Miracle-dz/UniFAR-FTUs huggingface dataset:
Asiatic Acid Alleviates Myocardial Ischemia-Reperfusion Injury by Inhibiting the ROS-Mediated Mitochondria-Dependent Apoptosis Pathway

Myocardial ischemia-reperfusion injury (MIRI) is a major cause of heart failure in patients with coronary heart disease (CHD). Mitochondrial dysfunction is the crucial factor of MIRI; oxidative stress caused by mitochondrial reactive oxygen species (ROS) aggravates myocardial cell damage through the mitochondria-dependent apoptosis pathway. Asiatic acid (AA) is a type of pentacyclic triterpene compound purified from the traditional Chinese medicine Centella asiatica, and its protective pharmacological activities have been reported in various disease models. This study is aimed at investigating the protective effects of AA and the underlying mechanisms in MIRI. To achieve this goal, an animal model of MIRI in vivo and a cell model of oxygen-glucose deprivation/reperfusion (OGD/R) in vitro were established. The results show that AA exerts a protective effect on MIRI by improving cardiac function and reducing cardiomyocyte damage. Due to its antioxidant properties, AA alleviates mitochondrial oxidative stress, as evidenced by the stable mitochondrial structure, maintained mitochondrial membrane potential (MMP), and reduced ROS generation, otherwise due to its antiapoptotic properties. AA inhibits the mitogen-activated protein kinase (MAPK)/mitochondria-dependent apoptosis pathway, as evidenced by the limited phosphorylation of p38-MAPK and JNK-MAPK, balanced proportion of Bcl-2/Bax, reduced cytochrome c release, inhibition of caspase cascade, and reduced apoptosis. In conclusion, our study confirms that AA exerts cardiac-protective effects by regulating ROS-induced oxidative stress via the MAPK/mitochondria-dependent apoptosis pathway; the results provide new evidence that AA may represent a potential treatment for CHD patients.
ARNI in HFrEF—One-Centre Experience in the Era before the 2021 ESC HF Recommendations

Background: Sacubitril/valsartan, an angiotensin receptor–neprilysin inhibitor (ARNI), has demonstrated a survival benefit and reduces heart failure hospitalization in patients with heart failure with reduced left ventricular ejection fraction (HFrEF); however, our experience in this field is limited. This study aimed to summarize a real clinical practice of the use of ARNI in HFrEF patients hospitalized due to HFrEF in the era before the 2021 ESC HF recommendations, as well as assess their clinical outcome with regard to ARNI administration. Methods and Materials: Overall, 613 patients with HFrEF hospitalized in 2018–2020 were enrolled into a retrospective one-centre cross-sectional analysis. The study population was categorized into patients receiving (82/13.4%) and not-receiving (531/82.6%) ARNI. Clinical outcomes defined as rehospitalization, number of rehospitalizations, time to the first rehospitalization and death from any cause were analysed in the 1–2 year follow-up in the ARNI and non-ARNI groups, matched as to age and LVEF. Results: Clinical characteristics revealed the following differences between ARNI and non-ARNI groups: A higher percentage of cardiovascular implantable electronic devices (CIED) (p = 0.014) and defibrillators with cardiac resynchronization therapy (CRT-D) (p = 0.038), higher frequency of atrial fibrillation (p = 0.002) and history of stroke (p = 0.024) were in the ARNI group. The percentage of patients with HFrEF NYHA III/IV presented an increasing trend to be higher in the ARNI (64.1%) as compared to the non-ARNI group (51.5%, p = 0.154). Incidence of rehospitalization, number of rehospitalizations and time to the first rehospitalization were comparable between the groups. There were no differences between the numbers of deaths of any cause in the ARNI (28%) and non-ARNI (28%) groups. The independent negative predictor of death in the whole population of ARNI and non-ARNI groups was the coexistence of coronary artery disease (CAD) (beta= −0.924, HR 0.806, p = 0.011). Conclusions: Our current positive experience in ARNI therapy is limited to extremely severe patients with HFrEF. Regardless of the more advanced HF and HF comorbidities, the patients treated with ARNI presented similar mortality and rehospitalizations as the patients treated by standard therapy.
Aqueous Extracts of Three Herbs Allelopathically Inhibit Lettuce Germination but Promote Seedling Growth at Low Concentrations

