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3. Light Curve for Type Ia Supernova Candidate AT 2018we

Author

Willamo, T., Ala-Könni, J., Arvo, J., Pippa, I., and Salo, T.

Subjects
Astrophysics - Solar and Stellar Astrophysics, Astrophysics - High Energy Astrophysical Phenomena
Abstract

We present photometric follow-up observations of the supernova candidate AT 2018we, which was discovered by the Gaia photometric alerts system. The first Gaia detection of the object was made Feb 12, 2018. Our observations, made in Cousins R and Johnson B band, range from Feb 20 to May 5, 2018. From our observations, we have constructed a light curve, which supports the initial prediction of type Ia, included in the Gaia alert. Based on this classification, we have also estimated the distance to its assumed host galaxy, which was found to be around 43 Mpc., Comment: 9 pages, 3 figures, 4 tables; typos corrected in section 1

Published
2018

4. Entire Dirichlet series with monotonous coefficients and logarithmic h-measure

Author

Panchuk, S. I., Salo, T. M., and Skaskiv, O. B.

Subjects
Mathematics - Complex Variables, 30B20, 30D20
Abstract

Let $F$ be an entire function represented by absolutely convergent for all $z\in\mathbb{C}$ Dirichlet series of the form $ F(z) = \sum\nolimits_{n=0}^{+\infty} a_{n}e^{z\lambda_{n}},$\ where a sequence $(\lambda_n)$ such that $\lambda_n\in\mathbb{R}\ \ (n\geq0)$, $\lambda_n\not=\lambda_k$ for any $n\not=k$ and $(\forall n\geq 0):\ 0\leq\lambda_n<\beta:=\sup\{\lambda_j:\ j\geq0\}\leq +\infty.$ {Let $h$ be non-decrease positive continuous function on $[0,+\infty)$ and $\Phi$ increase positive continuous on $[0,+\infty)$ function.} In this paper we {find} the condition {on} $(\mu_n)$ and $(\lambda_n)$ {such that} the relation $F(x+iy)=(1+o(1))a_{\nu(x, F)}e^{(x+iy)\lambda_{\nu(x, F)}} $ holds as $x\to +\infty$\ outside some set $E$ of finite logarithmic $h$-measure uniformly in $y\in\mathbb{R}$.

Published
2015

5. The minimum modulus of gap power series and h-measure of exceptional sets

Author

Salo, T. M. and Skaskiv, O. B.

Subjects
Mathematics - Complex Variables
Abstract

For entire Dirichlet series of the form $F(z)=\sum\limits_{n=0}^{+\infty} a_{n}e^{z\lambda_n},\ 0\le\lambda_n\uparrow+\infty\ (n\to+\infty)$, we establish conditions under which the relation $$ F(x+iy)=(1+o(1))a_{\nu(x,F)}e^{(x+iy)\lambda_{\nu(x,F)}} $$ is true as $x\to+\infty$ outside some set $E$ such that $\text{ h-meas }(E)=\int_{E}dh(x)<+\infty$ uniformly in $y\in\Bbb{R}$, where $h(x)$ is positive continuous function increasing to $+\infty$ on $[0,+\infty)$ with non-decreasing to $+\infty$ derivative.

Published
2015

6. COMPOSITION OF ENTIRE FUNCTION AND ANALYTIC FUNCTIONS IN THE UNIT BALL WITH A VANISHED GRADIENT.

Author

Bandura, A. I., Salo, T. M., and Skaskiv, O. B.

Subjects
MATHEMATICAL inequalities, MATHEMATICAL analysis, NUMERICAL analysis, ANALYTIC functions, VECTOR-valued measures
Abstract

The composition H(z) = f(Φ(z)) is studied, where f is an entire function of a single complex variable and Φ is an analytic function in the n-dimensional unit ball Bn, n ≥ 2, with a vanished gradient. We found conditions by the function Φ providing boundedness of the L-index in joint variables for the function H, if the function f has bounded l-index for some positive continuous function l and L(w) = l(Φ(w))(max{1, |Φ′ w1 (w)|}, . . ., max{1, |Φ′ wn(w)|}): Bn → Rn +. Such a constructed vector-valued function L: Bn → Rn + allows us to consider a function Φ with a nonempty zero set for its gradient. The obtained results complement earlier published results with grad Φ(w) = ∇Φ(z) = (∂Φ(w) ∂w1, . . ., ∂Φ(w) ∂wn) ̸= 0. We prove the following statement (Theorem 3): Suppose that the function l: C → R+ satisfies some condition for the regularity of behavior. Let g: C → C be an entire function of bounded l-index N(g, l), and Φ: Bn → C be an analytic function such that the vector-valued function L(w): Bn → Rn + defined above also satisfies some conditions for regularity of behavior. If there exists C2 ≥ 1 such that for all w ∈ Bn and for all J ∈ Zn + \ {0} with ∥J∥ ≤ N(g, l) + 1, one has |Φ(J)(w)| ≤ C2(l(Φ(w)))1/(N(g,l)+1)(|∇|Φ(w))J, then the analytic function H(w) = g(Φ(w)): Bn → C has bounded L-index in joint variables. [ABSTRACT FROM AUTHOR]

Published
2024
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7. The Past, Present, and Future of the Brain Imaging Data Structure (BIDS)

Author

Poldrack, R, Markiewicz, C, Appelhoff, S, Ashar, Y, Auer, T, Baillet, S, Bansal, S, Beltrachini, L, Benar, C, Bertazzoli, G, Bhogawar, S, Blair, R, Bortoletto, M, Boudreau, M, Brooks, T, Calhoun, V, Castelli, F, Clement, P, Cohen, A, Cohen-Adad, J, D'Ambrosio, S, de Hollander, G, de la Iglesia-Vayá, M, de la Vega, A, Delorme, A, Devinsky, O, Draschkow, D, Duff, E, Dupre, E, Earl, E, Esteban, O, Feingold, F, Flandin, G, Galassi, A, Gallitto, G, Ganz, M, Gau, R, Gholam, J, Ghosh, S, Giacomel, A, Gillman, A, Gleeson, P, Gramfort, A, Guay, S, Guidali, G, Halchenko, Y, Handwerker, D, Hardcastle, N, Herholz, P, Hermes, D, Honey, C, Innis, R, Ioanas, H, Jahn, A, Karakuzu, A, Keator, D, Kiar, G, Kincses, B, Laird, A, Lau, J, Lazari, A, Legarreta, J, Li, A, Li, X, Love, B, Lu, H, Marcantoni, E, Maumet, C, Mazzamuto, G, Meisler, S, Mikkelsen, M, Mutsaerts, H, Nichols, T, Nikolaidis, A, Nilsonne, G, Niso, G, Norgaard, M, Okell, T, Oostenveld, R, Ort, E, Park, P, Pawlik, M, Pernet, C, Pestilli, F, Petr, J, Phillips, C, Poline, J, Pollonini, L, Raamana, P, Ritter, P, Rizzo, G, Robbins, K, Rockhill, A, Rogers, C, Rokem, A, Rorden, C, Routier, A, Saborit-Torres, J, Salo, T, Schirner, M, Smith, R, Spisak, T, Sprenger, J, Swann, N, Szinte, M, Takerkart, S, Thirion, B, Thomas, A, Torabian, S, Varoquaux, G, Voytek, B, Welzel, J, Wilson, M, Yarkoni, T, Gorgolewski, K, Poldrack, Russell A., Markiewicz, Christopher J., Appelhoff, Stefan, Ashar, Yoni K., Auer, Tibor, Baillet, Sylvain, Bansal, Shashank, Beltrachini, Leandro, Benar, Christian G., Bertazzoli, Giacomo, Bhogawar, Suyash, Blair, Ross W., Bortoletto, Marta, Boudreau, Mathieu, Brooks, Teon L., Calhoun, Vince D., Castelli, Filippo Maria, Clement, Patricia, Cohen, Alexander L., Cohen-Adad, Julien, D'Ambrosio, Sasha, de Hollander, Gilles, de la Iglesia-Vayá, María, de la Vega, Alejandro, Delorme, Arnaud, Devinsky, Orrin, Draschkow, Dejan, Duff, Eugene Paul, DuPre, Elizabeth, Earl, Eric, Esteban, Oscar, Feingold, Franklin W., Flandin, Guillaume, Galassi, Anthony, Gallitto, Giuseppe, Ganz, Melanie, Gau, Rémi, Gholam, James, Ghosh, Satrajit S., Giacomel, Alessio, Gillman, Ashley G., Gleeson, Padraig, Gramfort, Alexandre, Guay, Samuel, Guidali, Giacomo, Halchenko, Yaroslav O., Handwerker, Daniel A., Hardcastle, Nell, Herholz, Peer, Hermes, Dora, Honey, Christopher J., Innis, Robert B., Ioanas, Horea-Ioan, Jahn, Andrew, Karakuzu, Agah, Keator, David B., Kiar, Gregory, Kincses, Balint, Laird, Angela R., Lau, Jonathan C., Lazari, Alberto, Legarreta, Jon Haitz, Li, Adam, Li, Xiangrui, Love, Bradley C., Lu, Hanzhang, Marcantoni, Eleonora, Maumet, Camille, Mazzamuto, Giacomo, Meisler, Steven L., Mikkelsen, Mark, Mutsaerts, Henk, Nichols, Thomas E., Nikolaidis, Aki, Nilsonne, Gustav, Niso, Guiomar, Norgaard, Martin, Okell, Thomas W., Oostenveld, Robert, Ort, Eduard, Park, Patrick J., Pawlik, Mateusz, Pernet, Cyril R., Pestilli, Franco, Petr, Jan, Phillips, Christophe, Poline, Jean-Baptiste, Pollonini, Luca, Raamana, Pradeep Reddy, Ritter, Petra, Rizzo, Gaia, Robbins, Kay A., Rockhill, Alexander P., Rogers, Christine, Rokem, Ariel, Rorden, Chris, Routier, Alexandre, Saborit-Torres, Jose Manuel, Salo, Taylor, Schirner, Michael, Smith, Robert E., Spisak, Tamas, Sprenger, Julia, Swann, Nicole C., Szinte, Martin, Takerkart, Sylvain, Thirion, Bertrand, Thomas, Adam G., Torabian, Sajjad, Varoquaux, Gael, Voytek, Bradley, Welzel, Julius, Wilson, Martin, Yarkoni, Tal, Gorgolewski, Krzysztof J., Poldrack, R, Markiewicz, C, Appelhoff, S, Ashar, Y, Auer, T, Baillet, S, Bansal, S, Beltrachini, L, Benar, C, Bertazzoli, G, Bhogawar, S, Blair, R, Bortoletto, M, Boudreau, M, Brooks, T, Calhoun, V, Castelli, F, Clement, P, Cohen, A, Cohen-Adad, J, D'Ambrosio, S, de Hollander, G, de la Iglesia-Vayá, M, de la Vega, A, Delorme, A, Devinsky, O, Draschkow, D, Duff, E, Dupre, E, Earl, E, Esteban, O, Feingold, F, Flandin, G, Galassi, A, Gallitto, G, Ganz, M, Gau, R, Gholam, J, Ghosh, S, Giacomel, A, Gillman, A, Gleeson, P, Gramfort, A, Guay, S, Guidali, G, Halchenko, Y, Handwerker, D, Hardcastle, N, Herholz, P, Hermes, D, Honey, C, Innis, R, Ioanas, H, Jahn, A, Karakuzu, A, Keator, D, Kiar, G, Kincses, B, Laird, A, Lau, J, Lazari, A, Legarreta, J, Li, A, Li, X, Love, B, Lu, H, Marcantoni, E, Maumet, C, Mazzamuto, G, Meisler, S, Mikkelsen, M, Mutsaerts, H, Nichols, T, Nikolaidis, A, Nilsonne, G, Niso, G, Norgaard, M, Okell, T, Oostenveld, R, Ort, E, Park, P, Pawlik, M, Pernet, C, Pestilli, F, Petr, J, Phillips, C, Poline, J, Pollonini, L, Raamana, P, Ritter, P, Rizzo, G, Robbins, K, Rockhill, A, Rogers, C, Rokem, A, Rorden, C, Routier, A, Saborit-Torres, J, Salo, T, Schirner, M, Smith, R, Spisak, T, Sprenger, J, Swann, N, Szinte, M, Takerkart, S, Thirion, B, Thomas, A, Torabian, S, Varoquaux, G, Voytek, B, Welzel, J, Wilson, M, Yarkoni, T, Gorgolewski, K, Poldrack, Russell A., Markiewicz, Christopher J., Appelhoff, Stefan, Ashar, Yoni K., Auer, Tibor, Baillet, Sylvain, Bansal, Shashank, Beltrachini, Leandro, Benar, Christian G., Bertazzoli, Giacomo, Bhogawar, Suyash, Blair, Ross W., Bortoletto, Marta, Boudreau, Mathieu, Brooks, Teon L., Calhoun, Vince D., Castelli, Filippo Maria, Clement, Patricia, Cohen, Alexander L., Cohen-Adad, Julien, D'Ambrosio, Sasha, de Hollander, Gilles, de la Iglesia-Vayá, María, de la Vega, Alejandro, Delorme, Arnaud, Devinsky, Orrin, Draschkow, Dejan, Duff, Eugene Paul, DuPre, Elizabeth, Earl, Eric, Esteban, Oscar, Feingold, Franklin W., Flandin, Guillaume, Galassi, Anthony, Gallitto, Giuseppe, Ganz, Melanie, Gau, Rémi, Gholam, James, Ghosh, Satrajit S., Giacomel, Alessio, Gillman, Ashley G., Gleeson, Padraig, Gramfort, Alexandre, Guay, Samuel, Guidali, Giacomo, Halchenko, Yaroslav O., Handwerker, Daniel A., Hardcastle, Nell, Herholz, Peer, Hermes, Dora, Honey, Christopher J., Innis, Robert B., Ioanas, Horea-Ioan, Jahn, Andrew, Karakuzu, Agah, Keator, David B., Kiar, Gregory, Kincses, Balint, Laird, Angela R., Lau, Jonathan C., Lazari, Alberto, Legarreta, Jon Haitz, Li, Adam, Li, Xiangrui, Love, Bradley C., Lu, Hanzhang, Marcantoni, Eleonora, Maumet, Camille, Mazzamuto, Giacomo, Meisler, Steven L., Mikkelsen, Mark, Mutsaerts, Henk, Nichols, Thomas E., Nikolaidis, Aki, Nilsonne, Gustav, Niso, Guiomar, Norgaard, Martin, Okell, Thomas W., Oostenveld, Robert, Ort, Eduard, Park, Patrick J., Pawlik, Mateusz, Pernet, Cyril R., Pestilli, Franco, Petr, Jan, Phillips, Christophe, Poline, Jean-Baptiste, Pollonini, Luca, Raamana, Pradeep Reddy, Ritter, Petra, Rizzo, Gaia, Robbins, Kay A., Rockhill, Alexander P., Rogers, Christine, Rokem, Ariel, Rorden, Chris, Routier, Alexandre, Saborit-Torres, Jose Manuel, Salo, Taylor, Schirner, Michael, Smith, Robert E., Spisak, Tamas, Sprenger, Julia, Swann, Nicole C., Szinte, Martin, Takerkart, Sylvain, Thirion, Bertrand, Thomas, Adam G., Torabian, Sajjad, Varoquaux, Gael, Voytek, Bradley, Welzel, Julius, Wilson, Martin, Yarkoni, Tal, and Gorgolewski, Krzysztof J.

