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1.
ACM Transactions on Computing for Healthcare ; 3(4) (no pagination), 2022.
Article in English | EMBASE | ID: covidwho-2315801

ABSTRACT

Federated learning is the process of developing machine learning models over datasets distributed across data centers such as hospitals, clinical research labs, and mobile devices while preventing data leakage. This survey examines previous research and studies on federated learning in the healthcare sector across a range of use cases and applications. Our survey shows what challenges, methods, and applications a practitioner should be aware of in the topic of federated learning. This paper aims to lay out existing research and list the possibilities of federated learning for healthcare industries.© 2022 Copyright held by the owner/author(s).

2.
Horizonte Medico ; 23(1) (no pagination), 2023.
Article in Spanish | EMBASE | ID: covidwho-2313336

ABSTRACT

Objective: To determine the characteristics and frequency of patients aged over 18 years with tuberculosis (TB) before (2019) and during (2020) the COVID-19 pandemic in a healthcare center (CS) in Lima, Peru. Material(s) and Method(s): A descriptive retrospective study that included medical records of 100 patients aged > 18 years enrolled in the TB program at CS Los Libertadores (SMP-Lima, Peru) from 2019 to 2020. Sociodemographic (sex, origin, age), clinical (admission/discharge status, body mass index, comorbidities, TB infection site, type of resistance, treatment regimen) and laboratory (smear microscopy, culture, drug susceptibility testing) variables were analyzed. Patients who did not have all the variables were excluded. An Excel database was prepared and a descriptive statistical analysis of the qualitative variables, expressed in frequencies, and quantitative variables, expressed in measures of central tendency (mean) and standard deviation, was performed using IBM SPSS Statistics. TB prevalence per year was determined, according to the population assigned to the healthcare center. Said information was obtained through the Tuberculosis Management Information System (SIGTB). Result(s): TB prevalence was 0.0015 % (49 patients) in 2019 and 0.075 % (51 patients) in 2020. In both years, the male sex and the age group between 18 and 29 years prevailed, and the most common site of infection were the lungs. In 2020, an increase in HIV comorbidity and mortality rate (0.074) was observed, as well as more positive smear microscopy cases. Conclusion(s): TB prevalence was higher in 2020, the first year of the COVID-19 pandemic, due to a reduced approach to TB programs as a result of the situation imposed by the pandemic. In addition, TB mortality rates raised in the same year, probably due to an increase in treatment dropouts or HIV and diabetes comorbidity rates.Copyright © La revista. Publicado por la Universidad de San Martin de Porres, Peru.

3.
Health Biotechnology and Biopharma ; 4(1):1-6, 2021.
Article in English | EMBASE | ID: covidwho-2290647

ABSTRACT

This note is prepared by the authors of a recent publication on shared genetic architecture of drug response based on summary statistics from genome-wide association studies (GWAS) to propose a drug repurposing approach for the treatment of coronavirus COVID-19. The authors proposed that in silico studies may be preceded by analyzing shared genetic architecture of drug response based on existing GWAS.Copyright © 2020, Health Biotechnology and Biopharma.

4.
Allergy: European Journal of Allergy and Clinical Immunology ; 78(Supplement 111):638, 2023.
Article in English | EMBASE | ID: covidwho-2306128

