bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA polymerase II CTD is dispensable for transcription and required for termination in human cells
Authors: Yahia Yousra , Pigeot Alexia , El Aabidine Amal Zine , Shah Nilay , Karasu Nezih , Forné Ignasi , Krebs Stefan , Blum Helmut , Esnault Cyril , Sexton Tom , Imhof Axel , Eick Dirk , Andrau Jean‐Christophe 
Published: July 2023

AbstractThe largest subunit of RNA polymerase (Pol) II harbors an evolutionarily conserved C‐terminal domain (CTD), composed of heptapeptide repeats, central to the transcriptional process. Here, we analyze the transcriptional phenotypes of a CTD‐Δ5 mutant that carries a large CTD truncation in human cells. Our data show that this mutant can transcribe genes in living cells but displays a pervasive phenotype with impaired termination, similar to but more severe than previously characterized mutations of CTD tyrosine residues. The CTD‐Δ5 mutant does not interact with the Mediator and Integrator complexes involved in the activation of transcription and processing of RNAs. Examination of long‐distance interactions and CTCF‐binding patterns in CTD‐Δ5 mutant cells reveals no changes in TAD domains or borders. Our data demonstrate that the CTD is largely dispensable for the act of transcription in living cells. We propose a model in which CTD‐depleted Pol II has a lower entry rate onto DNA but becomes pervasive once engaged in transcription, resulting in a defect in termination.
Two structurally defined Aβ polymorphs promote different pathological changes in susceptible mice
Authors: Gomez‐Gutierrez Ruben , Ghosh Ujjayini , Yau Wai‐Ming , Gamez Nazaret , Do Katherine , Kramm Carlos , Shirani Hamid , Vegas‐Gomez Laura , Schulz Jonathan , Moreno‐Gonzalez Ines , Gutierrez Antonia , Nilsson K Peter R , Tycko Robert , Soto Claudio , Morales Rodrigo 
Published: July 2023

AbstractMisfolded Aβ is involved in the progression of Alzheimer's disease (AD). However, the role of its polymorphic variants or conformational strains in AD pathogenesis is not fully understood. Here, we study the seeding properties of two structurally defined synthetic misfolded Aβ strains (termed 2F and 3F) using in vitro and in vivo assays. We show that 2F and 3F strains differ in their biochemical properties, including resistance to proteolysis, binding to strain‐specific dyes, and in vitro seeding. Injection of these strains into a transgenic mouse model produces different pathological features, namely different rates of aggregation, formation of different plaque types, tropism to specific brain regions, differential recruitment of Aβ40/Aβ42 peptides, and induction of microglial and astroglial responses. Importantly, the aggregates induced by 2F and 3F are structurally different as determined by ssNMR. Our study analyzes the biological properties of purified Aβ polymorphs that have been characterized at the atomic resolution level and provides relevant information on the pathological significance of misfolded Aβ strains.
ВАГОМІСТЬ ВПЛИВУ НЕМАТЕРІАЛЬНИХ ЧИННИКІВ НА МОТИВАЦІЮ ПЕРСОНАЛУ ПІДПРИЄМСТВА
Authors: Romaniuk M.D. , Romaniuk T.M. 
Published: July 2023

Інтеграція української економіки до ЄС та в інші міжнародні структури вимагає кардинальних змін у мотивації трудового та ін­телектуального потенціалу персоналу підпри­ємств. Мета мотивації - це одержання найвищої віддачі від використання наявного працересурсного потенціалу, що дозволяє підвищити загальну ефективність і прибутковість діяльності підприємств з ефективним застосуванням матеріальних і нематеріальних чинників. У статті розглянуто вплив нематеріальних чинників на мотивацію персоналу підприємства. Визначено, що ефективність системи мотивації за нинішніх умов передбачає присутність не лише матеріальних чинників, таких як високий дохід, але і нематеріальних, що пов'язані з стабільністю місця роботи, з досягненням власних цілей, бажанням проявляти ініціативу і відповідальність. Це пов'язано з тим, мотиваційні стимули включають лише матеріальну складову, залишаючи поза увагою нематеріальну, а тому запропоновано формування такого мотиваційного механізму, який має враховувати як матеріальну мотивацію, так і виявлення та реалізацію нематеріальних чинників мотивації праці персоналу підприємства. З’ясовано та охарактеризовано, що до основних нематеріальних чинників які спонукають персонал до більш ефективної роботи належать: належні умови праці; соціально-психологічний клімат; особистий приклад керівника.; індивідуальний підхід до працівника; термін виконання поставлених завдань; врахування інтересів та можливостей працівника; підтримка працівників у безперервному навчанні,підвищенні кваліфікації а також можливості саморозвитку та самовираження працівників. Обґрунтовано, що до нетрадиційних методів мотивування персоналу відносяться моральні стимули, патерналізинг, організаційні стимули участь в управлінні, кар’єра і розвиток, участь у прибутку та капіталі. Запропоновано широко застосовувати нетрадиційні види нематеріальної мотивації і, зокрема,: інструментальний, професійний, патріотичний, господарський.
The management of Clostridioides difficile infection: from empirism to evidence
Authors: Deac Ioana Ș. , Ofrim Adriana M. , Fărcaș Radu A. , Grad Simona , Popa Ștefan Lucian , Dumitrașcu Dan L 
Published: July 2023

