2,179 research outputs found
Coccidioidomycosis: Experience From a Children’s Hospital in an Area of Endemicity
No full textThe incidence of coccidioidomycosis is increasing, and published pediatric experience is limited. This study further characterizes pediatric coccidioidomycosis by describing experience with 64 patients cared for at Children’s Hospital of Los Angeles over 20 years, with focus on sites of involvement and severity, as well as serologic profiles of affected children. Key words. disseminated coccidioidomycosis; pulmonary coccidioidomycosis. Coccidioidomycosis is caused by Coccidioides immitis/ posadasii and is an endemic mycosis of the Southwestern United States and certain arid areas of Mexico and Central and South America [1, 2]. Although most infec-tions are asymptomatic or self-limiting, clinical progression may include severe pulmonary compromise with or with-out dissemination to extrathoracic sites such as bone, joints, skin, soft tissue, or central nervous system (CNS), while dissemination can occur even in the absence of signif-icant respiratory disease [2]. Recent epidemiologic data suggest an increasing incidence and distribution of this in-fection, and 10 % of older adults are diagnosed in nonen-demic locales and have no history of residence in an endemic area [3–5]. Coccidioidomycosis in adults has been well studied; recently, growing interest in coccidioidal infection in children has resulted in clinical reports of pertinent data [6–8]. In 2002, over 40 % of hospitalized children with coccidioidomycosis were inpatients in a non-endemic area, underscoring the importance of expanding reported experience in pediatrics to inform physicians car-ing for children [6]. This study was undertaken to provide further characteriza-tion of the sites of involvement, predisposing factors, clinical course, and progression in children with coccidioidomycosis
Machine Learning-Based Prediction of Rule Violations for Drug-Likeness Assessment in Peptide Molecules Using Random Forest Models
No full textPeptide therapeutics often fall outside classical small-molecule heuristics, such as Lipinski’s Rule of Five (Ro5), motivating the development of adapted filters and data-driven approaches to early drug-likeness assessment. We curated >300 k drug (small and peptide) and non-drug molecules from PubChem, extracted key molecular descriptors with RDKit, and generated three rule-violation counters for Ro5, the peptide-oriented beyond-Ro5 (bRo5) extension, and Muegge’s criteria. Random Forest (RF) classifier and regressor models (with 10, 20, and 30 trees) were trained and evaluated. Predictions for 26 peptide test molecules were compared with those from SwissADME, Molinspiration, and manual calculations. Model metrics were uniformly high (Ro5 accuracy/precision/recall = 1.0; Muegge ≈ 0.99), indicating effective learning. Ro5 violation counts matched reference values for 23/26 peptides; the remaining cases differed by +1 violation, reflecting larger structures and platform limits. bRo5 predictions showed near-complete agreement with manual values; minor discrepancies occurred in isolated peptides. Muegge’s predictions were internally consistent but tended to underestimate SwissADME by ~1 violation in several molecules. Four peptides (ML13–16) satisfied bRo5 boundaries; three also fully met Ro5. RF models thus provide fast and reliable in silico filters for peptide drug-likeness and can support the prioritisation of orally developable candidates
Synthesis of Peptide Molecules, Analogues of Lactoferricin and in Vitro Screening for Antimicrobial and Antitumor Activity // Синтезиране на пептидни молекули, аналози на лактоферицин, и изследване за антимикробно и противотуморно действие
No full textAntibiotic resistance and the increasing number of diagnosed oncological diseases affect all areas of healthcare, drain the economy, and impact society. The leading importance of developing resistant bacterial strains is the appointment of antibiotics without sufficient indications and an antibiogram, as well as the fact that they are not administered according to the prescription. Antimicrobial peptides (AMPs) are a promising class of compounds to combat increasing antibiotic resistance and have the potential to combat neoplastic diseases. Using the native structure of already known natural AMPs, their mimetics (analogues) can be synthesized through chemical methods. The thesis presents the synthesis, antimicrobial and antiproliferative effects of peptide mimetics of LfcinB (20-30). All studied analogues demonstrated high hydrolytic stability (>95%). The replacement of Arg21 with Lys and Trp22 with non-protein AKs potentiates or preserves the biological effect of the analogues, while the replacement of Arg20 leads to the loss of the effectiveness of the molecule. Аntimicrobial activity was demonstrated by LfcinB1, LfcinB3, LfcinB5 and LfcinB6 against S.aureus. A minimum fungicidal concentration was demonstrated only with LfcinB1. The observed activity (cytotoxic and antiproliferative) of the studied peptides is dose-dependent. The studied peptides did not exhibit a cytotoxic effect in the analysis performed on the non-tumorigenic cell line.