Research Outputs

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3D printed kombucha biomaterial as a tissue scaffold and L929 cell cytotoxicity assay
(Wiley, 2024) Yanbakan, Edaguel; Tuncel, Tugba; Kocak Sezgin, Ayse; Bozoglan, Emirhan; Berikten, Derya; Kar, Fatih; Department of Molecular Biology and Genetics; Bağlan, İlkyaz; Department of Molecular Biology and Genetics; College of Sciences
Tissue engineering includes the construction of tissue-organ scaffold. The advantage of three-dimensional scaffolds over two-dimensional scaffolds is that they provide homeostasis for a longer time. The microbial community in Symbiotic culture of bacteria and yeast (SCOBY) can be a source for kombucha (kombu tea) production. In this study, it was aimed to investigate the usage of SCOBY, which produces bacterial cellulose, as a biomaterial and 3D scaffold material. 3D printable biomaterial was obtained by partial hydrolysis of oolong tea and black tea kombucha biofilms. In order to investigate the usage of 3D kombucha biomaterial as a tissue scaffold, "L929 cell line 3D cell culture" was created and cell viability was tested in the biomaterial. At the end of the 21st day, black tea showed 51% and oolong tea 73% viability. The cytotoxicity of the materials prepared by lyophilizing oolong and black tea kombucha beverages in fibroblast cell culture was determined. Black tea IC50 value: 7.53 mg, oolong tea IC50 value is found as 6.05 mg. Fibroblast viability in 3D biomaterial + lyophilized oolong and black tea kombucha beverages, which were created using the amounts determined to these values, were investigated by cell culture Fibroblasts in lyophilized and 3D biomaterial showed viability of 58% in black tea and 78% in oolong tea at the end of the 7th day. In SEM analysis, it was concluded that fibroblast cells created adhesion to the biomaterial. 3D biomaterial from kombucha mushroom culture can be used as tissue scaffold and biomaterial.
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3D printed styrax liquidus (liquidambar orientalis miller)-loaded poly (l-lactic acid)/chitosan based wound dressing material: fabrication, characterization, and biocompatibility results
(Elsevier, 2023) Cakmak, Hanife Yuksel; Ege, Hasan; Yilmaz, Senanur; Agturk, Gokhan; Enguven, Gozde; Sarmis, Abdurrahman; Cakmak, Zeren; Gunduz, Oguzhan; Ege, Zeynep Ruya; Yöntem, Fulya Dal; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine
The medicinal plant of Styrax liquidus (ST) (sweet gum balsam) which extracted from Liquidambar orientalis Mill tree, was loaded into the 3D printed polylactic acid (PLA)/chitosan (CS) based 3D printed scaffolds to investigate its wound healing and closure effect, in this study. The morphological and chemical properties of the ST loaded 3D printed scaffolds with different concentrations (1 %, 2 %, and 3 % wt) were investigated by Scanning Electron Microscopy (SEM) and Fourier Transform Infrared Spectroscopy (FT-IR), respectively. In addition, the me-chanical and thermal properties of the materials were investigated by Tensile test and Differential Scanning Calorimetry (DSC), respectively. The antimicrobial activities of the ST loaded 3D printed scaffolds and their incubation media in the PBS (pH 7.4, at 37 degrees C for 24 h) were investigated on two Gram-positive and two Gram -negative standard pathogenic bacteria with the agar disc diffusion method. The colorimetric MTT assay was used to determine the cell viability of human fibroblast cells (CCD-1072Sk) incubated with free ST, ST loaded, and unloaded 3D printed scaffolds. The 1 % and 2 % (wt) ST loaded PLA/CS/ST 3D printed scaffolds showed an increase in the cell number. Annexin V/PI double stain assay was performed to test whether early or late apoptosis was induced in the PLA/CS/1 % ST and PLA/CS/2 % ST loaded groups and the results were consistent with the MTT assay. Furthermore, a wound healing assay was carried out to investigate the effect of ST loaded 3D printed scaffolds on wound healing in CCD-1072Sk cells. The highest wound closure compared to the control group was observed on cells treated with PLA/CS/1 % ST for 72 h. According to the results, novel biocompatible ST loaded 3D printed scaffolds with antimicrobial effect can be used as wound healing material for potential tissue engineering applications.
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3D-printed micrometer-scale wireless magnetic cilia with metachronal programmability
(Amer Assoc Advancement Science, 2023) Zhang, Shuaizhong; Hu, Xinghao; Li, Meng; Bozuyuk, Ugur; Zhang, Rongjing; Suadiye, Eylul; Han, Jie; Wang, Fan; Onck, Patrick; Department of Mechanical Engineering; Sitti, Metin; Department of Mechanical Engineering; College of Engineering; School of Medicine
Biological cilia play essential roles in self-propulsion, food capture, and cell transportation by performing coor-dinated metachronal motions. Experimental studies to emulate the biological cilia metachronal coordination are challenging at the micrometer length scale because of current limitations in fabrication methods and ma-terials. We report on the creation of wirelessly actuated magnetic artificial cilia with biocompatibility and meta-chronal programmability at the micrometer length scale. Each cilium is fabricated by direct laser printing a silk fibroin hydrogel beam affixed to a hard magnetic FePt Janus microparticle. The 3D-printed cilia show stable actuation performance, high temperature resistance, and high mechanical endurance. Programmable meta-chronal coordination can be achieved by programming the orientation of the identically magnetized FePt Janus microparticles, which enables the generation of versatile microfluidic patterns. Our platform offers an unprecedented solution to create bioinspired microcilia for programmable microfluidic systems, biomedical en-gineering, and biocompatible implants.