Abstract

The Brain Imaging Data Structure (BIDS) is a community-driven standard for the organization of data and metadata from a growing range of neuroscience modalities. This paper is meant as a history of how the standard has developed and grown over time. We outline the principles behind the project, the mechanisms by which it has been extended, and some of the challenges being addressed as it evolves. We also discuss the lessons learned through the project, with the aim of enabling researchers in other domains to learn from the success of BIDS.

Published
2024

8. The Past, Present, and Future of the Brain Imaging Data Structure (BIDS)

Author

Poldrack, R. A., Markiewicz, C. J., Appelhoff, S., Ashar, Y. K., Auer, T., Baillet, S., Bansal, S., Beltrachini, L., Bertazzoli, G., Bhogawar, S., Blair, R. W., Bortoletto, M., Boudreau, M., Brooks, T. L., Bénar, C. G., Calhoun, V. D., Castelli, F. M., Clement, P., Cohen, A. L., Cohen-Adad, J., Dambrosio, S., Delorme, A., Devinsky, O., Draschkow, D., Duff, E. P., Dupre, E., Earl, E., Esteban, O., Feingold, F. W., Flandin, G., Galassi, A., Gallitto, G., Ganz, M., Gholam, J., Ghosh, S. S., Giacomel, A., Gillman, A. G., Gleeson, P., Gramfort, A., Guay, S., Guidali, G., Halchenko, Y. O., Handwerker, D. A., Hardcastle, N., Herholz, P., Hermes, D., Honey, C. J., Innis, R. B., Ioanas, H.-I., Jahn, A., Karakuzu, A., Keator, D. B., Kiar, G., Kincses, B., Laird, A. R., Lau, J. C., Lazari, A., Legarreta, J. H., Li, A., Li, X., Love, B. C., Lu, H., Maumet, C., Mazzamuto, G., Meisler, S. L., Mikkelsen, M., Mutsaerts, H., Nichols, T. E., Nikolaidis, A., Nilsonne, G., Niso, G., Norgaard, M., Okell, T. W., Oostenveld, R., Ort, E., Park, P. J., Pawlik, M., Pernet, C. R., Pestilli, F., (0000-0002-3201-6002) Petr, J., Phillips, C., Poline, J.-B., Pollonini, L., Raamana, P. R., Ritter, P., Rizzo, G., Robbins, K. A., Rockhill, A. P., Rogers, C., Rokem, A., Rorden, C., Routier, A., Saborit-Torres, J. M., Salo, T., Schirner, M., Smith, R. E., Spisak, T., Sprenger, J., Swann, N. C., Szinte, M., Takerkart, S., Thirion, B., Thomas, A. G., Torabian, S., Varoquaux, G., Vaya, M. D. L. I., Voytek, B., Welzel, J., Wilson, M., Hollander, G., Vega, A., Gorgolewski, K. J., Poldrack, R. A., Markiewicz, C. J., Appelhoff, S., Ashar, Y. K., Auer, T., Baillet, S., Bansal, S., Beltrachini, L., Bertazzoli, G., Bhogawar, S., Blair, R. W., Bortoletto, M., Boudreau, M., Brooks, T. L., Bénar, C. G., Calhoun, V. D., Castelli, F. M., Clement, P., Cohen, A. L., Cohen-Adad, J., Dambrosio, S., Delorme, A., Devinsky, O., Draschkow, D., Duff, E. P., Dupre, E., Earl, E., Esteban, O., Feingold, F. W., Flandin, G., Galassi, A., Gallitto, G., Ganz, M., Gholam, J., Ghosh, S. S., Giacomel, A., Gillman, A. G., Gleeson, P., Gramfort, A., Guay, S., Guidali, G., Halchenko, Y. O., Handwerker, D. A., Hardcastle, N., Herholz, P., Hermes, D., Honey, C. J., Innis, R. B., Ioanas, H.-I., Jahn, A., Karakuzu, A., Keator, D. B., Kiar, G., Kincses, B., Laird, A. R., Lau, J. C., Lazari, A., Legarreta, J. H., Li, A., Li, X., Love, B. C., Lu, H., Maumet, C., Mazzamuto, G., Meisler, S. L., Mikkelsen, M., Mutsaerts, H., Nichols, T. E., Nikolaidis, A., Nilsonne, G., Niso, G., Norgaard, M., Okell, T. W., Oostenveld, R., Ort, E., Park, P. J., Pawlik, M., Pernet, C. R., Pestilli, F., (0000-0002-3201-6002) Petr, J., Phillips, C., Poline, J.-B., Pollonini, L., Raamana, P. R., Ritter, P., Rizzo, G., Robbins, K. A., Rockhill, A. P., Rogers, C., Rokem, A., Rorden, C., Routier, A., Saborit-Torres, J. M., Salo, T., Schirner, M., Smith, R. E., Spisak, T., Sprenger, J., Swann, N. C., Szinte, M., Takerkart, S., Thirion, B., Thomas, A. G., Torabian, S., Varoquaux, G., Vaya, M. D. L. I., Voytek, B., Welzel, J., Wilson, M., Hollander, G., Vega, A., and Gorgolewski, K. J.

Abstract

The Brain Imaging Data Structure (BIDS) is a community-driven standard for the organization of data and metadata from a growing range of neuroscience modalities. This paper is meant as a history of how the standard has developed and grown over time. We outline the principles behind the project, and the mechanisms by which it has been extended. We also discuss the lessons learned through the project, with the aim of enabling researchers in other domains to learn from the success of BIDS.

Published
2024

11. A CMOS-Based Tactile Sensor for Continuous Blood Pressure Monitoring

Author

Kirstein, K. -U., Sedivy, J., Salo, T., Hagleitner, C., Vancura, T., and Hierlemann, A.

Subjects
Computer Science - Other Computer Science
Abstract

A monolithic integrated tactile sensor array is presented, which is used to perform non-invasive blood pressure monitoring of a patient. The advantage of this device compared to a hand cuff based approach is the capability of recording continuous blood pressure data. The capacitive, membrane-based sensor device is fabricated in an industrial CMOS-technology combined with post-CMOS micromachining. The capacitance change is detected by a S?-modulator. The modulator is operated at a sampling rate of 128kS/s and achieves a resolution of 12bit with an external decimation filter and an OSR of 128., Comment: Submitted on behalf of EDAA (http://www.edaa.com/)

Published
2007

15. UNIFORM ESTIMATES FOR LOCAL PROPERTIES OF ANALYTIC FUNCTIONS IN A COMPLETE REINAHRDT DOMAIN.

Author

BANDURA, A. I. and SALO, T. M.

Subjects
ANALYTIC functions, DERIVATIVES (Mathematics), MATHEMATICAL bounds, CONTINUOUS functions, MATHEMATICAL variables, VECTOR-valued measures
Abstract

Using recent estimates of maximum modulus for partial derivatives of the analytic functions with bounded L-index in joint variables we describe maximum modulus of these functions at the polydisc skeleton with given radii by the maximum modulus with lesser radii. Such a description is sufficient and necessary condition of boundedness of L-index in joint variables for functions which are analytic in a complete Reinhardt domain. The vector-valued function L is a positive and continuous function in the domain and its values at a point is greater than reciprocal of distance from the point to the boundary of the Reinhardt domain multiplied by some constant. [ABSTRACT FROM AUTHOR]

Published
2024
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16. Effects of a 360° virtual counselling environment on patient anxiety and CCTA process time:a randomised controlled trial

Author

Paalimäki-Paakki, K. (Karoliina), Virtanen, M. (Mari), Henner, A. (Anja), Vähänikkilä, H. (Hannu), Nieminen, M. T. (Miika T.), Schroderus-Salo, T. (Tanja), Kääriäinen, M. (Maria), Paalimäki-Paakki, K. (Karoliina), Virtanen, M. (Mari), Henner, A. (Anja), Vähänikkilä, H. (Hannu), Nieminen, M. T. (Miika T.), Schroderus-Salo, T. (Tanja), and Kääriäinen, M. (Maria)

Abstract

Introduction: This study investigated whether a 360° virtual counselling environment (360°VCE) was more effective at decreasing patients’ anxiety than routine standard of care counselling for patients undergoing coronary computed tomography angiography (CCTA), and if there was any difference in the process times for both of these groups. Methods: A total of 86 patients underwent CCTA in this randomised controlled trial. Patients were randomly assigned to intervention and control groups. The 360°VCE was developed using spherical panoramic images and non-immersive 360° technology. The primary outcome, anxiety, was measured using the State-Trait Anxiety Inventory (STAI). The secondary outcome, CCTA process time, was measured from the time of arrival in the department until end of examination. Results: Pre-scan anxiety was lower among patients in the 360°VCE group immediately before CCTA in comparison to patients in the control group (p = 0.015). Women demonstrated higher levels of anxiety than men in both groups. No between-group differences were discerned in CCTA process time. Conclusions: Access to 360°VCE can reduce patients’ pre-CCTA anxiety levels. Implications for practice: The presented results can be used to improve patient counselling and care, reduce anxiety among patients undergoing CCTA, and optimise the CCTA examination procedure.