Clostridioides difficile infection (CDI) in clinical practice represents a challenge for its management and also prevention of recurrence. Even though there are updated guidelines for infection prevention, control and treatment, CDI remains a leading cause of healthcare acquired diarrhea with increasing incidence in the community. We present here a synthesis of the most recent international guidelines on the management of CDI.
In 2021 updated guidelines on the treatment of CDI in adults were published by the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA), American College of Gastroenterology (ACG) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). These guidelines focused on CDI management in adults, including new data on the clinical efficacy of Fidaxomicin (FDX) and Bezlotoxumab. The 2017 publication of IDSA and SHEA - Clinical Practice Guidelines for Clostridium difficile infection also included pediatric treatment recommendations that are not a part of the 2021 update. Vancomycin (VAN) treatment for an initial CDI episode remains an acceptable alternative to FDX, considering the monetary and logistical challenge of acquiring FDX.
There is growing literature on fecal microbiota transplantation (FMT) and the 2021 guidelines describe its role in severe complicated refractory CDI cases and for which surgical management is not feasible. Moreover, there are new data on the secondary prophylaxis with VAN in refractory CDI in patients with risk factors who receive broad spectrum antibiotics.
Current aspects in biobanking for personalised oncology investigations and treatments
Authors: Policiuc Liliana , Nutu Andreea , Zanoaga Oana , Mehterov Nikolay , Braicu Cornelia , Berindan-Neagoe Ioana 
Published: July 2023

Background/Aim. A biobank is an organization that gathers, refines, preserves and provides access to biospecimens along with relevant clinical data that can be used in applied or clinical research. Biobanking is a critical component of the scientific foundation for personalized medicine; this implies the accessibility of high-quality human biospecimens, such as blood, tissue, and other body fluids, along with the patient clinical data that goes with them.
Methods. This paper summarizes the function of biobanks in oncology and the requirements for biobank development in translational and clinical research.
Results. Biobanks raise numerous ethical issues that government agencies address by enacting particular laws. To develop personalized medicine, biobanks are crucial, given that the availability of an extensive collection of patient samples with thoroughly annotated clinical and pathological data is an essential necessity. Also, data related to biobanking raises complex ethical, legal, and social issues, particularly concerning the protection of donor privacy and the appropriate use of collected samples. International standards have been developed to address these issues to ensure biobanking practices’ quality, safety, and integrity.
Conclusions. Biobanking is vital in advancing biomedical research, supporting clinical applications, and enhancing our understanding of human health and disease. Using real-world data and biobanking can accelerate medical research, support personalized medicine initiatives, and improve patient care.
Tras el Azafrán Minoico
Authors: Morro Mas Antoni Miquel 
Published: July 2023

Este ensayo propone el abordaje mitopoiético de la cultura material minoica en la práctica artística contemporánea. En primer lugar, partiendo de fuentes arqueológicas se enfatiza su singularidad, de la que pueden obtenerse aprendizajes significativos y un enfoque holístico ante los actuales debates de género, espirituales y medioambientales. En segundo lugar, se presta atención a uno de sus programas pictóricos, propuesto aquí como ejemplo paradigmático en la convergencia del arte, sociedad, economía y religión minoicas. Y en tercer lugar, entendiendo que la práctica artística puede promover una comprensión del mundo más unitaria y afectiva, se propone un desarrollo escultórico con la mujer posicionada como sujeto principal, para contribuir a la deconstrucción del paradigma dual que determina las relaciones entre las personas y como aporte a la espiritualidad feminista.
Impact of sexual and neurogenic lower urinary tract dysfunction on multiple sclerosis patients' quality of life and health perceptions
Authors: EŞKUT Neslihan , KÖŞKDERELİOĞLU Aslı 
Published: July 2023