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A Bayesian network analysis to examine the effects of HIV stigma processes on self-concept and depressive symptoms among persons living with HIV
(Wiley, 2024) Pala, Andrea Norcini; Department of Psychology; Turan, Bülent; Department of Psychology; College of Social Sciences and Humanities
Objective: This study examines the relationships between HIV stigma dimensions, self-related mechanisms, and depressive symptoms among persons living with HIV. Background: HIV stigma hinders the well-being of individuals living with HIV, which is linked to depressive symptoms and increased risk of poor clinical outcomes. However, the mechanisms underlying stigma's impact on depression are poorly understood. Psychosocial theories propose that experiencing HIV stigma leads to internalized stigma, impacting self-concept and mental health. Method: Using Bayesian network analysis, we explored associations among HIV stigma processes (experienced, anticipated, internalized, perceived community stigma, and HIV status disclosure) and self-related mechanisms (self-esteem, fear of negative evaluation [FNE], self-blame coping, and social exclusion), and depressive symptoms. Results: Our diverse sample of 204 individuals, primarily men, gay/bisexual, Black, and lower-middle SES, who experienced stigma showed increased anticipated, internalized, and perceived community stigma, FNE, and depressive symptoms. Internalized stigma contributed to self-blame coping and higher depressive symptoms. Anticipated and perceived community stigma and FNE correlated with increased social exclusion. Discussion: This study investigates potential mechanisms through which HIV stigma may impact depression. Identifying these mechanisms establishes a foundation for future research to inform targeted interventions, enhancing mental health and HIV outcomes among individuals living with HIV, especially from minority backgrounds. Insights gained guide evidence-based interventions to mitigate HIV stigma's detrimental effects, ultimately improving overall well-being and health-related outcomes for people with HIV.
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A case of left testicular artery with high origin passing through a left renal vein fenestration
(Via Medica Medical Publishers, 2024) Yılmaz, Ebru; Tatar, Cem; Keskin, Aleyna; Yalçın, Büşra; Gürses, İlke Ali; Graduate School of Health Sciences; School of Medicine
Background: Fenestrations of are extremely rare in the venous system, especially renal veins. This paper aims to present a case of left renal vein fenestration where a high origin testicular artery passes through it. Materials and Methods The variation was observed incidentally in a 74-year-old Caucasian male cadaver during routine retroperitoneal dissections for second year medical students. Results: A fenestration in the mid portion of the left renal vein was observed. The length and height of the fenestration was 23 and 3.6 millimeters, respectively. The left testicular artery passed through the fenestration and followed a normal course distal to the fenestration. Posterior to the left renal vein, the testicular artery originated from the lateral aspect of abdominal aorta, just caudal to the left renal artery. On the right side, the testicular artery had a similar high origin, and two renal arteries were present. No venous variations were observed on the right side. Conclusions: The long course of the left renal vein is a factor of preference for donor kidney selection. Uncommon variations of the left renal veins, such as fenestrations, might result in a change in surgical technique and would put the left donor kidney at risk of prolonged anastomosis time and lower survival rates.
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A case of pathologic complete response after neoadjuvant triplet chemotherapy for locally advanced colon cancer with mismatch repair enzyme proficiency
(Via Medica, 2023) Kocak, Mehmet Zahid; Cakir, Murat; Kerimoglu, Ulku; Araz, Murat; Eryilmaz, Melek Karakurt; Artac, Mehmet; Yumuk, Perran Fulden; School of Medicine
Patients with potentially resectable colon cancer and expected to have negative margins should undergo resection rather than neoadjuvant chemotherapy. Recent studies have suggested that neoadjuvant immunotherapy may be an option for tumors with mismatch repair enzyme deficiency (dMMR), but standard treatment for locally advanced colon cancer with mismatch repair enzyme proficiency (pMMR) is still unclear. A 37-year-old male patient was diagnosed with clinical stage IIIC (T4b N1a M0) transverse colon cancer. Mismatch repair proteins were proficient. After 3 cycles of oxaliplatin (85 mg/m(2), day 1), irinotecan (150 mg/m2, IV, day 1), leucovorin (200 mg/m(2), IV, day 1), and 5-fluorouracil (3000 mg/m(2), 46 hours of continuous infusion initiating from day 1), there was a remarkable reduction in the tumoral mass on the abdominal computed tomography. A right hemicolectomy was performed. A pathologic complete response was obtained. Although there is no consensus on which patients are suitable for neoadjuvant therapy in pMMR locally advanced colon cancer, triplet chemotherapy may be a reasonable option in selected patients.