Published
2023

17. Evaluation of in vitro and in vivo personalized cancer treatment assays for oral squamous cell carcinoma

Author

Wahbi, W. (Wafa), Korelin, K. (Katja), Sieviläinen, M. (Meri), Karihtala, P. (Peeter), Wilkman, T. (Tommy), Tarkkanen, J. (Jussi), Salo, T. (Tuula), Al-Samadi, A. (Ahmed), Wahbi, W. (Wafa), Korelin, K. (Katja), Sieviläinen, M. (Meri), Karihtala, P. (Peeter), Wilkman, T. (Tommy), Tarkkanen, J. (Jussi), Salo, T. (Tuula), and Al-Samadi, A. (Ahmed)

Abstract

Background: Oral squamous cell carcinoma (OSCC) is a common cancer with a high heterogeneity and few approved treatments. OSCC is one of the least explored areas for precision oncology. In this study, we aimed to test the reliability of our three established rapid cancer systemic treatment-testing assays: human tumour-derived matrix (Myogel)-coated well-plates, zebrafish xenografts, and 3D microfluidic chips. Methods: Chemo-, radio- and targeted-therapy testing in Myogel-coated wells and zebrafish xenografts was conducted nine times using five samples; two primary and three metastatic lymph node samples from three OSCC patients. Peripheral blood mononuclear cells (PBMNCs) were isolated from the patients’ blood. The response of the tumour cells to radio-, chemo-, and targeted therapy was tested using Myogel-coated wells and zebrafish larvae xenografts. The tumour cells’ response to immunotherapy was tested using 3D microfluidic chips. The cells’ sensitivity to the treatments was compared with the patients’ clinical response. Primary and metastatic lymph node tissue-derived DNA samples from two patients underwent whole exome sequencing to compare the mutational profiles of the samples. Results: Test results were in line with patients’ responses in 7/9 (77%) zebrafish xenograft assays and 5/9 (55%) Myogel-coated wells assays. Immunotherapy testing was done using one metastatic patient sample which matched the patients’ response. Differences in responses to treatments between primary and metastatic samples of the same patient were detected in 50% of the zebrafish larvae assays. Conclusions: Our results show the potential of using personalized cancer treatment testing assays — specifically zebrafish xenografts that revealed promising results — in OSCC patient samples.

Published
2023

18. Detection of herpes simplex virus in oral tongue squamous cell carcinoma

Author

Koivikko, T. (Tiina), Rodrigues, P. C. (Priscila Campioni), Vehviläinen, M. (Mari), Hyvönen, P. (Petra), Sundquist, E. (Elias), Arffman, R. K. (Riikka K.), Al-Samadi, A. (Ahmed), Välimaa, H. (Hanna), Salo, T. (Tuula), Risteli, M. (Maija), Koivikko, T. (Tiina), Rodrigues, P. C. (Priscila Campioni), Vehviläinen, M. (Mari), Hyvönen, P. (Petra), Sundquist, E. (Elias), Arffman, R. K. (Riikka K.), Al-Samadi, A. (Ahmed), Välimaa, H. (Hanna), Salo, T. (Tuula), and Risteli, M. (Maija)

Abstract

Introduction: Oral tongue squamous cell carcinoma (OTSCC) is the most common cancer of the oral cavity. Contradictory results have been observed on the involvement of herpes simplex virus 1 (HSV-1) in oral squamous cell carcinomas. Here, we aimed to study the predominance of HSV-1 or HSV-2 in oral HSV infections and to investigate the presence of HSV-1 in OTSCC and its effect on carcinoma cell viability and invasion. Methods: The distribution of HSV types one and two in diagnostic samples taken from suspected oral HSV infections was determined from the Helsinki University Hospital Laboratory database. We then analysed 67 OTSCC samples for HSV-1 infection using immunohistochemical staining. We further tested the effects of HSV-1 using six concentrations (0.00001–1.0 multiplicity of infection [MOI]) on viability and two concentrations (0.001 and 0.1 MOI) on invasion of highly invasive metastatic HSC-3 and less invasive primary SCC-25 OTSCC cell lines using MTT and Myogel-coated Transwell invasion assays. Results: Altogether 321 oropharyngeal samples were diagnosed positive for HSV during the study period. HSV-1 was the predominant (97.8%) HSV type compared with HSV-2 (detected in 2.2% of samples). HSV-1 was also detected in 24% of the OTSCC samples and had no association with patient survival or recurrence. OTSCC cells were viable even after 6 days with low viral load (0.00001, 0.0001, 0.001 MOI) of HSV-1. In both cell lines, 0.001 MOI did not affect cell invasion. However, 0.1 MOI significantly reduced cell invasion in HSC-3 cells. Discussion: HSV-1 infection is predominant compared with HSV-2 in the oral cavity. HSV-1 is detected in OTSCC samples without clinical significance, and OTSCC cell survival or invasion was not affected at low doses of HSV-1.

Published
2023

19. Polypodium leucotomos targets multiple aspects of oral carcinogenesis and it is a potential antitumor phytotherapy against tongue cancer growth

Author

Lacerda, P. A. (Pammela A.), Oenning, L. C. (Luan C.), Bellato, G. C. (Guilherme Cuoghi), Lopes-Santos, L. (Lucilene), Antunes, N. d. (Natalícia de Jesus), Mariz, B. A. (Bruno Augusto Linhares Almeida), Teixeira, G. (Gabriela), Vasconcelos, R. (Rafael), Simões, G. F. (Gustavo Ferreira), de Souza, I. A. (Ivani Aparecida), Pinto, C. A. (Clóvis Antônio Lopes), Salo, T. (Tuula), Coletta, R. D. (Ricardo D.), Augusto, T. M. (Taize M.), de Oliveira, C. E. (Carine Ervolino), Cervigne, N. K. (Nilva K.), Lacerda, P. A. (Pammela A.), Oenning, L. C. (Luan C.), Bellato, G. C. (Guilherme Cuoghi), Lopes-Santos, L. (Lucilene), Antunes, N. d. (Natalícia de Jesus), Mariz, B. A. (Bruno Augusto Linhares Almeida), Teixeira, G. (Gabriela), Vasconcelos, R. (Rafael), Simões, G. F. (Gustavo Ferreira), de Souza, I. A. (Ivani Aparecida), Pinto, C. A. (Clóvis Antônio Lopes), Salo, T. (Tuula), Coletta, R. D. (Ricardo D.), Augusto, T. M. (Taize M.), de Oliveira, C. E. (Carine Ervolino), and Cervigne, N. K. (Nilva K.)

Abstract

Introduction: Oral cancer refers to malignant tumors, of which 90% are squamous cell carcinomas (OSCCs). These malignancies exhibit rapid progression, poor prognosis, and often mutilating therapeutical approaches. The determination of a prophylactic and/or therapeutic antitumor role of the polyphenolic extract Polypodium leucotomos(PL) would be relevant in developing new tools for prevention and treatment. Methods: We aimed to determine the antitumor effect of PL by treating OSCC cell lines with PL metabolites and evaluating its action during OSCC progression in vivo. Results: PL treatment successfully impaired cell cycling and proliferation, migration, and invasion, enhanced apoptosis, and modulated macrophage polarization associated with the tumoral immune-inflammatory response of tongue cancer cell lines (TSCC). PL treatment significantly decreased the expression of MMP1 (p < 0.01) and MMP2 (p < 0.001), and increased the expression of TIMP1 (p < 0.001) and TIMP2 (p < 0.0001) in these cells. The mesenchymal-epithelial transition phenotype was promoted in cells treated with PL, through upregulation of E-CAD (p < 0.001) and reduction of N-CAD (p < 0.05). PL restrained OSCC progression in vivo by inhibiting tumor volume growth and decreasing the number of severe dysplasia lesions and squamous cell carcinomas. Ki-67 was significantly higher expressed in tongue tissues of animals not treated with PL(p < 0.05), and a notable reduction in Bcl2 (p < 0.05) and Pcna (p < 0.05) cell proliferation-associated genes was found in dysplastic lesions and TSCCs of PL-treated mice. Finally, N-cad(Cdh2), Vim, and Twist were significantly reduced in tongue tissues treated with PL. Conclusions: PL significantly decreased OSCC carcinogenic processes in vitro and inhibited tumor progression in vivo. PL also appears to contribute to the modulation of immune-inflammatory oral tumor-associated responses. Taken together, these results suggest that PL plays

Published
2023

20. Stress induced phosphoprotein 1 overexpression controls proliferation, migration and invasion and is associated with poor survival in oral squamous cell carcinoma

Author

Dourado, M. R. (Mauricio Rocha), Elseragy, A. (Amr), da Costa, B. C. (Bruno Cesar), Téo, F. H. (Fábio Haach), Guimarães, G. N. (Gustavo Narvaes), Machado, R. A. (Renato Assis), Risteli, M. (Maija), Wahbi, W. (Wafa), Rocha, C. A. (Clarissa Araujo Gurgel), Paranaíba, L. M. (Lívia Máris Ribeiro), González-Arriagada, W. A. (Wilfredo Alejandro), da Silva, S. D. (Sabrina Daniela), Rangel, A. L. (Ana Lucia Carrinho Ayroza), Marques, M. R. (Marcelo Rocha), Junior, C. R. (Carlos Rossa), Salo, T. (Tuula), Coletta, R. D. (Ricardo D.), Dourado, M. R. (Mauricio Rocha), Elseragy, A. (Amr), da Costa, B. C. (Bruno Cesar), Téo, F. H. (Fábio Haach), Guimarães, G. N. (Gustavo Narvaes), Machado, R. A. (Renato Assis), Risteli, M. (Maija), Wahbi, W. (Wafa), Rocha, C. A. (Clarissa Araujo Gurgel), Paranaíba, L. M. (Lívia Máris Ribeiro), González-Arriagada, W. A. (Wilfredo Alejandro), da Silva, S. D. (Sabrina Daniela), Rangel, A. L. (Ana Lucia Carrinho Ayroza), Marques, M. R. (Marcelo Rocha), Junior, C. R. (Carlos Rossa), Salo, T. (Tuula), and Coletta, R. D. (Ricardo D.)

Abstract

Objective: Although there have been remarkable achievements in the molecular landscape of oral squamous cell carcinoma (OSCC) in recent years, bringing advances in the understanding of its pathogenesis, development and progression, little has been applied in the prognosis and choosing the optimal treatment. In this study, we explored the influence of the stress induced phosphoprotein 1 (STIP1), which is frequently reported to be highly expressed in many cancers, in OSCCs. Methods: STIP1 expression was assessed in the TCGA database and in two independent cohorts by immunohistochemistry. Knockdown strategy was applied in OSCC cell lines to determine the impact of STIP1 on viability, proliferation, migration and invasion. The zebrafish model was applied for studying tumor formation and metastasis in vivo. The association of STIP1 and miR-218-5p was explored by bioinformatics and mimics transfection. Results: STIP1 was highly expressed in OSCCs and significantly associated with shortened survival and higher risk of recurrence. STIP1 down-regulation decreased proliferation, migration and invasion of tumor cells, and reduced the number of metastases in the Zebrafish model. STIP1 and miR-218-5p were inversely expressed, and the transfection of miR-218-5p mimics into OSCC cells decreased STIP1 levels as well as proliferation, migration and invasion. Conclusion: Our findings show that STIP1 overexpression, which is inversely associated with miR-218-5p levels, contributes to OSCC aggressiveness by controlling proliferation, migration and invasion and is a determinant of poor prognosis.

