bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pulmonary Inflammatory Response in Lethal COVID-19 Reveals Potential Therapeutic Targets and Drugs in Phases III/IV Clinical Trials
Authors: López-Cortés Andrés , Guerrero Santiago , Ortiz-Prado Esteban , Yumiceba Verónica , Vera-Guapi Antonella , León Cáceres Ángela , Simbaña-Rivera Katherine , Gómez-Jaramillo Ana María , Echeverría-Garcés Gabriela , García-Cárdenas Jennyfer M. , Guevara-Ramírez Patricia , Cabrera-Andrade Alejandro , Puig San Andrés Lourdes , Cevallos-Robalino Doménica , Bautista Jhommara , Armendáriz-Castillo Isaac , Pérez-Villa Andy , Abad-Sojos Andrea , Ramos-Medina María José , León-Sosa Ariana , Abarca Estefanía , Pérez-Meza Álvaro A. , Nieto-Jaramillo Karol , Jácome Andrea V. , Morillo Andrea , Arias-Erazo Fernanda , Fuenmayor-González Luis , Quiñones Luis Abel , Kyriakidis Nikolaos C. 
Published: March 2022

Background: It is imperative to identify drugs that allow treating symptoms of severe COVID-19. Respiratory failure is the main cause of death in severe COVID-19 patients, and the host inflammatory response at the lungs remains poorly understood.Methods: Therefore, we retrieved data from post-mortem lungs from COVID-19 patients and performed in-depth in silico analyses of single-nucleus RNA sequencing data, inflammatory protein interactome network, and shortest pathways to physiological phenotypes to reveal potential therapeutic targets and drugs in advanced-stage COVID-19 clinical trials.Results: Herein, we analyzed transcriptomics data of 719 inflammatory response genes across 19 cell types (116,313 nuclei) from lung autopsies. The functional enrichment analysis of the 233 significantly expressed genes showed that the most relevant biological annotations were inflammatory response, innate immune response, cytokine production, interferon production, macrophage activation, blood coagulation, NLRP3 inflammasome complex, and the TLR, JAK-STAT, NF-κB, TNF, oncostatin M signaling pathways. Subsequently, we identified 34 essential inflammatory proteins with both high-confidence protein interactions and shortest pathways to inflammation, cell death, glycolysis, and angiogenesis.Conclusion: We propose three small molecules (baricitinib, eritoran, and montelukast) that can be considered for treating severe COVID-19 symptoms after being thoroughly evaluated in COVID-19 clinical trials.
Challenges in the Development of Drug Delivery Systems Based on Small Extracellular Vesicles for Therapy of Brain Diseases
Authors: Loch-Neckel Gecioni , Matos Ana Teresa , Vaz Ana Rita , Brites Dora 
Published: March 2022

Small extracellular vesicles (sEVs) have ∼30–200 nm diameter size and may act as carriers of different cargoes, depending on the cell of origin or on the physiological/pathological condition. As endogenous nanovesicles, sEVs are important in intercellular communication and have many of the desirable features of an ideal drug delivery system. sEVs are naturally biocompatible, with superior targeting capability, safety profile, nanometric size, and can be loaded with both lipophilic and hydrophilic agents. Because of their biochemical and physical properties, sEVs are considered a promising strategy over other delivery vehicles in the central nervous system (CNS) since they freely cross the blood-brain barrier and they can be directed to specific nerve cells, potentiating a more precise targeting of their cargo. In addition, sEVs remain stable in the peripheral circulation, making them attractive nanocarrier systems to promote neuroregeneration. This review focuses on the recent progress in methods for manufacturing, isolating, and engineering sEVs that can be used as a therapeutic strategy to overcome neurodegeneration associated with pathologies of the CNS, with particular emphasis on Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis diseases, as well as on brain tumors.
Ribociclib Inhibits P-gp-Mediated Multidrug Resistance in Human Epidermoid Carcinoma Cells
Authors: Zhang Lei , Ye Biwei , Lin Yunfeng , Li Yi-Dong , Wang Jing-Quan , Chen Zhuo , Ping Feng-Feng , Chen Zhe-Sheng 
Published: March 2022

