Search

Lactobacillus acidophilus surface layer proteins (SLPs) self-assemble into a monolayer that is non-covalently bound to the outer surface of the cells. There they are in direct contact with the environment, environmental stressors and gut components of the host in which the organism resides. The role of L. acidophilus SLPs is not entirely understood, although SLPs seem to be essential for bacterial growth. We constructed three L. acidophilus L-92 strains, each expressing a mutant of the most abundant SLP, SlpA. Each carried a 12-amino acid c-myc epitope substitution at a different position in the protein. A strain was also obtained that expressed the SlpA paralog SlpB from an originally silent slpB gene. All four strains behaved differently with respect to growth under various stress conditions, such as the presence of salt, ox gall or ethanol, suggesting that SlpA affects stress tolerance in L. acidophilus L-92. Also, the four mutants showed differential in vitro binding ability to human host cell proteins such as uromodulin or dendritic cell (DC)-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN). Furthermore, co-culture of murine immature DCs with a mutant strain expressing one of the recombinant SlpA proteins changed the concentrations of the cytokines IL-10 and IL-12. Our data suggest that SlpA and SlpB of L. acidophilus participate in bacterial stress tolerance and binding to uromodulin or DC-SIGN, possibly leading to effective immune-modification.

Extracorporeal life support (ECLS) is an essential component of a modern congenital cardiac surgery program. The circuit components and bedside management team may, however, vary among institutions. Here, we evaluate our initial experience with a modified ventricular assist device-based ECLS circuit primarily managed by the bedside nurse. We hypothesize that our outcomes are comparable to Extracorporeal Life Support Organization (ELSO) registry data. All patients who received ECLS from January 1, 2016 to December 31, 2019 at a single institution were included. Primary outcomes were survival to ECLS decannulation and discharge or transfer. Secondary outcomes included complications from ECLS. Data were compared to available ELSO registry data. Thirty-seven patients underwent 44 ECLS runs during the study period. Forty percent of patients had single ventricle physiology. Nearly 46% of patients received ECLS as part of extracorporeal cardiopulmonary resuscitation (eCPR). Survival to ECLS decannulation (68.2%) and survival to discharge or transfer (61.4%) did not differ from overall ELSO outcomes (69.7%, P = .870 and 50.7%, P = .136), as well as survival to discharge or transfer in a comparable cohort of ELSO centers (53.1%, P = .081). Patients with complications had a lower rate of survival to discharge or transfer but this did not reach statistical significance (47.7% vs. 75.0%, P = .455). Neurologic (50.0%), hemorrhagic (45.5%), and renal complications (31.8%) were most common in this cohort. A modified ventricular assist device-based ECLS circuit with primary management by the bedside nurse can provide comparable support in a neonatal and pediatric cardiac surgery population. Cost analyses and further delineation of the complication profile are necessary for a complete characterization of this system.

More often associated with hedonism and cheap thrills than with notions of alienation and suffering, Beat literature has rarely been envisaged from the perspective of the paradoxical dynamics at play in the writings. What this book evidences is that the sacrosanct quest for transcendence staged by Kerouac and by Ginsberg is underpinned, primarily, by a trope of nullification that acts as a menace for the self. This tropism for destruction and death is not only emblematic of their works, it is also used as a literary strategy that seeks to conquer the fear of self-annihilation through the writing itself. It is precisely this interplay—approached through an Existentialism that simultaneously converges upon the Transcendentalist legacy of Beat writing—which probes the paradoxical dimension of the texts, enabling the mythological figure of Thanatos to take centre stage. The critical synergy of the book, brought about by relating American literature and culture to European thought, enables in-depth analyses of a selection of novels and poems, grasped through their aesthetic, ontological and historical dimensions. Shedding new light on the literary strategies of two widely misunderstood American writers of the twentieth century, this captivating study into the drives for self-destruction and self-liberation encapsulated by Kerouac and Ginsberg sets out to reinvent the well-worn definition of ‘Beat’ through its original approach—an essential critical piece for all those interested in the American counterculture.

