Search

The paper focuses on knowledge generation, a topic frequently overlooked in the traditional debates in epistemology and philosophy of science. We focus on investigation as the primary process generating knowledge and its products. Investigation is taken as a generalization of the research process that includes similar knowledge-generating practices in aboriginal communities. To characterize the complexity of investigation processes and their products we go beyond traditional epistemological characterization of knowledge in terms of mental states and turn to the concept of routine. Investigation processes share a common symbolic representation form which we call here a knowledge thread. The dynamics of the knowledge thread may be characterized by two intertwined tiers: cognitive and institutional. Using examples from our previous studies, especially on the recent discovery of microRNAs in molecular biology, we illustrate the dynamics of threads and claim that it is susceptible to the social network analysis which, however, requires insightful applications and sound interpretation of the results. Such an interpretation, as we suggest, may further be elaborated on the grounds of anthropological theories of distributed agency and distributed cognition.

Background: The recent development of new antileukemic therapies (anti-CD20 monoclonal antibodies, Bruton tyrosine kinase inhbitors, phosphoinositide 3-kinase inhibitors, and B-cell lymyphoma-2 antagonists) improved the progression-free survival (PFS) compared with selected standard regimens in clinical trials for patients with relapsed/refractory chronic lymphocytic leukemia (CLL). Unfortunately, the relative efficacy of all possible therapeutic options remains unknown because there is no direct evidence for all possible comparisons. Objectives: We aimed to compare the efficacy and safety of novel agents, chemotherapy, and immunotherapy using a Bayesian network meta-analysis (NMA). Design: Systematic literature review with Bayesian NMA. Methods: An extensive systematic literature review of randomized clinical trials for relapsed/refractory CLL was performed. We searched for articles indexed in medical databases (MEDLINE, Embase, The Cochrane Library) and gray literature that could be further implemented into the Bayesian NMA. Results: The systematic search identified 15 randomized trials that formed networks comparing PFS, overall survival (OS), overall response rates, and serious adverse events. Our study showed that all regimens containing novel agents significantly prolonged PFS compared with standard chemoimmunotherapy and immunotherapy. Among targeted drugs, venetoclax (VEN) + rituximab (RTX) had comparable efficacy in terms of PFS to zanubrutinib (ZAN) [hazard ratio (95% credible interval), 1.10 (0.59–2.08)], acalabrutinib (ACA) [0.78 (0.47–1.30)], ibrutinib (IBR) monotherapy [0.72 (0.41–1.27)], and other IBR-based regimens. ZAN was superior to IBR monotherapy [0.65 (0.49–0.86)] but not to ACA [0.71 (0.49–1.02)]. There were no significant differences in OS in any of the above comparisons. Conclusion: All novel therapies have better efficacy than chemoimmunotherapy and immunotherapy regimens. Among novel agents, the relative efficacy of VEN + RTX was similar to all BTKi, while ZAN was superior to IBR and comparable to ACA. Trial registration: PROSPERO CRD42022304330. [ABSTRACT FROM AUTHOR]

The aim of this paper is to examine a complex pattern of mutual interdependence between Unified Growth Theory (subroutine) and the evolution of the entire field of economic growth theories (main routine) from a philosophical and methodological perspective. The analysis utilises the recently introduced concept of research routine (and respectively, subroutine) aimed at an explanation of the evolution of scientific research. The study identifies the influence of the subroutine (and its specific concept of demographic transition) on the core concepts of the main routine: human capital, population growth and learning. The results are based on network analyses of extensive bibliometric evidence from Scopus and the Web of Knowledge.