Антибиотичната резистентност и нарастващия брой диагностицирани онкологични заболявания, засягат всички сфери на здравеопазването, изтощава икономиката и има отражение върху обществото. Водещо значение за развитието на резистентни бактериални щамове има назначаването на антибиотиците без достатъчно показания, без направена антибиограма както и това, че не се прилагат съгласно предписанието. Антимикробните пептиди (АМП) са обещаващ клас съединения за справяне с нарастващата антибиотична резистентност и имат потенциал за борба с неопластичните заболявания. Използвайки нативната структура на вече познати природни АМП, чрез химични методи, могат да се създадат техни миметици (аналози). В настоящия труд е представен синтезът, антимикробните и антипролиферативните ефекти на пептидни миметици на LfcinB(20-30). Всички изследвани аналози демонстрират висока хидролитична стабилност (>95%). Замяната на Arg21 с Lys и Trp22 с небелтъчни АК, потенцира или запазва биологичният ефект на аналозите, докато замяната на Arg20, води до загубата на ефективността на молекулата., Антимикробна активност демонстрират LfcinB1, LfcinB3, LfcinB5 и LfcinB6 срещу S.aureus. Минимална фунгицидна концентрация е доказана само при LfcinB1. При изследваните пептиди наблюдаваната активност (цитотоксична и антипролиферативна) е от дозозависим тип. При проведеният NRU-анализ върху нетуморогенната клетъчна линия BALB/c 3T3 изследваните пептиди не проявяват цитотоксичен ефект, при концентрации по-малки от 1000 µМ
On the deep philosophical knowledge in the study meditations on Quixote of José Ortega y Gasset in comparabilness
No full textText se pokouší interpretovat z komparativního hlediska koncepce hlubinného filosofického poznání ve studii španělského filosofa Josého Ortegy y Gasseta Meditace o Quijotovi. Interpretace filosofického poznání hledáme prostřednictvím metafory lesa, která se objevuje jako metafora hlubinného poznání v textu J. Ortegy y Gasseta. Metafora lesa se objevuje i ve filosofické knize Ernsta Jüngra Chůze lesem. Snažíme se vysvětlit rozdíly a shody v jejím použití u obou filosofických studií. Příspěvek se dále věnuje také interpretaci koncepce románového žánru a vztahům mezi čtenářem, hrdinou a autorem v tomto žánru. K závěrům se dostávám porovnáním koncepcí José Ortegy y Gasseta a Michaila Michajloviče Bachtina a na základě interpretace zmíněných studií obou autorů.The text is trying to interprete the conception of the deep philosophical knowledge of the Spanish philosopher Jose Ortega y Gasset in his study Meditations on Quixote in comparableness. The text explains the deep philosophical knowledge through the explanation of metaphor, such as metaphor of the forest, one of the most important metaphors of the knowledge. This metaphor could be found also in the study of Ernst Jünger The Forest passage and in this text are seen the similarities and differencies between the conceptions of the metaphor in both philosophical studies. The text ex¬plores the conception of the novel as a genre and the relationships between the author of the novel, its protagonists and the reader. The conclusive conceptions are done as a result of a comparison between the theories of the novel of J. Ortega y Gasset and Michail M. Bachtin among others
On the deep philosophical knowledge in the study meditations on Quixote of José Ortega y Gasset in comparabilness
Full text linkText se pokouší interpretovat z komparativního hlediska koncepce hlubinného filosofického poznání ve studii španělského filosofa Josého Ortegy y Gasseta Meditace o Quijotovi. Interpretace filosofického poznání hledáme prostřednictvím metafory lesa, která se objevuje jako metafora hlubinného poznání v textu J. Ortegy y Gasseta. Metafora lesa se objevuje i ve filosofické knize Ernsta Jüngra Chůze lesem. Snažíme se vysvětlit rozdíly a shody v jejím použití u obou filosofických studií. Příspěvek se dále věnuje také interpretaci koncepce románového žánru a vztahům mezi čtenářem, hrdinou a autorem v tomto žánru. K závěrům se dostávám porovnáním koncepcí José Ortegy y Gasseta a Michaila Michajloviče Bachtina a na základě interpretace zmíněných studií obou autorů.The text is trying to interprete the conception of the deep philosophical knowledge of the Spanish philosopher Jose Ortega y Gasset in his study Meditations on Quixote in comparableness. The text explains the deep philosophical knowledge through the explanation of metaphor, such as metaphor of the forest, one of the most important metaphors of the knowledge. This metaphor could be found also in the study of Ernst Jünger The Forest passage and in this text are seen the similarities and differencies between the conceptions of the metaphor in both philosophical studies. The text ex¬plores the conception of the novel as a genre and the relationships between the author of the novel, its protagonists and the reader. The conclusive conceptions are done as a result of a comparison between the theories of the novel of J. Ortega y Gasset and Michail M. Bachtin among others