Allelopathy is an important process in plant communities. The effects of allelopathy on seed germination and seedling development have been extensively investigated. However, the influences of extract soaking time and concentration on the foregoing parameters are poorly understood. Here, we conducted a seed germination assay to determine the allelopathic effects of the donor herbs Achnatherum splendens (Trin.) Nevski, Artemisia frigida Willd. , and Stellera chamaejasme L. , from a degraded grassland ecosystem in northern China, on lettuce (Lactuca sativa L.) seed germination and early seedling growth. Extract soaking times (12 h or 24 h) did not exhibit significantly different effects on lettuce seed germination or seedling development. However, all aqueous herb extracts inhibited lettuce seed germination and root length (RI < 0) and promoted lettuce shoot length, stem length, leaf length, and leaf width (RI > 0) at both low (0.005 g mL−1) and high (0.05 g mL−1) concentrations. Moreover, A. splendens extracts increased seedling biomass (RI > 0) and synthetical allelopathic effect (SE > 0) at both concentrations. In contrast, both A. frigida and S. chamaejasme extracts had hormesis effects, which stimulate at low concentrations (RI > 0) but inhibit at high concentrations (RI < 0) on seedling biomass and synthetical allelopathic effect (SE). The results suggest that allelopathic potential may be an important mechanism driving the dominance of A. frigida and S. chamaejasme in degraded grasslands. Reseeding allelopathy-promoting species such as A. splendens may be beneficial to grassland restoration. The present study also demonstrated that seedling biomass, root and shoot length, and seed germination rate are the optimal bioindicators in allelopathy assays and could be more representative when they are combined with the results of multivariate analyses.
Information Retrieval from Photoplethysmographic Sensors: A Comprehensive Comparison of Practical Interpolation and Breath-Extraction Techniques at Different Sampling Rates

The increasingly widespread diffusion of wearable devices makes possible the continuous monitoring of vital signs, such as heart rate (HR), heart rate variability (HRV), and breath signal. However, these devices usually do not record the “gold-standard” signals, namely the electrocardiography (ECG) and respiratory activity, but a single photoplethysmographic (PPG) signal, which can be exploited to estimate HR and respiratory activity. In addition, these devices employ low sampling rates to limit power consumption. Hence, proper methods should be adopted to compensate for the resulting increased discretization error, while diverse breath-extraction algorithms may be differently sensitive to PPG sampling rate. Here, we assessed the efficacy of parabola interpolation, cubic-spline, and linear regression methods to improve the accuracy of the inter-beat intervals (IBIs) extracted from PPG sampled at decreasing rates from 64 to 8 Hz. PPG-derived IBIs and HRV indices were compared with those extracted from a standard ECG. In addition, breath signals extracted from PPG using three different techniques were compared with the gold-standard signal from a thoracic belt. Signals were recorded from eight healthy volunteers during an experimental protocol comprising sitting and standing postures and a controlled respiration task. Parabola and cubic-spline interpolation significantly increased IBIs accuracy at 32, 16, and 8 Hz sampling rates. Concerning breath signal extraction, the method holding higher accuracy was based on PPG bandpass filtering. Our results support the efficacy of parabola and spline interpolations to improve the accuracy of the IBIs obtained from low-sampling rate PPG signals, and also indicate a robust method for breath signal extraction.
Patients’ Perceptions of Pharmacogenetic Testing and Access to Their Results: State of the Art in Spain and Systematic Review