Background and aims This study aimed to evaluate whether there is a difference in human papillomavirus (HPV), smear, and cervical biopsy results between patients with and without diabetes mellitus (DM). Methods Retrospectively, 136 patients with positive high risk (HR) HPV screening results with and without DM who underwent colposcopy between 2015 and 2019 were identified. The clinicopathological characteristics and HR HPV screening results were reported and analyzed. The results of the patients with and without DM were compared. Results HPV 16 positivity, Atypical Squamous Cells of Undetermined Significance (ASCUS), and Cervical Intraepithelial Neoplasia 1 (CIN 1) in smear and biopsy results were higher in patients with DM than patients without DM. Conclusions The higher HPV positivity in patients with diabetes may require reforming the frequency and method of cervical cancer screening to be applied to this patient group.

Objective: Toinvestigate the efficacy of oral 10 mg Hyoscine N Butyl Bromur (HBB) on painperception of the patients who underwent endometrial biopsy with Pipelle.Material and Method: Thecharts of the patients who were 18-49 years and underwent endometrial biopsy with Pipelle for evaluation ofabnormal uterine bleeding at xxxxxxxxxxxxxxxxxxxxxxxxxxxxx between September 2018and September 2019 were retrospectively evaluated. 48 patients were seperated asHBB Group who used oral 10 mg HBB 30 minutes before endometrial biopsy and 56patients as Control Group who did not used any pain relief medication before endometrialbiopsy. Results: Therewere no statistically significant difference between two groups in age, BMI,parity, number of vaginal and cesarean births, nulliparity, multipartiy, andmenopausal status. On the other hand, VAS (0) scores which were recordedimmediately after endometrial biopsy and VAS (30) scores which were recorded 30minutes after endometrial biopsy of the patients of the HBB Group were lowerthan the Control Group (59,3 ± 21,12 vs 86,42 ± 10.95, ve 19,09 ± 23,85 vs55,71 ± 21,67 respectively; p≤0,001).Conclusion: 10mg oral HBB when taken 30 minutes before intervention, significantly decreasespain associated with Pipelle endometrial biopsy. This data might help toincrease the endication spectrum of HBB for analgesic purposes in gynecologyfield., Amaç: Buçalışmanın amacı Pipelle ile yapılan endometrial biyopsi işlemi öncesinde oralyoldan alınan 10 mg Hyosine N Butil Bromur (HBB)’nin analjezik etkinliğinideğerlendirmektir.Gerek ve Yöntem: Eylül2018- Eylül 2019 tarihleri arasında, xxxxxxxxxxxxx, anormal uterin kanamanındeğerlendirilmesi için Pipelle ile endometriyal biyopsi yapılmış, 18-49 yaşarasındaki hastaların dosyaları retrospektif olarak incelendi. Endometriyalbiyopsi işleminin 30 dakika öncesinde oral yoldan 10 mg HBB kullanan 48hasta HBB Grubu, endometriyal biyopsi işlemi öncesinde hiçbir analjezikkullanmayan 56 hasta ise Kontrol Grubu olarak ayrıldı.Bulgular: Yaş,vücut kitle indeksi, parite, vajinal ve sezaryen doğum sayısı, nulliparite,multiparite ve menopozal durum parametreleri açısından 2 grup arasında farkgözükmezken endometriyal biyopsinin hemen sonrasında kaydedilmiş VAS (0) veendometriyal biyopsiden 30 dakika sonra kaydedilmiş olan VAS (30) skorları HBBGrubunda Kontrol Grubuna göre daha düşük saptandı (sırasıyla 59,3 ± 21,12 vs86,42 ± 10.95, ve 19,09 ± 23,85 vs 55,71 ± 21,67; p≤0,001)Sonuç: Endometriyalbiyopsi işleminden 30 dakika önce oral yoldan alınan 10 mg HBB’nin,endometriyal biyopsi sırasında ve işlemden 30 dakika sonrasında analjeziketkinliği vardır. Bu data HBB’nin diğer jinekolojik endikasyonlar ilekullanımının yaygınlaşmasına yardımcı olabilir.

