ABSTRACT
It is known that inflammatory cytokines exacerbate the persistence and severity of various disease states. Breast cancer is the most frequently detected cancer among women worldwide and our recent studies suggest that the inflammatory state of breast (BrCa) cancer, a byproduct of elevated cytokine expression, induces epigenetic modifications leading to increased recurrence. Ongoing NCI clinical trial data (ClinicalTrials.gov, CCC19, NCT04354701) indicates that among patients with cancer and COVID-19, the mortality is high, and the most prevalent malignancies are of breast [21%] and prostate [16%] origin. Due to the risk of cytokine storm during SARS-CoV-2 infection, it is crucial to identify potential mechanisms of hyperinflammation in BrCa patients. In this study, we have evaluated the level of copy number alteration (CNA) of different inflammatory cytokines including IL-8, IL-1b, IL6, IL-8, GM-CSF, TNF-alpha and many others using cBioportal platform which includes over sixty-nine thousand tumor samples (n>69,000 from 213 different studies) from over 33 different cancers. We found that IL-8 has the highest level of amplification in different breast cancers subtypes. Besides, we also analyzed serum samples from BrCa patients, both recurrent and non-recurrent, by different proteomics methods to identify serum cytokines involved in prognosis and recurrence. Comparative data analysis between non-recurrent BrCa against recurrent BrCa patients identified several proteins with very high significance, mostly proteins associated with epigenetic pathways including HDAC9 (P = 0.0035), HDAC5 (P = 0.013), and HDAC7 (P = 0.020). Besides, we identified differential expression of several pro-inflammatory cytokines and immune regulators (IL-8, IL-4, IL-18, IL-12p70) that were present only in recurrent BrCa patient serum. Our data indicate that inflammatory processes contribute to epigenetic modifications that ultimately play a critical role in breast cancer recurrence. In terms of COVID-19 associated co-morbidity, the already dysregulated inflammatory state of BrCa patients may increase their susceptibility to cytokine-storm, leading to increased severity of COVID-related complications and increased mortality rate. Specifically, we hypothesize that the identified elevated level of IL-8 in BrCa patients may lead to a higher basal level of inflammation and contribute to the risk of attaining cytokine-storm during SARS-CoV-2 infection, making it a valuable target for future studies.
ABSTRACT
Coronavirus disease 2019 (COVID-19) outbreak started in Wuhan, China when people started with the symptoms of respiratory disorder. The onset of this disease have symptoms like fever, dry cough, fatigue, and difficulty in breathing. The nature of SARS-CoV-2 seems highly contagious as it also can be spread with asymptomatically infected individuals. It has been more than a year which this outbreak have been announced as a pandemic by World Health Organization (WHO) due to major public health crisis and uncontrollable around the globe. Some countries have taken initiatives in inventing vaccines and step up in the clinical trial process since a vaccine is an all-powerful tool which it always been a saviour in fighting infectious disease. In searching for the vaccine, researchers had studied the previously published article of SARS-CoV or MERS as in the beginning, in light, there will be a suitable vaccine to fight this pandemic situation. Recent research on the vaccine has been tested to seek the right vaccine for COVID-19. This study is to focus on the current vaccine development against COVID-19 and to explore the potential vaccines' characteristics that have been studied by the previous proven research findings. This review was done based on the research articles and reviews published until the end of April 2021 through established scientific search engines and related scientific platforms based on the inclusion criteria with its related keywords like coronavirus, SARS-CoV-2, COVID-19 Vaccine, clinical trials, and COVID-19 vaccine development. This review summarized a few vaccine candidates that have entered clinical trials and some supported evidence from Phase I until Phase III clinical trial studies that have been published and reported. In this review, 12 vaccine candidates have the potential to against SARS-CoV-2. Thus, their vaccine platform, characteristic as well as its efficacy studies have been discussed.Copyright © RJPT All right reserved.
ABSTRACT
Coronavirus disease 2019 (COVID-19) outbreak started in Wuhan, China when people started with the symptoms of respiratory disorder. The onset of this disease have symptoms like fever, dry cough, fatigue, and difficulty in breathing. The nature of SARS-CoV-2 seems highly contagious as it also can be spread with asymptomatically infected individuals. It has been more than a year which this outbreak have been announced as a pandemic by World Health Organization (WHO) due to major public health crisis and uncontrollable around the globe. Some countries have taken initiatives in inventing vaccines and step up in the clinical trial process since a vaccine is an all-powerful tool which it always been a saviour in fighting infectious disease. In searching for the vaccine, researchers had studied the previously published article of SARS-CoV or MERS as in the beginning, in light, there will be a suitable vaccine to fight this pandemic situation. Recent research on the vaccine has been tested to seek the right vaccine for COVID-19. This study is to focus on the current vaccine development against COVID-19 and to explore the potential vaccines' characteristics that have been studied by the previous proven research findings. This review was done based on the research articles and reviews published until the end of April 2021 through established scientific search engines and related scientific platforms based on the inclusion criteria with its related keywords like coronavirus, SARS-CoV-2, COVID-19 Vaccine, clinical trials, and COVID-19 vaccine development. This review summarized a few vaccine candidates that have entered clinical trials and some supported evidence from Phase I until Phase III clinical trial studies that have been published and reported. In this review, 12 vaccine candidates have the potential to against SARS-CoV-2. Thus, their vaccine platform, characteristic as well as its efficacy studies have been discussed. Copyright © RJPT All right reserved.