The process of clinical pharmacogenetics implementation depends on patients’ and general population’s perceptions. To date, no study has been published addressing Spanish patients’ opinions on pharmacogenetic testing, the availability of the results, and the need for signing informed consent. In this work, we contacted 146 patients that had been previously genotyped at our laboratory and 46 healthy volunteers that had participated in a bioequivalence clinical trial at the Clinical Pharmacology Department of Hospital Universitario de La Princesa and consented to pharmacogenetic testing for research purposes. From the latter, 108 and 34, respectively, responded to the questionnaire (i.e., a response rate of 74%); Participants were scheduled for a face-to-face, telephone, or videoconference interview and were asked a total of 27 questions in Spanish. Great or almost complete acceptance of pharmacogenetic testing was observed (99.3%), age and university education level being the main predictors of acceptance rates and understanding (multivariate analysis, p = 0.004, R2 = 0.17, age being inversely proportional to acceptance rates and understanding and university level being related to higher acceptance rates and understanding compared to other education levels). Mixed perceptions were observed on the requirement of written informed consent (55.6% in favor); therefore, it seems recommendable to continue requesting it for the upcoming years until more perceptions are collected. The majority of participants (95.8%) preferred storing pharmacogenetic results in medical records rather than in electronic sources (55.6%) and highly agreed with the possibility of carrying their results on a portable card (91.5%). Patients agreed to broad genetic testing, including biomarkers unrelated to their disease (93.7%) or with little clinically relevant evidence (94.4%). Patients apparently rely on clinician’s or pharmacogeneticist’s interpretation and seem, therefore, open to the generation of ethically challenging information. Finally, although most patients (68.3%) agreed with universal population testing, some were reluctant, probably due to the related costs and sustainability of the Spanish Health System. This was especially evident in the group of patients who were older and with a likely higher proportion of pensioners.
Fighting Fire with Fire: Immunogenicity of Viral Vectored Vaccines against COVID-19

The persistent expansion of the coronavirus disease 2019 (COVID-19) global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires the rapid development of safe and effective countermeasures to reduce transmission, morbidity, and mortality. Several highly efficacious vaccines are actively being deployed around the globe to expedite mass vaccination and control of COVID-19. Notably, viral vectored vaccines (VVVs) are among the first to be approved for global distribution and use. In this review, we examine the humoral, cellular, and innate immune responses elicited by viral vectors, and the immune correlates of protection against COVID-19 in preclinical and clinical studies. We also discuss the durability and breadth of immune response induced by VVVs and boosters. Finally, we present challenges associated with VVVs and offer solutions for overcoming certain limitations of current vaccine regimens. Collectively, this review provides the rationale for expanding the portfolio of VVVs against SARS-CoV-2.
Role of Microbiota-Gut-Brain Axis in Regulating Dopaminergic Signaling

Dopamine is a neurotransmitter that plays a critical role both peripherally and centrally in vital functions such as cognition, reward, satiety, voluntary motor movements, pleasure, and motivation. Optimal dopamine bioavailability is essential for normal brain functioning and protection against the development of neurological diseases. Emerging evidence shows that gut microbiota have significant roles in maintaining adequate concentrations of dopamine via intricate, bidirectional communication known as the microbiota-gut-brain axis. The vagus nerve, immune system, hypothalamus–pituitary–adrenal axis, and microbial metabolites serve as important mediators of the reciprocal microbiota-gut-brain signaling. Furthermore, gut microbiota contain intrinsic enzymatic activity that is highly involved in dopamine metabolism, facilitating dopamine synthesis as well as its metabolite breakdown. This review examines the relationship between key genera of gut microbiota such as Prevotella, Bacteroides, Lactobacillus, Bifidobacterium, Clostridium, Enterococcus, and Ruminococcus and their effects on dopamine. The effects of gut dysbiosis on dopamine bioavailability and the subsequent impact on dopamine-related pathological conditions such as Parkinson’s disease are also discussed. Understanding the role of gut microbiota in modulating dopamine activity and bioavailability both in the periphery and in the central nervous system can help identify new therapeutic targets as well as optimize available methods to prevent, delay, or restore dopaminergic deficits in neurologic and metabolic disorders.
Assessment on anti-SARS-CoV-2 receptor-binding domain antibodies among CoronaVac-vaccinated Indonesian adults