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A CCG expansion in ABCD3 causes oculopharyngodistal myopathy in individuals of European ancestry
(Nature Portfolio, 2024) Cortese, Andrea; Beecroft, Sarah J.; Facchini, Stefano; Curro, Riccardo; Cabrera-Serrano, Macarena; Stevanovski, Igor; Chintalaphani, Sanjog R.; Gamaarachchi, Hasindu; Weisburd, Ben; Folland, Chiara; Monahan, Gavin; Scriba, Carolin K.; Dofash, Lein; Johari, Mridul; Grosz, Bianca R.; Ellis, Melina; Fearnley, Liam G.; Tankard, Rick; Read, Justin; Merve, Ashirwad; Dominik, Natalia; Vegezzi, Elisa; Schnekenberg, Ricardo P.; Fernandez-Eulate, Gorka; Masingue, Marion; Giovannini, Diane; Delatycki, Martin B.; Storey, Elsdon; Gardner, Mac; Amor, David J.; Nicholson, Garth; Vucic, Steve; Henderson, Robert D.; Robertson, Thomas; Dyke, Jason; Fabian, Vicki; Mastaglia, Frank; Davis, Mark R.; Kennerson, Marina; Quinlivan, Ros; Hammans, Simon; Tucci, Arianna; Bahlo, Melanie; McLean, Catriona A.; Laing, Nigel G.; Stojkovic, Tanya; Houlden, Henry; Hanna, Michael G.; Deveson, Ira W.; Lockhart, Paul J.; Lamont, Phillipa J.; Fahey, Michael C.; Bugiardini, Enrico; Ravenscroft, Gianina; Yesil, Gozde; Malfatti, Edoardo; Lilliker, James B.; Wicklund, Matthew; Pitceathly, Robert D. S.; Brady, Stefen; Brais, Bernard; Pellerin, David; Zuchner, Stephan; Danzi, Matt C.; Grandis, Marina; Comi, Giacomo P.; Corti, Stefania P.; Abati, Elena; Toscano, Antonio; Manini, Arianna; Ghia, Arianna; Tassorelli, Cristina; Quartesan, Ilaria; Simone, Roberto; Rossor, Alexander M.; Reilly, Mary M.; Carroll, Liam; Straub, Volker; Udd, Bjarne; Chen, Zhiyong; Bonne, Gisele; Oflazer, Piraye; Başak, Ayşe Nazlı; Kayserili, Hülya; ; School of Medicine;
Oculopharyngodistal myopathy (OPDM) is an inherited myopathy manifesting with ptosis, dysphagia and distal weakness. Pathologically it is characterised by rimmed vacuoles and intranuclear inclusions on muscle biopsy. In recent years CGG center dot CCG repeat expansion in four different genes were identified in OPDM individuals in Asian populations. None of these have been found in affected individuals of non-Asian ancestry. In this study we describe the identification of CCG expansions in ABCD3, ranging from 118 to 694 repeats, in 35 affected individuals across eight unrelated OPDM families of European ancestry. ABCD3 transcript appears upregulated in fibroblasts and skeletal muscle from OPDM individuals, suggesting a potential role of over-expression of CCG repeat containing ABCD3 transcript in progressive skeletal muscle degeneration. The study provides further evidence of the role of non-coding repeat expansions in unsolved neuromuscular diseases and strengthens the association between the CGG center dot CCG repeat motif and a specific pattern of muscle weakness.
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A characterization of heaviness in terms of relative symplectic cohomology
(Wiley, 2024) Mak, Cheuk Yu; Sun, Yuhan; Department of Mathematics; Varolgüneş, Umut; Department of Mathematics; College of Sciences
For a compact subset K$K$ of a closed symplectic manifold (M,omega)$(M, \omega)$, we prove that K$K$ is heavy if and only if its relative symplectic cohomology over the Novikov field is nonzero. As an application, we show that if two compact sets are not heavy and Poisson commuting, then their union is also not heavy. A discussion on superheaviness together with some partial results is also included.
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A cross sectional study evaluating the relationship of acne to androgenetic alopecia subtype and severity
(Springer, 2024) Kazan, Didem; Gencebay, Gullu; Caf, Nazli; Esen, Beril Kara; Oba, Muazzez Cigdem; Özkoca, Defne; Koç University Hospital
The circulating androgens have a role in the pathogenesis of both acne vulgaris and androgenetic alopecia; an association between these two have been found previously. The aim of this study is to investigate the relationship of the severity of acne vulgaris lesions to the subtype of AGA; and to validate the relationship between severities of acne vulgaris and AGA. This study was conducted cross-sectionally at five different dermatology clinics. Male and female androgenetic alopecia patients with comorbid acne vulgaris have been included. The age, gender, severity of acne lesions, subtype of androgenetic alopecia and the severity of androgenetic alopecia were noted. The severity of acne lesions were graded according to the Global Acne Severity Scale and androgenetic alopecia was graded according to the Hamilton and Ludwig Scales. SPSS v 21 was used for the statistical analysis. A total of 101 patients have been included (12 male and 89 female). The mean age of the patients with severe acne was statistically significantly lower (p = 0.020). The difference in terms of gender was statistically insignificant (p = 0.388). The severity of acne vulgaris was found to be independent of the severity and of the subtype of AGA; p = 0.623 and 0.870 respectively. Neither a relationship between the severity of androgenetic alopecia and severity of acne; nor a relationship between acne severity and androgenetic alopecia subtype were found in this study. Thus we report that, acne severity is independent of the subtype and stage of the co-existing androgenetic alopecia.
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A cross-linguistic approach to children's reasoning: Turkish- and English-speaking children's use of metatalk
(John Wiley and Sons Inc, 2024) Hartwell, Kirstie; Köymen, Bahar; Özkan, Fatma Ece; Graduate School of Social Sciences and Humanities
When collaboratively solving problems, children discuss information reliability, for example, whether claims are based on direct or indirect observation, termed as “metatalk”. Unlike English in which evidential marking is optional, languages with obligatory evidential marking such as Turkish, might provide children some advantages in communicating the reliability of their claims. The current preregistered online study investigated Turkish- and English-speaking 3- and 5-year-old children's (N = 144) use of metatalk. The child and the experimenter (E) were asked to decide in which of the two houses a toy was hiding. One house had the toy's footprints. When E left the Zoom meeting, an informant told the child that the toy was in the other house without the footprints in three within-subjects conditions. In the direct-observation condition, the child witnessed the informant move the toy. In the indirect-witness condition, the informant checked both houses and said that the toy was in the other house. In the indirect-hearsay condition, the informant simply said that the toy was in the other house. When E returned, the child had to convince E about how they knew the toy was in the other house using metatalk (e.g., “I saw it move”). Turkish-speaking children used metatalk more often than did English-speaking children, especially in the direct-observation condition. In the two indirect conditions, both groups of 5-year-olds were similar in their use of metatalk, but Turkish speaking 3-year-olds produced metatalk more often than did English-speaking 3-year-olds. Thus, languages with obligatory evidential marking might facilitate children's collaborative reasoning. Research Highlights: Children as young as 3 years of age can produce metatalk. Turkish-speaking children produce metatalk more often than English-speaking children. The difference between the two linguistic groups is more pronounced at age 3.