ABSTRACT

Background: Covid 19 is a global epidemic. One of the most important steps in the fight against this epidemic is vaccination. mRNA vaccines are used in vaccination in our country. Among the additives in the vaccine, the substance with the highest allergenic risk is polyethylene glucose (PEG). There are different molecular weights of PEG. Another additive that has a high risk of cross-reaction with PEG as an additive is POLISORBAT 80. Skin tests with drugs containing PEG and POLISORBAT 80 and, if available, tests with vaccines are instructive. Among the drugs containing PEG: Moxifloxacin tablet, ciprofloxacin tablet, Amoxicillin clavulanic acid tablet;Medicines containing polysorbate include: Omalizumab vaccine, Mepolizumab vaccine. The results of the skin test with PEG-containing methylprednisolone (DEPO-MEDROL) and POLYSORBAT-containing triamcinolone (KENACORT-A) in order to be evaluated in terms of vaccine in our 2 patients who had multiple drug sensitivities before were shared. Method(s): Case 1: 33 y, F *There are diagnoses of urticaria and angioedema. Urticaria 30 minutes after taking aspirin, levofloxacin, cefdinir tablet;5 minutes after taking ciprofloxacin tablets, he has anaphylaxis. *Applies before Biontec vaccine. *The patient had a history of anaphylaxis with PEG-containing ciprofloxacin. In the skin tests performed with DEPO-MEDROL and KENACORT-A, 1/100 intradermal test was positive. *The patient for whom Biontec vaccine was not recommended received Synovac vaccine without any problems. Case 2: 52 years, F * He has a diagnosis of urticaria. 5 minutes after general anesthesia and local anesthesia;The patient who had cardiac arrest 3 times was evaluated. The patient, who had Synovac for 2 times without any problems, wanted to have the 3rd dose of Biontec vaccine. *Tested with general -local anesthetic agents. *Ciprofloxacin skin tests are negative;Urticaria plaques developed after 30 minutes of 1/4 tb in oral provocation. In the skin tests performed with DEPO-MEDROL and KENACORT-A, 1/100 intradermal test was positive. *Biontec vaccine is not recommended. Result(s): A safer vaccination is ensured by testing with additives in Covid 19 vaccines. Conclusion(s): Drug additives should also be kept in mind in patients with multiple drug allergies.

5.
Journal of Pediatric & Adolescent Gynecology ; 36(2):246-246, 2023.
Article in English | Academic Search Complete | ID: covidwho-2263558

ABSTRACT

The COVID-19 pandemic has been shown to result in a change in the incidence of respiratory tract infection 1-3. It is unknown whether the pandemic has the same impact on vulvovaginitis among girls and adolescents. This study aims to explore the potential changes in the epidemiology, pathogenic pattern, and drug susceptibility of girls with vulvovaginitis before and during COVID-19 pandemic in China. A retrospective study of prepubertal and adolescent girls (below 18 years old) diagnosed with vulvovaginitis between 2018 and 2021. The study was approved by the Human Subjects Committees of the Children's Hospital, Zhejiang University School of Medicine (approval number 2019-IBR-103). Out-patient clinic, Department of Pediatric and Adolescent Gynecology (PAG) in the Children's Hospital, Zhejiang University School of Medicine. The inclusion criteria were as follows: 1) patients who were clinically diagnosed with genital inflammation at their first clinical visit;2) patients with abnormal vaginal discharge which was collected for microbiological investigation and drug sensitivity test. Demographic data, clinical features and laboratory study findings were analyzed. A total of 4644 cases of vulvovaginitis were identified during the study period, including 2427 cases in 2018-2019 before COVID-19 pandemic, and 2217 cases in 2020-2021 during COVID-19 pandemic. The average age was 7.55± 3.20 years and 8.24±3.33 years, respectively. The proportion of vulvovaginitis in the age group of 0-6 years significantly decreased from 40.23% (971/2427) in 2018-2019 to 31.30% (694/2217) in 2020-2021 (χ2=38.52, p <.001). The proportion of vulvovaginitis in the age group of 10-18 years increased from 30.09% (727/2427) in 2018-2019 to 39.60% (878/2217) in 2020-2021 (χ2=47.69, p <.001). Compared with 2018-2019, the major causative pathogens were similar in 2020-2021. The detection rates of Haemophilus influenzae, Streptococcus pyogene and Streptococcus pneumoniae in 2020-2021 were decreased (118/709 vs 268/648, 144/709 vs 277/648, 5/709 vs 20/648). The detection rates of Escherichia coli, Klebsiella pneumoniae and Candida Albicans were increased (96/709 vs 37/648, 19/709 vs 7/648, 206/709 vs 112/648). Concerning the drug susceptibility test of Haemophilus influenzae, the sensitivity to ampicillin/sulbactam and amoxicillin/clavulanate increased after the pandemic by 5.55% (χ2=7.44, P < 0.05) and 13.39% (χ2=12.18, P < 0.05) respectively. The COVID-19 has been found to result in similar changes in the epidemiology of vulvovaginitis in terms of the age distribution, and proportion of causative pathogens. There was no significant difference between drug susceptibility tests for most strains except Haemophilus influenzae. [ FROM AUTHOR] Copyright of Journal of Pediatric & Adolescent Gynecology is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