Amac: Kontrasepsiyon istenmeyen gebeligi onler. Dogum kontrolu eski zamanlardan beri kullanilmaktadir. Bu olgu sunumunda servikal kitleyi taklit eden eski moda bir dogum kontrol yontemini tartisacagiz. Olgu sunumu: Akrabalarina gore 100 yasinda, ancak kimlik kartina gore 96 yasindaki, bir kadin tenesmus sikayeti ile Zonguldak Bulent Ecevit Universitesi Saglik Uygulama ve Arastirma Hastanesi Jinekoloji Klinigine kabul edildi. Genel anestezi altinda kontrollu bir sekilde 4x4x3 cm servikal kitle ekstrakte edildi. Rengi gri, yuvarlak ve sert naturdeydi. Muhtemelen 60 yil once dogum kontrolu icin kullanilan bir balmumu parcasiydi. Sonuc: Osmanli doneminde, hibiscus koku gibi bazi bitki kokleri kontraseptif bariyer yontemi olarak kullanilmistir. Ancak bazi Turk kadinlari hala hastamizda goruldugu gibi geleneksel yontemleri kullanmaktadir. Istenmeyen gebeliklerin onlenmesi icin, ozellikle evlilik oncesi, guvenli dogum kontrol yontemleri hakkinda halk egitimi verilmesi onemlidir.

Penelitian ini menguraikan tentang metode perancangan dan pembuatan sistem informasi kartu kendali belanja berbasis WEB dengan memanfaatkan perkembangan ilmu teknologi. Proses pekerjaan perkantoran saat ini tidak terlepas dari penggunaan teknologi sebagai pengelolaan keuangan dengan menggunakan sistem informasi berbasis WEB akan lebih mudah digunakan karena sistem informasi ini biasa dibuka melalui semua browser internet.Pembuatan sistem informasi kartu kendali ini dengan menggunakan software PHP dan MySQL.Sistem informasi ini mengendalikan antara pagu/flapon anggaran dengan realisasi yang akan diajukan oleh SKPD kepada Badan Pengelolaan Keuangan dan Aset Daerah sehingga menjadi tupoksi dari Badan Pengelolaan Keuangan dan Aset Daerah.WEB adalah suatu halaman yang saling berhubungan yang umumnya berada pada peladen yang sama berisikan kumpulan informasi yang disediakan secara perorangan, kelompok, atau organisasi. WEB menyediakan platform terbuka bagi para pengembang dalam menciptakan sistem informasi mereka sendiri untuk digunakan oleh bermacam peranti bergerak. WEB tidak hanya dibutuhkan untuk kalangan bisnis tetapi juga berlaku untuk kalangan perkantoran. Dengan adanya sistem informasi ini dapat mempermudah pegawai dalam melakukan pekerjaan pengendalian realisasi belanja yang akan diajukan.Kartu kendali belanja adalah sebuah kartu yang dipergunakan untuk pencatatan belanja/realisasi sebagai pengendali/batasan agar tidak melebihi dari ketentuan yang telah diatur dalam suatu organisasi.