Published
2023

21. Predictive features and potential treatment targets for oral tongue cancer

Author

Salo, T. (Tuula), Almangush, A. (Alhadi), Elseragy, A. (Amr), Salo, T. (Tuula), Almangush, A. (Alhadi), and Elseragy, A. (Amr)

Abstract

Oral tongue squamous cell carcinoma (OTSCC) stands as the most common malignancy in the oral cavity. It is characterized by its aggressive course and has the worst prognosis of all types of squamous cell carcinoma (SCC) originating in the oral cavity region. For early-stage OTSCC, surgery is typically the standard treatment. On the other hand, for advanced cases, radiotherapy with or without chemo-, targeted, or immunotherapy is given depending on the tumor nature and patient´s general health condition. Histopathologic prognostic features play an important role in evaluating the aggressiveness of many carcinomas. The World Health Organization (WHO) histopathologic grading system is commonly used to classify OTSCC and other head and neck cancers based on their histopathological characteristics. However, WHO grading as a predictive feature has been widely criticized due to its low predictive power, especially for early-stage OTSCC. Therefore, we suggested incorporating tumor budding (TB) into the WHO histopathologic grading system to improve its prognostic value in early-stage OTSCC. Based on our results, tumor budding (TB), worst pattern of invasion (WPOI) and tumor-stroma ratio (TSR) have shown promising prognostic value in early OTSCC. Moreover, Extensive research has shown that tertiary lymphoid structures (TLSs) are associated with improved survival in early-stage oral tongue squamous cell carcinoma (OTSCC) by enhancing anti-tumor immunity. The absence of TLSs is significantly associated with high mortality; Thus, TLS formation may be a future approach to improving OTSCC patients’ survival. In addition to utilizing histopathological parameters in improving the prediction of OSCC, potential signature proteins have been intensively examined by immuno-histochemistry, and none of those proteins have been identified so far in a clinical use. Stress-induced phosphoprotein 1 (STIP1) overexpression in OSCC is associated with shorter cancer-specific survival, inc, Tiivistelmä Suun kielen levyepiteelisyöpä (OTSCC) on suuontelon yleisin pahanlaatuinen syöpä. Sille on ominaista sen aggressiivinen kulku, ja sillä on huonoin ennuste kaikista suuontelon alueelta peräisin olevista levyepiteelisyöpätyypeistä (SCC). Varhaisen vaiheen OTSCC:lle leikkaus on tyypillisesti vakiohoito. Toisaalta pitkälle edenneissä tapauksissa annetaan sädehoitoa kemo-, kohdennettu- tai immunoterapian kanssa tai ilman sitä riippuen kasvaimen luonteesta ja potilaan yleisestä terveydentilasta. Histopatologisilla ennusteominaisuuksilla on tärkeä rooli monien karsinoomien aggressiivisuuden arvioinnissa. Maailman terveysjärjestön (WHO) histopatologista luokitusjärjestelmää käytetään yleisesti OTSCC:n ja muiden pään ja kaulan syöpien luokittelemiseen niiden histopatologisten ominaisuuksien perusteella. WHO:n luokittelu ennustavana ominaisuutena on kuitenkin saanut laajaa kritiikkiä sen alhaisen ennustevoiman vuoksi, erityisesti varhaisen vaiheen OTSCC:n osalta. Siksi ehdotimme tuumorin orulun (TB) sisällyttämistä WHO:n histopatologiseen luokitusjärjestelmään sen ennustearvon parantamiseksi varhaisen vaiheen OTSCC:ssä. Tuloksiemme perusteella tuumorin muodostuminen (TB), pahin invaasiomalli (WPOI) ja kasvain-strooman suhde (TSR) ovat osoittaneet lupaavaa ennustearvoa varhaisessa OTSCC:ssä. Lisäksi laaja tutkimus on osoittanut, että tertiääriset lymfoidirakenteet (TLS:t) liittyvät parantuneeseen eloonjäämiseen alkuvaiheen suun kielen levyepiteelikarsinoomassa (OTSCC) tehostamalla kasvainten vastaista immuniteettia. TLS:ien puuttuminen liittyy merkittävästi korkeaan kuolleisuuteen; Siten TLS:n muodostuminen voi olla tulevaisuuden lähestymistapa OTSCC-potilaiden eloonjäämisen parantamiseen. Sen lisäksi, että histopatologisia parametreja on käytetty OSCC:n ennustamisen parantamisessa, mahdollisia allekirjoitusproteiineja on tutkittu intensiivisesti immunohistokemialla, eikä mitään näistä proteiineista ole toistaiseksi tunnistettu kliinisessä käytössä. Stressin aiheut

Published
2023

22. Intake and sources of dietary fibre and dietary fibre fractions in Finnish children

Author

Salo, T. E. (Tuuli E. I.), Niinistö, S. (Sari), Korhonen, T. E. (Tuuli E.), Pastell, H. (Helena), Reinivuo, H. (Heli), Takkinen, H.-M. (Hanna-Mari), Ilonen, J. (Jorma), Toppari, J. (Jorma), Knip, M. (Mikael), Veijola, R. (Riitta), Virtanen, S. M. (Suvi M.), Salo, T. E. (Tuuli E. I.), Niinistö, S. (Sari), Korhonen, T. E. (Tuuli E.), Pastell, H. (Helena), Reinivuo, H. (Heli), Takkinen, H.-M. (Hanna-Mari), Ilonen, J. (Jorma), Toppari, J. (Jorma), Knip, M. (Mikael), Veijola, R. (Riitta), and Virtanen, S. M. (Suvi M.)

Abstract

The current definition of dietary fibre was adopted by the Codex Alimentarius Commission in 2009, but implementation requires updating food composition databases with values based on appropriate analysis methods. Previous data on population intakes of dietary fibre fractions are sparse. We studied the intake and sources of total dietary fibre (TDF) and dietary fibre fractions insoluble dietary fibre (IDF), dietary fibre soluble in water but insoluble in 76 % aqueous ethanol (SDFP) and dietary fibre soluble in water and soluble in 76 % aqueous ethanol (SDFS) in Finnish children based on new CODEX-compliant values of the Finnish National Food Composition Database Fineli. Our sample included 5193 children at increased genetic risk of type 1 diabetes from the Type 1 Diabetes Prediction and Prevention birth cohort, born between 1996 and 2004. We assessed the intake and sources based on 3-day food records collected at the ages of 6 months, 1, 3 and 6 years. Both absolute and energy-adjusted intakes of TDF were associated with age, sex and breast-feeding status of the child. Children of older parents, parents with a higher level of education, non-smoking mothers and children with no older siblings had higher energy-adjusted TDF intake. IDF was the major dietary fibre fraction in non-breastfed children, followed by SDFP and SDFS. Cereal products, fruits and berries, potatoes and vegetables were major food sources of dietary fibre. Breast milk was a major source of dietary fibre in 6-month-olds due to its human milk oligosaccharide content and resulted in high SDFS intakes in breastfed children.

Published
2023

23. TWIST1 regulates proliferation, migration, and invasion and is a prognostic marker for oral tongue squamous cell carcinoma

Author

de Morais, E. F. (Everton Freitas), de Farias Morais, H. G. (Hannah Gil), de Moura Santos, E. (Edilmar), Barboza, C. A. (Carlos Augusto Galvão), Téo, F. H. (Fábio Haach), Salo, T. (Tuula), Coletta, R. D. (Ricardo D.), de Almeida Freitas, R. (Roseana), de Morais, E. F. (Everton Freitas), de Farias Morais, H. G. (Hannah Gil), de Moura Santos, E. (Edilmar), Barboza, C. A. (Carlos Augusto Galvão), Téo, F. H. (Fábio Haach), Salo, T. (Tuula), Coletta, R. D. (Ricardo D.), and de Almeida Freitas, R. (Roseana)

Abstract

Background: Epithelial–mesenchymal transition is one of the main mechanisms for tumor progression and metastasis. Transcription factors such as TWIST1 are key regulators of the epithelial–mesenchymal transition and are regarded as potential therapeutic targets for the treatment of cancer. The purpose of this study was to examine TWIST1 as a possible epithelial-mesenchymal transition-related prognostic biomarker in oral epithelial dysplasia and oral tongue squamous cell carcinomas, as well as the biological behavior of TWIST1-silencing in oral tongue squamous cell carcinomas cell lines. Methods: Immunohistochemical analysis of TWIST1, E-cadherin, and N-cadherin was carried out in 47 samples representing oral epithelial dysplasia and 41 oral tongue squamous cell carcinomas. The suppression of TWIST1 expression was performed using shRNA-expression vectors in HSC-3 and SCC-9 cells to investigate in vitro the impact of TWIST1 on proliferation, apoptosis, viability, migration, and invasion of SCC-9 and HSC-3 cells. Results: The expression of nuclear TWIST1 was significantly higher in oral tongue squamous cell carcinomas than in oral epithelial dysplasis (p < 0.0001), whereas TWIST1 in the cytoplasm was more expressed in oral epithelial dysplasis (p = 0.012). The high cytoplasmic expression of TWIST1 was significantly associated with shortened overall survival (p < 0.05), and increased nuclear TWIST1 expression was significantly related to high risk of recurrence (p = 0.03). Knockdown of TWIST1 in oral tongue squamous cell carcinomas cells induced the expression of E-cadherin and inhibited N-cadherin, which were followed by decreased proliferation, migration, and invasion. Conclusions: Our research suggests that TWIST1 is linked to the development of oral tongue carcinogenesis and may be used as a prognostic indicator and therapeutic target for oral tongue squamous cell carcinomas patients.

Published
2023

24. Novel human lymph node-derived matrix supports the adhesion of metastatic oral carcinoma cells

Author

Naakka, E. (Erika), Wahbi, W. (Wafa), Tiikkaja, R. (Riia), Juurikka, K. (Krista), Sandvik, T. (Toni), Koivunen, P. (Petri), Autio, T. (Timo), Tikanto, J. (Jukka), Väisänen, J. (Janne), Tuominen, H. (Hannu), Talvensaari-Mattila, A. (Anne), Al-Samadi, A. (Ahmed), Soliymani, R. (Rabah), Åström, P. (Pirjo), Risteli, M. (Maija), Salo, T. (Tuula), Naakka, E. (Erika), Wahbi, W. (Wafa), Tiikkaja, R. (Riia), Juurikka, K. (Krista), Sandvik, T. (Toni), Koivunen, P. (Petri), Autio, T. (Timo), Tikanto, J. (Jukka), Väisänen, J. (Janne), Tuominen, H. (Hannu), Talvensaari-Mattila, A. (Anne), Al-Samadi, A. (Ahmed), Soliymani, R. (Rabah), Åström, P. (Pirjo), Risteli, M. (Maija), and Salo, T. (Tuula)

Abstract

Background: 3D culture is increasingly used in cancer research, as it allows the growth of cells in an environment that mimics in vivo conditions. Metastases are the primary cause of morbidity and mortality in cancer patients, and solid tumour metastases are mostly located in lymph nodes. Currently, there are no techniques that model the pre-metastatic lymph node microenvironment in vitro. In this study, we prepared a novel extracellular matrix, Lymphogel, which is derived from lymph nodes, mimicking the tumour microenvironment (TME) of metastatic carcinoma cells. We tested the suitability of the new matrix in various functional experiments and compared the results with those obtained using existing matrices. Methods: We used both commercial and patient-derived primary and metastatic oral tongue squamous cell carcinoma (OTSCC) cell lines. We characterized the functional differences of these cells using three different matrices (human uterine leiomyoma-derived Myogel, human pre-metastatic neck lymph node-derived Lymphogel (h-LG), porcine normal neck lymph node-derived Lymphogel (p-LG) in proliferation, adhesion, migration and invasion assays. We also performed proteomic analyses to compare the different matrices in relation to their functional properties. Results: OTSCC cells exhibited different adhesion and invasion patterns depending on the matrix. Metastatic cell lines showed improved ability to adhere to h-LG, but the effects of the matrices on cell invasion fluctuated non-significantly between the cell lines. Proteomic analyses showed that the protein composition between matrices was highly variable; Myogel contained 618, p-LG 1823 and h-LG 1520 different proteins. The comparison of all three matrices revealed only 120 common proteins. Analysis of cellular pathways and processes associated with proteomes of each matrix revealed similarities of Myogel with h-LG but less with p-LG. Similarly, p-LG contained the least adhesion-related proteins compared wit

Published
2023

25. Prognostic histological markers in oral tongue squamous cell carcinoma patients treated with (chemo)radiotherapy

Author

Hyytiäinen, A. (Aini), Mroueh, R. (Rayan), Peltonen, J. (Johanna), Wennerstrand, P. (Pia), Mäkitie, A. (Antti), Al-Samadi, A. (Ahmed), Ventelä, S. (Sami), Salo, T. (Tuula), Hyytiäinen, A. (Aini), Mroueh, R. (Rayan), Peltonen, J. (Johanna), Wennerstrand, P. (Pia), Mäkitie, A. (Antti), Al-Samadi, A. (Ahmed), Ventelä, S. (Sami), and Salo, T. (Tuula)

Abstract

Treatment of oral tongue squamous cell carcinoma (OTSCC) frequently includes surgery with postoperative radiotherapy (RT) or chemoradiotherapy (CRT). Resistance to RT or CRT remains a major clinical challenge and highlights the need to identify predictive markers for it. We included 71 OTSCC patients treated with surgery combined with RT or CRT. We evaluated the association between tumor budding, tumor–stroma ratio (TSR), depth of invasion (DOI), tumor-infiltrating lymphocytes (TILs), hypoxia-inducible factor-1alpha (HIF-1alpha) expression, octamer-binding transcription factor 4 (OCT4) expression, high-endothelial venules (HEVs), and disease-free survival (DFS) using uni- and multivariate analyses. No significant association was observed between the different histological and molecular markers (TSR, DOI, TILs, HEV, HIF-1alph, OCT4) and DFS. However, an associative trend between DOI, budding, and DFS was noted. Further studies with larger cohorts are needed to explore the prognostic value of DOI and budding for OTSCC patients treated with postoperative RT or CRT.