The efficacy of cancer chemotherapy can be attenuated or abrogated by multidrug resistance (MDR) in cancer cells. In this study, we determined the effect of the CDK4/6 inhibitor, ribociclib (or LEE011), on P-glycoprotein (P-gp)-mediated MDR in the human epidermoid carcinoma MDR cell line, KB-C2, which is widely used for studying P-gp-mediated MDR in cancers. The incubation of KB-C2 cells with ribociclib (3–9 µM) increased the efficacy of colchicine, a substrate for P-gp. The cell expression of P-gp was down-regulated at both translation and transcription levels. Furthermore, ribociclib produced a 3.5-fold increase in the basal activity of P-gp ATPase, and the concentration required to increase basal activity by 50% (EC50) was 0.04 μM. Docking studies indicated that ribociclib interacted with the drug-substrate binding site of P-gp. The short-term and long-term intracellular accumulation of doxorubicin greatly increased in the KB-C2 cells co-cultured with ribociclib, indicating ribociclib inhibited the drug efflux activity of P-gp. The results of our study indicate that LEE011 may be a potential agent for combined therapy of the cancers with P-gp mediated MDR.
Post-exercise Hypotension in Patients With Coronary Artery Disease
Authors: Iellamo Ferdinando , Perrone Marco Alfonso , Caminiti Giuseppe , Volterrani Maurizio , Legramante Jacopo M. 
Published: March 2022

Background: Blood pressure (BP) and hemodynamic changes occurring in the recovery phase after a single bout of exercise have not been extensively studied in coronary artery patients, despite the potential clinical implications of reducing BP through exercise. This study aimed at investigating the hemodynamic and arterial baroreflex mechanisms possibly involved in post-exercise hypotension (PEH) in patients with coronary artery disease.Methods: In 42 normotensive coronary artery patients undergone a Cardiac Rehabilitation Program, we evaluated before and after their daily exercise training session: blood pressure (BP) and heart rate (HR). In a subgroup (n = 29), daily BP profile was also evaluated by ambulatory BP monitoring. In those patients showing PEH (n = 15), we evaluated: Cardiac Output (CO), Stroke Volume (SV), total peripheral resistances (TPR), forearm (FVR) and calf (CVR) vascular resistances, and spontaneous baroreflex sensitivity (BRS).Results: After exercise TPR was significantly reduced with a similar contribution from CVR and FVR, whereas CO and SV significantly increased. BRS showed a significant reduction mainly due to a BRS decrease in response to hypertensive stimuli. Systolic BP (SBP) was significantly reduced for 12 h after the end of a single exercise session.Conclusion: These findings indicate that in coronary artery patients, the recovery phase after exercise is characterized by PEH which is mediated mainly by a generalized peripheral vasodilation and appears to influence BP behavior throughout the daily life. Finally, the cardiac component of the arterial baroreflex seems to contribute indirectly to BP reduction occurring after exercise.
The eEgg: Evaluation of a New Device to Measure Pain
Authors: Böing-Meßing Dshamilja M. , Tomschi Fabian , Cegla Thomas , Hilberg Thomas 
Published: March 2022

Aim: The aim of this study was to evaluate whether pain stimuli can be measured validly and reliably by the eEgg (electronic Egg), a new device to measure pain intensity, in comparison to the hand dynamometer.Methods: This study consists of screening and diagnostic tests conforming to the standard criterion of handgrip strength measurement. Fifty healthy participants (25 women, 25 men; age, 39.1 ± 13.7 years) participated in this study. The approach of intermodal comparison was used to transfer different degrees of pain sensations into measurable handgrip strength values. This included an intensity comparison of 10-100% of the subjective maximum handgrip strength and an application of thermal stimuli of 34-48°C. The eEgg was compared to the numeric rating scale (NRS) as a categorization method regarding the subjective assessment of pain. An online questionnaire was distributed to test the evaluation of the product’s features.Results: Regarding the experiment’s validity, the handgrip strength values showed significant (p &lt; 0.05) positive correlations between the eEgg and the hand dynamometer (intensities: r=0.328 to r=0.550; thermal stimuli: r=0.353 to r=0.614). The reliability results showed good to very good correlations (p &lt; 0.05) in the calculated ICC (intraclass correlation coefficient) values between the individual measurement devices: eEgg intensities: ICC=0.621 to 0.851; thermal stimuli: ICC=0.487 to 0.776 and hand dynamometer intensities: ICC= 0.789 to 0.974; thermal stimuli: ICC=0.716 to 0.910.Conclusion: The new eEgg device shows strong correlations with the hand dynamometer. The central limitation focuses on the obligatory use of an arbitrary unit (AU) for the eEgg. The results of the study indicate that this device can be used in medical and therapeutic practice in the future.
Patterns of and Rationale for the Co-use of Methamphetamine and Opioids: Findings From Qualitative Interviews in New Mexico and Nevada
Authors: Rhed Brittany D. , Harding Robert W. , Marks Charles , Wagner Katherine T. , Fiuty Phillip , Page Kimberly , Wagner Karla D. 
Published: March 2022