Metode Agile merupakan salah satu bentuk pendekatan metode pengembangan sistem yang berkembang saat ini untuk pemodelan perangkat lunak yang mengutamakan fleksibilitas dan kedinamisan setiap prosesnya terhadap perubahan-perubahan yang terjadi, dimana perubahan-perubahan tersebut dapat dilakukan pada setiap tahapan proses yang ada. Salah satu metode Agile yang ada adalah pendekatan Extreme Programming (Extreme Programming Approach). Perbedaan Extreme Programming Approach (XP) dibandingkan dengan metode lainnya yaitu tidak memiliki dokumentasi secara formal dalam setiap tahapan proses konstruksinya. Adapun tahapan-tahapan yang harus dilalui dalam XP Approach antara lain: Tahapan explorasi, perencanaan, iterasi pengembangan sistem, dan tahapan akhir. Keunggulan dari XP Approach ini adalah perancangan perangkat lunak yang dilakukan tidak akan diubah, hanya sistem yang sedang dibangun saja yang berubah, dengan kata lain XP Approach memungkinkan tidak adanya dokumentasi formal yang dapat digunakan sebagai alat ukur bahwa aplikasi telah selesai dibangun, namun aplikasi dikatakan telah selesai apabila klien tidak melakukan penambahan analisis kebutuhan (requirement) pada aplikasi. Penambahan atau perubahan requirement ini tidak dibatasi, sehingga apapun keinginan klien akan dipenuhi. Melalui pendekatan XP ini akan dibangun sebuah aplikasi yang diperuntukkan untuk sistem penjualan berbasis online (E-commerce) dengan prinsip business to customer (B2C). E-commerce ini diperuntukkan bagi penjual khususnya yang bergerak di bidang UMKM pada wilayah Kabupaten Musirawas Utara yang ingin mengembangkan kegiatan jual beli barang dagangan kepada customer secara online.

Pendidikan Kewarganegaraan (PKn) merupakan salah satu disiplin ilmu wajib yang dipelajari di lembaga pendidikan atau sekolah. Hasil observasi awal peneliti di SD Setia Budi Abadi Perbaungan ditemukan bahwa hasil belajar dan ketuntasan siswa masih tergolong rendah. Identifikasi beberapa masalah terkait dengan pelajaran PKn yaitu :(1) Rendahnya hasil belajar dan ketuntasan belajar PKn siswa, (2)Metode mengajar yang digunakan guru dalam mengajarkan PKn kurang bervariasi dan cenderung ceramah, dan (3) Guru juga kurang melibatkan siswa aktif dalam belajar. Berdasarkan analisa tersebut salah satu metode dalam memecahkan masalah tersebut yaitu penggunaan metode demonstrasi dengan menggunakan media audio visual. Metode audio visual digunakan untuk merancang strategi atau metode pembelajaran yang kreatif dan inovatif sehingga diharapakan siswa juga lebih termotivasi karena ada cara belajar yang baru dan mendapatkan hasil yang lebih optimal.

The purpose of this research to see how management Hazardous and Toxic Material Waste Judging From the Aspects of Industrial Relations and Corporate Social Responsibility. This type of research used in this research is descriptive research with a qualitative approach. The results of this study show that the management of Hazardous and Toxic Material Waste Judging from the aspects of industrial relations and corporate social responsibility, although there are still some shortcomings. Such as that there are still many industrial companies that are not very aggressive in carrying out the B3 waste management process. This proves that the policies governing waste management have not been so effectively applied in life, this can be caused by several factors such as lack of awareness in managing B3 waste, a less strict supervision system, and also rules that are felt to be not too binding so that many do not manage B3 waste properly.

The purpose of this research to see how The Role of Local Government in Improving the Quality of Terminal Management (Study at the Office of Transportation, Communication and Information, Tebo Regency). This type of research used in this research is descriptive research with a qualitative approach. The results of this study show that the 1. The Department of Transportation, Communication and Information Technology of Tebo Regency has managed terminal quality such as establishing a terminal as an UPTD so that it can further maximize public services in the transportation sector, provide facilities to UPTD in improving the quality of terminal management, giving authority to UPTD for terminal management both in the service sector and in the area of local revenue, directing public transportation to utilize the terminal.