Published
2023

26. Exploring the combination of tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding with WHO histopathological grading on early-stage oral squamous cell carcinoma prognosis

Author

Silva, G. V. (Gabriela Vivili Domingues), Da Silva Dolens, E. (Eder), Paranaíba, L. M. (Lívia Máris Ribeiro), Ayroza, A. L. (Ana Lúcia Carrinho), Gurgel Rocha, C. A. (Clarissa Araujo), Almangush, A. (Alhadi), Salo, T. (Tuula), Brennan, P. A. (Peter A.), Coletta, R. D. (Ricardo D.), Silva, G. V. (Gabriela Vivili Domingues), Da Silva Dolens, E. (Eder), Paranaíba, L. M. (Lívia Máris Ribeiro), Ayroza, A. L. (Ana Lúcia Carrinho), Gurgel Rocha, C. A. (Clarissa Araujo), Almangush, A. (Alhadi), Salo, T. (Tuula), Brennan, P. A. (Peter A.), and Coletta, R. D. (Ricardo D.)

Abstract

Background: While the relevance of the World Health Organization histopathological grading system as a prognostic tool for oral squamous cell carcinoma has received many critics, other histopathological features such as tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding are displaying promising results. Here, we evaluated the prognostic impact of the incorporation of tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding into World Health Organization histopathological grading for patients with oral squamous cell carcinoma. Methods: A total of 95 patients with early-stage oral squamous cell carcinoma were enrolled in the study, and World Health Organization tumor grading, tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding were evaluated in surgical slides stained with hematoxylin and eosin. Survival analyses for cancer-specific survival and disease-free survival were performed using Cox regression models, and receiver operating characteristic curves were applied for assessment of the performance of the combinations. Results: Tumor-stroma ratio (stroma-rich) was significantly and independently associated with both shortened cancer-specific survival and poor disease-free survival, individually and in combination with World Health Organization histopathological grading. The combination of tumor-stroma ratio with World Health Organization grading did not improve the discriminatory ability compared to tumor-stroma ratio alone. Although low tumor-infiltrating lymphocytes were associated with shortened cancer-specific survival, the association did not withstand multivariate analysis. However, in combination with World Health Organization grading, low tumor-infiltrating lymphocytes were independently associated with poor cancer-specific survival. The combination of tumor-infiltrating lymphocytes and World Health Organization histopathological grading displayed a better discrimination of poor cancer-specific survi

Published
2023

27. The effect of matrices on the gene expression profile of patient-derived head and neck carcinoma cells for in vitro therapy testing

Author

Hyytiäinen, A. (Aini), Korelin, K. (Katja), Toriseva, M. (Mervi), Wilkman, T. (Tommy), Kainulainen, S. (Satu), Mesimäki, K. (Karri), Routila, J. (Johannes), Ventelä, S. (Sami), Irjala, H. (Heikki), Nees, M. (Matthias), Al-Samadi, A. (Ahmed), Salo, T. (Tuula), Hyytiäinen, A. (Aini), Korelin, K. (Katja), Toriseva, M. (Mervi), Wilkman, T. (Tommy), Kainulainen, S. (Satu), Mesimäki, K. (Karri), Routila, J. (Johannes), Ventelä, S. (Sami), Irjala, H. (Heikki), Nees, M. (Matthias), Al-Samadi, A. (Ahmed), and Salo, T. (Tuula)

Abstract

Objective: Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive tumor with a 5-year mortality rate of ~ 50%. New in vitro methods are needed for testing patients’ cancer cell response to anti-cancer treatments. We aimed to investigate how the gene expression of fresh carcinoma tissue samples and freshly digested single cancer cells change after short-term cell culturing on plastic, Matrigel or Myogel. Additionally, we studied the effect of these changes on the cancer cells’ response to anti-cancer treatments. Materials/methods: Fresh tissue samples from HNSCC patients were obtained perioperatively and single cells were enzymatically isolated and cultured on either plastic, Matrigel or Myogel. We treated the cultured cells with cisplatin, cetuximab, and irradiation; and performed cell viability measurement. RNA was isolated from fresh tissue samples, freshly isolated single cells and cultured cells, and RNA sequencing transcriptome profiling and gene set enrichment analysis were performed. Results: Cancer cells obtained from fresh tissue samples changed their gene expression regardless of the culturing conditions, which may be due to the enzymatic digestion of the tissue. Myogel was more effective than Matrigel at supporting the upregulation of pathways related to cancer cell proliferation and invasion. The impacts of anti-cancer treatments varied between culturing conditions. Conclusions: Our study showed the challenge of in vitro cancer drug testing using enzymatic cell digestion. The upregulation of many targeted pathways in the cultured cells may partially explain the common clinical failure of the targeted cancer drugs that pass the in vitro testing.