6.
Infect Drug Resist ; 16: 1849-1863, 2023.
Article in English | MEDLINE | ID: covidwho-2288586

ABSTRACT

Objective: The aim of this study was to analyze the prevalence of vaginal flora and drug resistance in bacterial vaginitis among girls. Methods: A total of 3099 girls (0-10 years old) with vaginitis who visited the Beijing Children's Hospital from January 2020 to December 2021 were included in the present study. The clinical data, results of bacterial culture of vaginal secretions, and drug sensitivity reports of the subjects were collected and analyzed. Results: Of the 3099 girls with vaginitis, 399 girls had a positive bacterial culture of vaginal secretions. Nineteen types of bacteria were cultured from the vaginal secretions of these 399 girls, with a total of 419 strains. The top three infective bacteria were Haemophilus influenzae (127 strains, 30.31%), Staphylococcus aureus (66 strains, 15.75%), and Streptococcus agalactiae (32 strains, 7.64%). Additionally, 20 girls were simultaneously infected with two types of bacteria. Staphylococcus aureus, Group G Streptococcus, Haemophilus parainfluenzae, and Pseudomonas aeruginosa more frequently occurred in mixed infections. The number and bacterial detection rate among school-age girls were higher than those of preschool-age girls. We found seasonal variation in infection rates, and vaginitis among girls was higher in summer. Recurrence of vaginitis in girls was not related to the type of pathogenic bacteria in the infection. Drug sensitivity analyses showed that the resistance rates of clindamycin and erythromycin were generally high, 70-100%. After the coronavirus disease 2019 outbreak, the resistance rates of some antibiotics had decreased to varying degrees. Conclusion: Improving the understanding of vaginal flora and drug resistance in girls with vaginitis will facilitate the selection of highly effective and sensitive antibacterial drugs and reduce the production of drug-resistant strains.

7.
Egyptian Journal of Medical Human Genetics ; 24(1) (no pagination), 2023.
Article in English | EMBASE | ID: covidwho-2231698

ABSTRACT

Background: Tuberculosis (TB) is considered one of the most infectious diseases in the world. In this study, we intended to examine the epidemiology of tuberculosis by MIRU-VNTR to define the changes that occur in the transmission of tuberculosis in the region during the COVID-19 era. A total of 120 Mycobacterium tuberculosis isolates were collected from sputum samples of patients referred to East Azerbaijan Center TB from December 2020 to August 2021. Demographic information such as age, sex, place of birth, previous TB history, and relevant medical data was collected. The proportion method was performed for drug susceptibility testing, and the PCR-based MIRU-VNTR method was applied to identify molecular epidemiology relationships. Result(s): The isolates were collected from 78 male (65%) and 39 female (32.5%) Iranian patients and 3 (2.5%) Azerbaijani patients. Ninety-three distinct patterns were identified including 15 clustered patterns and 36 unique patterns. The largest cluster was composed of seven isolates. Furthermore, one cluster with 5 members, four clusters with 3 members, and nine clusters with 2 members. In MIRU-VNTR typing, 75 clusters belonged to the Tabriz region and just 3 to the Republic of Azerbaijan. All isolates were sensitive to rifampin, isoniazid, and ethambutol. Conclusion(s): Results of the current study showed COVID-19 pandemic had a direct effect on the transmission and diagnosis of tuberculosis. Less diagnosis and less clustering can indicate public controls and hygiene, and the use of masks had a direct effect on the transmission and diagnosis of tuberculosis. However, misidentification and less focus on other respiratory infections are expected during the pandemic. Studies on the co-infection of COVID-19 and tuberculosis and the role of mask and sanitization against TB are strongly recommended. Copyright © 2023, The Author(s).