An ideal dressing should ensure that the wound remains moist with exudates but not macerated. Currently, there is no dressing available to suit all wounds, at all stages of the healing process. Although silver-containing dressings are the gold standard for burn wound care, few high-level trials have been completed comparing the clinical utilities of these dressings. In our study, five different types of wound dressings: carboxymethyl cellulose hydrofiber dressing with ionized silver (CMCH-Ag), polyethylene-polyethylene terephthalate aqua fiber dressing with elementary silver (PPAF-Ag), calcium alginate (CA), calcium + zinc alginate (CZA), and 0.2% nitrofurazone-embedded (NF) gauze dressings were compared in regard to histopathological parameters. Children aged between 0 and 18 years with small or middle-sized partial-thickness burns that affected less than 30% of the total body surface area were included in this study. The study groups (CMCH-Ag, PPAF-Ag, CA, and CZA) and the control group (NF) were randomly attained. Wound healing was evaluated by punch biopsies on the 21st day. The thickness of the stratum corneum and the epithelium, the number of papillae, and the papillary length were calculated and compared. The histological parameters of healing, except the stratum corneum thickness, did not show any statistical significance among the groups (P > .05). The dressings that included silver, calcium, or zinc showed useful and similar effects in noninfective burn wounds when compared with nitrofurazone-only dressings. Thus, it may be concluded that silver-containing wound dressings should not be considered as the gold standard in noninfective partial-thickness burn wounds in children.

BACKGROUND Donors with drowning or asphyxiation (DA) as a mechanism of death (MOD) are considered high risk in pediatric lung transplantation. We sought to evaluate whether recipients of DA donors had negatively impacted outcomes. METHODS Pediatric recipients recorded in the United Network for Organ Sharing registry between 2000 and 2019 were included. Primary stratification was donor MOD. Propensity matching with a 1:1 ratio was performed to balance the DA and non-DA MOD donor cohorts. Cox multivariable regression was used to determine the risk-adjusted impact of donor MOD. A subanalysis of the effect of lung allocation score was also evaluated. RESULTS A total of 1016 patients underwent bilateral lung transplantation during the study period, including 888 (85.6%) from non-DA donors and 128 (14.4%) from DA donors. Survival at 90 days, 1 year, and 2 years were similar in the matched and unmatched cohorts regardless of the donor MOD. Moreover, separate risk-adjusted analysis of drowning and asphyxiated donors was similar to other MOD donors at 30 days, 1 year, and 5 years. Similar survival findings persisted regardless of pretransplant lung allocation score. Although the rates of posttransplant stroke (1.0% versus 3.1%, P = 0.04) and the length of hospital stay (19 versus 22 d, P = 0.004) were elevated in the unmatched DA MOD recipients, these differences were mitigated after propensity matching. CONCLUSIONS This study evaluated the impact of DA MOD donors in pediatric lung transplant recipients and found similar rates of complications and survival in a propensity-matched cohort. These data collectively support the consideration of DA MOD donors for use in pediatric lung transplantation.

Background: Despite significant improvement in outcomes with truncus arteriosus (TA) repair, right ventricular outflow tract (RVOT) reconstruction with a right ventricular to pulmonary artery (RV-to-PA) conduit remains a source of long-term reintervention and reoperation. This study evaluated our experience with reintervention in homograft and polytetrafluoroethylene (PTFE) RV-to-PA conduits in neonates. Methods: Primary TA repairs from 2004 to 2016 at a single institution were included. Stratification was based on RVOT reconstruction with PTFE or homograft conduit. Primary outcome was operative conduit replacement. Secondary outcomes included the rates and types of catheter-based conduit interventions. Results: Twenty-eight patients underwent primary TA repair and 89.3% (n = 25) of them had RVOT reconstruction with a homograft (28.0%, n = 7) or PTFE (72.0%, n = 18) conduit. Rates of reoperation for conduit replacement and catheter-based interventions were similar between those with PTFE and homograft conduits (85.7% vs 72.2%, P = .49 and 57.1% vs 83.3%, P = .11, respectively). Additionally, the median time to conduit replacement and catheter-based conduit interventions were comparable. In multivariable analysis, conduit size, but not conduit type, was a predictor of conduit revision (hazard ratio: 1.66, 95% confidence interval: 1.11-2.49, P = .02). At five-year and ten-year follow-up, patients with PTFE conduits had better survival than those with homograft conduits (100.0% vs 71.4%, P = .02); however, no mortalities were associated with conduit reoperations or catheter-based reinterventions. Conclusions: Polytetrafluoroethylene and homograft RVOT reconstruction in neonatal TA repair demonstrate similar durability as defined by reoperation and reintervention rates. The validation of the durability of PTFE conduits in neonatal TA repair requires confirmatory studies in larger cohorts.

