Miracle-dz/UniFAR-FTUs huggingface dataset:
Population Pharmacokinetic-Pharmacodynamic Model of Oxfendazole in Healthy Adults in a Multiple Ascending Dose and Food Effect Study and Target Attainment Analysis

Oxfendazole is a potent veterinary antiparasitic drug undergoing development for human use to treat multiple parasitic infections. Results from two recently completed phase I clinical trials conducted in healthy adults showed that the pharmacokinetics of oxfendazole is nonlinear, affected by food, and, after the administration of repeated doses, appeared to mildly affect hemoglobin concentrations. ABSTRACT Oxfendazole is a potent veterinary antiparasitic drug undergoing development for human use to treat multiple parasitic infections. Results from two recently completed phase I clinical trials conducted in healthy adults showed that the pharmacokinetics of oxfendazole is nonlinear, affected by food, and, after the administration of repeated doses, appeared to mildly affect hemoglobin concentrations. To facilitate oxfendazole dose optimization for its use in patient populations, the relationship among oxfendazole dose, pharmacokinetics, and hemoglobin concentration was quantitatively characterized using population pharmacokinetic-pharmacodynamic modeling. In fasting subjects, oxfendazole pharmacokinetics was well described by a one-compartment model with first-order absorption and elimination. The change in oxfendazole pharmacokinetics when administered following a fatty meal was captured by an absorption model with one transit compartment and increased bioavailability. The effect of oxfendazole exposure on hemoglobin concentration in healthy adults was characterized by a life span indirect response model in which oxfendazole has positive but minor inhibitory effect on red blood cell synthesis. Further simulation indicated that oxfendazole has a low risk of posing a safety concern regarding hemoglobin concentration, even at a high oxfendazole dose of 60 mg/kg of body weight once daily. The final model was further used to perform comprehensive target attainment simulations for whipworm infection and filariasis at various dose regimens and target attainment criteria. The results of our modeling work, when adopted appropriately, have the potential to greatly facilitate oxfendazole dose regimen optimization in patient populations with different types of parasitic infections.
Effects of presentation modality and duration on children’s strategy use: A study in computational estimation

Two experiments were run to determine how presentation modality and duration influence children’s arithmetic performance and strategy selection. Third and fourth graders were asked to find estimates for two-digit addition problems (e.g., 52 + 39). Children were tested in three conditions: (1) time-unlimited visual, (2) time-limited visual, or (3) time-limited auditory conditions. Moreover, we assessed children’s working-memory updating and arithmetic fluency. Children were told which strategy to use on each problem to assess arithmetic performance while executing strategies, in Experiment 1, and were asked to choose the best strategy of three available strategies to assess strategy selection, in Experiment 2. Presentation modality influenced strategy execution (i.e., children were faster and more accurate in problems under visual than auditory conditions) but only in children with low updating abilities. In contrast, presentation modality had no effect on children’s strategy selection. Presentation duration had an effect on both strategy execution and strategy selection with time-limited presentation leading to a decline in children’s performance. Interestingly, specifically in children with low updating abilities, time-limited presentation led to poorer performance. Hence, efficient updating seemed to compensate for detrimental effects of auditory in comparison to visual and time-limited in comparison to time-unlimited presentation. These findings have important implications for determining conditions under which children execute strategies most efficiently and select the best strategy on each problem most often, as well as for understanding mechanisms underlying strategic behaviour.
Molecular weight determination of adeno‐associate virus serotype 8 virus‐like particle either carrying or lacking genome via native nES gas‐phase electrophoretic molecular mobility analysis and nESI QRTOF mass spectrometry