ABSTRACT
Background: Bispecific antibodies (bsAb) are a promising class of therapeutics in RRMM. While hypogammaglobinemia (HGG) is anticipated due to plasma cell depletion, there is a lack of information about the degree of secondary immunodeficiency and resultant infectious complications. We investigated the kinetics of HGG in patients with RRMM on bsAb therapy. Methods: We identified and followed 42 patients treated on early clinical trials of bsAb at our institution between 2019 and 2021. Serial immunoglobulin levels and infections were obtained from the start of therapy until last follow up or 3 months after study exit. Results: 49 treatment courses were included from 42 individual patients. All patients were triple class exposed with a median of 5 prior lines of therapy. The median age was 67 (44-85) years, with 49% females. African Americans accounted for 18% of patients. 96% of patients had at least one prior ASCT. 90% of patients received bsAb targeting BCMA including 7 patients who received more than one line of BCMA targeting therapies. At a median follow up 9.5 (0.9-28.6) months, 40.8% of patients remained on bsAb therapy. At the start of therapy, the median IgG, IgA, and IgM levels were 560 (44-9436), 15 (5-3886) and 6 (5-64) mg/dL, respectively and 50% of patients had severe HGG (≤400mg/dl). Serum IgG levels reached a nadir at 3 months while, IgA and IgM at 1 month, from the start of therapy. The median nadir levels of IgG were 159 (40-2996) mg/dL, while it was < 5 mg/dL for both IgA and IgM. IgG levels were below the detectable range (< 40 mg/dl) in 28% of patients at some point during therapy. IgA and IgM were also below the detectable range (< 5 mg/dl) in 50% and 60% of patients, respectively. At last follow-up, the median IgG levels were 444 (40-1860) mg/dL and IgA 5 (5-254) mg/dL and IgM 5 (5-44) mg/dL. Additionally, 38% of patients remained severely hypogammaglobinemic. 57% (24/42) of patients received IVIG supplements in the current series. About 71% of patients had at least one infectious event and the cumulative incidence of infections progressively increased with increasing duration of therapy with risk at 3, 6, 9 12, 15 months being 41%, 57%, 64%, 67% and 70%, respectively. Among these, 54% of infection were bacterial. Viral infection accounted for 41% of infections. A third of patients had new infectious events during the first 90 days following stopping bsAb treatment. 57% (8/14) of patients did not mount a response to the primary COVID19 immunization series. Among the five patients with repeat antibody titers after the booster dose, 50% were still not able to mount an antibody response. Conclusions: bsAb therapy in RRMM can be associated with profound and prolonged HGG. The cumulative risk of infection correlated with the degree of HGG and progressively increases with treatment and persisted months after being off therapy. Additionally, an impaired antibody response to the COVID-19 immunization series was also noted.
ABSTRACT
Rationale: To report a case of cervicobrachial variant of acute inflammatory demyelinating polyneuropathy presenting with papilledema and GQ1b positivity. Patient concern: A 35-year-old female, 68 days postpartum, presented with headache, vomiting, and gait difficulty in swallowing with bilateral upper limb weakness and difficulty in walking, 13 days after ChAdOx1 nCoV-19 vaccination. Diagnosis: Guillain-Barre syndrome with GQ1b positivity. Intervention: Five cycles of plasmapheresis were given. Outcome: The patient's clinical condition improved. Palatal weakness improved and she could walk without support. There were mild sensory symptoms involving upper limbs which gradually improved. Lessons: AIDP should be considered in case of weakness following ChAdOx1 nCoV-19 vaccination. Albumino-cytological dissociation and anti-GQ1b positivity are needed to confirmed the diagnosis.