8.
Pharmaceutical Technology ; 45(10):30-32, 2021.
Article in English | EMBASE | ID: covidwho-2169918
9.
Infektsionnye Bolezni ; 20(2):33-40, 2022.
Article in Russian | EMBASE | ID: covidwho-2044284

ABSTRACT

Severe course of COVID-19 in inpatients can be caused by a number of reasons, including viral and bacterial superinfections. Empirical use of antibiotics, as well as poor infectious control stimulate the emergence and spread of multidrug-resistant bacteria. Klebsiella pneumoniae is the most common carbapenemase-producing bacterial pathogen causing nosocomial infections. These strains became significantly widespread during the COVID-19 pandemic. Objective. To analyze phenotypic and genetic characteristics of K. pneumoniae strains as the dominant bacterial pathogen in severe COVID-19 patients in the intensive care unit. Patients and methods. This study included 38 COVID-19 patients (including 6 patients with severe disease) treated in the intensive care units of Moscow and Saint Petersburg hospitals for infectious diseases between July 2020 and December 2020. All patients signed an informed consent to participate in the study;patient data was anonymized. The following samples were collected: sputum, bronchoalveolar lavage, and nasopharyngeal swabs. We performed bacteriological identification of isolated bacterial strains, drug susceptibility testing, and whole genome sequencing of K. pneumoniae strains. Results. The majority of K. pneumoniae strains isolated from patients with severe COVID-19 contained clusters of aerobactin and enterobacterin genes. However, some of them (strains 90 and 124) also contained clusters of yersiniabactin genes. These genes are associated with high virulence and ability to form biofilms. The isolated strains belonged to four sequence types (ST874, ST395, ST147, ST15) that are characterized by high virulence and antibiotic resistance. These K. pneumoniae strains can be considered as one of the major causes of severe and lethal COVID-19. Conclusion. Our findings suggest that the detection rate of K. pneumoniae in COVID-19 patients increased from 30% to 70% during the pandemic. Phenotypic tests demonstrated that more than 80% of the strains were resistant to most antibiotics used in patients with complicated COVID-19. The combination of hypervirulence and antibiotic resistance is crucial for nosocomial transmission of these strains and their effect on the disease outcome. The emergence of hyper-resistant pathogens necessitates regular epidemiological monitoring and robust infection control in Russian hospitals, especially in intensive care units.