Of the three main areas of science studies that emerged after WWII (Kawalec, 2018), namely social studies of science, economics of knowledge and scientometrics, it was the latter that gained particular prominence in science policy around the 1990’s with the advent of New Public Management (Pollitt, Thiel, & Homburg, 2007). One of its focal areas has been identification of emerging topics in science. They are incessantly assumed to be an outcome of a simple cumulative progress of scientific knowledge (Price, 1976; Merton, 1988; Bird, 2007; Fochler, 2016). In my paper I challenge this assumption of simple cumulativity and argue that the emergence of breakthrough topics in science is preceded by a sequence of transformation phases. Using the example of “microRNA&cancer” as an emergent topic identified by a quantitative analysis of a large dataset of publications (Small et al. 2014) I demonstrate that the proposed analysis of transformation phases complements big data quantitative analyses with theoretical understanding of the dynamics mechanism and, in effect, leads to a more adequate characterization of the topic itself as well as a more precise identification of the source publications. While the proposed method uses a more complex (meso-level) unit of analysis (i.e. “research routines”) instead of citations and co-occurrence of single publications (micro-level), it integrates quantitative with qualitative analyses.

Objective: This study aimed to compare the safety profile of tyrosine kinase inhibitors (TKIs) approved for use as monotherapy or combination therapy for the first-line treatment of adult patients with metastatic clear cell renal cell carcinoma (RCC). Methods: A systematic review with frequentist network meta-analysis (NMA) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included randomized controlled trials (RCTs) investigating the use of: cabozantinib, pazopanib, sorafenib, sunitinib, tivozanib, cabozantinib + nivolumab, lenvatinib + pembrolizumab, axitinib + avelumab, and axitinib + pembrolizumab in previously untreated adult patients with metastatic clear cell RCC. Eligible studies were identified by two reviewers in MEDLINE (via PubMed), EMBASE, and Cochrane Library. The risk of bias for RCTs was assessed using the Cochrane Collaboration tool. The P score was used to determine the treatment ranking. The mean probability of an event along with the relative measures of the NMA was considered with the treatment rankings. Results: A total of 13 RCTs were included in the systematic review and NMA. Sorafenib and tivozanib used as monotherapy were the best treatment options. Sorafenib achieved the highest P score for treatment discontinuation due to adverse events (AEs), fatigue, nausea, vomiting of any grade, and hypertension of any grade or grade ≥3. Tivozanib achieved the highest P score for AEs, grade ≥3 AEs, dose modifications due to AEs, and grade ≥3 diarrhea. Sunitinib was the best treatment option in terms of diarrhea and dysphonia of any grade, while cabozantinib, pazopanib, and axitinib + pembrolizumab-in terms of grade ≥3 fatigue, nausea, and vomiting. TKIs used in combination were shown to have a poorer safety profile than those used as monotherapy. Lenvatinib + pembrolizumab was considered the worst option in terms of any AEs, grade ≥3 AEs, treatment discontinuation due to AEs, dose modifications due to AEs, fatigue of any grade, nausea, vomiting, and grade ≥3 nausea. Axitinib + avelumab was the worst treatment option in terms of dysphonia, grade ≥3 diarrhea, and hypertension, while cabozantinib + nivolumab was the worst option in terms of grade ≥3 vomiting. Interestingly, among the other safety endpoints, cabozantinib monotherapy had the lowest P score for diarrhea and hypertension of any grade. Conclusion: The general safety profile, including common AEs, is better when TKIs are used as monotherapy vs. in combination with immunological agents. To confirm these findings, further research is needed, including large RCTs. [ABSTRACT FROM AUTHOR]

Pathologies of the pineal gland region are frequently encountered in daily neurosurgical practice. It is important to remember that, besides usually asymptomatic pineal gland cysts, neoplasms of a different origin may also occur in this region. The rarity of the most dangerous lesions - pineal gland apoplexy and pineal tumors - might cause problems with proper diagnosis and treatment. Their occurrence is commonly associated with symptomatic hydrocephalus caused by aqueductal stenosis. Currently, in such cases, endoscopic procedures, including endoscopic third ventriculostomy (ETV), are commonly and widely chosen as treatment options. Endoscopic procedures not only enable decompression of hydrocephalus but also further diagnosis of its cause. Herein, we present 3 case reports of endoscopic treatment with ETV performed in patients with hydrocephalus related to pineal region pathologies. [ABSTRACT FROM AUTHOR]