied the change in the individual component over time of the MetS using mixed effect models. Results: MetS at baseline was present in 5740 (82%) patients; these were more often white and had more often albuminuria and heart failure, had lower eGFR and HDL-cholesterol, and higher blood pressure, body mass index, waist circumference, and triglycerides. In the placebo group, patients with MetS had a higher risk of all outcomes including cardiovascular death: HR=1.73 (95%CI=1.01-2.98), heart failure hospitalization: HR=2.64 (95%CI=1.22, 5.72), and new or worsening nephropathy: HR=3.11 (95%CI=2.17-4.46). The beneficial effect of empagliflozin was consistent on all cardio-renal outcomes regardless of presence of MetS.Conclusions: A large proportion of the EMPA-REG OUTCOME population fulfills the criteria for MetS. Those with MetS had increased risk of adverse cardio-renal outcomes. Compared with placebo, empagliflozin improved cardio-renal outcomes in patients with and without MetS.
A high-throughput Galectin-9 imaging assay for quantifying nanoparticle uptake, endosomal escape and functional RNA delivery
Authors: Munson Michael , O'Driscoll Gwen , Silva Andreia , Lázaro-Ibáñez Elisa , Gallud Audrey , Wilson John , Collén Anna , Winters Elin Esbjörner , Sabirsh Alan 
Published: November 2020

Abstract
RNA-based therapies have great potential to treat many undruggable human diseases. However, their efficacy, in particular for mRNA, remains hampered by poor cellular delivery and limited endosomal escape. Advances in the development and rational optimisation of delivery vectors, such as lipid nanoparticles (LNPs), are impeded by the limited availability of screening methods that probe the intracellular processing of LNPs in sufficient detail.
We have developed a high-throughput imaging-based endosomal escape assay utilising a Galectin-9 reporter and fluorescently labelled mRNA to probe correlations between nanoparticle-mediated uptake, endosomal escape frequency, and mRNA translation. This assay has, furthermore, been integrated with a screening platform for nanoparticle formulation to optimise LNPs. We show that Galectin-9 recruitment is a robust, quantitative reporter of endosomal escape events induced by different mRNA delivery nanoparticles and small molecules. We also identify nanoparticles with superior escape properties and demonstrate significant cell line variances in endosomal escape response, highlighting the need for fine-tuning of delivery formulations for specific applications.
Improved 3D-QSAR Prediction by Multiple Conformational Alignments and Molecular Docking Studies to Design and Discover HIV-I Protease Inhibitors
Authors: Patel Paresh K. , Bhatt Hardik G. 
Published: November 2020

Background:
Inhibition of HIV-I protease enzyme is a strategic step for providing better
treatment in retrovirus infections, which avoids resistance and possesses less toxicity.

Objectives:
In the course of our research to discover new and potent protease inhibitors, 3D-QSAR
(CoMFA and CoMSIA) models were generated using 3 different alignment techniques, including
multifit alignment, docking based and Distill based alignment for 63 compounds. Novel molecules
were designed from the output of this study.

Methods:
A total of 3 alignment methods were used to generate CoMFA and CoMSIA models. A
Distill based alignment method was considered a better method according to different validation parameters.
A 3D-QSAR model was generated and contour maps were discussed. The biological activity
of designed molecules was predicted using the generated QSAR model to validate QSAR.
The newly designed molecules were docked to predict binding affinity.

Results:
In CoMFA, leave one out cross-validated coefficient (q2), conventional coefficient (r2) and
predicted correlation coefficient (r2
Predicted) values were found to be 0.721, 0.991 and 0.780, respectively.
The best obtained CoMSIA model also showed significant cross-validated coefficient (q2),
conventional coefficient (r2) and predicted correlation coefficient (r2
Predicted) values of 0.714, 0.987
and 0.721, respectively. Steric and electrostatic contour maps generated from CoMFA and hydrophobic
and hydrogen bond donor and hydrogen bond acceptor contour maps from CoMSIA models
were used to design new and bioactive protease inhibitors by incorporating bioisosterism and
knowledge-based structure-activity relationship.

Conclusion:
The results from both these approaches, ligand-based drug design and structure-based
drug design, are adequate and promising to discover protease inhibitors.
Atherosclerotic Process in Seroreverter Children and Adolescents Exposed to Fetal Antiretroviral Therapy
Authors: Martins Paula , Pires António , Santos José Luis , Sena Cristina , Seiça Raquel 
Published: November 2020

Background:
Human immunodeficiency virus infection is a recognized risk factor for
premature atherosclerosis in children and adolescents. However, the atherosclerotic process in uninfected
children exposed in utero to the virus and antiretroviral therapy is less clear.

Objective:
To determine the potential cardiovascular risk associated to this in utero milieu exposition.

Material and Methods:
A total of 115 individuals were studied (77 in the sample group and 38 in
the controls). Eighteen analytical mediators involved in the atherogenic pathways (metabolic dysregulation,
inflammation, and prothrombotic state) were analyzed. The carotid intima-media thickness,
which is a subclinical marker of atherosclerosis, was also measured.

Results:
No significant statistical differences were identified between the sample and control
groups, either in the biochemical or the echographic markers.

Conclusion:
In utero exposure to the HIV virus and antiretroviral therapy in uninfected children
and adolescents is not correlated to accelerated atherosclerosis.
Cytotoxic T Lymphocyte Antigen 4 Gene +49 A/G (rs231775) Polymorphism and Susceptibility to Systemic Lupus Erythematosus
Authors: Kishk Rania Mohammed , Abdellatif Maii Abdelraheem , Eldesouki Raghda Elsawi , Fawzy Mohamed , Abdelhady Shaymaa Abdelraheem , Fouad Marwa Mohamed 
Published: November 2020

Aim:To assess the probable role of +49AG polymorphism in susceptibility to SLE in an Egyptian population.Background:Systemic lupus erythematosus (SLE) is a compound inflammatory chronic disease distinguished through the release of autoantibodies. Cytotoxic T lymphocyte associated antigen-4 is a main down controller of T-cell response; its dysregulation could affect SLE pathogenesis by altered T cells activation to self-antigens.Objectives:To evaluate the CTLA-4 +49AG allelic and genotype frequency in a sample of the Egyptian population and correlate them with disease susceptibility and clinical severity.Materials and methods:Including 100 patients with SLE and 100 healthy controls (age and gender matched), CTLA-4 exon 1 49 A>G Genotyping was done using Real-Time PCR.Results:No difference was noticed in genotype or allele distributions of the studied polymorphism between both groups. Similar genotypes and allele frequencies were established for the 2 groups after their stratification by the age of disease onset, clinical course, or severity.Conclusion:CTLA-4 +49AG gene polymorphism is not linked with the liability to develop SLE in the studied Egyptian population. Yet it is significantly related to disease severity.