IntroductionMethamphetamine use and methamphetamine-involved deaths have increased dramatically since 2015, and opioid-related deaths now frequently involve methamphetamine. Nevada and New Mexico are states with elevated rates of opioid and methamphetamine use. In this paper, we report results from a qualitative analysis that examined patterns of methamphetamine and opioid co-use over participants' lifespan, factors that influence those patterns, and implications for health outcomes among users.MethodsProject AMPED was a multisite, mixed-methods study of methamphetamine use in Northern New Mexico and Northern Nevada. Between December 2019 and May 2020, qualitative interview participants were asked to describe their patterns of and reasons for co-administration of opioids and methamphetamine.ResultsWe interviewed 21 people who reported using methamphetamine in the past 3 months. Four primary patterns of methamphetamine and opioid co-use were identified: [1] using both methamphetamine and heroin, either simultaneously or sequentially (n = 12), [2] using methamphetamine along with methadone (n = 4), [3] using prescription opioids and methamphetamine (n = 1), and [4] using only methamphetamine (n = 4). Among those who used methamphetamine and heroin simultaneously or sequentially, motivations drew from a desire to enhance the effect of one drug or another, to feel the “up and down” of the “perfect ratio” of a goofball, or to mitigate unwanted effects of one or the other. Among those who used methamphetamine and methadone, motivations focused on alleviating the sedative effects of methadone.ConclusionTo address the emergent trend of increasing methamphetamine-related deaths, researchers, health care professionals, and community health workers must acknowledge the decision-making processes behind co-use of opioids and methamphetamine, including the perceived benefits and harms of co-use. There is an urgent need to address underlying issues associated with drug use-related harms, and to design interventions and models of treatment that holistically address participants' concerns.
The Effect of Perceived Threat Avoidability of COVID-19 on Coping Strategies and Psychic Anxiety Among Chinese College Students in the Early Stage of COVID-19 Pandemic
Authors: Wu Jinnan , Zheng Yelianghui , Xiong Shankuo , Zhang Wenpei , Guo Shanshan 
Published: March 2022

BackgroundThe novel coronavirus disease 2019 (COVID-19) outbreak has seriously threatened the mental health of college students. This study intended to invest whether perceived threat avoidability of COVID-19 relates to psychic anxiety among college students during the early stage of the COVID-19 pandemic, as well as the mediating roles of COVID-19-specific wishful thinking and COVID-19-specific protective behaviors in this relationship.MethodsA cross-sectional study was conducted in China, using a random sampling method (February 6–25, 2020). Self-reported questionnaires were conducted online included the Perceived Threat Avoidability of COVID-19 Scale, COVID-19-specific Wishful Thinking Scale, COVID-19-specific Protective Behaviors Scale, and the Hamilton Psychogenic Anxiety Scale. The data were analyzed using Structural equation modeling and Bootstrapping procedure.ResultsA total of 2922 samples were collected in this study. Perceived threat avoidability of COVID-19 is negatively related to psychic anxiety (β = −0.158, p&lt; 0.001), and both COVID-19-specific wishful thinking (β = −0.006, p = 0.029, 95% CI: [−0.012, −0.001]) and protective behaviors (β = −0.029, p&lt; 0.001, 95% CI: [−0.043, −0.018]) mediate this relationship. Also, COVID-19-specific wishful thinking is found to correlate with COVID-19-specific protective behaviors negatively (β = −0.112, p &lt; 0.001).ConclusionPerceived threat avoidability of COVID-19 contributes to psychic anxiety among college students. COVID-19-specific wishful thinking strategy plays a negative mediating role and increases the level of anxiety; COVID-19-specific protective behaviors strategy plays a positive mediating role and reduces the level of anxiety; meanwhile, wishful thinking also suppresses college students from adopting protective behaviors.
Gender Differences in the Associations Between Physical Activity, Smartphone Use, and Weight Stigma
Authors: Xu Ping , Chen Jung-Sheng , Chang Yen-Ling , Wang Xiaodong , Jiang Xingyong , Griffiths Mark D. , Pakpour Amir H. , Lin Chung-Ying 
Published: March 2022