Purpose: To investigate the impact of neurogenic lower urinary tract dysfunction (NLUTD) and sexual dysfunction (SD) on multiple sclerosis (MS) patients' quality of life and health perceptions and evaluate the possible relationship with disease parameters.
Materials and Methods: A total of 192 patients with MS were included in the study. Along with the King's Health (KHQ) and COOP/WONCA questionnaires, Arizona Sexual Experience Scale (ASEX), Beck Depression Scale (BDI), Monitoring My Multiple Sclerosis Scale (MMMS) were used to evaluate the patients’ quality of life and self-perception of health.
Results: The median age of the patients was 39.5 years (18–66 years). In contrast, SD was present in 34.4%, 51.6% of the patients presented with NLUTD. Patients with NLUTD had significant differences in terms of age, education level, duration of disease, EDSS, BDI, ASEX, and MMMS scores. The majority of the study group had minor disability (82.8% had an EDSS score less than 3). Patients with SD showed higher disability, depression, and disrupted self-perception of their health status. In addition, quality of life measures correlated with the presence of NLUTD, SD and depression along with higher disability and altered self perception of their health status.
Conclusion: NLUTD and SD significantly effect quality of life and well being. Increasing awareness about the impact of NLUTD and SD symptoms in patients with MS will provide a comprehensive approach in clinical practice.
Modulatory effects of Hypericum perforatum extract on sciatic nerve injury-induced peripheral neuropathy: an experimental study on mice
Authors: SARIYILDIZ Aylin , KAPLAN Halil Mahir , ŞİNGİRİK Ergin , KOZANOGLU Erkan 
Published: July 2023

Purpose: The effect of Hypericum perforatum (HP), which is a medicinal plant, on sciatic nerve injury-induced peripheral neuropathy has been less studied so far. The current experimental study aimed to investigate the neuroprotective and antinociceptive effects of Hypericum perforatum (HP) extract on sciatic nerve injury-induced peripheral neuropathy in mice.
Materials and Methods: In the present study, 18 Balb/C albino mice were allocated equally into three groups. The first group was determined as controls, and no procedure was performed on these mice. Neuropathy was generated by the partial sciatic nerve ligation method on mice allocated to the second and third groups. Mice in the third group received HP extract at a dose of 70 mg/kg per day for fourteen days. Nociception (cold allodynia) was evaluated using the cold plate test at the end of the experimental period. Tumor necrosis factor –αlpha (TNF-α) and interleukin-6 (IL-6) in plasma; inducible nitric oxide synthase (iNOS), phospholipase A2, cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-κB), caspase-3, Bcl-2, and Bax levels in sciatic nerve were measured by enzyme-linked immunosorbent assay test.
Results: Cold plate latencies (sec) of the neuropathy + HP, neuropathy, and control groups were 8.33 ± 0.67, 5.17 ± 0.60, and 13 ± 0.73, respectively. Plasma TNF-α, IL-6 levels, and sciatic nerve iNOS, COX-2, NF-κB, caspase-3, and Bax levels were significantly decreased after HP supplementation. Bcl-2 levels of the neuropathy + HP, neuropathy, and control groups were 9.92 ± 0.71, 5.37 ± 0.53, and 13.65 ± 0.68, respectively.
Conclusion: HP has improved oxidative, inflammatory, and apoptotic responses, as well as cytokine levels in plasma and sciatic nerves of mice. It has been concluded that HP provided neuroprotective, anti-inflammatory, and antinociceptive effects in experimental mice with sciatic nerve injury models, which is suggested to guide future studies on neuropathic pain management.
Rosuvastatin relaxes rat thoracic aorta, pulmonary artery, and trachea via nitric oxide, prostanoids, and potassium channels
Authors: ŞAHİNTÜRK Serdar 
Published: July 2023

