bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of QbD strategies in the inoculum expansion of a mAb production process
Authors: Böhl Ole Jacob , Schellenberg Jana , Bahnemann Janina , Hitzmann Bernd , Scheper Thomas , Solle Dörte 
Published: December 2020

AbstractThe quality by design approach was introduced to the biopharmaceutical industry over 15 years ago. This principle is widely implemented in the characterization of monoclonal antibody production processes. Anyway, the early process phase, namely the inoculum expansion, was not yet investigated and characterized for most processes. In order to increase the understanding of early process parameter interactions and their influence on the later production process, a risk assessment followed by a design of experiments approach was conducted. The DoE included the critical parameters methotrexate (MTX) concentration, initial passage viable cell density and passage duration. Multivariate data analysis led to mathematical regression models and the establishment of a designated design space for the studied parameters. It was found that the passage duration as well as the initial viable cell density for each passage during the inoculum expansion have severe effects on the growth rate and viability of the early process phase. Furthermore, the variations during the inoculum expansion directly influenced the production process responses. This carry‐over of factor effects highlights the crucial impact of early process failures and the importance of process analysis and control during the first part of mAb production processes.
Functional food mixtures: Inhibition of lipid peroxidation, HMGCoA reductase, and ACAT2 in hypercholesterolemia‐induced rats
Authors: Mohd Rosmi Noor Syafiqa Aqila , Shafie Nurul Husna , Azlan Azrina , Abdullah Maizaton Atmadini 
Published: December 2020

AbstractMixtures of selected functional foods (MSFF) were composed of nattokinase (fermented soybean), red yeast rice extract, Ginkgo biloba, oat fiber, garlic, bee pollen, and propolis as anti‐hypercholesterolemic were studied. The goal of this study was to determine the bioactive compounds in these mixtures and their cholesterol‐lowering potential effects (biochemical profiles, lipid peroxidation, liver tissue histopathology, and enzymatic activity analysis; HMGCoA reductase and ACAT2. The LC‐MS/MS analysis showed that bioactive compounds such as Monacolin K, naringin, tocopherol, and glutamate, which have potential as anti‐hypercholesterolemic agents, were present in these functional food mixtures. MSFF supplementation at 50 mg/kg 100 mg/kg and 200 mg/kg showed substantial reductions in serum lipid profiles (TC and LDL) (p < .05). The serum liver profiles of AST (115.33 ± 8.69 U/L) and ALT (61.00 ± 1.00 U/L) were significantly reduced (p < .05) with MSFF supplementation at 200 mg/kg. MDA lipid peroxidation has also decreased significantly (p < .05) in serum (3.69 ± 0.42 μmol/L) and liver (15.04 ± 0.97 μmol/mg) tissues and has been shown to protect against hepatic steatosis. The significant (p < .05) inhibition activity of HMGCoA reductase (163.82 ± 3.50 pg/ml) and ACAT2 (348.35 ± 18.85 pg/ml) was also attributed by the supplementation of MSFF at 200 mg/kg.
Limitations of preoperative cytology for medullary thyroid cancer: Proposal for improved preoperative diagnosis for optimal initial medullary thyroid carcinoma specific surgery
Authors: Workman Alan D. , Soylu Selen , Kamani Dipti , Nourmahnad Anahita , Kyriazidis Natalia , Saade Ryan , Ren Yin , Wirth Lori , Faquin William C. , Onenerk Ayşe M. , Nikiforov Yuri E. , Al‐Qurayshi Zaid , Kandil Emad , Kloos Richard T. , Eldeiry Leslie , Lubitz Carrie , Stathatos Nikolaos , Randolph Gregory W. 
Published: December 2020

AbstractBackgroundPreoperative diagnosis of medullary thyroid carcinoma (MTC) is often difficult, given the poor sensitivity of fine‐needle aspiration (FNA) cytology for MTC. This study investigates this issue and presents recommendations for improving preoperative diagnostic paradigms in MTC cases.Design/MethodHistopathologically confirmed MTC patients with preoperative cytologic assessment of index nodules were enrolled. FNA diagnosis, final pathology, and surgery details were collected.ResultsOut of 71 patients, 49 (69%) were diagnosed by FNA as either definitive MTC (35, 49%) or suspected MTC (14, 20%) and 22 (31%) patients had no indication of MTC on FNA.ConclusionIn a tertiary‐care setting, one‐third of subjects had an FNA interpretation that did not suggest the possibility of MTC. The limitations of preoperative diagnosis are especially problematic for MTC as they can cause delayed or incomplete treatment. Additional testing is proposed to improve preoperative diagnosis and surgical care of MTC patients.
A snapshot of COVID‐19 infection in patients with solid tumors
Authors: Fuentes‐Antrás Jesús , Manzano Aránzazu , Marquina Gloria , Paz Mateo , Aguado Carlos , Granja Mónica , Benítez Javier , Ortega Justo , Priego Araceli , González Carlos , Tejerina‐Peces Julia , Flores Paloma , de Sa Alfonso López , Toledano Carmen , Olalla Jennifer , de Luna Alicia , Bartolomé Jorge , Pérez‐Segura Pedro 
Published: December 2020