10.
Journal of Public Health in Africa ; 13:26-27, 2022.
Article in English | EMBASE | ID: covidwho-2006896

ABSTRACT

Introduction/ Background: Tuberculosis(TB) and COVID-19 pandemics are airbone diseases of public health threat globally. They also share some clinical signs and symptoms. We, therefore, took advantage of collected sputum samples at the early stage of COVID-19 outbreak in Ghana to conduct differential diagnoses of long standing endemic respiratory illness, particularly tuberculosis. Methods: Sputum samples collected through the enhanced national surveys from suspected COVID-19 patients and contact tracing cases were analyzed for TB. The sputum samples were processed using Cepheid's GeneXpert-MTB/RIF assay in pools of 4 samples to determine the presence of Mycobacterium tuberculosis complex. Positive pools were then decoupled and analyzed individually. Details of positive TB samples were forwarded to the NTP for appropriate case management. Chi-square-test, Fischer's exact test, or logistic regression where appropriate was used to test for statistical significance. P=values <0.05 were regarded as statistically significant at a 95% confidence level. All statistical analyses were carried out in Stata. Results: Seven-hundred and seventy-four sputum samples were analyzed for Mycobacterium tuberculosis in both suspected COVID-19 cases (679/774, 87.7%) and their contacts (95/774,12.3%). A total of 111(14.3%) were diagnosed with SARS CoV2 infection and six (0.8%) out of the 774 individuals tested positive for pulmonary tuberculosis: five(83.3%) males and one(16.7%) female. Drug susceptibility analysis identified 1(16.7%) rifampicin-resistant tuberculosis case. Out of the six TB positive cases, 2 (33.3%) tested positive for COVID- 19 indicating a coinfection. Stratifying by demography, three out of the six (50%) were from the Ayawaso-West-District. All positive cases received appropriate treatment at the respective sub district according to the national guidelines. Impact: Misdiagnosis of respiratory infections potentially leads to mismanagement with its concomitant clinical and public health implications. There is need for differential diagnosis of respiratory infections to advice proper clinical management. Conclusion: The discovery of TB positive patients among suspected COVID-19 patients harbingers the untold stories of undiagnosed TB in our communities. Our findings therefore highlight the need for differential diagnosis among COVID-19 suspected cases and regular active TB surveillance in TB endemic settings.

11.
EPMA J ; 12(3): 265-305, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1920184

ABSTRACT

Endothelin-1 (ET-1) is involved in the regulation of a myriad of processes highly relevant for physical and mental well-being; female and male health; in the modulation of senses, pain, stress reactions and drug sensitivity as well as healing processes, amongst others. Shifted ET-1 homeostasis may influence and predict the development and progression of suboptimal health conditions, metabolic impairments with cascading complications, ageing and related pathologies, cardiovascular diseases, neurodegenerative pathologies, aggressive malignancies, modulating, therefore, individual outcomes of both non-communicable and infectious diseases such as COVID-19. This article provides an in-depth analysis of the involvement of ET-1 and related regulatory pathways in physiological and pathophysiological processes and estimates its capacity as a predictor of ageing and related pathologies,a sensor of lifestyle quality and progression of suboptimal health conditions to diseases for their targeted preventionand as a potent target for cost-effective treatments tailored to the person.

12.
Lung India ; 39(SUPPL 1):S8-S9, 2022.
Article in English | EMBASE | ID: covidwho-1857236

ABSTRACT

Background: Amidst fight against COVID-19 pandemic, efforts to mitigate other communicable disease threatening public health including TB has taken a back step. Limited evidence exists about the change in prevalence of Pediatric Dr. TB post 2020. Objective: The study aimed to find out the change in prevalence of Pediatric DR TB pre and post 2020. Methods: Descriptive retrospective and prospective study. Pediatric Dr. TB was defined on the basis of Gene X pert/ line probe assay and/ or drug susceptibility testing (DST). Results: Prevalence of Pediatric Dr. TB in year 2018, 2019, 2020 and 2021 (January-September) were 17.4%, 15.1%, 18.4% and 16.6% respectively in the age group of 1-18 years. Majority (93.9%, 90.5%, 89.5%, 96.8%) had pulmonary TB. Cumulative prevalence of Pediatric Dr. TB for the 24 months of year 2018 & 2019 was 16.3% while it was 17.6% for the 21 months of year 2020 & 2021 (January-September). It reveals an increase of 4.1%. On extrapolating the prevalence rate of Dr. TB for the 9 months of year 2021, prevalence rate of Dr. TB by the end of year 2021 is expected to be 22.1%. Among Dr. TB, prevalence (%) of XDR TB;MDR TB;monoresistant TB for year 2018, 2019, 2020 & 2021 was (10.9,88.0,1.1), (5.1,92.8,2.1), (3.4,94.9,1.7) and (7.4,91.6,1.0) respectively. Conclusion: With this report of increase in prevalence of Pediatric Dr. TB, it has become the need of the hour to start focusing on TB vigorously and to take uncompromising relentless measures to achieve the country's vision to eliminate TB by 2025.