The immunogenicity of CoronaVac among Indonesian adults at the academic premises was investigated. Two doses of CoronaVac vaccine induced a complete seroconversion on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) naïve adults with titers of anti-SARS-CoV-2 receptor-binding domain (RBD) antibodies ranging from 9.1 to 151.9 U/mL. The median value was lower than the one observed in recovered adults with mild coronavirus disease 2019 (38.7 vs. 114.5 U/mL). Nonetheless, 93.6% of the vaccinated adults, in contrast to 76.5% of the recovered adults, displayed inhibition rates above the cut-off to block RBD-angiotensin-converting enzyme 2 binding. This suggests that two doses of CoronaVac were immunogenic and likely to be protective among Indonesian adults.
Training Load, Maturity Timing and Future National Team Selection in National Youth Basketball Players

Despite its importance to the management of training stress, monotony and recovery from exercise, training load has not been quantified during periods of intensity training in youths. This study aimed to (1) examine and quantify the training load (TL) in youth national team basketball players during a 2-week training camp according to maturity timing and (2) determine which parameters were related to under-18 (U18) national team selection. Twenty-nine U-16 national team basketball players underwent an anthropometric assessment to determine maturity timing. Players were categorised by maturity timing (early vs. average), whilst TL parameters during a 2-week training camp (i.e., 21 sessions) prior to FIBA U16 European Championship were used for group comparison and to predict future U-18 national team selection. The early-maturing players, who were taller and heavier (p < 0.05), experienced greater training strain in week 1 (p < 0.05) only. Irrespective of maturity timing, training loads in week 2 were predictive of onward selection for the U-18 national team. Conclusion: Based on present findings, practitioners are encouraged to develop their athletes’ ability to tolerate high weekly loads, but also to be mindful that athletes’ perceived exertion during national team training may be influenced by maturity timing.
A Prospective Randomized Study Comparing Ceftolozane/Tazobactam to Standard of Care in the Management of Neutropenia and Fever in Patients With Hematological Malignancies

Abstract Background With increased use of antibiotics in high-risk patients, the investigation of new antibiotics to cover potentially resistant pathogens is warranted. In this prospective randomized trial, we compared ceftolozane/tazobactam (C/T), a new cephalosporin/β-lactamase inhibitor, to the standard of care (SOC) for the empiric treatment of neutropenia and fever in patients with hematological malignancies. Methods We enrolled 100 patients to receive intravenous (IV) C/T or SOC antibiotics (cefepime, piperacillin/tazobactam, or meropenem) in combination with gram-positive antibacterial agents. We evaluated responses at the end of IV therapy (EOIV), test of cure (TOC; days 21–28), and late follow-up (LFU; days 35–42). Results We analyzed 47 C/T patients and 50 SOC patients. C/T patients had a higher rate of favorable clinical response at EOIV (87% vs 72%). A 1-sided noninferiority analysis indicated that C/T was at least not inferior to the SOC for favorable clinical response at EOIV (P = .002), TOC (P = .004), and LFU (P = .002). Superiority tests showed that C/T led to significantly lower rates of clinical failure at TOC (6% vs 30%; P = .003) and LFU (9% vs 30%; P = .008). C/T and SOC patients with documented infections had similar rates of favorable microbiological response. Serious adverse events leading to drug discontinuation (2% vs 0%; P = .48) and overall mortality (6% vs 4%; P = .67) were similar in both groups. Conclusions The empiric use of C/T in high-risk patients with hematological malignancies and febrile neutropenia is safe and associated with better clinical outcomes than SOC antimicrobial agents. Clinical Trials Registration NCT03485950.
The Design and Evaluation of StudySieve: A Tool That Supports Student-Generated Free-Response Questions, Answers and Evaluations