BackgroundPhysical activity (PA) is important for health. However, there is little evidence on how weight stigma, time spent on sedentary activities (including smartphone, social media, online learning), time spent on outdoor activity, and nomophobia associate with PA among Chinese individuals with consideration of gender. The present study examined the aforementioned associations in the COVID-19 pandemic era.MethodsUniversity students (N = 3,135; 1,798 females, 1,337 males) with a mean age of 19.65 years (SD = 2.38) years completed an online survey from November to December, 2021. The online survey assessed weight stigma (using the Perceived Weight Stigma Scale and Weight Bias Internalization Scale), PA (using the International Physical Activity Questionnaire Short Form), time spent on different activities (using self-designed items for time on smartphone, outdoor activity, social media, and online learning), and nomophobia (using the Nomophobia Questionnaire). Parallel mediation models were constructed (dependent variable: PA; mediators: perceived weight stigma, weight-related self-stigma, time spent on smartphone, time spent on outdoor activity, time spent on social media, and time spent online learning; independent variable: nomophobia) and evaluated using Hayes' Process Macro Model 4 (IBM SPSS 20.0).ResultsWeight-related self-stigma (β = −0.06; p = 0.03), time spent on outdoor activity (β = 0.21; p &lt; 0.001), time spent on social media (β = 0.07; p = 0.02), time spent on online learning (β = 0.06; p = 0.03), and nomophobia (β = −0.07; p = 0.01) were all significant factors explaining the PA among female participants. Perceived weight stigma (β = −0.07; p = 0.01), time spent on outdoor activity (β = 0.27; p &lt; 0.001), and time spent on online learning (β = 0.10; p = 0.002) were all significant factors explaining PA among male participants.ConclusionChinese healthcare providers should design programs on weight stigma reduction and outdoor activity improvement to enhance PA among university students.
Validity and Psychometric Evaluation of the Chinese Version of the 5-Item WHO Well-Being Index
Authors: Fung Sai-fu , Kong Chris Yiu Wah , Liu Yi-man , Huang Qian , Xiong Zike , Jiang Zhiquan , Zhu Fangfang , Chen Zhenting , Sun Kun , Zhao Huiqin , Yu Ping 
Published: March 2022

AimsThis article evaluates the psychometric properties of the Chinese version of the 5-item WHO Well-Being Index (WHO-5) in mainland China.MethodsTwo cross-sectional studies with 1,414 participants from a university in China were conducted. The Chinese version of the WHO-5 was assessed to determine its internal consistency, concurrent validity, factorial validity, and construct validity.ResultsThe results indicate that the WHO-5 is unidimensional and has good internal consistency, with Cronbach'sa= 0.85 and 0.81 in Study 1 (n= 903) and Study 2 (n= 511), respectively. The findings also demonstrate that the WHO-5 has good concurrent validity with other well-established measures of wellbeing, self-efficacy, self-esteem, and mental wellbeing. The results of confirmatory factor analysis also suggest that the scale has a good model fit.ConclusionsThis study provides empirical data demonstrating that the Chinese version of the WHO-5 has good psychometric properties. The scale can be a useful measure in epistemological studies and clinical research related to wellbeing in Chinese populations.
Applying a Multi-Method Framework to Analyze the Multispectral Acoustic Response of the Seafloor
Authors: Menandro Pedro S. , Bastos Alex C. , Misiuk Benjamin , Brown Craig J. 
Published: March 2022

Improvements to acoustic seafloor mapping systems have motivated novel marine geological and benthic biological research. Multibeam echosounders (MBES) have become a mainstream tool for acoustic remote sensing of the seabed. Recently, “multispectral” MBES backscatter, which is acquired at multiple operating frequencies, has been developed to characterize the seabed in greater detail, yet methods for the use of these data are still being explored. Here, we evaluate the potential for seabed discrimination using multispectral backscatter data within a multi-method framework. We present a novel MBES dataset acquired using four operating frequencies (170, 280, 400, and 700 kHz) near the Doce River mouth, situated on the eastern Brazilian continental shelf. Image-based and angular range analysis methods were applied to characterize the multifrequency response of the seabed. The large amount of information resulting from these methods complicates a manual seabed segmentation solution. The data were therefore summarized using a combination of dimensionality reduction and density-based clustering, enabling hierarchical spatial classification of the seabed with sparse ground-truth. This approach provided an effective solution to synthesizing these data spatially to identify two distinct acoustic seabed classes, with four subclasses within one of the broader classes, which corresponded closely with seafloor sediment samples collected at the site. The multispectral backscatter data also provided information in likely, unknown, sub-surface substrate differences at this site. The study demonstrates that the adoption of a multi-method framework combining image-based and angular range analysis methods with multispectral MBES data can offer significant advantages for seafloor characterization and mapping.
Clinical and Economic Effectiveness of the Drug Sakubitril/ Valsartan in Treatment of Patients with Chronic Heart Failure with the Reduced Ejection Fraction in Conditions of Healthcare System of the Republic of Belarus
Authors: Захаренко А.Г. 
Published: March 2022