AbstractCoronavirus disease 2019 (COVID‐19) pandemic is affecting a high percentage of the population at an unprecedented rate. Cancer patients comprise a subgroup especially vulnerable to this infection. Herein, we present a prospective analysis of epidemiological, clinical, radiological and laboratory data of consecutive adult cancer patients seen in the Clínico San Carlos University Hospital (Madrid, Spain), and admitted to hospital and tested for COVID‐19 between 21 February 2020 and 8 May 2020 due to clinical suspicion of infection. Data from 73 patients with confirmed COVID‐19 and active solid tumors or diagnosed within the previous 5 years were analyzed. The most frequent malignancy was lung cancer (19%) and 54 patients (74%) were on active cancer treatment. Most common findings on presentation included cough (55%), fever (52%) and dyspnea (45%), and 32 (44%) patients showed oxygen saturation levels below 95%. Radiologically, 54 (73%) patients presented an abnormal pattern, the most frequent being infiltrates (64%). 18 (24.7%) patients died in hospital and 55 (75.3%) were discharged with clinical resolution of the event. Multivariable logistic regression adjusted for age and tumor stage showed higher odds of in‐hospital death associated with a history of cardiovascular disease, hospitalization in the previous 30 days, and several features on admission including dyspnea, higher qSOFA score, higher C‐reactive protein levels and an abnormal neutrophil count. We present prospective, real‐world evidence that can help articulate cancer care protocols for patients infected with SARS‐CoV‐2, with special focus on features on admission that can stratify patients with a higher risk of death from COVID‐19.
Practical application of Westgard Sigma rules with run size in analytical biochemistry processes in clinical settings
Authors: Peng SongQing , Zhang JinFei , Zhou WuQiong , Mao WeiLin , Han Zhong 
Published: December 2020

AbstractBackgroundThe performance of 18 routine chemical detection methods was evaluated by the sigma (σ) metric, and Westgard Sigma rules with run size were used to establish internal quality control (IQC) standards to reduce patient risks.Materials and methodsExternal quality assessment (EQA) and internal quality control data from 18 assays in a biochemical laboratory were collected from January to June 2020. The sigma values of each assay were calculated, based on the bias, total error allowable, and coefficient of variation, appropriate quality control rules were selected. According to the quality goal index, the main causes of poor performance were determined to guide quality improvement.ResultsAt IQC material level 1, seven of the 18 assays achieved five sigma (excellent), and five assays (UA, Crea, AMY, TC and Na) showed world‐class performance. At IQC material level 2, 14 of the 18 assays achieved 5 sigma (excellent), and thirteen assays (UA, ALT, CK, Crea, AMY, K, AST, ALP, Na, LDH, Mg, TC and GGT) showed world‐class performance. The quality goal index (QGI) was calculated for items with analysis performance <5 sigma, and the main causes of poor performance were determined to guide quality improvement.ConclusionsWestgard sigma rules with run size are an effective tool for evaluating the performance of biochemical assays. These rules can be used to more simply and intuitively select the quality control strategy of related items and reduce the risk to patients.
A human diversity analysis of culture and gender in Asian American men's intimate partner violence perpetration
Authors: Kyler‐Yano Jason Z. , Mankowski Eric S. 
Published: December 2020