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A framework for evaluating the safety and homogenizing effect of freeway traffic controllers on mixed traffic conditions
(Springer Heidelberg, 2023) Silgu, Mehmet Ali; Graduate School of Sciences and Engineering
Due to recent advancements in connected and autonomous vehicles (CAVs), freeway traffic control (FTC) has become a trendy area of research. Combining CAVs and control measures has opened more efficient traffic flow possibilities. However, while there is extensive research on how traffic control and CAVs can enhance traffic flow performance, their safety benefits should be evaluated more comprehensively. It is challenging to distinguish their contributions to traffic flow safety. Studies on the safety of CAVs in traffic flow indicate that traffic flow safety improves with higher market penetration rates (MPR) of CAVs. However, this finding only sometimes aligns with the traffic flow performance effects of CAVs on freeways. This paper introduces a framework for assessing the safety effects of FTC strategies in mixed traffic scenarios involving human-driven vehicles and CAVs. The proposed framework is tested through a microsimulation-based case study in Istanbul, Turkey. The results show that, despite varying MPRs, the safety effects of CAVs and FTC methods do not consistently reduce the number of conflicts in the traffic flow context.
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A genetic cause for intractable seizures: atypical Gaucher disease with a novel pathological variant
(WILEY, 2024) Üçem, Selen; Avcı, Şahin; Gürses, Rabia Candan; School of Medicine; Koç University Hospital
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A global action agenda for turning the tide on fatty liver disease
(Wolters Kluwer Medknow Publications, 2023) Lazarus, Jeffrey V.Mark, Henry E.Allen, Alina M.Arab, Juan PabloCarrieri, PatriziaNoureddin, MazenAlazawi, WilliamAlkhouri, NaimAlqahtani, Saleh A.Anstee, Quentin M.Arrese, MarcoBataller, RamonBerg, ThomasBrennan, Paul N.Burra, PatriziaCastro-Narro, Graciela E.Cortez-Pinto, HelenaCusi, KennethDedes, NikosDuseja, AjayFrancque, Sven M.Gastaldelli, AmaliaHagström, HannesHuang, Terry T.-K.Wajcman, Dana IvancovskyKautz, AchimKopka, Christopher J.Krag, AleksanderNewsome, Philip N.Rinella, Mary E.Romero, DianaSarin, Shiv KumarSilva, MarceloSpearman, C. WendyTerrault, Norah A.Tsochatzis, Emmanuel A.Valenti, LucaVillota-Rivas, MarcelaZelber-Sagi, ShiraSchattenberg, Jörn MWong, Vincent Wai-SunYounossi, Zobair MAberg, FredrikAdams, Leon A.Al-Naamani, KhalidAlbadawy, Reda M.Alexa, ZinaidaAllison, MichaelAlnaser, Faisal AbdullatifAlswat, KhalidAlvares-Da-Silva, Mario R.Alvaro, DomenicoAlves-Bezerra, MicheleAndrade, Raul J.Awuku, Yaw AsanteBaatarkhuu, OidovBaffy, GyorgyBakieva, Shokhista RBansal, Meena B.Barouki, Robert, Batterham, Rachel L.Behling, CynthiaBelfort-DeAguiar, RenataBerzigotti, AnnalisaBetel, MichaelBianco, CristianaBosi, EmanueleBoursier, JeromeBrunt, Elizabeth M.Bugianesi, ElisabettaByrne, Christopher J.Cabrejos, Maria Cecilia CabreraCaldwell, StephenCarr, RotonyaFernández, Marlen Ivón CastellanosCastera, LaurentCastillo-López, Maria GabrielaCaussy, CyrielleCerda-Reyes, EiraCeriello, AntonioChan, Wah-KheongChang, YoosooCharatcharoenwitthaya, PhunchaiChavez-Tapia, NorbertoChung, Raymond T.Colombo, MassimoCoppell, Kirsten J.Cotrim, Helma P.Craxi, AntonioCrespo, JavierDassanayake, AnuradhaDavidson, Nicholas O.de Knegt, Robert J.de Ledinghen, VictorDemir, MünevverDesalegn, HailemichaelDiago, MoisesDillon, John FDimmig, BruceDirac, M. AshworthDirchwolf, MelisaDufour, Jean-FrançoisDvorak, KarelEkstedt, MattiasEl-Kassas, MohamedElsanousi, Osama M.Elsharkawy, Ahmed M.Elwakil, Reda M.Eskridge, WayneEslam, MohammedEsmat, GamalFan, Jian-GaoFerraz, Maria LuciaFlisiak, RobertFortin, DavideFouad, YasserFriedman, Scott LFuchs, MichaelGadano, AdrianGeerts, Anja, Geier, AndreasGeorge, JacobGerber, Lynn H.Ghazinyan, Hasmik L.Gheorghe, LianaKile, Denise GiangolaGirala, MarcosBee, George Goh BoonGoossens, NicolasGraupera, IsabelGrønbæk, HenningHamid, SaeedHebditch, VanessaHenry, ZacharyHickman, Ingrid J.Hobbs, L. AnsleyHocking, Samantha L.Hofmann, Wolf PeterIdilman, RamazanIruzubieta, PaulaIsaacs, ScottIsakov, Vasily A.Ismail, Mona H.Jamal, Mohammad H.Jarvis, HelenJepsen, PeterJornayvaz, François R.Sudhamshu K.C.Kakizaki, SatoruKarpen, SaulKawaguchi, TakumiKeating, Shelley E.Khader, YousefKim, Seung UpKim, WonKleiner, David E.Koek, GerKomas, Narcisse Patrice JosephKondili, Loreta A.Koot, Bart G.Korenjak, MarkoKotsiliti, EleniKoulla, YiannoulaKugelmas, CarinaKugelmas, MarceloLabidi, AsmaLange, Naomi F.Lazo, MarianaLeite, NathalieLin, Han-ChiehLkhagvaa, UndramLong, Michelle T.Lopez-Jaramillo, PatricioLozano, AdelinaMacedo, Maria PaulaMalekzadeh, RezaMarchesini, GiulioMarciano, SebastianMartinez, KimMartínez Vázquez, Sophia E., Mateva, LyudmilaMato, José M.Mbendi, Charles N.McCary, Alexis GordenMcIntyre, JeffMcKee, MartinMendive, Juan M.Mikolasevic, IvanaMiller, Pamela S.Milovanovic, TamaraMilton, TerriMoreno-Alcantar, RosalbaMorgan, Timothy R.Motala, Ayesha A.Muris, JeanMusso, CarlaNava-González, Edna J.Negro, FrancescoNersesov, Alexander V.Neuschwander-Tetri, Brent A.Nikolova, DafinaNorris, SuzanneNovak, KatjaOcama, PonsianoOng, Janus P.Ong-Go, ArlinkingOnyekwere, CharlesPadilla-Machaca, P. MartinPais, RalucaPan, Calvin