Time-Tested Strategies in Modern Context: A Bibliometric Study of Chemotherapy's Continued Importance in Colorectal Cancer Treatment.

In the landscape of colorectal cancer treatment, classical chemotherapeutic agents such as 5-fluorouracil, capecitabine, irinotecan, oxaliplatin, trifluridine, and tipiracil have historically played a pivotal role. This study presents a comprehensive bibliometric analysis of the top 100 most influential articles focusing on these classic chemotherapy drugs in the management of colorectal cancer. With this, we shed light on their current importance, despite the emergence of new therapeutic targets and treatments in the field of oncology. Systematically evaluating research outputs, this analysis reveals a prevalence of co-authorship among institutions, countries (led by the United States, China, and Europe), and researchers highlighting the global and collaborative nature of efforts in research, utilization, and development of these drugs. Three thematic axes lead the research: pharmacogenetics, the development of new pharmaceutical forms, and the use of adjuvants. This research serves as a foundation for future endeavors, aiding researchers, clinicians, and policymakers in making informed decisions about the direction of research and development in the dynamic field of colorectal cancer therapy.

Detailed stratified GWAS analysis for severe COVID-19 in four European populations.

Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a ~0.9-Mb inversion polymorphism that creates two highly differentiated haplotypes and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative including non-Caucasian individuals, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.

A Bibliometric Evaluation of the Top 100 Cited Dimethyl Fumarate Articles.

Dimethyl fumarate is a cytoprotective and immunomodulatory drug used in the treatment of multiple sclerosis. We performed a bibliometric study examining the characteristics and trends of the top 100 cited articles that include dimethyl fumarate in the title. On 21 September 2020 we carried out an electronic search in the Web of Science (WOS), seeking articles that include the following terms within the title: dimethyl fumarate, BG-12, or Tecfidera. To focus our investigation on original research, we refined the search to include only articles, early access, others, case report, and clinical trials. We obtained a total of 1115 items, which were cited 7169 times, had a citation density of 6.43 citations/item, and an h-index of 40. Around 2010, there was a jump in the number of published articles per year, rising from 5 articles/year up to 12 articles/year. We sorted all the items by the number of citations and selected the top 100 most cited (T100). The T100 had 4164 citations, with a density of 37 citations/year and contained 16 classic research articles. They were published between 1961 and 2018; the years 2010-2018 amassed nearly 80% of the T100. We noted 17 research areas with articles in the T100. Of these, the number one ranking went to neurosciences/neurology with 39 articles, and chemistry ranked second on the T100 list with 14 items. We noticed that the percentage of articles belonging to different journals changed depending on the time period. Chemistry held the highest number of papers during 1961-2000, while pharmacology andneurosciences/neurology led the 2001-2018 interval. A total of 478 authors from 145 institutions and 25 countries were included in the T100 ranking. The paper by Gold R et al. was the most successful with 14 articles, 1.823 citations and a density of 140.23 citations/year. The biotechnological company Biogen led the T100 list with 20 articles. With 59 published articles, the USA was the leading country in publications. We concluded that this study analyzed the use of and research on dimethyl fumarate from a different perspective, which will allow the readership (expert or not) to understand the relevance of classic and recent literature on this topic.

A descriptive and validation study of a predictive model of severity of SARS-COV-2 infection.

Objectives: The strain the SARS-COV-2 pandemic is putting on hospitals requires that predictive values are identified for a rapid triage and management of patients at a higher risk of developing severe COVID-19. We developed and validated a prognostic model of COVID-19 severity. Methods: A descriptive, comparative study of patients with positive vs. negative PCR-RT for SARS-COV-2 and of patients who developed moderate vs. severe COVID-19 was conducted. The model was built based on analytical and demographic data and comorbidities of patients seen in an Emergency Department with symptoms consistent with COVID-19. A logistic regression model was designed from data of the COVID-19-positive cohort. Results: The sample was composed of 410 COVID-positive patients (303 with moderate disease and 107 with severe disease) and 81 COVID-negative patients. The predictive variables identified included lactate dehydrogenase, C-reactive protein, total proteins, urea, and platelets. Internal calibration showed an area under the ROC curve (AUC) of 0.88 (CI 95%: 0.85-0.92), with a rate of correct classifications of 85.2% for a cut-off value of 0.5. External validation (100 patients) yielded an AUC of 0.79 (95% CI: 0.71-0.89), with a rate of correct classifications of 73%. Conclusions: The predictive model identifies patients at a higher risk of developing severe COVID-19 at Emergency Department, with a first blood test and common parameters used in a clinical laboratory. This model may be a valuable tool for clinical planning and decision-making.

A bibliometric evaluation of the top 100 cited natalizumab articles.

Natalizumab is being used in recurrent multiple sclerosis despite its history of market withdrawal due to lethal cases. We have carried out a bibliometric analysis of this drug from 1999 to February 2020 in order to assess the real impact of the use natalizumab with the goal to identify the key articles that sustain the current knowledge on the therapeutic possibilities of this compound. We have extracted from the Web of Science the top 100 most cited records (T100) and tabulated data on the journal, authors, publication year, number of citations, countries and institutions of publication, T100-records, citation density and citations per record of the works. The 100 most cited articles were selected from a total of 32,507 citations out of 2817 publications with an h-number of 74, 11.54 citations/publication, and a density of 1544.79 citations/year. Citations ranged from 63 of the paper placed in the 100th position (T100) to 1940 of the paper in the first position (T1). T2 was cited 888 times, and the difference in the number of citations between T1 and T2 was higher than that between T2 and T10. T1, T2 and T3 are clinical trials. When articles are arranged by institution and nationality having more than 10 T100 articles, biotechnology company Biogen and the USA, respectively, lead the ranking, but we also find that 8 out of 10 are academic European institutions. A co-authorship analysis reveals an intense collaborative activity between countries and institutions. We conclude that the clinical and academic communities have shown a sustained interest in natalizumab for the therapy of recurrent multiple sclerosis over the last 20 years.

Genomewide Association Study of Severe Covid-19 with Respiratory Failure.

BACKGROUND: There is considerable variation in disease behavior among patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19). Genomewide association analysis may allow for the identification of potential genetic factors involved in the development of Covid-19. METHODS: We conducted a genomewide association study involving 1980 patients with Covid-19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe. After quality control and the exclusion of population outliers, 835 patients and 1255 control participants from Italy and 775 patients and 950 control participants from Spain were included in the final analysis. In total, we analyzed 8,582,968 single-nucleotide polymorphisms and conducted a meta-analysis of the two case-control panels. RESULTS: We detected cross-replicating associations with rs11385942 at locus 3p21.31 and with rs657152 at locus 9q34.2, which were significant at the genomewide level (P<5×10-8) in the meta-analysis of the two case-control panels (odds ratio, 1.77; 95% confidence interval [CI], 1.48 to 2.11; P = 1.15×10-10; and odds ratio, 1.32; 95% CI, 1.20 to 1.47; P = 4.95×10-8, respectively). At locus 3p21.31, the association signal spanned the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1. The association signal at locus 9q34.2 coincided with the ABO blood group locus; in this cohort, a blood-group-specific analysis showed a higher risk in blood group A than in other blood groups (odds ratio, 1.45; 95% CI, 1.20 to 1.75; P = 1.48×10-4) and a protective effect in blood group O as compared with other blood groups (odds ratio, 0.65; 95% CI, 0.53 to 0.79; P = 1.06×10-5). CONCLUSIONS: We identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system. (Funded by Stein Erik Hagen and others.).