AbstractThis integrative literature review aims to fill the gap in our understanding of the cultural and gendered predictors of intimate partner violence (IPV) perpetration by Asian American men. A comprehensive search using PsycINFO returned N = 24 peer‐reviewed journal articles that examine Asian American men's IPV perpetration and patriarchal gender role norms and that met inclusion criteria. Patriarchal gender role norms consistently predicted IPV perpetration. However, the associations between acculturation/enculturation and IPV perpetration were less clear. Greater enculturation (Asian cultural identification) was associated with more patriarchal gender role norms while greater acculturation (mainstream US cultural identification) was associated with more masculine gender role strain. Additionally, violence in the family of origin consistently predicted later IPV perpetration as an adult. Results suggest that integrating multiple dimensions of human diversity (e.g., culture, gender, and power) in intersectional models may best explain Asian American men's IPV perpetration.
COVID‐19 therapy with mesenchymal stromal cells (MSC) and convalescent plasma must consider exosome involvement: Do the exosomes in convalescent plasma antagonize the weak immune antibodies?
Authors: Askenase Philip W. 
Published: December 2020

AbstractExosome extracellular vesicles as biologic therapy for COVID‐19 are discussed for two areas. The first involves the growing use of mesenchymal stromal cells (MSCs) for the profound clinical cytokine storm and severe pneumonia in COVID‐19 patients. Instead, it is recommended to treat alternatively with their MSC‐released exosomes. This is because many reports in the literature and our data have shown that the release of exosomes from the in vivo administered MSC is actually responsible for their beneficial effects. Further, the exosomes are superior, simpler and clinically more convenient compared to their parental MSC. Additionally, in the context of COVID‐19, the known tendency of MSC to intravascularly aggregate causing lung dysfunction might synergize with the pneumonia aspects, and the tendency of MSC peripheral vascular micro aggregates might synergize with the vascular clots of the COVID‐19 disease process, causing significant central or peripheral vascular insufficiency. The second exosome therapeutic area for severe COVID‐19 involves use of convalescent plasma for its content of acquired immune antibodies that must consider the role in this therapy of contained nearly trillions of exosomes. Many of these derive from activated immune modulating cells and likely can function to transfer miRNAs that acting epigenetically to also influence the convalescent plasma recipient response to the virus. There is sufficient evidence, like recovery of patients with antibody deficiencies, to postulate that the antibodies actually have little effect and that immune resistance is principally due to T cell mechanisms. Further, COVID‐19 convalescent plasma has remarkably weak beneficial effects if compared to what was expected from many prior studies. This may be due to the dysfunctional immune response to the infection and resulting weak Ab that may be impaired further by antagonistic exosomes in the convalescent plasma. At the least, pre selection of plasma for the best antibodies and relevant exosomes would produce the most optimum therapy for very severely affected COVID‐19 patients.
Adipose‐derived mesenchymal stem cells reduce autophagy in stroke mice by extracellular vesicle transfer of miR‐25
Authors: Kuang Yaoyun , Zheng Xuan , Zhang Lin , Ai Xiaoyu , Venkataramani Vivek , Kilic Ertugrul , Hermann Dirk M. , Majid Arshad , Bähr Mathias , Doeppner Thorsten R. 
Published: December 2020

AbstractGrafted mesenchymal stem cells (MSCs) yield neuroprotection in preclinical stroke models by secreting extracellular vesicles (EVs). The neuroprotective cargo of EVs, however, has not yet been identified. To investigate such cargo and its underlying mechanism, primary neurons were exposed to oxygen‐glucose‐deprivation (OGD) and cocultured with adipose‐derived MSCs (ADMSCs) or ADMSC‐secreted EVs. Under such conditions, both ADMSCs and ADMSC‐secreted EVs significantly reduced neuronal death. Screening for signalling cascades being involved in the interaction between ADMSCs and neurons revealed a decreased autophagic flux as well as a declined p53‐BNIP3 activity in neurons receiving either treatment paradigm. However, the aforementioned effects were reversed when ADMSCs were pretreated with the inhibitor of exosomal secretion GW4869 or when Hrs was knocked down. In light of miR‐25‐3p being the most highly expressed miRNA in ADMSC‐EVs interacting with the p53 pathway, further in vitro work focused on this pathway. Indeed, a miR‐25‐3p oligonucleotide mimic reduced cell death, whereas the anti‐oligonucleotide increased autophagic flux and cell death by modulating p53‐BNIP3 signalling in primary neurons exposed to OGD. Likewise, native ADMSC‐EVs but not EVs obtained from ADMSCs pretreated with the anti‐miR‐25‐3p oligonucleotide (ADMSC‐EVsanti‐miR‐25‐3p) confirmed the aforementioned in vitro observations in C57BL/6 mice exposed to cerebral ischemia. The infarct size was reduced, and neurological recovery was increased in mice treated with native ADMSC‐EVs when compared to ADMSC‐EVsanti‐miR‐25‐3p. ADMSCs induce neuroprotection by improved autophagic flux through secreted EVs containing miR‐25‐3p. Hence, our work uncovers a novel key factor in naturally secreted ADMSC‐EVs for the regulation of autophagy and induction of neuroprotection in a preclinical stroke model.
Functional assays to assess the therapeutic potential of extracellular vesicles
Authors: Nguyen Vivian V.T. , Witwer Kenneth W. , Verhaar Marianne C. , Strunk Dirk , van Balkom Bas W.M. 
Published: December 2020