Purpose: This study aimed to determine the functional effects and mechanisms of the action of rosuvastatin on vascular and tracheal smooth muscle tissues.
Materials and Methods: Vascular and tracheal rings (2-3 mm) isolated from the thoracic aortas, pulmonary arteries, and tracheas of Wistar Albino male rats (250-300 g) were placed in chambers in the isolated tissue bath system. As the resting tension, 1 g was selected. Vascular rings contracted with 10-6 M phenylephrine after a 90-minute equilibration period. Tracheal rings contracted with 10-5 M acetylcholine. After the contraction was steady, rosuvastatin (10-8-10-4 M) was cumulatively applied to the vascular and tracheal rings. The defined experimental methodology was repeated following the incubation of selective inhibitors of signaling pathways and K+ channel blockers to ascertain rosuvastatin's functional effect mechanisms.
Results: In the precontracted rat vascular and tracheal rings, rosuvastatin induced concentration-dependent relaxation. The maximal relaxation level in vessel samples was 96%. On the other hand, the maximal relaxation level in tracheal samples was found to be 75%. The vasorelaxant effects of rosuvastatin were dramatically attenuated by endothelium removal, L-NAME treatment, and indomethacin incubation (up to 27%). With the incubation of tetraethylammonium, glyburide, 4-Aminopyridine, and anandamide, rosuvastatin-mediated vascular smooth muscle relaxation levels were significantly decreased (up to 38%). Moreover, With the incubation of tetraethylammonium, glyburide, and 4-Aminopyridine rosuvastatin-mediated tracheal smooth muscle relaxation levels were significantly decreased (up to 30%).
Conclusion: Rosuvastatin has a noticeable relaxing effect on the vascular and tracheal smooth muscles. The vasorelaxant effect of rosuvastatin involves intact endothelium, nitric oxide, prostanoids, and K+ channels (BKCa, KV, and KATP channels). Furthermore, nitric oxide, prostanoids, BKCa channels, KV channels, and KATP channels play a role in rosuvastatin-induced tracheal smooth muscle relaxation
Praktik Jual Beli Saren untuk Pengobatan Perspektif Hukum Islam
Authors: Munawaroh Nadhatul , Abdullah Fuady , Ningrum Trisna Setya 
Published: July 2023

In the modern era like today, there are still many traditional products circulating whose benefits have not been clinically tested. One of these products is saren which is made from chicken blood. The use of saren as a drug is not based on advice or advice from medical experts. So, it is not known for certain whether the saren is good for consumption or not, especially for health. Moreover, the perpetrators in the transaction are Muslims. Thus, this study was conducted to find out how Islamic law reviews the practice of buying and selling, as well as what factors are behind the practice of buying and selling saren for the drug. The approach used in this research is a qualitative approach (field research), while the data collection uses the methods of observation, interviews and documentation. From the results of this study it can be concluded that the saren product is unclean and forbidden in Islamic law. Even though the saren product has undergone various production processes, the law is still haram and there is no istiḥālah on it. In addition, from a medical point of view, in the saren there are also toxic substances that can harm people who consume it. So that the use of saren as a medicine is just a belief of the local community. The factors behind the practice of buying and selling saren for these drugs are based on economic factors, cultural factors, religious and educational factors.
Pada era modern seperti sekarang ini, masih banyak beredar produk tradisional yang manfaatnya belum teruji secara klinis. Salah satu produk tersebut adalah saren yang terbuat dari darah ayam. Penggunaan saren sebagai obat tersebut tidak berdasarkan saran atau anjuran dari ahli medis. Sehingga tidak diketahui secara pasti apakah saren tersebut baik untuk dikonsumsi atau tidak, terutama untuk kesehatan. Apalagi para pelaku dalam transaksi tersebut adalah seorang muslim. Dengan demikian, penelitian ini dilakukan untuk mengetahui bagaimana hukum Islam meninjau praktik jual beli tersebut, serta faktor apa saja yang melatar belakangi terjadinya praktik jual beli saren untuk obat tersebut. Pendekatan yang digunakan pada penelitian ini adalah pendekatan kualitatif (field research), sedangkan pengumpulan datanya menggunakan metode observasi, wawancara dan dokumentasi. Dari hasil penelitian ini dapat disimpulkan bahwa produk saren tersebut hukumnya najis serta diharamkan dalam hukum Islam. Meskipun produk saren tersebut telah mengalam beragai proses produksi, hukumnya tetaplah haram dan tidak ada istiḥālah atasnya. Selain itu dari segi medis, di dalam saren juga terdapat zat racun yang dapat membahayakan orang yang mengkonsumsinya. Sehingga penggunaan saren sebagai obat tersebut hanyalah sekedar kepercayaan masyarakat setempat. Adapun yang menjadi faktor yang melatarbelakangi terjadinya praktik jual beli saren untuk obat tersebut adalah karena didasari oleh faktor ekonomi, faktor budaya, faktor agama dan pendidikan.
Akad Qardh Perspektif Fatwa DSN-MUI tentang Qardh
Authors: Ikafitria Rakhma , Wahid Soleh Hasan , Islami Lutvia Izzul , Putri Rahma Zafira 
Published: July 2023