13.
Traditional Medicine Research ; 7(3), 2022.
Article in English | EMBASE | ID: covidwho-1822801

ABSTRACT

Coronaviruses exist widely in nature, can cause cross-species transmission, and pose serious threats to human and animal health. Over the past 20 years, coronaviruses have led to three major epidemics that have caused global panic, including severe acute respiratory syndrome, Middle East respiratory syndrome, and coronavirus disease-19. At present, coronavirus disease-19 not only spreads rapidly, but also mutates easily to escape host immune response, becoming more pathogenic. At present, there are no effective specific therapeutic drugs or vaccines. Drugs targeting severe acute respiratory syndrome coronavirus 2 and the host cell defense system that have been developed based on the structure and replication cycle of coronaviruses have a certain broad-spectrum antiviral effect;however, their efficacy still needs to be demonstrated in further clinical trials. Traditional Chinese medicine has an indispensable role in the ongoing response to coronavirus disease-19. Anti-virus treatment with traditional Chinese medicine has advantages such as broad-spectrum application, low toxicity and side effects, low susceptibility to drug resistance, and overall comprehensive regulation. Therefore, researches on effective components and mechanisms of action of the anti-viral effects of traditional Chinese medicine have increasingly gained attention. The present paper examines coronaviruses, specifically summarizing the genomes, replication mechanisms, and mutant strains. Afterward, the therapeutic effects and mechanisms of action of modern broad-spectrum anti-coronavirus drugs and traditional Chinese medicine are summarized. By considering the virus and the targets in the host comprehensively, in addition to the beneficial multi-target and multi-path antiviral effects of traditional Chinese medicines, this paper could guide the development of treatment strategies for broad-spectrum anti-coronavirus traditional Chinese medicines, and could facilitate the modernization and globalization of traditional Chinese medicine.