Сакубитрил/валсартан является лекарственным препаратом с доказанной эффективностью в плане снижения сердечно-сосудистой заболеваемости и смертности среди пациентов с сердечной недостаточностью со сниженной фракцией выброса. Широкое внедрение в клиническую практику требует оценки экономической эффективности препарата в условиях системы здравоохранения Республики Беларусь, что явилось целью настоящего исследования. Экономический анализ базируется на данных о клинической эффективности сакубитрила/валсартана в сравнении с эналаприлом из международных клинических исследований PARADIGM-HF и PIONEER-HF и локальных белорусских данных о стоимости сравниваемых препаратов и ресурсов здравоохранения. Анализ затратной эффективности применения сакубитрила/валсартана у стабильных пациентов с хронической сердечной недостаточностью продемонстрировал меньшую стоимость годичного ведения пациента без неблагоприятных сердечно-сосудистых событий в сравнении с эналаприлом (7142 против 7251 рубля). Ранняя терапия сакубитрилом/валсартаном, инициированная после эпизода декомпенсации сердечной недостаточности, за период в 60 дней демонстрирует экономию бюджета в размере 11,74%. Использование сакубитрила/валсартана в терапии пациентов с сердечной недостаточностью со сниженной фракцией выброса является экономически эффективным.
Sacubitrile/valsartan is a drug with proven effectiveness in reducing cardiovascular morbidity and mortality among patients with heart failure with a reduced ejection fraction. Widespread introduction in clinical practice requires assessment of the economic effectiveness of the drug in the healthcare system of the Republic of Belarus, which was the purpose of this study. The economic analysis is based on the data on the clinical effectiveness of sacubitrile/valsartan, if compared to enalapril from the international clinical studies PARADIGM-HF and PIONEER-HF and local Belarusian data on the cost of the compared drugs and healthcare resources. Analysis of the cost-effectiveness of using sacubitrile/valsartan in stable patients with chronic heart failure showed a lower cost of a year of patient management without adverse cardiovascular events, if compared with enalapril (7142 versus 7251 rubles). Early sacubitril/valsartan therapy initiated after an episode of heart failure decompensation over the period of 60 days demonstrates the budget savings of 11.74%. The use of sacubitrile / valsartan in treatment of patients with heart failure with the reduced ejection fraction is cost-effective.
Dramat w rodzinie. Ostatnie lata życia Hürrem zwanej Roksolaną
Authors: Wróbel Piotr 
Published: March 2022

Hürrem (ur. ok. 1505, zm. 1558), zwana w zachodnich źródłach Roksolaną (lub Roksaną), należy do najbardziej barwnych postaci związanych z Turcją. Historia branki i niewolnicy, która w czasie swego pobytu w haremie sułtańskim (prawdopodobnie w latach 1521–1558) awansowała do roli żony sułtana i jednej z najbardziej wpływowych osób w imperium Osmanów, wywoływała żywe zainteresowanie już u jej współczesnych. Z czasem stała się inspiracją dla licznych artystów, pisarzy i twórców, wchodząc na trwałe do europejskiej kultury.
W rzeczywistości wiarygodnych informacji na jej temat jest niewiele. Wynika to z faktu, iż harem był miejscem izolowanym, a kronikarze osmańscy niechętnie pisali o kobietach. Pewniejsze informacje pochodzą od ludzi z Zachodu, ale oni mieli trudny dostęp do dworu sułtana. Dyplomaci weneccy i francuscy, często działający jak szpiedzy, gromadzili jednak starannie wiadomości z dworu, na marginesie donosząc o żonie sułtana. Głównie na podstawie ich relacji w artykule dokonano próby naszkicowania sytuacji Roksolany w ostatnich latach jej życia. Autor dochodzi do konkluzji, że choć udało się jej zdobyć i do końca życia utrzymać niezwykle silną, jak na kobietę, pozycję na dworze, jednak wprowadzone zmiany nieuchronnie prowadziły do rodzinnego dramatu, jakim było zamordowanie na rozkaz syna Selima jej drugiego syna Bajezyda wraz z wnukami.