ABSTRACT
The upstream oil and gas industry's digital transformation over the last few years has accelerated because of the COVID-19 pandemic. Data analytics and machine learning are key components of this digital transformation and have become essential skills for experienced petrotechnical professionals (PTPs) and aspiring entrants into the field. The objective of our work was to design and deliver a practical, engaging, and online microcredential certification program in upstream energy data analytics for PTPs. The program was conceived as a collaboration between academia (University of Houston's UH Energy) and industry (NExT, a Schlumberger company). It was designed as three belt levels (Bronze, Silver, and Gold), each containing three stackable badges of 12 to 15 hours duration per badge. Key design points included 1. Identifying an online platform for administration 2. Delivering convenient, interactive, live online sessions 3. Delivering hybrid classes blending lectures and hands-on laboratories 4. Designing laboratories using upstream datasets across various stages of oilfield expertise 5. Administering test and quizzes, Kaggle competitions, and team projects. The program contents were designed incorporating appropriate instructional design practices for effective online class delivery. The design and delivery of the laboratories using a code-free approach by leveraging visual programming offers PTPs and new entrants a unique opportunity to learn data analytics concepts without the traditional concern of learning to code. Additionally, the collaboration between academia and industry enables delivering a program that combines academic rigor with application of the skills and knowledge to solve problems facing the industry using the real-world datasets. As a pilot program, all three badges of the Bronze belt were scheduled and successfully delivered during July and August 2020, as six 2-hour sessions per badge. From a total of 26 students registered in badge 1, 24 completed it, resulting in a completion rate of 92%. Out of these students, 19 registered and completed badge 2 and badge 3, resulting in the completion rates of 100%. Based on the success of the pilot program, a second delivery of the Bronze belt with 18 participants was offered from October 2020 through January 2021. All 18 participants completed all three badges. Feedback from participants attests to the success of the pilot program as seen in the following excerpts: • "A very good course and instructors. I have already recommended the course to a friend and I will continue to be an advocate for the course." • "Teachers are very receptive to questions and it is a joy to hear their lectures." • "I found the University of Houston course to be both highly engaging and incredibly informative. The course teaches basic principles of data science without being bogged down by the specific coding language". © 2021, Society of Petroleum Engineers
ABSTRACT
COVID-19 is a global issue, with over 6.25 million cases in 213 countries and territories on June 1, 2020. Althoughthis virus infects all groups, data indicate that the risk for severe disease and death is much higher in older men, which coincides with the same group of patients at risk for prostate cancer. A recent Italian study investigated theprevalence and severity of COVID-19 in men with prostate cancer. This study indicated that of a total of 4,532 men with COVID-19, from the Veneto region of Italy, 9.5% (n=430) had cancer and out of those around 30% (n=118) hadprostate cancer. Data also indicated that male cancer patients had a 1.8-fold increased risk of COVID-19 infectionand developed a more severe disease. Interestingly, they observed that the prostate cancer patients (n=4) treated with androgen-deprivation therapy (ADT) were less likely to develop COVID-19, and in those who were infected, thedisease was less severe. In this current study, we focused on determining the genetic basis of the higher COVID-19prevalence and severity in male patients and particularly for prostate cancer patients. Researchers found two genesthat are essential for severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). ACE2 is a SARS-CoV-2receptor, whereas the serine protease, TMPRSS2, primes the virus for cell entry through cleavage of the viral spikeprotein (S). The expression of TMPRSS2 is significantly high in normal prostate tissue and is regulated in large partby an androgen response element in the promoter region. Therefore, we decided to investigate the status of thesetwo genes in various tumors from The Cancer Genome Atlas (TCGA) database using the cBioportal platform. Weanalyzed over 46,000 tumor samples from 176 studies and found that aggressive metastatic prostate cancer, including neuroendocrine prostate cancer (NEPC), has significantly higher amplification (copy number alteration) ofthe ACE2 and TMPRSS2 genes compared to other cancers. Next, we focused on drugs that could simultaneouslytarget ACE2 or TMPRSS2 and oncogenic pathways and would be beneficial for prostate cancer patients infected with SARS-CoV-2. Although several inhibitors are validated in literature for both ACE2 and TMPRSS2, very limitedstudies were performed to see the effect on cancer cells. Therefore, we analyzed a cytotoxic effect database of over130,000 drugs on NCI-60 cell lines with COMPARE algorithm and found two relevant compounds, NSC-148958 (FT-701) and NSC-280594 (triciribine phosphate), which target ACE2 and TMPRSS2, respectively. Computational dataare currently validating different prostate cancer cell-lines and their response to these drugs. In summary, ourfindings provide the premise that men who are at risk for or diagnosed with prostate cancer may be moresusceptible to severe infection and death in response to SARS-CoV-2 due to the high expression of ACE2 andTMPRSS2, and triciribine phosphate and FT-701 could be a therapeutic intervention to target co-occurrence ofCOVID-19 and prostate cancer.