Narrowing the Theory’s or Study’s Scope May Increase Practical Relevance

Numerous articles in top IS journals note as a limitation and lack of generalizability that their findings are specific to a certain type of technology, culture, and so on. We argue that this generalizability concern is about limited scope (e.g., explanatory breadth). The IS literature notes this preference for generalizability as a characteristic of good science and it is sometimes confused with statistical generalizability. We argue that such generalizability can be in conflict with explanation or prediction accuracy. An increase in scope (e.g., increasing explanatory breadth) can decrease explanation or prediction accuracy. Thus, in sciences such as cancer research, where explanation and prediction accuracy are highly valued, the cancer accounts (generally speaking) have become increasingly narrower (and less generalizable). IS thinking has not yet benefitted from these considerations. Whether generalizability is valued should be linked with the research aims. If the aim is practical applicability through explanation or prediction accuracy, then “limited” generalizability could be a strength rather than a weakness

Mechanistic Explanations and Deliberate Misrepresentations

The philosophy of mechanisms has developed rapidly during the last 30 years. As mechanisms-based explanations (MBEs) are often seen as an alternative to nomological, law-based explanations, MBEs could be relevant in IS. We begin by offering a short history of mechanistic philosophy and set out to clarify the contemporary landscape. We then suggest that mechanistic models provide an alternative to variance and process models in IS. Finally, we highlight how MBEs typically contain deliberate misrepresentations. Although MBEs have recently been advocated as critical realist (CR) accounts in IS, idealizations (deliberate misrepresentations) seem to violate some fundamental tenets of CR and research method principles for CR. Idealizations in MBEs, therefore, may risk being regarded as flawed in IS. If it turns out that CR cannot account for idealizations, naturalism can, and it does so without extra-philosophical baggage

A Translational Approach Towards More Cost-Effective Lung Cancer Treatments

Lung cancer, globally the second most common cancer, causes 1.8 million deaths annually with 2 million new cases. It\u27s also one of Finland\u27s deadliest cancers. Chemotherapeutic agents, targeted drugs and radiation therapy have been the mainstay in oncologic treatment for lung cancer patients for decades. Checkpoint inhibitors (e.g. nivolumab, pembrolizumab, atezolizumab) have changed the landscape also in lung cancer. These drugs awake patients own immune system to attack cancer cells. These drugs are widely used in different cancers and they have efficacy also in lung cancer, but only in a minority of patients. Checkpoint inhibitors also induce autoimmune side effects. Majority are mild, but often irreversible, such as hypothyroidism or diabetes. Life-threatening and fatal adverse events are rare, but they also occur. Neither treatment response nor adverse effects can be predicted individually. In Finland, these drugs cost app. 10 000€ per month per one patient increasing the economic burden to our society. Thus, we need better understanding of lung cancer biology to be able to offer individual therapies in patient-centered manner, but also within the limits of the carrying capacity of our society. In 10-15% of lung adenocarcinomas there is a driver EGFR-mutation. Checkpoint inhibitor are ineffective in this type. However, EGFR pathway targeted agents, such as osimertinib, deliver often sustainable responses, but unfortunately resistance mechanism arise in this subtype as well. We need to better understand also the resistance mechanism in EGFR mutated subtypes to better tailor the best optimal treatment sequences to our patients. Translational research, that combines the basic science of lung cancer biology with patient characteristics and treatment outcomes, is a crucial tool in responding to these demands. Tumor microenvironment plays an important role in carcinogenesis, as well as in treatment response, especially acidic environment is immunosuppressive and promotes cancer cell survival. Mucins are a large family of transmembrane glycoproteins expressed on epithelial membranes, including airways. They form the protective immunogenic glycocalyx against microbes as well as pollutants, e.g., carcinogens in tobacco smoke. They are involved in lung cancer formation and in drug resistance forming an important compartment of the tumor microenvironment protecting cancer cells from immune system. Mucins function also as a signaling platform orchestrating cell proliferation, migration and metastasis. Our hypothesis is that dysfunctional regulation and expression of mucin 13, a member of mucin family, provides an immunosuppressive environment and associates with poor response to checkpoint inhibition and poor survival. Mucin 13 is also involved in EGFR signaling. Analyzing mucin 13 with advanced biomolecular techniques using tumor and serum samples of Finnish lung cancer patients combined with clinical characteristics and treatment outcomes will elucidate the biological mechanisms and improve patient selection for optimal treatments

Spiritual well-being correlates with quality of life of both cancer and non-cancer patients in palliative care - further validation of EORTC QLQ-SWB32 in Finnish