Asking students to reflect on course content and ask questions about that content has been shown to improve comprehension in numerous domains. More recently, tools have been developed to store multiple-choice questions created by students in an online repository where they can be shared, evaluated and discussed with their peers. Although benefits are reported from the use of such systems, multiple-choice questions are not suitable for all teaching contexts: many instructors prefer to use free-response questions to assess learning. This thesis describes the development and evaluation of an online tool designed to support pedagogies involving student generated free-response questions. Using a design-based research methodology, an online tool named StudySieve was designed, implemented and evaluated in naturalistic educational settings. StudySieve was used in three large undergraduate Computer Science courses in which students developed questions with sample solutions, answered the questions contributed by their peers and evaluated both questions and answers. The effectiveness of free-response question generation and related activities is evaluated by considering the response from students, the nature of the questions created and the relationship between activity and subsequent exam performance. Students believe that the activities of question generation, answering questions and evaluating both questions and answers do help them learn. They rarely write more questions than required for assessment, but many students use the questions generated by their peers to practice prior to exams. The questions created by students reflect all the major topics of a course covered prior to the question generation activity, but the cognitive level of student generated questions tends to be lower than those generated by instructors. Although student question-generation activity is correlated with exam performance, the correlations can be explained by other levels of activity in a course. However, students who write questions on a topic sometimes have improved performance in exams on that topic compared with students who have not authored a question on the topic. Generating free-response questions is a valuable educational activity, but the exact conditions that result in improved exam performance require further investigation by future research.
Historical, Morphological and Syntactic Patterns of Tundra Nenets Dual System

Tundra Nenets is one of a few Uralic languages retained the dual system. A broad range of previous studies on proto-languages, morphology, morphophonology, and syntax of Tundra Nenets are reviewed in this paper, for the purpose of shaping a comprehensive framework of dual number in Tundra Nenets. Both diachronic and synchronic characteristics of dual system are discussed in this paper, where morphological and syntactic patterns of dual number (e.g., nominal declension, verbal inflection, construction of pronouns and dual quantifier agreement) are thoroughly analysed. This paper yields several key findings as following. According to the analysis, the development of dual patterns in Proto-Uralic and Proto-Samoyedic serves as the fundamental factors for the dual system in modern Tundra Nenets. Besides, an analogous but uneven correspondence between dual and plural in terms of various inflections provides evidence for the role of dual as a derivative from plural. Additionally, “dual dilemma” summarised and proposed by this paper refers to the complications that emerge in the alternative syntactic expressions of dual number, revealing different outcomes in certain contexts. Moreover, despite the differences in orthography and diacritics among scholars, there is a relatively undoubted consensus over the real grammatical representations of dual forms in Tundra Nenets. Dialectal differences and pragmatic features of Tundra Nenets dual system await further research. These results shed light on the special status of dual number in Tundra Nenets with a long tradition and the significant function of dual for specifying meanings in morphological and syntactic aspects of this language.
Sustaining an HIV Prevention and Wellness Program for Sexual Gender Minorities during the COVID-19 Pandemic

Improving mental health, body image, and financial stability is paramount to achieving viral suppression and maintaining HIV-negative status for minoritized communities. The purpose of this paper is to describe the lessons learned from maintenance of an HIV prevention and wellness program during the COVID-19 pandemic. A three-session program was implemented in a hybrid format to account for county-wide restrictions and reopening processes. Lessons learned include the utility of a hybrid format, importance of CBPR partnership, innovation in virtual platform, value of social media presence and upkeep, and use of multiple methods to ascertain evaluative data. Sustaining an HIV prevention and wellness program requires strong research collaborations and ongoing engagement with priority populations and the flexibility to pivot as needed.