Although the effect of religious belief on morally relevant behavior is well demonstrated, the reverse influence is less known. In this research, we examined the influence of morality on religious belief. In the first study, we used two samples from Turkey and the United States, and specifically tested the hypothesis that intergroup tolerance predicts a shift in meta-ethical views toward subjective morality, which in turn predicts decreased religious belief. To examine the relationship between intergroup tolerance and religiosity via subjective morality, a structural equation model (SEM) was run. SEM results yielded good fit to the data for both samples. Intergroup tolerance positively predicted subjective morality, and in turn, morality negatively predicted religiosity. The bias-corrected bootstrap analysis confirmed the mediation, indicating that the association between intergroup tolerance and religious belief was mediated via subjective morality. In Study 2, we probed for the causal relationship, and the results showed that manipulating intergroup tolerance increases subjective morality, but does not influence religiosity. Therefore, we found only partial evidence for our proposed model that tolerance causally influences subjective morality, but not religiosity.

Objective The aim of this study was to investigate whether there were differences in the Paneth cells between children with acute appendicitis (AA) and those with normal appendix (NA), and to reveal the distribution of and morphological changes in Paneth cells in appendix inflammation. Materials and Methods The data of 63 patients who underwent appendectomy diagnosed with acute appendicitis between January 2021 and December 2022, including age, gender, operative diagnosis, and postoperative histopathological examination results, were analyzed retrospectively. To evaluate the distribution and changes of Paneth cells throughout AA and NA groups, samples with hematoxylin and eosin (H & E)-stained sections were obtained from the Department of Histopathology's archives. Selected blocks were stained with Masson-Trichrome. The number of Paneth cells and the degree of granular density in the appendicitis tissues were statistically evaluated and compared with the results of the control group. Results A total of 63 appendectomies were performed, including 31 incidental appendectomies and 32 performed for preoperative diagnosis of acute appendicitis. There were no statistically significant differences between the groups that underwent surgery for AA and the NA in terms of gender and age (p>0.05). It was observed that the number of Paneth cells and granule density decreased significantly in acute appendicitis (AA) group (p

Penggunaan teknologi komputer semakin banyak setelah adanya penggabungan dariteknologi komputer dan teknologi komunikasi. Proses bimbingan saat ini masih dilakukan dengantatap muka langsung sesuai dengan jadwal dosen pembimbing saat berada di kampus. Adapunkendala yang menyebabkan proses pengerjaan tugas akhir mahasiswa terhambat, yaitu kesulitanmahasiswa dan dosen untuk mengadakan pertemuan dalam rangka bimbingan tugas akhir(skripsi) dikarenakan perbedaan jadwal dosen pembimbing dan mahasiswa yang datang untukbimbingan. Mahasiswa yang tidak mengetahui tentang jadwal dosen pembimbing saat berada dikampus, itu menyebabkan mahasiswa yang datang jarang bertemu dengan dosen pembimbing.Untuk itu dibutuhkan informasi jadwal dosen, agar mahasiswa bisa mengetahui jadwal dosenpembimbingnya saat berada di kampus. Pembuatan aplikasi bimbingan skripsi untuk mahasiswaberbasis android ini menggunakan bahasa pemrograman PHP dan Mysql. Dengan adanya aplikasibimbingan skripsi ini, dapat membantu dan memajukan dalam proses bimbingan skripsi, sertasebagai kontrol kepada mahasiswa yang melakukan bimbingan khususnya untuk mahasiswa. Daripembahasan yang telah dilakukan pada bab-bab sebelumnya, dapat ditarik kesimpulan bahwaAplikasi Bimbingan Skripsi Untuk Mahasiswa Berbasis Web Mobile merupakan alternative yangdapat digunakan sebagai media yang cepat dalam proses bimbingan skripsi dan dapatmeningkatkan pelayanan terhadap mahasiswa.