Q.Panduro, ArturoPanigrahi, Manas K.Papatheodoridis, GeorgiosParuk, ImranPatel, KeyurPenha-Goncalves, CarlosPérez, Norma M.Pérez-Escobar, JuanitaPericàs, Juan M.Perseghin, GianlucaPessoa, Mário GuimarãesPetta, Salvatorede Oliveira, Claudia Pinto Marques SouzaPrabhakaran, DorairajPryke, RachelPyrsopoulos, NikolaosRabiee, AtoosaRamji, AlnoorRatziu, VladRavendhran, NatarajanRay, KatrinaRoden, MichaelRomeo, StefanoRomero-Gómez, ManuelRotman, YaronRouabhia, SamirRowe, Ian A.Sadirova, ShakhloAlkhatry, Maryam SalemSalupere, Riina., Satapathy, Sanjaya K.Schwimmer, Jeffrey B.Sebastiani, GiadaSeim, LynnSeki, YosukeSerme, Abdel KarimShapiro, DavidSharvadze, LaliShaw, Jonathan E.Shawa, Isaac ThomShenoy, ThrivikramaShibolet, OrenShimakawa, YusukeShubrook, Jay H.Singh, Shivaram PrasadSinkala, EdfordSkladany, LubomirSkrypnyk, IgorSong, Myeong JunSookoian, SilviaSoriano, Joan B.Sridharan, KannanStefan, NorbertStine, Jonathan G.Stratakis, NikosSheriff, Dhastagir SultanSundaram, Shikha S.Svegliati-Baroni, GianlucaSwain, Mark G.Tacke, FrankTaheri, ShahradTan, Soek-SiamTapper, Elliot B.Targher, GiovanniTcaciuc, EugenThiele, MajaTiniakos, DinaTolmane, IevaTorre, AldoTorres, Esther A.Treeprasertsuk, SombatTrenell, MichaelTurcan, SvetlanaTurcanu, AdelaValantinas, Jonasvan Kleef, Laurens A.Velasco, Jose Antonio Velarde RuizVesterhus, MetteVilar-Gomez, EduardoWaked, ImamWattacheril, JuliaWedemeyer, HeinerWilkins, FondaWillemse, JoséWong, Robert J.Yilmaz, YusufYki-Järvinen, HanneleYu, Ming-Lung, Yumuk, Volkan, Zheng, Kenneth I.Zheng, Ming-Hua.; Zeybel, Müjdat; School of Medicine
Background and Aims: Fatty liver disease is a major public health threat due to its very high prevalence and related morbidity and mortality. Focused and dedicated interventions are urgently needed to target disease prevention, treatment, and care. Approach and Results: We developed an aligned, prioritized action agenda for the global fatty liver disease community of practice. Following a Delphi methodology over 2 rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the action priorities using Qualtrics XM, indicating agreement using a 4-point Likert-scale and providing written feedback. Priorities were revised between rounds, and in R2, panelists also ranked the priorities within 6 domains: epidemiology, treatment and care, models of care, education and awareness, patient and community perspectives, and leadership and public health policy. The consensus fatty liver disease action agenda encompasses 29 priorities. In R2, the mean percentage of “agree” responses was 82.4%, with all individual priorities having at least a super-majority of agreement (> 66.7% “agree”). The highest-ranked action priorities included collaboration between liver specialists and primary care doctors on early diagnosis, action to address the needs of people living with multiple morbidities, and the incorporation of fatty liver disease into relevant non-communicable disease strategies and guidance. Conclusions: This consensus-driven multidisciplinary fatty liver disease action agenda developed by care providers, clinical researchers, and public health and policy experts provides a path to reduce fatty liver disease prevalence and improve health outcomes. To implement this agenda, concerted efforts will be needed at the global, regional, and national levels.
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A high pan-immune-inflammation value before chemoradiotherapy indicates poor outcomes in patients with small-cell lung cancer
(Sage Publications Inc, 2023) Kucuk, Ahmet; Topkan, Erkan; Ozkan, Emine Elif; Ozturk, Duriye; Pehlivan, Berrin; Selek, Uğur; School of Medicine
Objectives: The objective of our study was to assess the prognostic significance of the Pan-Immune-Inflammation Value (PIV) before concurrent chemoradiation (C-CRT) and prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer (SCLC). Methods: The medical records of LS-SCLC patients who underwent C-CRT and PCI between January 2010 and December 2021 were retrospectively analyzed. PIV values were calculated using the peripheral blood samples obtained within the past 7 days before the initiation of treatment: PIV = [neutrophils x platelets x monocytes] & DIVIDE; lymphocytes. Using receiver operating characteristic (ROC) curve analysis, the optimal pretreatment PIV cutoff values that can partition the study population into two groups with substantially distinct progression-free survival (PFS) and overall survival (OS) outcomes were determined. The relationship between PIV values and OS outcomes was the primary outcome measure. Results: Eighty-nine eligible patients were divided into two PIV groups at an optimal cutoff of 417 [Area under curve (AUC): 73.2%; sensitivity: 70.4%; specificity: 66.7%]: Group 1: PIV < 417 (N = 36) and Group 2: PIV & GE; 417 (N = 53). Comparative analyses revealed that patients with PIV < 417 had significantly longer OS (25.0 vs 14.0 months, p < .001) and PFS (18.0 vs 8.9 months, p = .004) compared to patients with PIV & GE; 417. The outcomes of the multivariate analysis have verified the independent significance of pretreatment PIV concerning PFS (p < .001) and OS (p < .001) outcomes. Conclusion: The findings of this retrospective study indicate that the pretreatment PIV is a reliable and independent prognostic biomarker for patients with LS-SCLC who were treated with C-CRT and PCI.
