It has been more than three decades since the first monoclonal antibody was approved by the United States Food and Drug Administration (US FDA) in 1986, and during this time, antibody engineering has ...dramatically evolved. Current antibody drugs have increasingly fewer adverse effects due to their high specificity. As a result, therapeutic antibodies have become the predominant class of new drugs developed in recent years. Over the past five years, antibodies have become the best-selling drugs in the pharmaceutical market, and in 2018, eight of the top ten bestselling drugs worldwide were biologics. The global therapeutic monoclonal antibody market was valued at approximately US$115.2 billion in 2018 and is expected to generate revenue of $150 billion by the end of 2019 and $300 billion by 2025. Thus, the market for therapeutic antibody drugs has experienced explosive growth as new drugs have been approved for treating various human diseases, including many cancers, autoimmune, metabolic and infectious diseases. As of December 2019, 79 therapeutic mAbs have been approved by the US FDA, but there is still significant growth potential. This review summarizes the latest market trends and outlines the preeminent antibody engineering technologies used in the development of therapeutic antibody drugs, such as humanization of monoclonal antibodies, phage display, the human antibody mouse, single B cell antibody technology, and affinity maturation. Finally, future applications and perspectives are also discussed.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The coronavirus disease 2019 (COVID-19) pandemic is an exceptional public health crisis that demands the timely creation of new therapeutics and viral detection. Owing to their high specificity and ...reliability, monoclonal antibodies (mAbs) have emerged as powerful tools to treat and detect numerous diseases. Hence, many researchers have begun to urgently develop Ab-based kits for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Ab drugs for use as COVID-19 therapeutic agents. The detailed structure of the SARS-CoV-2 spike protein is known, and since this protein is key for viral infection, its receptor-binding domain (RBD) has become a major target for therapeutic Ab development. Because SARS-CoV-2 is an RNA virus with a high mutation rate, especially under the selective pressure of aggressively deployed prophylactic vaccines and neutralizing Abs, the use of Ab cocktails is expected to be an important strategy for effective COVID-19 treatment. Moreover, SARS-CoV-2 infection may stimulate an overactive immune response, resulting in a cytokine storm that drives severe disease progression. Abs to combat cytokine storms have also been under intense development as treatments for COVID-19. In addition to their use as drugs, Abs are currently being utilized in SARS-CoV-2 detection tests, including antigen and immunoglobulin tests. Such Ab-based detection tests are crucial surveillance tools that can be used to prevent the spread of COVID-19. Herein, we highlight some key points regarding mAb-based detection tests and treatments for the COVID-19 pandemic.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Combinatorial phage library is a powerful research tool for high-throughput screening of protein interactions. Of all available molecular display techniques, phage display has proven to be the most ...popular approach. Screening phage-displayed random peptide libraries is an effective means of identifying peptides that can bind target molecules and regulate their function. Phage-displayed peptide libraries can be used for (i) B-cell and T-cell epitope mapping, (ii) selection of bioactive peptides bound to receptors or proteins, disease-specific antigen mimics, peptides bound to non-protein targets, cell-specific peptides, or organ-specific peptides, and (iii) development of peptide-mediated drug delivery systems and other applications. Targeting peptides identified using phage display technology may be useful for basic research and translational medicine. In this review article, we summarize the latest technological advancements in the application of phage-displayed peptide libraries to applied biomedical sciences.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Mechanical power (MP) refers to the energy delivered by a ventilator to the respiratory system per unit of time. MP referenced to predicted body weight (PBW) or respiratory system compliance have ...better predictive value for mortality than MP alone in acute respiratory distress syndrome (ARDS). Our objective was to assess the potential impact of consecutive changes of MP on hospital mortality among ARDS patients receiving extracorporeal membrane oxygenation (ECMO).
We performed a retrospective analysis of patients with severe ARDS receiving ECMO in a tertiary care referral center in Taiwan between May 2006 and October 2015. Serial changes of MP during ECMO were recorded.
A total of 152 patients with severe ARDS rescued with ECMO were analyzed. Overall hospital mortality was 53.3%. There were no significant differences between survivors and nonsurvivors in terms of baseline values of MP or other ventilator settings. Cox regression models demonstrated that mean MP alone, MP referenced to PBW, and MP referenced to compliance during the first 3 days of ECMO were all independently associated with hospital mortality. Higher MP referenced to compliance (HR 2.289 95% CI 1.214-4.314, p = 0.010) was associated with a higher risk of death than MP itself (HR 1.060 95% CI 1.018-1.104, p = 0.005) or MP referenced to PBW (HR 1.004 95% CI 1.002-1.007, p < 0.001). The 90-day hospital mortality of patients with high MP (> 14.4 J/min) during the first 3 days of ECMO was significantly higher than that of patients with low MP (≦ 14.4 J/min) (70.7% vs. 46.8%, p = 0.004), and the 90-day hospital mortality of patients with high MP referenced to compliance (> 0.53 J/min/ml/cm H
O) during the first 3 days of ECMO was significantly higher than that of patients with low MP referenced to compliance (≦ 0.53 J/min/ml/cm H
O) (63.6% vs. 29.7%, p < 0.001).
MP during the first 3 days of ECMO was the only ventilatory variable independently associated with 90-day hospital mortality, and MP referenced to compliance during ECMO was more predictive for mortality than was MP alone.