AbstractAn important aspect in the development of extracellular vesicle (EV) therapeutics is identifying and quantifying the key features defining their identity, purity, sterility, potency and stability to ensure batch‐to‐batch reproducibility of their therapeutic efficacy. Apart from EV‐inherent features, therapeutic efficacy depends on a variety of additional parameters, like dosing, frequency of application, and administration route, some of which can be addressed only in clinical trials. Before initiating clinical trials, EV‐inherent features should be tested in well‐standardized quantitative assays in vitro or in appropriate animal models in vivo. Ideally, such assays would predict if a particular EV preparation has the potential to achieve its intended therapeutic effects, and could be further developed into formal potency assays as published by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use guidelines. Furthermore, such assays should facilitate the comparison of EV preparations produced in different batches, on different manufacturing platforms or deriving from different cell sources. For now, a wide spectrum of in vitro and in vivo assays has been used to interrogate the therapeutic functions of EVs. However, many cannot accurately predict therapeutic potential. Indeed, several unique challenges make it difficult to set up reliable assays to assess the therapeutic potential of EVs, and to develop such assays into formal potency tests. Here, we discuss challenges and opportunities around in vitro and in vivo testing of EV therapeutic potential, including the need for harmonization, establishment of formal potency assays and novel developments for functional testing.
Interpretative immune targets and contemporary position for vaccine development against SARS‐CoV‐2: A systematic review
Authors: Chauhan Nidhi , Soni Shringika , Gupta Abhinandan , Aslam Mohammad , Jain Utkarsh 
Published: December 2020

AbstractThe year 2020 started with the emergence of novel coronavirus, severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), which causes COVID‐19 infection. Soon after the first evidence was reported in Wuhan, China, the World Health Organization declared global public health emergency and imminent need to understand the pathogenicity of the virus was required in limited time. Once the genome sequence of the virus was delineated, scientists across the world started working on the development of vaccines. Although, some laboratories have been using previously developed vaccine platforms from severe acute respiratory syndrome coronavirus (SARS) and middle east respiratory syndrome‐related coronavirus and apply them in COVID‐19 vaccines due to genetic similarities between coronaviruses. We have conducted a literature review to assess the background and current status of COVID‐19 vaccines. The worldwide implementation and strategies for COVID‐19 vaccine development are summarized from studies reported in years 2015–2020. While discussing the vaccine candidates, we have also explained interpretative immune responses of SARS‐CoV‐2 infection. There are several vaccine candidates at preclinical and clinical stages; however, only 42 vaccines are under clinical trials. Therefore, more industry collaborations and financial supports to COVID‐19 studies are needed for mass‐scale vaccine development. To develop effective vaccine platforms against SARS‐CoV‐2, the genetic resemblance with other coronaviruses are being evaluated which may further promote fast‐track trials on previously developed SARS‐CoV vaccines.
Rhamnolipid–Metal Ions (CrVI and PbII) Complexes: Spectrophotometric, Conductometric, and Surface Tension Measurement Studies
Authors: Hari Om , Upadhyay Santosh K. 
Published: December 2020