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A moderated mediation analysis of HIV and intersectional stigmas and antiretroviral adherence in people living with HIV in the Dominican Republic
(Springer/Plenum Publishers, 2024) Yigit, Ibrahim; Paulino-Ramirez, Robert; Waters, John; Long, Dustin M.; Budhwani, Henna; Turan, Janet Molzan; School of Medicine
Experiencing HIV and intersectional stigmas in healthcare settings may affect antiretroviral treatment (ART) adherence among people with HIV (PWH), given their need for frequent interactions with clinical settings and healthcare providers. Considering the importance of reducing stigmas to promote well-being and the need to elucidate how stigma influences health across various settings, we examined how experienced HIV stigma in Dominican Republic healthcare settings impacts ART adherence through internalized HIV stigma and whether race or sexual orientation stigma moderates this relationship. Participants were 471 PWH (aged 17-71) who were recruited from two HIV clinics in the Dominican Republic in 2021-2022. Results revealed a significant mediation effect (B=-0.10, SE = 0.05, CI [-0.234, - 0.014]) after adjusting for effect of age and time since HIV diagnosis, suggesting that experienced HIV stigma in healthcare settings was associated with more internalized HIV stigma (B = 0.39, SE = 0.11, p = .001), subsequently linked to lower ART adherence (B=-0.26, SE = 0.11, p = .016). The indirect effect was significant at low levels of race stigma (B=-0.16, SE = 0.09, CI [-0.369, - 0.001]) but not at high levels of race stigma (B=-0.06, SE = 0.05, CI [-0.175, 0.038]). This indirect effect was also significant at low levels of sexual orientation stigma (B=-0.19, SE = 0.10, CI [-0.401, - 0.023]) but not at high levels of sexual orientation stigma (B=-0.04, SE = 0.06, CI [-0.160, 0.074]). These findings suggest that addressing experienced HIV stigma in Dominican Republic healthcare settings, along with various dimensions of HIV-related stigma (e.g., internalized stigma) and intersecting stigmas (e.g., race, sexual orientation), is vital for improving health outcomes, such as optimal ART adherence. Experimentar estigmas relacionados con el VIH e interseccionales en entornos de atenci & oacute;n m & eacute;dica puede afectar la adherencia al tratamiento antirretroviral (TAR) entre las personas que viven con VIH (PVVIH), dado que necesitan interacciones frecuentes con entornos cl & iacute;nicos y proveedores de atenci & oacute;n m & eacute;dica. Considerando la importancia de reducir los estigmas para promover el bienestar y la necesidad de esclarecer c & oacute;mo el estigma influye en la salud en diversos contextos, examinamos c & oacute;mo el estigma del VIH experimentado en entornos de atenci & oacute;n m & eacute;dica en la Rep & uacute;blica Dominicana impacta la adherencia al TAR a trav & eacute;s del estigma internalizado del VIH y si el estigma racial o de orientaci & oacute;n sexual modera esta relaci & oacute;n. Los participantes fueron 471 PVVIH (de 17 a 71 a & ntilde;os) que fueron reclutados de dos cl & iacute;nicas de VIH en la Rep & uacute;blica Dominicana en 2021-2022. Los resultados revelaron un efecto de mediaci & oacute;n significativo (B=-0.10, SE = 0.05, CI [-0.234, - 0.014]) despu & eacute;s de ajustar por el efecto de la edad y el tiempo desde el diagn & oacute;stico de VIH, sugiriendo que el estigma del VIH experimentado en entornos de atenci & oacute;n m & eacute;dica estaba asociado con un mayor estigma internalizado del VIH (B = 0.39, SE = 0.11, p = .001), vinculado posteriormente a una menor adherencia al TAR (B=-0.26, SE = 0.11, p = .016). El efecto indirecto fue significativo en niveles bajos de estigma racial (B=-0.16, SE = 0.09, CI [-0.369, - 0.001]) pero no en niveles altos de estigma racial (B=-0.06, SE = 0.05, CI [-0.175, 0.038]). Este efecto indirecto tambi & eacute;n fue significativo en niveles bajos de estigma por orientaci & oacute;n sexual (B=-0.19, SE = 0.10, CI [-0.401, - 0.023]) pero no en niveles altos de estigma por orientaci & oacute;n sexual (B=-0.04, SE = 0.06, CI [-0.160, 0.074]). Estos hallazgos sugieren que abordar el estigma del VIH experimentado en entornos de atenci & oacute;n m & eacute;dica en la Rep & uacute;blica Dominicana, junto con diversas dimensiones del estigma relacionado con el VIH (por ejemplo, estigma internalizado) y estigmas interseccionales (por ejemplo, raza, orientaci & oacute;n sexual), es vital para mejorar los resultados de salud, como la adherencia & oacute;ptima al TAR.