With the increasing penetration of renewable energy, power system inertia is reduced; thus, frequency stability faces tremendous challenges. Offshore wind farms (WFs) are often integrated to the grid ...through a voltage-source-converter-based high-voltage direct current (VSC-HVDC) transmission. However, traditional WFs cannot provide frequency support owing to the decoupling characteristics of VSC-HVDC. Modern WFs may support frequency regulation, but the recovery of rotor speeds of wind turbines (WTs) would cause a considerable second frequency drop (SFD). To resolve these problems, this paper presents a coordinated control strategy for a VSC-HVDC-connected WF with a battery energy storage system (BESS) for providing frequency support. The proposed strategy enhances the synthetic inertia by allowing WFs and BESSs to participate in frequency regulation, in which the VSC-HVDC transmission supports frequency regulation by regulating its DC-link voltage, and the BESS provides the required power during the rotor-speed recovery of WTs. Thus, SFD can be prevented. In this paper, the case studies considered the operating scenarios for the outage of synchronous generators and variable wind-speeds. The simulation results verify the effectiveness and the robustness of the proposed control strategy and demonstrate the superiority of the proposed strategy over other existing strategies.
Asymptomatic erosive esophagitis (AEE) is commonly found in men, and might be a risk factor of developing esophageal adenocarcinoma. We aimed to determine if specific dietary habits increase the risk ...of AEE in asymptomatic Taiwanese men.
We recruited male adults undergoing upper gastrointestinal endoscopy for health check. We excluded subjects with reflux symptoms, or taking anti-reflux medications or drugs that potentially impair lower esophageal sphincter function or cause mucosal injury. The frequency of consuming reflux-provoking diets including alcohol, tea, coffee, tomato/citric juice, chocolate, sweet food, and spicy food was assessed. The erosive esophagitis was diagnosed based on the Los Angeles Classification after endoscopy. Frequent consumption of a specific diet was defined as ≥4 days/week of consuming that diet.
A total of 1256 participants were recruited. After excluding 424 ineligible subjects, AEE was identified in 180 (22%) among 832 asymptomatic subjects. The risk of AEE increased with the number of days per week of consuming alcohol or tea: nondrinkers (19%, 17%), occasional drinkers (<1 day/week; 19%, 15%), regular drinkers (1-3 days/week; 26%, 21%), frequent drinkers (4-6 days/week; 32%, 22%), and daily drinkers (42%, 28%), respectively (trend test P < 0.001 for both). Multivariate analysis showed that hiatus hernia (adjusted odds ratio (aOR) 5.0, 95% confidence interval (CI) 2.6-9.6), drinking alcohol ≥4 days/week (aOR 2.3, 95% CI 1.3-4.0), and drinking tea ≥4 days/week (aOR 1.6, 95% CI 1.1-2.3) are independent risk factors of AEE. The risk of AEE was 3.8 times greater for those drinking both alcohol and tea ≥4 days/week than the non-drinkers.
Frequent alcohol and tea consumption increased the risk of AEE in Taiwanese men.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The high level of occupational stress and burnout among nurses can lead to insomnia, anxiety, and depression. However, the actual risks for healthcare-seeking for these stress-related mental health ...problems among nurses are still unclear. The aim of this study was to explore the risks and influencing factors of treated anxiety, depression, and insomnia among nurses. We used claims data obtained from the 2010 National Health Insurance Research Database (NHIRD) in Taiwan. Hospital nurses who had at least 3 coded ambulatory care claims or 1 inpatient claim with a principal diagnosis of anxiety, depression, or insomnia were identified. A cohort of 46,120 nurses and 92,240 matched controls were included. All the study subjects were followed up until the onset of any of the aforementioned outcomes, death, or the end of 2012. Results showed that the adjusted hazard ratios (HRs) for treated anxiety, depression, and insomnia among all the nurses were 0.91 (95% CI, 0.88-0.95), 0.59 (95% CI, 0.55-0.63), and 1.43 (95% CI, 1.38-1.48), respectively. Furthermore, the risks of these psychiatric problems in healthcare-seeking nurses were affected by age, gender, hospital level, and job tenure. Our findings suggest that hospital nurses have lower hazards of treated anxiety and depression than the general population, although they have a higher hazard of treated insomnia. There may be undertreatment in some subgroups of nurses with different demographic and working characteristics.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mitigation strategies of the coronavirus disease 2019 (COVID-19) pandemic have been greatly hindered by the continuous emergence of SARS-CoV-2 variants. New sensitive, rapid diagnostic tests for the ...wide-spectrum detection of viral variants are needed. We generated a panel of 41 monoclonal antibodies against the SARS-CoV-2 nucleocapsid protein (NP) by using mice hybridoma techniques. Of these mAbs, nine exhibited high binding activities and were applied in latex-based lateral flow immunoassays (LFIAs). The LFIAs utilizing NP-mAb-7 and -40 had the best sensitivity and lowest limit of detection: 8 pg for purified NP and 625 TCID50/mL for the authentic virus (hCoV-19/Taiwan/4/2020). The specificity tests showed that the NP-mAb-40/7 LFIA strips did not cross-react with five human coronavirus strains or 20 other common respiratory pathogens. Importantly, we found that 10 NP mutants, including alpha (B.1.1.7), beta (B.1.351), gamma (P.1), and delta (B.1.617.2) variants, could be detected by NP-mAb-40/7 LFIA strips. A clinical study (n = 60) of the NP-mAb-40/7 LFIA strips demonstrated a specificity of 100% and sensitivity of 90% in infected individuals with cycle threshold (Ct) values < 29.5. These anti-NP mAbs have strong potential for use in the clinical detection of SARS-CoV-2 infection, whether the virus is wild-type or a variant of concern.
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