14.
Leukemia and Lymphoma ; 62(SUPPL 1):S70-S72, 2021.
Article in English | EMBASE | ID: covidwho-1747047

ABSTRACT

The BCL2-specific inhibitor, venetoclax, has demonstrated remarkable clinical activity in the treatment of chronic lymphocytic leukemia (CLL), either alone or in combination with CD20 antibodies. Nevertheless, patients who fail to attain a complete remission relapse, and require further therapy. Data on retreatment with venetoclax at disease progression are currently limited. Here, we report patterns of clonal evolution in an R/R CLL patient that has demonstrated successful retreatment. A 57 year-old lady with chemotherapy- refractory (FCR, RCHOP, high dose methyl prednisolone) TP53 mutant CLL was treated for 21 months with single-agent venetoclax in 2014 (NCT01889186). She attained an MRD positive CR with the resolution of massive lymphadenopathy and with only low-level (0.01%) disease in the bone marrow. However, she subsequently progressed rapidly with a lymphocyte doubling time of only 4 weeks and was treated with tirabrutinib and idelalisib in combination (NCT02968563) from December 2015 for 37 months before progressing December 2019. She was retreated with venetoclax and rituximab but died of COVID-19-induced respiratory failure in March 2020. To study the clonal evolution underlying these events, in vitro drug sensitivity assays and whole exome sequencing (WES) were used to study peripheral blood mononuclear (PBMC) and bone marrow samples. WES of sample 1 showed multiple mutations in CLL driver genes: SF3B1 R625C, KMT2C R4434Q, and TP53 R110L at VAFs of 37, 17, 35%, respectively. Mutations in other genes associated with CLL included FANCA L217F (47%) and SPEN P3402S (46%). At disease progression (sample 2), following venetoclax, there was the loss of detectable (WES at 100× coverage) TP53 R110L (with loss of 17p deletion on interphase FISH and analysis of copy number) but maintenance of SF3B1 R625C (44%), KMT2C R4434Q 30%), FANCA L217F (47%), and SPEN P3402S (55%). These data, therefore, suggest the TP53 mutant subclone was largely lost during therapy. No other mutations were identified as possible resistance mediators. There were no detectable BCL2 mutations. In vitro drug sensitivity testing to venetoclax showed an EC50 of 228nM (CLL EC50 usually 3-5 nM). The patient was then treated with the BTK inhibitor tirabrutinib in combination with idelalisib, with an excellent clinical response. After 10 months (sample 3, during the lymphocytosis induced by BTKi/PI3Kdi) SF3B1, KMT2C, FANCA, and SPEN mutations were detected at VAFs of 26, 30, 54, and 56%, respectively. At this point the TP53 R110L mutation was detected again at a VAF of 4%, indicating that stopping venetoclax allowed the clone to re-emerge. At this time, there were no detectable BTK or PLCG2 mutations. The patient then responded for a further 37 months before disease progression. At progression (sample 4), SF3B1, KMT2C, FANCA, and SPEN mutations were still detected in the peripheral blood at VAFs of 43, 31, 48, and 50%, respectively. The VAF of the TP53 R110L mutation had increased to 33%. Additionally, a BTK mutation (T474I) was identified with a VAF of 16%. Identical results were obtained using a bone marrow sample. Now, however, in vitro analysis demonstrated a high degree of sensitivity to venetoclax (EC50 0.72 nM). The patient was, therefore, retreated with venetoclax and rituximab. At the point of re-treatment, VAFs were maintained, with the emergence of a new subclonal NOTCH1 G1001D mutation at a VAF of 3%. The patient, unfortunately, died 4 months after commencing therapy due to COVID-19 associated pneumonitis. A full disease reassessment was not made but the patient's blood count had normalized, with rapid clearance of CLL cells from the peripheral blood, recovery of normal hematological indices, resolution of splenomegaly, and partial resolution of lymphadenopathy on CT scan. These data, therefore, suggest that re-treatment with venetoclax in CLL can be successful. Regaining sensitivity to venetoclax may largely depend on shifting clonal dynamics. The molecular basis of venetoclax resistance in this case is currently being investigated. A so in this particular case, it appears that the TP53 mutant subclone was more sensitive to BCL2 inhibition than TP53 wild-type subclone(s), and was largely eliminated by initial venetoclax treatment, contrasting with recently published data suggesting resistance of TP53 mutant hematological malignancies to BCL2 inhibition due to increased thresholds for BAX/BAK activation (Thijssen et al., 2021).

15.
Brief Bioinform ; 23(1)2022 01 17.
Article in English | MEDLINE | ID: covidwho-1393161

ABSTRACT

Chemosensitivity assays are commonly used for preclinical drug discovery and clinical trial optimization. However, data from independent assays are often discordant, largely attributed to uncharacterized variation in the experimental materials and protocols. We report here the launching of Minimal Information for Chemosensitivity Assays (MICHA), accessed via https://micha-protocol.org. Distinguished from existing efforts that are often lacking support from data integration tools, MICHA can automatically extract publicly available information to facilitate the assay annotation including: 1) compounds, 2) samples, 3) reagents and 4) data processing methods. For example, MICHA provides an integrative web server and database to obtain compound annotation including chemical structures, targets and disease indications. In addition, the annotation of cell line samples, assay protocols and literature references can be greatly eased by retrieving manually curated catalogues. Once the annotation is complete, MICHA can export a report that conforms to the FAIR principle (Findable, Accessible, Interoperable and Reusable) of drug screening studies. To consolidate the utility of MICHA, we provide FAIRified protocols from five major cancer drug screening studies as well as six recently conducted COVID-19 studies. With the MICHA web server and database, we envisage a wider adoption of a community-driven effort to improve the open access of drug sensitivity assays.

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