Publisher Copyright: © 2023. The Author(s).BACKGROUND: The European Organisation for Research and Treatment of Cancer (EORTC) has developed the Spiritual Well-being Questionnaire (EORTC QLQ-SWB32), a measure of spiritual well-being validated with people receiving palliative care for cancer, although its usefulness is not restricted to that population. We aimed to translate and validate this tool in Finnish and to study the relationship between spiritual well-being (SWB) and quality of life (QOL). METHODS: A Finnish translation was produced according to the guidelines of EORTC and included forward- and back-translations. Face, content, construct and convergence/divergence validity and reliability were studied in a prospective manner. QOL was assessed with EORTC QLQ-C30 and 15D questionnaires. Sixteen individuals participated in the pilot testing. 101 cancer patients drawn from oncology units, and 89 patients with other chronic diseases drawn from religious communities in different parts of the country participated in the validation stage. Retest was obtained from 16 individuals (8 cancer and 8 non-cancer patients). Inclusion criteria included patients with either a well-defined palliative care plan, or who would benefit from palliative care, as well as the capacity to understand and communicate in Finnish. RESULTS: The translation appeared understandable and acceptable. Factorial analysis identified four scoring scales with high Cronbach alfa values: Relationship with Self (0.73), Relationship with Others (0.84), Relationship with Something Greater (0.82), Existential (0.81), and, additionally, a scale on Relationship with God (0.85). There was a significant correlation between SWB and QOL in all participants. CONCLUSIONS: The Finnish translation of EORTC QLQ-SWB32 is a valid and reliable measure both for research and clinical practice. SWB is correlated with QOL in cancer and non-cancer patients undergoing palliative care or who are eligible for it.Peer reviewe

Rapid diagnosis and initiation of treatment has a crucial role in the prognosis of primary central nervous system lymphoma

Non peer reviewe

Real-world Data : MCL2 Protocol Demonstrates Excellent Treatment Results among Patients with Mantle Cell Lymphoma Not Fulfilling the Original Trial Inclusion Criteria

Non peer reviewe

Survival of patients with mantle cell lymphoma in the rituximab era : Retrospective binational analysis between 2000 and 2020

Mantle cell lymphoma (MCL) is a rare peripheral B-cell lymphoma characterised by eventual relapse and progression towards a more aggressive disease biology. With the introduction of rituximab- and cytarabine-based immunochemotherapy regimens, the prognosis of the disease has changed dramatically over the last two decades. To assess the real-world survival of patients with MCL, we used a population-based cohort of 564 patients with MCL who were diagnosed and treated between 2000 and 2020. Patient data were collected from seven Finnish treatment centres and one Spanish treatment centre. For the entire patient population, we report a 2-year overall survival (OS) rate of 77%, a 5-year OS of 58%, and a 10-year OS of 32%. The estimated median OS was 80 months after diagnosis. MCL is associated with increased mortality across the entire patient population. Additionally, we assessed the survival of patients after MCL relapse with the aim of establishing a cut-off point of prognostic significance. Based on our statistical analysis of survival after the first relapse, disease progression within 24 months of the initial diagnosis should be considered as a strong indicator of poor prognosis.publishedVersionPeer reviewe

PDZ-LIM domain proteins and α-actinin at the muscle Z-disk

Abstract The Z-disk is a sophisticated structure that connects adjacent sarcomeres in striated muscle myofibrils. α-Actinin provides strength to the Z-disks by crosslinking the actin filaments of adjacent sarcomeres. α-Actinin is an antiparallel homodimer, composed of an N-terminal actin binding domain (ABD), the central rod domain, and two pairs of C-terminal EF-hands. The PDZ-LIM domain proteins interact with α-actinin at the Z-disk. Of these proteins, only the actinin-associated LIM protein (ALP), Z-band alternatively spliced PDZ-containing protein (ZASP/Cypher) and C-terminal LIM protein (CLP36) have a ZASP/Cypher-like (ZM) motif consisting of 26-27 conserved residues in the internal region between the PDZ and LIM domains. The aim of this work was to understand the molecular interplay between the ZM-motif containing members of the PDZ-LIM proteins and α-actinin. To unveil the biological relevance of the interaction between the PDZ-LIM proteins and α-actinin, naturally occurring human ZASP/Cypher mutations were analyzed. Two interaction sites were found between ALP, CLP36 and α-actinin using recombinant purified proteins in surface plasmon resonance (SPR) analysis. The PDZ domain of ALP and CLP36 recognized the C-terminus of α-actinin, whereas the internal regions bound to the rod domain. Further characterization showed that the ALP internal region adopts and extended conformation when interacting with α-actinin and that the ZM-motif partly mediated the interaction, but did not define the entire interaction area. ZASP/Cypher also interacted and competed with ALP in binding to the rod domain. The internal fragments containing the ZM-motif were important for co-localization of ALP and ZASP/Cypher with α-actinin at the Z-disks and on stress fibers. The absence of ALP and ZASP/Cypher in focal contacts indicates that other interacting molecules, for instance vinculin and integrin, may compete in binding to the rod in these areas or additional proteins are required in targeting to these locations. The co-localization of the ZASP/Cypher with α-actinin could be released by disrupting the stress fibers leading to an accumulation of α-actinin in the cell periphery, whereas ZASP/Cypher was not in these areas. This suggests that an intact cytoskeleton is important for ZASP/Cypher interaction with α-actinin. Earlier studies have shown that mutations in the ZASP/Cypher internal region are associated with muscular diseases. These mutations, however, did not affect ZASP/Cypher co-localization with α-actinin or the stability of ZASP/Cypher proteins. The Z-disk possesses a stretch sensor, which is involved in triggering hypertrophic growth as a compensatory mechanism to increased workloads. α-Actinin is a docking site of molecules that are involved in hypertrophic signaling cascades mediated by calsarcin-calcineurin and protein kinase C (PKC) isoforms. The internal interaction site may be involved in targeting PKCs, which bind to the LIM domains of ZASP/Cypher, to the Z-disks. The similar location of the internal interaction site with calsarcin on the rod suggests that ZASP/Cypher, ALP and CLP36 may regulate calsarcin-mediated hypertrophic signaling