In routine diagnostic pathology, cancer biopsies are preserved by formalin-fixed, paraffin-embedding (FFPE) procedures for examination of (intra-) cellular morphology. Such procedures inadvertently induce DNA fragmentation, which compromises sequencing-based analyses of chromosomal rearrangements. Yet, rearrangements drive many types of hematolymphoid malignancies and solid tumors, and their manifestation is instructive for diagnosis, prognosis, and treatment. Here, we present FFPE-targeted locus capture (FFPE-TLC) for targeted sequencing of proximity-ligation products formed in FFPE tissue blocks, and PLIER, a computational framework that allows automated identification and characterization of rearrangements involving selected, clinically relevant, loci. FFPE-TLC, blindly applied to 149 lymphoma and control FFPE samples, identifies the known and previously uncharacterized rearrangement partners. It outperforms fluorescence in situ hybridization (FISH) in sensitivity and specificity, and shows clear advantages over standard capture-NGS methods, finding rearrangements involving repetitive sequences which they typically miss. FFPE-TLC is therefore a powerful clinical diagnostics tool for accurate targeted rearrangement detection in FFPE specimens., Preservation of cancer biopsies by FFPE introduces DNA fragmentation, hindering analysis of rearrangements. Here the authors introduce FFPE Targeted Locus Capture for identification of translocations in preserved samples.

Background: Cancer is caused by somatic DNA alterations, comprising single/small nucleotide variants (SNVs), somatic copy number alterations (SCNAs) and chromosomal rearrangement structural variants (SVs). We previously demonstrated that SVs are recurrently identified in hundreds of genes and are highly prevalent in common fragile site genes, e.g., in MACROD2 in >40% of colorectal cancers (CRCs). However, computational methods that discriminate SV-driver from SV-passenger events are lacking and laboratory methods to detect SVs at nucleotide resolution from routinely obtained formalin-fixed paraffin-embedded (FFPE) tumor tissue material are underdeveloped. Therefore, despite the abundant presence of SVs, knowledge about their biological and clinical impact is limited. Aim: The aim of our studies is to identify genes of which the function is frequently affected by SV, to understand how these genes contribute to CRC pathogenesis, and to translate these SVs into clinically relevant biomarkers. Methods: We made use of publicly available deep whole genome DNA sequencing data and tumor-matched RNA sequencing data from the Hartwig Medical Foundation to develop the algorithm ‘CoBRA’: Computation of Biologically Relevant Alterations. Adenoma-derived organoids were used for CRISPR/Cas9-mediated gene modulation for functional analysis of SV-driver events. Cergentis’ targeted locus capture (FFPE-TLC) technology was used to detect SVs at nucleotide resolution from FFPE material, which were translated into droplet digital PCR (ddPCR) assays for the detection of SVs in cell-free circulating tumor DNA (ctDNA) in liquid biopsies. Results: The CoBRA algorithm associated the presence of SV-events in frequently affected genes to the extent in which genome-wide RNA sequencing data were altered. In this way, CoBRA ranked SV-events in genes according to their putative impact on tumor biology. SVs in MACROD2 ranked among those with the highest impact on tumor biology. Therefore, we generated focal deletions in MACROD2 in adenoma-derived organoids for functional analyses. Moreover, using FFPE tumor tissue material we detected SVs at nucleotide resolution in MACROD2 and three other genes in 21 out of 29 patients. SVs were verified by PCR on tumor tissue and subsequently translated into ddPCR biomarker assays for detection of SVs in ctDNA in blood from the same patients. Conclusions: We developed the computational method CoBRA and succeeded to detect SVs with high impact on tumor biology. These SVs are prioritized for functional analysis in pre-malignant adenoma-derived organoids; for targeted detection in routinely obtained FFPE tumor tissue material; and for translation into liquid biopsy ctDNA assays. Proof of concept was delivered for MACROD2. Our novel computational and laboratory methodologies provide valuable tools to effectively explore the biological and clinical impact of SVs, which will contribute to our understanding of these common recurrent somatic alterations in CRC and their translation into clinically relevant biomarker applications. Citation Format: Elise van Bree, Carmen Rubio Alarcón, Soufyan Lakbir, Ellen Stelloo, Caterina Buranelli, Amber Hondema, Iris van 't Erve, Daan Vessies, Pien Delis-van Diemen, Marianne Tijssen, Anne Bolijn, Mirthe Lanfermeijer, Dorothe Linders, Joost Swennenhuis, Daan van den Broek, Jaap Heringa, Gerrit Meijer, Beatriz Carvalho, Harma Feitsma, Sanne Abeln, Remond J. A. Fijneman. Structural variants in the pathogenesis of colorectal cancer: The elephant in the room [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr A020.