Consumer awareness and market trends in OTC drugs and food supplements: a 10-year comparative study in Bulgaria
Full text linkThis study identifies a significant shift in consumer trust toward healthcare professionals, particularly physicians, as key influencers in the selection of OTC drugs and food supplements (χ² = 10.88, p ≤ 0.01). Trust in pharmacists remained stable over the decade (χ² = 0.10, p ≥ 0.05). In 2023, 68.0% of respondents reported using supplements only when needed, compared to 34.3% in 2013 (χ² = 38.2, p ≤ 0.001), indicating more rational use. Nearly half (49.1%) acknowledged that some supplements may pose health risks. These findings underscore the need for enhanced regulatory oversight and targeted communication strategies to combat misinformation, manage risk perception, and support evidence-based self-medication
MEMBANGUN WEBSITE ALUMNI D-III MANAJEMEN INFORMATIKA BERBASIS MULTI-AUTHOR DAN REGISTRASI AKUN DENGAN MENGGUNAKAN WORDPRESS 4.4.2
No full textWebsite multi-author berbasis Content Management System (CMS) merupakan website, dimana para pengguna dari Website Content Management System (WCMS) tersebut, dapat mendaftarkan akun mereka secara bebas. Pada projek ini akan dikembangkan sebuah website multi-author front-end, yang nantinya pendaftar yang ingin mendaftar terlebih dahulu harus mendapat persetujuan dari admin. Plugin front-end dari website ini merupakan plugin yang sangat powerfull, dimana pengguna yang bukan merupakan admin dapat mem-posting satu atau banyak artikel di website tersebut. Tetapi dengan syarat artikel yang di posting harus mendapatkan persetujuan dari admin yang mengelola. Websitemulti-author berbasis Conten Management System (CMS) ini juga dapat digunakan sebagai website untuk bersilaturahim antara sesama alumni, sebagai media informasi, sebagai media komunikasiantar alumni dan instansi nantinya
Evolusi Dinamis Perilaku Non-Player Character Pada Game Space Shooter Menggunakan NSGA-II
Full text linkDalam permainan space shooter terdapat musuh yang dikendalikan oleh Non-Player Character (NPC) statis dimana player dapat terus berusaha beradaptasi terhadap perilaku dari musuh. Pada akhirnya, permainan menjadi membosankan karena perilaku NPC telah diketahui oleh player. Dalam penelitian ini dikembangkan implementasi kecerdasan buatan dimana NPC dapat mengevolusi dirinya sendiri, sehingga mampu merespon perilaku player. Evolusi dinamis NPC dapat memberikan pengalaman bermain yang menyenangkan karena perilaku NPC dapat menyesuaikan perilaku player. Non-Dominated Sorting Genetic Algorithm II (NSGA-II) dalam simulasi digunakan untuk mengatur “titik evolusi” terhadap NPC. Dimana dengan memeriksa parameter keputusan dari perilaku playar untuk dapat mengevolusi perilaku dari musuh (NPC). Kemudian Non-Dominated Sorting Genetic Algorithm II (NSGA-II) digunakan untuk mencari optimal solution untuk mengoptimalkan evolusi dinamis NPC pada level berikutnya. Hal ini bertujuan untuk menyeimbangkan perilaku musuh terhadap player. Simulasi menggunkan NSGA-II menghasilkan solusi optimal dalam bentuk grafik dengan 2 obyektif (speed dan health) dari NPC. Berdasarkan hasil simulasi, kestabilan berada pada generasi ke-5 dengan populasi=50, probabilitas persilangan (pc) = 1, probabilitas mutasi (pm)= 1/n, indeks distribusi persilangan (η_c)=20, dan indeks distribusi mutasi (η_m)=20.
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Abstrak – In Space Game, the NPC enemies have a static ability or behaviour where the player can be easily learn to adapted and challenge the NPCs. In the end, it makes the player become boring and don't want to play the game anymore. This research is develop an intelligent NPC that can be adapt to player style in playing the game. The NPC can be evolve and adjust itself based on the player behaviour in playing game and giving a proper difficulty to the game itself. This implementation will be make game more fun and enjoyable. NSGA II is the algorithm that will used to arrange the evolution of NPCs. This algorithm is used to evaluate the parameter that will determine NPCs behaviour change. Beside that, this research also used NSGA-II to optimized the paramater before it used to determined the NPCs behaviour change in every level of the game. Simulation it self used NSGA-II to produce optimal solution in graphic representation based on two objective parameter, speed and health. Result of simulation shown the optimized result will be produce the best solution after the five generation with total population is 50. crossover probability (pc)=0.9, mutation probability (pm)=1/n, index of distribution crossover (ηc)=20, index of distribution mutation (ηm) =20
Safety but Limited Efficacy of Unconditioned Donor Lymphocyte Infusions (DLI) in Patients Treated with Post-Transplantation Cyclophosphamide (PTCy) without Serotherapy
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