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A multi-centre longitudinal study analysing multiple sclerosis disease-modifying therapy prescribing patterns during the Covid-19 pandemic
(Springer Science and Business Media Deutschland GmbH, 2024) Lal, Anoushka P.; Foong, Yi Chao; Sanfilippo, Paul G.; Spelman, Tim; Rath, Louise; Levitz, David; Fabis-Pedrini, Marzena; Foschi, Matteo; Habek, Mario; Kalincik, Tomas; Roos, Izanne; Lechner-Scott, Jeannette; John, Nevin; Soysal, Aysun; D’Amico, Emanuele; Gouider, Riadh; Mrabet, Saloua; Gross-Paju, Katrin; Cárdenas-Robledo, Simón; Moghadasi, Abdorreza Naser; Sa, Maria Jose; Gray, Orla; Oh, Jiwon; Reddel, Stephen; Ramanathan, Sudarshini; Al-Harbi, Talal; Hardy, Todd A.; Ozakbas, Serkan; Alroughani, Raed; Kermode, Allan G.; Surcinelli, Andrea; Laureys, Guy; Eichau, Sara; Prat, Alexandre; Girard, Marc; Duquette, Pierre; Hodgkinson, Suzanne; Ramo-Tello, Cristina; Maimone, Davide; McCombe, Pamela; Spitaleri, Daniele; Sanchez-Menoyo, Jose Luis; Yetkin, Mehmet Fatih; Baghbanian, Seyed Mohammad; Karabudak, Rana; Al-Asmi, Abdullah; Jakob, Gregor Brecl; Khoury, Samia J.; Etemadifar, Masoud; van Pesch, Vincent; Buzzard, Katherine; Taylor, Bruce; Butzkueven, Helmut; Van der Walt, Anneke; Altıntaş, Ayşe; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine
Background: The COVID-19 pandemic raised concern amongst clinicians that disease-modifying therapies (DMT), particularly anti-CD20 monoclonal antibodies (mAb) and fingolimod, could worsen COVID-19 in people with multiple sclerosis (pwMS). This study aimed to examine DMT prescribing trends pre- and post-pandemic onset. Methods: A multi-centre longitudinal study with 8,771 participants from MSBase was conducted. Two time periods were defined: pre-pandemic (March 11 2018–March 10 2020) and post-pandemic onset (March 11 2020–11 March 2022). The association between time and prescribing trends was analysed using multivariable mixed-effects logistic regression. DMT initiation refers to first initiation of any DMT, whilst DMT switches indicate changing regimen within 6 months of last use. Results: Post-pandemic onset, there was a significant increase in DMT initiation/switching to natalizumab and cladribine [(Natalizumab-initiation: OR 1.72, 95% CI 1.39–2.13;switching: OR 1.66, 95% CI 1.40–1.98), (Cladribine-initiation: OR 1.43, 95% CI 1.09–1.87;switching: OR 1.67, 95% CI 1.41–1.98)]. Anti-CD20mAb initiation/switching decreased in the year of the pandemic, but recovered in the second year, such that overall odds increased slightly post-pandemic (initiation: OR 1.26, 95% CI 1.06–1.49;Switching: OR 1.15, 95% CI 1.02–1.29. Initiation/switching of fingolimod, interferon-beta, and alemtuzumab significantly decreased [(Fingolimod-initiation: OR 0.55, 95% CI 0.41–0.73;switching: OR 0.49, 95% CI 0.41–0.58), (Interferon-gamma-initiation: OR 0.48, 95% CI 0.41–0.57;switching: OR 0.78, 95% CI 0.62–0.99), (Alemtuzumab-initiation: OR 0.27, 95% CI 0.15–0.48;switching: OR 0.27, 95% CI 0.17–0.44)]. Conclusions: Post-pandemic onset, clinicians preferentially prescribed natalizumab and cladribine over anti-CD20 mAbs and fingolimod, likely to preserve efficacy but reduce perceived immunosuppressive risks. This could have implications for disease progression in pwMS. Our findings highlight the significance of equitable DMT access globally, and the importance of evidence-based decision-making in global health challenges. © The Author(s) 2024.
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A multicenter, retrospective archive study of radiological and clinical features of ALK-positive non-small cell lung cancer patients and crizotinib efficacy
(Lippincott Williams and Wilkins, 2024) Kilickap, Saadettin; Ozturk, Akin; Karadurmus, Nuri; Korkmaz, Taner; Cicin, Irfan; Paydas, Semra; Cilbir, Ebru; Sakalar, Teoman; Uysal, Mukremin; Yesil Cinkir, Havva; Uskent, Necdet; Demir, Necla; Sakin, Abdullah; Dursun, Oldac Uras; Aver, Birkan; Turhal, Nazim Serdar; Keskin, Serkan; Tural, Deniz; Eralp, Yesim; Bugdayci Basal, Fatma; Yasar, Hatime Arzu; Sendur, Mehmet Ali Nahit; Demirci, Umut; Cubukcu, Erdem; Karaagac, Mustafa; Cakar, Burcu; Tatli, Ali Murat; Yetisyigit, Tarkan; Urvay, Semiha; Gursoy, Pinar; Oyan, Basak; Turna, Zeynep Hande; Isikdogan, Abdurrahman; Olmez, Omer Fatih; Yazici, Ozan; Cabuk, Devrim; Seker, Mehmet Metin; Unal, Olcun Umit; Meydan, Nezih; Okutur, Sadi Kerem; Erman, Mustafa; Yumuk, Perran Fulden; Tunalı, Didem; School of Medicine
To evaluate radiological and clinical features in metastatic anaplastic lymphoma kinase+ non-small cell lung cancer patients and crizotinib efficacy in different lines. This national, non-interventional, multicenter, retrospective archive screening study evaluated demographic, clinical, and radiological imaging features, and treatment approaches in patients treated between 2013-2017. Totally 367 patients (54.8% males, median age at diagnosis 54 years) were included. Of them, 45.4% were smokers, and 8.7% had a family history of lung cancer. On radiological findings, 55.9% of the tumors were located peripherally, 7.7% of the patients had cavitary lesions, and 42.9% presented with pleural effusion. Pleural effusion was higher in nonsmokers than in smokers (37.3% vs. 25.3%, P = .018). About 47.4% of cases developed distant metastases during treatment, most frequently to the brain (26.2%). Chemotherapy was the first line treatment in 55.0%. Objective response rate was 61.9% (complete response: 7.6%; partial response: 54.2%). The highest complete and partial response rates were observed in patients who received crizotinib as the 2nd line treatment. The median progression-free survival was 14 months (standard error: 1.4, 95% confidence interval: 11.2-16.8 months). Crizotinib treatment lines yielded similar progression-free survival (P = .078). The most frequent treatment-related adverse event was fatigue (14.7%). Adrenal gland metastasis was significantly higher in males and smokers, and pleural involvement and effusion were significantly higher in nonsmokers-a novel finding that has not been reported previously. The radiological and histological characteristics were consistent with the literature data, but several differences in clinical characteristics might be related to population characteristics.