Published
2023

29. New insights into the genetic etiology of Alzheimer's disease and related dementias

Author

Bellenguez, C., Küçükali, F., Jansen, I. E., Kleineidam, L., Moreno-Grau, S., Amin, N., Naj, A. C., Campos-Martin, R., Grenier-Boley, B., Andrade, V., Holmans, P. A., Boland, A., Damotte, V., van der Lee, S. J., Costa, M. R., Kuulasmaa, T., Yang, Q., de Rojas, I., Bis, J. C., Yaqub, A., Prokic, I., Chapuis, J., Ahmad, S., Giedraitis, V., Aarsland, D., Garcia-Gonzalez, P., Abdelnour, C., Alarcón-Martín, E., Alcolea, D., Alegret, M., Alvarez, I., Álvarez, V., Armstrong, N. J., Tsolaki, A., Antúnez, C., Appollonio, I., Arcaro, M., Archetti, S., Pastor, A. A., Arosio, B., Athanasiu, L., Bailly, H., Banaj, N., Baquero, M., Barral, S., Beiser, A., Pastor, A. B., Below, J. E., Benchek, P., Benussi, L., Berr, C., Besse, C., Bessi, V., Binetti, G., Bizarro, A., Blesa, R., Boada, M., Boerwinkle, E., Borroni, B., Boschi, S., Bossù, P., Bråthen, G., Bressler, J., Bresner, C., Brodaty, H., Brookes, K. J., Brusco, L. I., Buiza-Rueda, D., Bûrger, K., Burholt, V., Bush, W. S., Calero, M., Cantwell, L. B., Chene, G., Chung, J., Cuccaro, M. L., Carracedo, Á., Cecchetti, R., Cervera-Carles, L., Charbonnier, C., Chen, H. -H., Chillotti, C., Ciccone, S., Claassen, J. A. H. R., Clark, C., Conti, E., Corma-Gómez, A., Costantini, E., Custodero, C., Daian, D., Dalmasso, M. C., Daniele, A., Dardiotis, E., Dartigues, J. -F., de Deyn, P. P., de Paiva Lopes, K., de Witte, L. D., Debette, S., Deckert, J., del Ser, T., Denning, N., Destefano, A., Dichgans, M., Diehl-Schmid, J., Diez-Fairen, M., Rossi, P. D., Djurovic, S., Duron, E., Düzel, E., Dufouil, C., Eiriksdottir, G., Engelborghs, S., Escott-Price, V., Espinosa, A., Ewers, M., Faber, K. M., Fabrizio, T., Nielsen, S. F., Fardo, D. W., Farotti, L., Fenoglio, C., Fernández-Fuertes, M., Ferrari, R., Ferreira, C. B., Ferri, E., Fin, B., Fischer, P., Fladby, T., Fließbach, K., Fongang, B., Fornage, M., Fortea, J., Foroud, T. M., Fostinelli, S., Fox, N. C., Franco-Macías, E., Bullido, M. J., Frank-García, A., Froelich, L., Fulton-Howard, B., Galimberti, D., García-Alberca, J. M., García-González, P., Garcia-Madrona, S., Garcia-Ribas, G., Ghidoni, R., Giegling, I., Giorgio, G., Goate, A. M., Goldhardt, O., Gomez-Fonseca, D., González-Pérez, A., Graff, C., Grande, G., Green, E., Grimmer, T., Grünblatt, E., Grunin, M., Gudnason, V., Guetta-Baranes, T., Haapasalo, A., Hadjigeorgiou, G., Haines, J. L., Hamilton-Nelson, K. L., Hampel, H., Hanon, O., Hardy, J., Hartmann, A. M., Hausner, L., Harwood, J., Heilmann-Heimbach, S., Helisalmi, S., Heneka, M. T., Hernández, I., Herrmann, M. J., Hoffmann, P., Holmes, C., Holstege, H., Vilas, R. H., Hulsman, M., Humphrey, J., Biessels, G. J., Jian, X., Johansson, C., Jun, G. R., Kastumata, Y., Kauwe, J., Kehoe, P. G., Kilander, L., Ståhlbom, A. K., Kivipelto, M., Koivisto, A., Kornhuber, J., Kosmidis, M. H., Kukull, W. A., Kuksa, P. P., Kunkle, B. W., Kuzma, A. B., Lage, C., Laukka, E. 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Impulsivity & Attention, APH - Personalized Medicine, APH - Methodology, Bellenguez, Céline [0000-0002-1240-7874], Küçükali, Fahri [0000-0002-3835-9639], Amin, Najaf [0000-0002-8944-1771], Holmans, Peter A [0000-0003-0870-9412], van der Lee, Sven J [0000-0003-1606-8643], Costa, Marcos R [0000-0002-4928-2163], Kuulasmaa, Teemu [0000-0002-1795-7314], Yang, Qiong [0000-0002-3658-1375], de Rojas, Itziar [0000-0002-2148-381X], Bis, Joshua C [0000-0002-3409-1110], Yaqub, Amber [0000-0002-3579-8054], Prokic, Ivana [0000-0002-0370-1473], Chapuis, Julien [0000-0002-5802-2857], Ahmad, Shahzad [0000-0002-8658-3790], Giedraitis, Vilmantas [0000-0003-3423-2021], Garcia-Gonzalez, Pablo [0000-0003-0125-5403], Alcolea, Daniel [0000-0002-3819-3245], Alvarez, Ignacio [0000-0002-8537-3935], Tsolaki, Anthoula [0000-0002-5563-7776], Baquero, Miquel [0000-0002-6861-1831], Pastor, Ana Belén [0000-0001-9637-4688], Berr, Claudine [0000-0001-5254-7655], Bessi, Valentina [0000-0002-6176-3584], Boada, Mercè [0000-0003-2617-3009], Bossù, Paola [0000-0002-1432-0078], Bråthen, Geir [0000-0003-3224-7983], Bressler, Jan [0000-0001-6578-4772], Bresner, Catherine [0000-0003-2673-9762], Brodaty, Henry [0000-0001-9487-6617], Brookes, Keeley J [0000-0003-2427-2513], Burholt, Vanessa [0000-0002-6789-127X], Bush, William S [0000-0002-9729-6519], Calero, Miguel [0000-0001-5366-3324], Chung, Jaeyoon [0000-0002-6431-9454], Cervera-Carles, Laura [0000-0003-2286-200X], Costantini, Emanuele [0000-0002-1096-8221], Dalmasso, Maria Carolina [0000-0002-4901-9955], de Paiva Lopes, Katia [0000-0002-0240-0126], de Witte, Lot D [0000-0002-7235-9958], Debette, Stéphanie [0000-0001-8675-7968], Del Ser, Teodoro [0000-0001-9806-7083], Dichgans, Martin [0000-0002-0654-387X], Diehl-Schmid, Janine [0000-0002-7745-1382], Diez-Fairen, Mónica [0000-0003-1882-0309], Djurovic, Srdjan [0000-0002-8140-8061], Dufouil, Carole [0000-0003-2442-4476], Escott-Price, Valentina [0000-0003-1784-5483], Ewers, Michael [0000-0001-5231-1714], Fabrizio, Tagliavini [0000-0003-1039-7315], Fladby, Tormod [0000-0002-9984-9797], Fornage, Myriam [0000-0003-0677-8158], Fox, Nick C [0000-0002-6660-657X], Bullido, María J [0000-0002-6477-1117], Froelich, Lutz [0000-0003-1494-0813], Galimberti, Daniela [0000-0002-9284-5953], García-Alberca, Jose Maria [0000-0003-2951-6644], Goate, Alison M [0000-0002-0576-2472], González-Pérez, Antonio [0000-0001-9771-5982], Green, Emma [0000-0002-8687-5590], Grünblatt, Edna [0000-0001-8505-7265], Gudnason, Vilmundur [0000-0001-5696-0084], Haapasalo, Annakaisa [0000-0003-0959-2957], Harwood, Janet [0000-0002-3225-0069], Heilmann-Heimbach, Stefanie [0000-0003-1057-465X], Herrmann, Martin J [0000-0001-9970-2122], Holstege, Henne [0000-0002-7688-3087], Biessels, Geert Jan [0000-0001-6862-2496], Jian, Xueqiu [0000-0002-0313-6494], Johansson, Charlotte [0000-0002-5351-1950], Jun, Gyungah R [0000-0002-3230-8697], Kastumata, Yuriko [0000-0002-0188-8094], Kehoe, Patrick G [0000-0002-7542-1139], Kornhuber, Johannes [0000-0002-8096-3987], Kosmidis, Mary H [0000-0001-8790-1220], Lage, Carmen [0000-0003-1703-121X], Launer, Lenore [0000-0002-3238-7612], Lee, Chien-Yueh [0000-0002-4304-974X], Lleó, Alberto [0000-0002-2568-5478], Lopez, Oscar [0000-0002-8546-8256], de Munain, Adolfo Lopez [0000-0002-9509-4032], Lunetta, Kathryn L [0000-0002-9268-810X], Ma, Yiyi [0000-0002-3609-8877], MacLeod, Catherine A [0000-0002-9314-7380], Marquié, Marta [0000-0002-0660-0950], Montes, Angel Martín [0000-0002-1694-786X], Mead, Simon [0000-0002-4326-1468], Medina, Miguel [0000-0002-7016-5340], Menéndez-González, Manuel [0000-0002-5218-0774], Mol, Merel [0000-0003-2533-2530], Morgan, Kevin [0000-0002-8217-2396], Nöthen, Markus M [0000-0002-8770-2464], Muchnik, Carolina [0000-0002-1542-3706], Nacmias, Benedetta [0000-0001-9338-9040], Nicolas, Gael [0000-0001-9391-7800], Nordestgaard, Børge G [0000-0002-1954-7220], Pasquier, Florence [0000-0001-9880-9788], Pastor, Pau [0000-0002-7493-8777], Peloso, Gina [0000-0002-5355-8636], Pérez-Cordón, Alba [0000-0002-6028-0791], Pérez-Tur, Jordi [0000-0002-9111-1712], Pericard, Pierre [0000-0001-8167-6448], Pineda, Juan A [0000-0002-3751-0296], Pisanu, Claudia [0000-0002-9151-4319], Posthuma, Danielle [0000-0001-7582-2365], Puerta, Raquel [0000-0002-1191-5893], Quenez, Olivier [0000-0002-8273-8505], Thomassen, Jesper Qvist [0000-0003-3484-9531], Real, Luis M [0000-0003-4932-7429], Reinders, Marcel JT [0000-0002-1148-1562], Reitz, Christiane [0000-0001-8757-7889], Riedel-Heller, Steffi [0000-0003-4321-6090], Rodriguez-Rodriguez, Eloy [0000-0001-7742-677X], Rongve, Arvid [0000-0002-0476-4134], Sáez, María Eugenia [0000-0001-9299-2534], Saltvedt, Ingvild [0000-0002-7897-9808], Juan, Pascual Sánchez [0000-0002-6081-8037], Sarnowski, Chloé [0000-0002-6090-7099], Satizabal, Claudia L [0000-0002-1115-4430], Schott, Jonathan M [0000-0003-2059-024X], Selbæk, Geir [0000-0001-6511-8219], Shadrin, Alexey A [0000-0002-7467-250X], Soininen, Hilkka [0000-0002-2785-9937], Solfrizzi, Vincenzo [0000-0002-8524-0315], Song, Yeunjoo [0000-0002-7452-3731], Sotolongo-Grau, Oscar [0000-0002-9679-0670], Spalletta, Gianfranco [0000-0002-7432-4249], Squassina, Alessio [0000-0001-7415-7607], Stordal, Eystein [0000-0002-2443-7923], Tosto, Giuseppe [0000-0001-7075-8245], Uitterlinden, Andre [0000-0002-7276-3387], Valladares, Otto [0000-0001-8055-2187], Broeckhoven, Christine Van [0000-0003-0183-7665], Vidal, Jean-Sébastien [0000-0001-6770-0720], Vogelgsang, Jonathan [0000-0001-9326-8193], Wagner, Michael [0000-0003-2589-6440], Wallon, David [0000-0002-2634-7198], Wiltfang, Jens [0000-0003-1492-5330], Woods, Bob [0000-0002-6781-651X], Yannakoulia, Mary [0000-0003-2171-7337], Zare, Habil [0000-0001-5902-6238], Zhang, Xiaoling [0000-0001-8237-1857], Farrer, Lindsay A [0000-0001-5533-4225], Psaty, Bruce M [0000-0002-7278-2190], Ghanbari, Mohsen [0000-0002-9476-7143], Raj, Towfique [0000-0002-9355-5704], Sachdev, Perminder [0000-0002-9595-3220], Mather, Karen [0000-0003-4143-8941], Ikram, M Arfan [0000-0003-0372-8585], Tsolaki, Magda [0000-0002-2072-8010], Pericak-Vance, Margaret A [0000-0001-7283-8804], Amouyel, Philippe [0000-0001-9088-234X], Williams, Julie [0000-0002-4069-0259], Frikke-Schmidt, Ruth [0000-0003-4084-5027], Seshadri, Sudha [0000-0001-6135-2622], Andreassen, Ole A [0000-0002-4461-3568], Sleegers, Kristel [0000-0002-0283-2332], van Duijn, Cornelia M [0000-0002-2374-9204], Sims, Rebecca [0000-0002-3885-1199], van der Flier, Wiesje M [0000-0001-8766-6224], Ramirez, Alfredo [0000-0003-4991-763X], Lambert, Jean-Charles [0000-0003-0829-7817], Apollo - University of Cambridge Repository, Complex Trait Genetics, Clinical sciences, Neuroprotection & Neuromodulation, Pathologic Biochemistry and Physiology, Clinical Biology, Epidemiology, Internal Medicine, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Med Staf Spec Psychiatrie (9), UAM. Departamento de Biología Molecular, University of Helsinki, Department of Neurosciences, HUS Internal Medicine and Rehabilitation, Timo Strandberg / Principal Investigator, Department of Medicine, Clinicum, HUS Neurocenter, Neurologian yksikkö, Centre of Excellence in Complex Disease Genetics, HUS Abdominal Center, Institut Pasteur, Institut National de la Santé et de la Recherche Médicale (France), European Commission, LabEx DISTALZ, Pérez-Tur, Jordi, University Children’s Hospital Basel (Suiza), INSERM (Francia), Lille Métropole Communauté Urbaine, Government of France (Francia), EADB, GR@ACE, DEGESCO, EADI, GERAD, Demgene, FinnGen, ADGC, CHARGE, Holmans, Peter A. [0000-0003-0870-9412], van der Lee, Sven J. [0000-0003-1606-8643], Costa, Marcos R. [0000-0002-4928-2163], Bis, Joshua C. [0000-0002-3409-1110], Brookes, Keeley J. [0000-0003-2427-2513], Bush, William S. [0000-0002-9729-6519], de Witte, Lot D. [0000-0002-7235-9958], del Ser, Teodoro [0000-0001-9806-7083], Fox, Nick C. [0000-0002-6660-657X], Bullido, María J. [0000-0002-6477-1117], Goate, Alison M. [0000-0002-0576-2472], Herrmann, Martin J. [0000-0001-9970-2122], Jun, Gyungah R. [0000-0002-3230-8697], Kehoe, Patrick G. [0000-0002-7542-1139], Kosmidis, Mary H. [0000-0001-8790-1220], Lunetta, Kathryn L. [0000-0002-9268-810X], MacLeod, Catherine A. [0000-0002-9314-7380], Nöthen, Markus M. [0000-0002-8770-2464], Nordestgaard, Børge G. [0000-0002-1954-7220], Pineda, Juan A. [0000-0002-3751-0296], Real, Luis M. [0000-0003-4932-7429], Reinders, Marcel J. T. [0000-0002-1148-1562], Satizabal, Claudia L. [0000-0002-1115-4430], Schott, Jonathan M. [0000-0003-2059-024X], Shadrin, Alexey A. [0000-0002-7467-250X], Farrer, Lindsay A. [0000-0001-5533-4225], Psaty, Bruce M. [0000-0002-7278-2190], Ikram, M. Arfan [0000-0003-0372-8585], Pericak-Vance, Margaret A. [0000-0001-7283-8804], Andreassen, Ole A. [0000-0002-4461-3568], van Duijn, Cornelia M. [0000-0002-2374-9204], van der Flier, Wiesje M. [0000-0001-8766-6224], and Molecular Neuroscience and Ageing Research (MOLAR)

Subjects
tau Proteins/genetics, Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1], Neurologi, MED/03 - GENETICA MEDICA, 45/43, Medizin, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], genetics [Alzheimer Disease], Genome-Wide Association Study, Humans, tau Proteins, Alzheimer Disease, Cognitive Dysfunction, VARIANTS, pathology [Alzheimer Disease], Tau Proteins, Settore BIO/13 - Biologia Applicata, Cognitive Dysfunction/psychology, 692/699/375/365/1283, IMPUTATION, article, 1184 Genetics, developmental biology, physiology, Biología y Biomedicina / Biología, AMYLOID-BETA, Settore MED/26 - NEUROLOGIA, Neurology, psychology [Cognitive Dysfunction], Medical Genetics, Human, Neuroscience(all), 631/208/205/2138, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, ddc:570, Genetics, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, METAANALYSIS, Medicinsk genetik, MED/26 - NEUROLOGIA, Alzheimer Disease/genetics, neurology, tau Protein, NECROSIS-FACTOR-ALPHA, RISK LOCI, genetics [tau Proteins], PREDICTION MODELS, Human medicine, GENERATION, RESPONSES
Abstract

25 páginas, 6 figuras, 2 tablas, Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele., This work was funded by a grant (EADB) from the EU Joint Programme – Neurodegenerative Disease Research. INSERM UMR1167 is also funded by the INSERM, Institut Pasteur de Lille, Lille Métropole Communauté Urbaine and French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). Full consortium acknowledgements and funding are in the Supplementary Not

Published
2022
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32. Growth factor expression is enhanced, and extracellular matrix proteins are depressed in healing skin wounds in septic patients compared with healthy controls

Author

Jaurila, H. (Henna), Koskela, M. (Marjo), Koivukangas, V. (Vesa), Gäddnäs, F. (Fiia), Salo, T. (Tuula), and Ala-Kokko, T. I. (Tero I.)