AbstractThe formation of rhamnolipid complexes with metal ions of chromium (VI) and lead (II) has been studied spectrophotometrically, conductometrically, and by surface tension measurement. The values of the critical micelle concentration (CMC) of rhamnolipid, obtained by spectroscopic, conductometric, and surface tension measurements, were 5.2 × 105, 5.0 × 105, and 5.3 × 105 mol.dm−3, respectively, which are in close agreement. An increase in CMC on increasing metal ion content in the rhamnolipid solution and a shift in λmax in the spectra of rhamnolipid indicated the formation of a complex between rhamnolipid and both the metal ions, namely, chromium (VI) and lead (II). The values of stability constants for the {rhamnolipid–chromium (VI)} and {rhamnolipid–lead (II)} complexes have been determined by spectroscopic data and were as 0.58 × 104 and 0.50 × 104 at 308 K, respectively.The thermodynamic parameters for micellization, namely, free energy change (∆Gmic), entropy change (∆Smic), and heat enthalpy change (∆Hmic), have been determined by conductivity measurements. An increase in the negative value of ∆Gmic and a decrease in the value of ∆Smicon increasing metal ion content in the surfactant solution indicated lower micellization of rhamnolipid in the presence of metal ions. The electrostatic attractions and entrapment of chromium (VI) in the micelles of the biosurfactants were found to be responsible for {rhamnolipid–lead (II)} and {rhamnolipid–chromium (VI)} complexes, respectively.
Bagging and non‐bagging treatment on the dissipation and residue of four mixed application pesticides on banana fruit
Authors: Wang Ye , Song Qingmei , Wang Fei , Tang Shouying , Pan Tingtiao , Zhang Yuping , Hu Deyu 
Published: December 2020

AbstractBACKGROUNDBananas are vulnerable to disease and insect pests after producing fruit. In order to increase the yield and produce high‐quality fruit, the insecticides and fungicides are mixed and applied 2–3 times on banana, then the fruit is bagged. Buprofezin, imidacloprid, difenoconazole, and pyraclostrobin are widely used on banana. However, there is a lack of research on the effect of fruit bagging on pesticide dissipation and residues on bananas.RESULTSA versatile liquid chromatography–tandem mass spectrometry method with modified QuEChERS sample preparation has been developed for the determination of buprofezin, imidacloprid, difenoconazole, and pyraclostrobin in bananas. The recovery of four pesticides was satisfactory (74.96–98.63%) with reasonable relative standard deviation (≤ 8.78%). In Hainan and Guangzhou, the half‐lives of the four pesticides were 4.68–13.9 and 5.63–20.4 days in non‐bagged and bagged bananas, respectively. The significance analysis of the half‐lives in the two sites showed that the dissipation rates of the three pesticides (imidacloprid, difenoconazole, pyraclostrobin) on whole bananas were significantly decreased by the effect of bagging (P < 0.05). However, there was no significant difference in the degradation of half‐life of buprofezin under bagging and without bagging (P > 0.05).CONCLUSIONThe high vapor pressure and the non‐systemic property cause buprofezin to evaporate and dissipate the fastest among the four studied pesticides. The ultimate residues of four pesticides in bananas are lower than the maximum residue limits in China after three times of mixed applications under bagging or non‐bagging. The results provide scientific data for evaluating the safety of four pesticides in banana bagging. © 2020 Society of Chemical Industry
Laryngeal Pathologies Associated with the Genre of Singing and Professional Singing Status in a Treatment‐Seeking Population
Authors: Rotsides Janine , Chen Sophia , Winchester Arianna , Amin Milan R. , Johnson Aaron M. 
Published: December 2020

Objectives/HypothesisSingers have high vocal demands and are at increased risk of developing voice disorders. Different singing genres place different technical demands on the voice. However, differences in laryngeal pathology based on genre have not been well‐researched. The purpose of this study was to determine the prevalence of laryngeal pathology in different genres of professional and amateur singers who present with a voice complaint.Study DesignRetrospective review.MethodsRetrospective review of patients seen at a tertiary laryngology practice. Self‐identified singers who reported their primary singing genre and categorized their singing as a full‐time job, part‐time job, or amateur involvement were included. Type and prevalence of pathology were calculated based on genre and professional status.ResultsOf the 302 self‐identified singers, 54% (n = 164) had laryngeal pathology. Among those with pathology, the most common finding was fibrotic lesion (38.4%, 63/164). Genres in which a majority of singers had pathology were other (69.2%, 9/13), choral (64.7%, 11/17), pop (63.2%, 12/19), musical theater (61.4%, 43/70), country (100%, 4/4), and Latin (100%, 2/2). The highest prevalence of pathology was seen in part‐time professional singers (62.2%, 41/66) and full‐time professionals (60.8%, 62/102), compared to amateurs (45.1%, 60/133).ConclusionsLaryngeal pathology is prevalent in singers presenting with a voice complaint. Regardless of genre or professional status, fibrotic lesions were the most common pathological finding. This study provides preliminary data on the prevalence of different laryngeal pathologies found in singers by genre and degree of professional involvement.Level of Evidence4 Laryngoscope, 131:2076–2080, 2021