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A multilevel analysis of the relationship between leaders’ experiential avoidance and followers’ well-being
(Springer, 2023) Koydemir, Selda; Fehn, Theresa; Bilgiç, Ilkyaz D.; Gauglitz, Iris; Schütz, Astrid; Varol, Melisa; Graduate School of Social Sciences and Humanities
Experiential avoidance is defined as a process involving excessive negative evaluations of difficult or unwanted feelings, thoughts, and sensations, an unwillingness to remain in contact with and express these experiences, and habitual attempts to avoid or control them. Experiential avoidance is closely associated with maladaptive functioning. Although the ability to connect with internal experiences has been considered an important element of effective leadership, this assumption has not yet been empirically tested. On the basis of the Acceptance and Commitment Therapy model of experiential avoidance and the propositions of leadership models (e.g., transformational and authentic leadership) that characterize leadership as an emotion-related process, we examined the relationship between leaders’ experiential avoidance and their followers’ well-being in a sample of leader-follower triads. Well-being outcomes were subjective happiness, purpose in life, and job satisfaction. We also tested the mediating roles of followers’ basic psychological need satisfaction and need frustration in this relationship. Multilevel mediation model analyses suggested that followers’ psychological need frustration but not need satisfaction mediated the relationship between leaders’ experiential avoidance and followers’ well-being outcomes. Thus, a rigid attitude toward one’s internal experiences as a leader is a risk factor for followers’ well-being because leaders with such attitudes may pay little attention to their followers and give rise to need frustration in their followers. Organizational efforts to increase leaders’ flexibility in dealing with negative experiences can help foster well-being among both leaders and their followers.
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A multinational cohort study examining sex differences in excess risk of death with graft function after kidney transplant
(Lippincott Williams and Wilkins, 2024) Vinson, A.J,; Zhang, X.; Dahhou, M.; Döhler, B.; Sapir-Pichhadze, R.; Cardinal, H.; Melk, A.; Wong, G.; Francis, A.; Pilmore, H.; Foster, B.J.; Süsal, Caner; Koç University Transplant Immunology Research Centre of Excellence (TIREX); School of Medicine; Koç University Hospital
Background: Kidney transplant recipients show sex differences in excess overall mortality risk that vary by donor sex and recipient age. However, whether the excess risk of death with graft function (DWGF) differs by recipient sex is unknown. Methods: In this study, we combined data from 3 of the largest transplant registries worldwide (Scientific Registry of Transplant Recipient, Australia and New Zealand Dialysis and Transplant Registry, and Collaborative Transplant Study) using individual patient data meta-analysis to compare the excess risk of DWGF between male and female recipients of a first deceased donor kidney transplant (1988-2019), conditional on donor sex and recipient age. Results: Among 463 895 individuals examined, when the donor was male, female recipients aged 0 to 12 y experienced a higher excess risk of DWGF than male recipients (relative excess risk 1.68; 95% confidence interval, 1.24-2.29); there were no significant differences in other age intervals or at any age when the donor was female. There was no statistically significant between-cohort heterogeneity. Conclusions: Given the lack of sex differences in the excess risk of DWGF (other than in prepubertal recipients of a male donor kidney) and the known greater excess overall mortality risk for female recipients compared with male recipients in the setting of a male donor, future study is required to characterize potential sex-specific causes of death after graft loss.
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A multinational cohort study uncovered sex differences in excess mortality after kidney transplant
(Elsevier Science Inc, 2023) Vinson, Amanda J.; Zhang, Xun; Dahhou, Mourad; Doehler, Bernd; Melk, Anette; Sapir-Pichhadze, Ruth; Cardinal, Heloise; Wong, Germaine; Francis, Anna; Pilmore, Helen; Foster, Bethany J.; Süsal, Caner; Koç University Transplant Immunology Research Centre of Excellence (TIREX); School of Medicine; Koç University Hospital
Worldwide and at all ages, males have a higher mortality risk than females. This mortality bias should be preserved in kidney transplant recipients unless there are sex differences in the effects of transplantation. Here we compared the excess risk of mortality (risk above the general population) in female versus male recipients of all ages recorded in three large transplant databases. This included first deceased donor kidney transplant recipients and accounted for the modifying effects of donor sex and recipient age. After harmonization of variables across cohorts, relative survival models were fitted in each cohort separately and results were combined using individual patient data meta-analysis among 466,892 individuals (1988-2019). When the donor was male, female recipients 0-12 years (Relative Excess Risk 1.54, 95% Confidence Interval 1.20-1.99), 13-24 years (1.17, 1.01-1.34), 25-44 years (1.11, 1.05-1.18) and 60 years and older (1.05, 1.02- 1.08) showed higher excess mortality risks than male recipients of the same age. When the donor was female, the Relative Excess Risk for those over 12 years were similar to those when the donor was male. There is a higher excess mortality risk in female than male recipients with differences larger at younger than older ages and only statistically significant when the donor was male. While these findings may be partly explained by the known sex differences in graft loss risks, sex differences in the risks of death with graft function may also contribute. Thus, higher risks in females than males suggest that management needs to be modified to optimize transplant outcomes among females.