Subjects
Male, Microbiology (medical), skin wound, Syndecans, Nerve Tissue Proteins, Epithelium, Pathology and Forensic Medicine, sepsis, Sepsis, Humans, Immunology and Allergy, Aged, Skin, Extracellular Matrix Proteins, Wound Healing, ECM, growth factor, Tenascin, General Medicine, Middle Aged, Extracellular Matrix, Up-Regulation, Case-Control Studies, immunohistochemistry, Intercellular Signaling Peptides and Proteins, Female
Abstract

Sepsis manifests as a dysregulated immune response to infection, damaging organs. Skin has a critical role in protecting the body. In sepsis, skin wound healing is impaired. The mechanisms behind it have been poorly studied. In this study, suction blister wounds were induced on intact abdominal skin in 15 septic patients. A single blister wound was biopsied from each patient and from 10 healthy controls. Immunohistochemical staining of growth factors and extracellular matrix (ECM) proteins was performed. Significance (p

Published
2022
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33. Amphipathic barbiturates as marine product mimics with cytolytic and immunogenic effects on head and neck squamous cell carcinoma cell lines

Author

von Hofsten, S. (Susannah), Langer, M. K. (Manuel K.), Korelin, K. (Katja), Magnussen, S. (Synnøve), Ausbacher, D. (Dominik), Anderssen, T. (Trude), Salo, T. (Tuula), Strøm, M. B. (Morten B.), Bayer, A. (Annette), Al-Samadi, A. (Ahmed), Berge, G. (Gerd), Department of Oral and Maxillofacial Diseases, HUS Head and Neck Center, and TRIMM - Translational Immunology Research Program

Subjects
calreticulin, Pharmacology, 317 Pharmacy, immunogenic cell death, cancer, head and neck squamous cell cancer (HNSCC), Pharmacology (medical), lysosomotropic, drug development
Abstract

Publisher Copyright: Copyright © 2023 von Hofsten, Langer, Korelin, Magnussen, Ausbacher, Anderssen, Salo, Strøm, Bayer, Al-Samadi and Berge. The incidence of head and neck squamous cell carcinoma (HNSCC) is increasing and the conventional treatments for this form of cancer can be tough. Despite the success of existing immunotherapies in some HNSCC patients, many do not respond to this type of treatment. Thus, the development of novel anti-cancer therapies should be prioritized. In the current study, the anticancer activity of a panel of novel compounds, herein termed marine product mimics (MPMs), against HNSCC cell lines is explored. The previously reported compound MPM-1, which is structurally related to the novel MPMs, was shown to have promising effects on the HNSCC cell line HSC-3. The results from the current study indicate that the novel MPMs are more potent than MPM-1 but cause a similar type of cell death. The results indicated that the MPMs must cross through the cell membrane to exert their action and that they are lysosomotropic. Further experiments showed that some of the MPMs could induce phosphorylation of eukaryotic initiation factor 2α (eIF2α) in HSC-3 and UT-SCC-24A cells, which indicates that they can activate the integrated stress response that is strongly associated with immunogenic cell death. Cell surface expression of calreticulin and release of HMGB1 and ATP, which are all hallmarks of immunogenic cell death, was also demonstrated in HSC-3 and UT-SCC-24A cells treated with MPMs. This suggests that the MPMs are interesting candidates for future HNSCC cancer therapies.

Published
2023

36. Verkkojen reunaväritykset

Author

Salo, T. (Tuomas)

Subjects
Matematiikka
Abstract

Tiivistelmä. Tämän tutkielman aiheena ovat verkkoteorian alle kuuluvat verkkojen reunaväritykset, joissa käsiteltävän silmukattoman verkon jokaiselle reunalle määrätään jokin väri. Ensimmäisessä luvussa pohjustetaan tätä varsinaista aihetta tutustumalla reunaväritysten käsittelyn kannalta olennaisimpiin verkkoteorian peruskäsitteisiin, kuten silmukkaan, vierekkäisiin reunoihin ja asteeseen, sekä erilaisiin verkkoihin. Toisessa luvussa käsitellään ensin reunavärityksiin liittyviä peruskäsitteitä ja määritellään sitten näiden pohjalta verkon reunakromaattinen luku. Reunakromaattisen luvun määrittämistä käsitellään sekä yksinkertaisen esimerkin että lauseiden kautta. Keskeisimmässä roolissa on kaksijakoisen verkon reunakromaattisen luvun osoittaminen. Reunaväritysten sovelluskohteena tarkastellaan lukujärjestysongelmaa, jossa tehtävänä on määrittää lukujärjestys kouluun mahdollisimman pienellä tuntimäärällä. Tutkielman lukijan on hyvä omata tietämystä yliopistotason matemaattisista merkinnöistä ja käsitteistä, mutta esitietoja verkkoteoriasta ei vaadita. Esimerkit ovat itse tehtyjä, ja todistuksia on tarvittaessa muokattu hieman sekä kirjoitettu yksityiskohtaisemmin kuin lähteessä.

Published
2022

39. The prognostic influence of lymphatic endothelium–specific hyaluronan receptor 1 in cancer: A systematic review

Author

Karinen, S. (Sini), Hujanen, R. (Roosa), Salo, T. (Tuula), and Salem, A. (Abdelhakim)

Subjects
Vesicular Transport Proteins, Review Article, Prognosis, lymphatic vessel endothelial hyaluronan receptor 1, Gene Expression Regulation, Neoplastic, Neoplasms, Biomarkers, Tumor, biomarker, cancer, metastasis, Humans, Neoplasm Invasiveness, prognosis, Review Articles
Abstract

Lymphangiogenesis is a key process in cancer development and metastasis. Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE‐1) is a widely used marker for lymphatic endothelial cells (LEC), which also mediates immune and cancer cell migration. Recently, LYVE‐1–positive tumor cells were shown to acquire LEC‐like phenotype and exploit this receptor for lymphatic dissemination. Furthermore, selective targeting of LYVE‐1 impaired the growth of cancer‐related vasculature and reduced metastasis in vivo, signifying its role in therapeutic and prognostic applications. Although numerous studies have investigated the role of LYVE‐1 in cancer, a unifying detailed review of its prognostic utility is lacking to date. Thus, we compiled and critically appraised evidence from clinical studies comprising a total of 2352 patients diagnosed with different types of cancer and using a variety of experimental approaches. Collectively, most studies revealed a significant association between LYVE‐1 overexpression and dismal outcome of at least one survival estimate. Furthermore, the importance of vasculature location, intra‐ or peritumoral, and the influence of various lymphangiogenesis‐related parameters, such as lymphatic vessel density and invasion, were discussed. However, the specificity of LYVE‐1 staining is challenged by its expression in non‐LEC cells, implying the need for double labelling to better estimate its prognostic significance. In conclusion, this is to our knowledge the first comprehensive systematic review on the prognostic value of LYVE‐1 in cancer. More well‐designed studies across different populations and the development of standardized protocols would be paramount for the consistency of LYVE‐1 findings and for its potential transferability to clinical practice in future., In spite of the fast‐growing pipeline of novel biomarkers, there is unmet need for accurate and reliable molecules that can facilitate risk stratification and individualized treatment decisions of cancer patients. The present comprehensive review is the first study to compile evidence and analyse the utility of LYVE‐1 for the mapping of the lymphatic vasculature, which also provided useful information, including current limitations, regarding the potential transferability of this intriguing marker to clinical practice in the future.

Published
2021

40. Cost of illness of oral lichen planus: a multicenter university hospital–based outpatient observational study

Author

Lajolo C., Rupe C., Gioco G., Giuliani M., Contaldo M., Salo T., Siponen M., Lajolo, C., Rupe, C., Gioco, G., Giuliani, M., Contaldo, M., Salo, T., and Siponen, M.

Subjects
Male, Oral medicine, Hospitals, University, Settore MED/28 - MALATTIE ODONTOSTOMATOLOGICHE, stomatognathic diseases, Oral lichen planu, Cost of illne, Chronic Disease, Outpatients, Oral lichen planus, Humans, Cost of illness, Female, General Dentistry, health care economics and organizations, Lichen Planus, Oral, Retrospective Studies
Abstract

Abstract Objectives To estimate the economic costs of oral lichen planus (OLP) through a multicenter university hospital–based outpatient study conducted in Italy and Finland. Materials and methods A multicenter retrospective study was conducted on patients affected by OLP to evaluate the economic cost of managing the disease. Direct costs concerning diagnostic procedures, therapeutic management, and follow-up visits were obtained from clinical records. Statistics was performed with IBM SPSS Statistics. Results One hundred and eight patients with a confirmed diagnosis of OLP (81 women and 27 men), 58 Italians and 50 Finnish, were enrolled in this study. The mean annual cost was 1087.2 euros per patient. The mean annual cost was higher in Finnish than in Italian cohort (1558.7 euros vs. 680.7 euros—p p p Conclusions OLP-related costs are very similar to other chronic oral disorders (i.e., periodontitis) with differences between investigated countries. Moreover, patients with more severe clinical features, who need immunosuppressive therapy, are facing more expensive costs. Clinical relevance. In this multicenter cost of illness study, we estimated the direct health care costs of OLP and we found that patients with more severe clinical features, who therefore need symptomatic therapy, are facing more expensive costs.

Published
2022

43. ANALYTIC IN THE UNIT POLYDISC FUNCTIONS OF BOUNDED L-INDEX IN DIRECTION.

Author

BANDURA, A. and SALO, T.

Subjects
CONTINUOUS functions, ANALYTIC functions, LOGARITHMIC functions, DIFFERENTIAL equations, INFINITE products
Abstract

The concept of bounded L-index in a direction b = (b1,. . ., bn) ∊ Cn \ {0} is generalized for a class of analytic functions in the unit polydisc, where L is some continuous function such that for every z = (z1, . . ., zn) ∊ Dn one has L(z) > β max1≤j≤n |bj/|1-|zj|, β = const > 1, Dn is the unit polydisc, i.e. Dn = {z ∊ Cn: |zj| ≤ 1, j ∊ {1, . . ., n}}. For functions from this class we obtain sufficient and necessary conditions providing boundedness of L-index in the direction. They describe local behavior of maximum modulus of derivatives for the analytic function F on every slice circle {z + tb: |t| = r/L(z)} by their values at the center of the circle, where t ∊ C. Other criterion describes similar local behavior of the minimum modulus via the maximum modulus for these functions. We proved an analog of the logarithmic criterion desribing estimate of logarithmic derivative outside some exceptional set by the function L. The set is generated by the union of all slice discs {z0 +tb: |t| ≤ r/L(z0)}, where z0 is a zero point of the function F. The analog also indicates the zero distribution of the function F is uniform over all slice discs. In one-dimensional case, the assertion has many applications to analytic theory of differential equations and infinite products, i.e. the Blaschke product, Naftalevich-Tsuji product. Analog of Hayman's Theorem is also deduced for the analytic functions in the unit polydisc. It indicates that in the definition of bounded L-index in direction it is possible to remove the factorials in the denominators. This allows to investigate properties of analytic solutions of directional differential equations. [ABSTRACT FROM AUTHOR]

Published
2023
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44. In vitro models as tools for screening treatment options of head and neck cancer

Author

Seliger, B. (Barbara), Al-Samadi, A. (Ahmed), Yang, B. (Bo), Salo, T. (Tuula), Wickenhauser, C. (Claudia), Seliger, B. (Barbara), Al-Samadi, A. (Ahmed), Yang, B. (Bo), Salo, T. (Tuula), and Wickenhauser, C. (Claudia)

Abstract

Various in vitro models using primary and established 2- and 3-dimensional cultures, multicellular tumor spheroids, standardized tumor slice cultures, tumor organoids, and microfluidic systems obtained from tumor lesions/biopsies of head and neck cancer (HNC) have been employed for exploring and monitoring treatment options. All of these in vitro models are to a different degree able to capture the diversity of tumors, recapitulate the disease genetically, histologically, and functionally and retain their tumorigenic potential upon xenotransplantation. The models were used for the characterization of the malignant features of the tumors and for in vitro screens of drugs approved for the treatment of HNC, including chemotherapy and radiotherapy as well as recently developed targeted therapies and immunotherapies, or for novel treatments not yet licensed for these tumor entities. The implementation of the best suitable model will enlarge our knowledge of the oncogenic properties of HNC, expand the drug repertoire and help to develop individually tailored treatment strategies resulting in the translation of these findings into the clinic. This review summarizes the different approaches using preclinical in vitro systems with their advantages and disadvantages and their implementation as preclinical platforms to predict disease course, evaluate biomarkers and test therapy efficacy.