Aim: The purpose of this study is to search the effects and treatment efficacies of topotecan and folic acid on the choriocarcinoma cultures generated in JAR cell culture. Material and Methods: Human choriocarcinoma-like JAR cell is augmented in the 10% fetal bovis serum and RPMI-1640 media, 95% air at 37°C with the existence of penicillin and streptomycin. Groups to apply topotecan or folic acid are identified as below:Topotecan dissolved in dimethyl sulphoxide (DMSO) and prepared as separate doses of 1, 5, 10 and 50 μg/ml. Substances are given to cells simultaneously. Results: In this study, the apoptotic effect of the use of topotecan only, in residual doses on JAR cell series is statistically significant. The use of folic acid only, in residual doses has found to decrease the apoptosis. In the combination of these two drugs in residual doses, the apoptotic effect of this drug is even more increased, and statistically significant. Conclusion: This is the first study which use the topotecan and folic acid separately and combined on JAR, a human choriocarcinoma cell line model, and evaluation of β-hCG and h-hCG by the means of immunoenzymatic method on the both two cell lines. Synergistic and apoptotic data gathered indicates that topotecan and folic acid can be one of the treatment options in order to struggle multi-drug resistance which is an enormous obstacle on treatment. However, the efficacy of drugs and effects of combination therapies might be disparate in vivo; therefore data must be supported by animal experiments and after that by clinical evaluations.

Abstract. The theory of morality as cooperation (MAC) argues that there are seven distinct and evolved universal moral foundations. Curry, Chesters, and Van Lissa (2019) developed a scale to test this theoretical approach and showed that the Relevance subscale of the MAC questionnaire (MAC-Q) fits data well, unlike the Judgment and full-form. However, an independent test of the validity of this questionnaire has not been hitherto conducted, and its relation with ideology is unknown. In the first study, we attempted to validate the Turkish form of MAC-Q and then examined the relationship with prosociality and political ideology. The results showed that the fit indices of MAC-Q Relevance are above the standard criteria, unlike the Judgment and full form ( n = 445), and significant relationships with prosociality and political ideology provided additional evidence for the validity. We used the MAC-Q Relevance in Study 2 ( n = 576, Turkey) and Study 3 ( n = 921, US), and investigated whether manipulating resource scarcity influences the endorsement of MAC. Although there was no effect of the manipulation, correlational findings provided some support for the predictive validity of MAC-Q. Overall, MAC-Q Relevance performs well in representing the lay notions of morality in both Turkey and the US, unlike full-form.