The purpose of this research is to explore the system of lending money under other people's names from the perspective of the DSN-MUI fatwa No. 19/DSN-MUI/IV/2001 Regarding Qardh in the Ngudi Makmur Farmer Group Association of Magetan, and what is the default settlement system? This study uses field research methods. At the same time, data collection is done through interviews, documentation, and observation. This observation concluded that the Ngudi Makmur Farmers Group Association gave illegal loans in other people's names. Because according to the DSN-MUI fatwa No. 19/DSN-MUI/IV/2001, Qardh is a loan given to a customer in need, and the card's terms, it is also explained that a loan is considered valid if the person holding the loan is the borrower. However, in this case, the management of Gapoktan Ngudi Makmur provides loans to non-members in the name of members, where members have died, but their names are used for loans of money by other people who are not members. Then the default dispute resolution system in Gapoktan Ngudi Makmur uses non-litigation channels, namely by negotiations carried out by deliberation between the parties, namely the combined management of the Ngudi Makmur farmer group and members who experience defaults to find a fair way out of the problems at hand. The settlement of defaults at Gapoktan Ngudi Makmur is by the DSN-MUI fatwa No. 19/DSN-MUI/IV/2001 Concerning Qardh.
Tujuan penelitian ini untuk mengeksplorasi sistem pemberian pinjaman uang dengan nama orang lain perspektif fatwa DSN-MUI No. 19/DSN-MUI/IV/2001 Tentang Qardh Pada Gabungan Kelompok Tani Ngudi Makmur Magetan, serta bagaimana sistem penyelesaian wanprestasinya? Dalam penelitian ini menggunakan metode penelitian lapangan. Sedangkan pengumpulan data dilakukan melalui wawancara, dokumentasi, dan observasi. Dari proses pengamatan ini disimpulkan bahwa Gabungan Kelompok Tani Ngudi Makmur memberikan pinjaman uang dengan nama orang lain tidak sah. Karena menurut fatwa DSN-MUI No. 19/DSN-MUI/IV/2001, Qardh adalah pinjaman yang diberikan kepada nasabah yang membutuhkan dan dalam syarat qardh juga dijelaskan bahwa pinjamanadianggap sah apabila yang memegang pinjaman adalah peminjam. Namun, dalam permasalahan ini pengurus Gapoktan Ngudi Makmur memberikan pinjaman uang kepada bukan anggota dengan nama anggota, dimana anggota sudah meninggal tetapi namanya digunakan untuk pinjaman uang oleh orang lain yang bukan anggota. Kemudian sistem penyelesaian sengketa wanprestasi di Gapoktan Ngudi Makmur menggunaan jalur non litigasi yaitu dengan negosiasi yang dilakukan dengan musyawarah oleh antara para pihak yaitu pengurus gabungan kelompok tani Ngudi Makmur dengan anggota yang mengalami wanprestasi untuk mencari jalan keluar yang adil dari permasalahan yang dihadapi. Penyelesaian wanprestasi di Gapoktan Ngudi Makmur ini sudah sesuai dengan fatwa DSN-MUI No. 19/DSN-MUI/IV/2001 Tentang Qardh.
Minimization of Cancer Cells with ATS Fuzzy Controller: An Application to Androgen Deprivation therapy
Authors: Dubey Priya , Kumar Surendra 
Published: July 2023

Abstract
Androgen deprivation therapy (ADT) is commonly used to treat prostate
cancer, but its 5-year survival rate remains low at 57%. Prolonged
ADT treatment can lead to increased toxicity and drug resistance. To
address these challenges, this study proposes adaptive therapy that
combines chemotherapy or immunotherapy with discontinuation of hormone
therapy. The study applies the super-twisting sliding mode control
(STSMC) algorithm to the ADT model to implement adaptive dosing
based on control laws derived from these algorithms. The main
objective is to quickly minimize cancer cells and reduce prolonged drug
exposure. An active control algorithm (ATS)-based Takagi-Sugeno fuzzy
controller is also introduced and compared to the STSMC design. The
ATS fuzzy controller significantly reduces therapy duration to six months
while maintaining global asymptotic stability. The controllers are implemented
using the Linear Matrix Inequality (LMI) algorithm and the
YALMIP toolbox, and their effectiveness is validated through MATLAB
and Simulink simulations. This study presents a novel approach
to improve prostate cancer treatment outcomes by integrating nonlinear
control algorithms and adaptive dosing strategies, aiming to reduce
treatment duration and minimize drug exposure, ultimately enhancing
patient outcomes in prostate cancer management.