Published
2022

45. Prognostic value of dysadherin in cancer:a systematic review and meta-analysis

Author

Niinivirta, A. (Aino), Salo, T. (Tuula), Åström, P. (Pirjo), Juurikka, K. (Krista), Risteli, M. (Maija), Niinivirta, A. (Aino), Salo, T. (Tuula), Åström, P. (Pirjo), Juurikka, K. (Krista), and Risteli, M. (Maija)

Abstract

Cancer is a leading cause of death worldwide and novel prognostic factors are reported with increasing numbers. Systematic reviews and meta-analyses on cumulative research data are crucial in estimating the true prognostic value of proposed factors. Dysadherin (FXYD Domain Containing Ion Transport Regulator 5; FXYD5) is a cell membrane glycoprotein that modulates Na+, K+-ATPase activity and cell-cell adhesion. It is abundantly expressed in a variety of cancer cells, but only in a limited number of normal cells and its levels are increased in many different tumor types. The expression or level of dysadherin has been suggested as an independent predictor for metastasis and poor prognosis by number of studies, yet we lack a definitive answer. In this study, we systematically evaluated the prognostic value of dysadherin in cancer and summarized the current knowledge on the subject. PubMed, Scopus, Web of Science and relevant clinical trial and preprint databases were searched for relevant publications and PRISMA and REMARK guidelines were applied in the process. After a careful review, a total of 23 original research articles were included. In each study, dysadherin was pointed as a marker for poor prognosis. Meta-analyses revealed 3- and 1.5-fold increases in the risk of death (fixed effects HR 3.08, 95% CI 1.88–5.06, RR 1.47, 95% CI 1.06–2.05 on overall survival, respectively) for patients with high (>50%) tumoral FXYD5 level. In many studies, a connection between dysadherin expression or level and metastatic behavior of the cancer as well as inverse correlation with E-cadherin level were reported. Thus, we conclude that dysadherin might be a useful prognostic biomarker in the assessment of disease survival of patients with solid tumors.

Published
2022

46. Insights into preservation of blood biomarkers in biobank samples

Author

Juurikka, K. (Krista), Åström, P. (Pirjo), Pekkala, T. (Tiina), Öhman, H. (Hanna), Sorsa, T. (Timo), Tervahartiala, T. (Taina), Salo, T. (Tuula), Lehenkari, P. (Petri), Nyberg, P. (Pia), Juurikka, K. (Krista), Åström, P. (Pirjo), Pekkala, T. (Tiina), Öhman, H. (Hanna), Sorsa, T. (Timo), Tervahartiala, T. (Taina), Salo, T. (Tuula), Lehenkari, P. (Petri), and Nyberg, P. (Pia)

Published
2022

47. Tertiary lymphoid structures associate with improved survival in early oral tongue cancer

Author

Almangush, A. (Alhadi), Bello, I. O. (Ibrahim O.), Elseragy, A. (Amr), Hagström, J. (Jaana), Haglund, C. (Caj), Kowalski, L. P. (Luiz Paulo), Nieminen, P. (Pentti), Coletta, R. D. (Ricardo D.), Mäkitie, A. A. (Antti A.), Salo, T. (Tuula), Leivo, I. (Ilmo), Almangush, A. (Alhadi), Bello, I. O. (Ibrahim O.), Elseragy, A. (Amr), Hagström, J. (Jaana), Haglund, C. (Caj), Kowalski, L. P. (Luiz Paulo), Nieminen, P. (Pentti), Coletta, R. D. (Ricardo D.), Mäkitie, A. A. (Antti A.), Salo, T. (Tuula), and Leivo, I. (Ilmo)

Abstract

Background: The clinical significance of tertiary lymphoid structures (TLSs) is not well-documented in early oral tongue squamous cell carcinoma (OTSCC). Methods: A total of 310 cases of early (cT1-2N0) OTSCC were included in this multicenter study. Assessment of TLSs was conducted on hematoxylin and eosin-stained sections. TLSs were assessed both in the central part of the tumor and at the invasive front area. Results: The presence of TLSs associated with improved survival of early OTSCC as presented by Kaplan–Meier survival analyses for disease-specific survival (P = 0.01) and overall survival (P = 0.006). In multivariable analyses, which included conventional prognostic factors, the absence of TLSs associated with worse disease-specific survival with a hazard ratio (HR) of 1.96 (95% CI 1.09–3.54; P = 0.025) and poor overall survival (HR 1.66, 95% CI 1.11–2.48; P = 0.014). Conclusion: Histological evaluation of TLSs predicts survival in early OTSCC. TLSs showed superior prognostic power independent of routine WHO grading and TNM staging system.

Published
2022

48. Emerging histopathologic markers in early-stage oral tongue cancer:a systematic review and meta-analysis

Author

Elseragy, A. (Amr), Bello, I. O. (Ibrahim O.), Wahab, A. (Awais), Coletta, R. D. (Ricardo D.), Mäkitie, A. A. (Antti A.), Leivo, I. (Ilmo), Almangush, A. (Alhadi), Salo, T. (Tuula), Elseragy, A. (Amr), Bello, I. O. (Ibrahim O.), Wahab, A. (Awais), Coletta, R. D. (Ricardo D.), Mäkitie, A. A. (Antti A.), Leivo, I. (Ilmo), Almangush, A. (Alhadi), and Salo, T. (Tuula)

Abstract

Although there are many histopathologic prognosticators, grading of early oral tongue squamous cell carcinoma (OTSCC) is still based on morphological cell differentiation which has low prognostic value. Here we summarize the emerging histopathological markers showing powerful prognostic value, but are not included in pathology reports. Using PubMed, Scopus, Ovid Medline, and Web of Science databases, a systematic literature search was preformed to identify early OTSCC studies that investigated the prognostic significance of hematoxylin–eosin-based histopathologic markers. Our meta-analysis showed that tumor budding was associated with overall survival (hazard ratio [HR] 2.32; 95% CI 1.40–3.84; p < 0.01) and disease-specific survival (DSS) (1.89; 95% CI 1.13–3.15; p = 0.02). Worst pattern of invasion was associated with disease-free survival (DFS) (1.95; 95% CI 1.04–3.64; p = 0.04). Tumor–stroma ratio was also associated with DFS (1.75, 95% CI 1.24–2.48; p < 0.01) and DSS (1.69; 95% CI 1.19–2.42; p < 0.01). Tumor budding, worst pattern of invasion, and tumor–stroma ratio have a promising prognostic value in early OTSCC. The evaluation and reporting of these markers is cost-effective and can be incorporated in daily practice.

Published
2022

49. miR-22 and miR-205 drive tumor aggressiveness of mucoepidermoid carcinomas of salivary glands

Author

Naakka, E. (Erika), Barros-Filho, M. C. (Mateus Camargo), Adnan-Awad, S. (Shady), Al-Samadi, A. (Ahmed), Marchi, F. A. (Fábio Albuquerque), Kuasne, H. (Hellen), Korelin, K. (Katja), Suleymanova, I. (Ilida), Brown, A. L. (Amy Louise), Scapulatempo-Neto, C. (Cristovam), Lourenço, S. V. (Silvia Vanessa), Castilho, R. M. (Rogério Moraes), Kowalski, L. P. (Luiz Paulo), Mäkitie, A. (Antti), Araújo, V. C. (Vera Cavalcanti), Leivo, I. (Ilmo), Rogatto, S. R. (Silvia Regina), Salo, T. (Tuula), Passador-Santos, F. (Fabricio), Naakka, E. (Erika), Barros-Filho, M. C. (Mateus Camargo), Adnan-Awad, S. (Shady), Al-Samadi, A. (Ahmed), Marchi, F. A. (Fábio Albuquerque), Kuasne, H. (Hellen), Korelin, K. (Katja), Suleymanova, I. (Ilida), Brown, A. L. (Amy Louise), Scapulatempo-Neto, C. (Cristovam), Lourenço, S. V. (Silvia Vanessa), Castilho, R. M. (Rogério Moraes), Kowalski, L. P. (Luiz Paulo), Mäkitie, A. (Antti), Araújo, V. C. (Vera Cavalcanti), Leivo, I. (Ilmo), Rogatto, S. R. (Silvia Regina), Salo, T. (Tuula), and Passador-Santos, F. (Fabricio)

Abstract

Objectives: To integrate mRNA and miRNA expression profiles of mucoepidermoid carcinomas (MECs) and normal salivary gland (NSGs) tissue samples and identify potential drivers. Material and Methods: Gene and miRNA expression arrays were performed in 35 MECs and six NSGs. Results: We found 46 differentially expressed (DE) miRNAs and 3,162 DE mRNAs. Supervised hierarchical clustering analysis of the DE transcripts revealed two clusters in both miRNA and mRNA profiles, which distinguished MEC from NSG samples. The integrative miRNA-mRNA analysis revealed a network comprising 696 negatively correlated interactions (44 miRNAs and 444 mRNAs) involving cell signaling, cell cycle, and cancer-related pathways. Increased expression levels of miR-205-5p and miR-224-5p and decreased expression levels of miR-139-3p, miR-145-3p, miR-148a-3p, miR-186-5p, miR-338-3p, miR-363-3p, and miR-4324 were significantly related to worse overall survival in MEC patients. Two overexpressed miRNAs in MEC (miR-22 and miR-205) were selected for inhibition by the CRISPR-Cas9 method. Cell viability, migration, and invasion assays were performed using an intermediate grade MEC cell line. Knockout of miR-205 reduced cell viability and enhanced ZEB2 expression, while miR-22 knockout reduced cell migration and invasion and enhanced ESR1 expression. Our results indicate a distinct transcriptomic profile of MEC compared to NSG, and the integrative analysis highlighted miRNA-mRNA interactions involving cancer-related pathways, including PTEN and PI3K/AKT. Conclusion: The in vitro functional studies revealed that miR-22 and miR-205 deficiencies reduced the viability, migration, and invasion of the MEC cells suggesting they are potential oncogenic drivers in MEC.

Published
2022

50. Oral microbiota:a new frontier in the pathogenesis and management of head and neck cancers

Author

Metsäniitty, M. (Marjut), Hasnat, S. (Shrabon), Salo, T. (Tuula), Salem, A. (Abdelhakim), Metsäniitty, M. (Marjut), Hasnat, S. (Shrabon), Salo, T. (Tuula), and Salem, A. (Abdelhakim)

Abstract

Head and neck squamous cell carcinoma (HNSCC) comprises the majority of tumors in head and neck tissues. The prognosis of HNSCC has not significantly improved for decades, signifying the need for new diagnostic and therapeutic targets. Recent evidence suggests that oral microbiota is associated with carcinogenesis. Thus, we conducted a comprehensive systematic review to evaluate the current evidence regarding the role of oral microbiota in HNSCC and whether their targeting may confer diagnostic, prognostic or therapeutic utility. Following the screening of 233 publications retrieved from multiple databases, 34 eligible studies comprising 2469 patients were compiled and critically appraised. Importantly, many oral pathogens, such as Porphyromonas gingivalis and Fusobacterium nucleatum were linked to certain oral potentially malignant lesions and various types of HNSCC. Furthermore, we summarized the association between the expression profiles of different oral bacterial species and their tumorigenic and prognostic effects in cancer patients. We also discussed the current limitations of this newly emerging area and the potential microbiota-related strategies for preventing and treating HNSCC. Whilst many clinical studies are underway to unravel the role of oral microbiota in cancer, the limited available data and experimental approaches reflect the newness of this promising yet challenging field.

Published
2022

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