Abstract Virus‐like particles (VLPs) are proteinaceous shells derived from viruses lacking any viral genomic material. Adeno‐associated virus (AAV) is a non‐enveloped icosahedral virus used as VLP delivery system in gene therapy (GT). Its success as vehicle for GT is due to its selective tropism, high level of transduction, and low immunogenicity. In this study, two preparations of AAV serotype 8 (AAV8) VLPs either carrying or lacking completely genomic cargo (i.e., non‐viral ssDNA) have been investigated by means of a native nano‐electrospray gas‐phase electrophoretic mobility molecular analyzer (GEMMA) (native nES GEMMA) and native nano‐electrospray ionization quadrupole reflectron time‐of‐flight mass spectrometry (MS) (native nESI QRTOF MS). nES GEMMA is based on electrophoretic mobility principles: single‐charge nanoparticles (NPs), that is, AAV8 particle, are separated in a laminar sheath flow of dry, particle‐free air and a tunable orthogonal electric field. Thus, the electrophoretic mobility diameter (EMD) of a bio‐NP (i.e., diameter of globular nano‐objects) is obtained at atmospheric pressure, which can be converted into its MW based on a correlation. First is the native nESI QRTOF. MS's goal is to keep the native biological conformation of an analyte during the passage into the vacuum. Subsequently, highly accurate MW values are obtained from multiple‐charged species after deconvolution. However, once applied to the analysis of megadalton species, native MS is challenging and requires customized instrumental modifications not readily available on standard devices. Hence, the analysis of AAV8 VLPs via native MS in our hands did not produce a defined charge state assignment, that is, charge deconvolution for exact MW determination was not possible. Nonetheless, the method we present is capable to estimate the MW of VLPs by combining the results from native nES GEMMA and native ESI QRTOF MS. In detail, our findings show a MW of 3.7 and 5.0 MDa for AAV8 VLPs either lacking or carrying an engineered genome, respectively.
Hydrothermal synthesis and influence of later heat treatment on the structural evolution, optical and electrical properties of nanostructured α-MoO3 single crystals

In the current study, α-MoO3 nanocrystals were successfully synthesized from ammonium heptamolybdate tetrahydrate using a simple hydrothermal route. The influence of calcination temperature on the structural, optical and electrical properties was systematically investigated for the MoO3 powder products. The XRD results were analyzed for these powders, revealing the formation of a mixed phase (β- and α-MoO3) at calcination temperatures ranging from 350 °C–450 °C, and hence a residual monoclinic phase still exists in the samples at the calcination temperature of 450 °C. Subsequently, the mixed phase was completely converted to a pure single phase of α-MoO3 at a calcination temperature of 500 °C. The optical properties of the MoO3 powders were investigated using the transformed diffuse reflectance technique according to Kubelka–Munk theory. For such a powder product, the results of the optical measurements demonstrated the realization of indirect and direct allowed transitions at the spectral ranges 3.31–3.91 eV and 3.66–4.27 eV, respectively. The indirect- and direct-allowed band-gaps of the MoO3 products were found to increase from 2.69–3.12 eV and from 3.43–3.64 eV, respectively, by increasing the calcination temperature from 350 °C–600 °C. The MoO3 powders calcined at different temperatures were converted into five dense tablets for performing the electrical measurements. These measurements were carried out at different working temperatures using a system operating under high vacuum conditions. The results revealed that the dc-conductivity of such a tablet typically increases by more than five orders of magnitude with an increase in the working temperature from 77–300 K. These results also demonstrated a high dependence of dc-conductivity on the calcination temperature for the MoO3 products. The dc-conductivity as a function of the operating temperature revealed the presence of at least three different electrical conduction mechanisms for the same MoO3 tablet.
Optimal Tracking in Switched Systems With Free Final Time and Fixed Mode Sequence Using Approximate Dynamic Programming

Optimal tracking in switched systems with fixed mode sequence and free final time is studied in this article. In the optimal control problem formulation, the switching times and the final time are treated as parameters. For solving the optimal control problem, approximate dynamic programming (ADP) is used. The ADP solution uses an inner loop to converge to the optimal policy at each time step. In order to decrease the computational burden of the solution, a new method is introduced, which uses evolving suboptimal policies (not the optimal policies), to learn the optimal solution. The effectiveness of the proposed solutions is evaluated through numerical simulations.
Current opportunities and new horizons into the genetic study of infertility

Introduction: An estimated 12.5% of couples experiencing fertility problems and almost 12% of reproductive age women have turned to health services at least once due to infertility. First trimester miscarriage is the most common clinical manifestation of infertility associated with a genetic cause. Patients, Materials and Methods: The scientific research was conducted at A.S. Medical Center in Bucharest, Romania, between January 2016 and December 2018, on a representative group of 1264 Caucasian patients diagnosed with infertility, from which the study group was selected, consisting of 273 patients who were further genetically investigated. Results: Chromosomal instability, identified in 14% of patients, has been encountered most frequently in women (7%), and least often in fetuses (2%), unlike other chromosomal anomalies, identified in 55% of patients, which were more common in fetuses (27%) and least frequently in men (9%). Recurrent pregnancy loss due to genetic causes was identified in 53% of cases, being determined by chromosomal instability in 16% of cases and by other chromosomal anomalies in 37% of cases. Infertility due to a genetic cause was identified in 83% of cases, being determined by chromosomal instability in 17% of cases and by other chromosomal anomalies encountered in 66% of cases. In genetic risk pregnancies in evolution, fetal chromosomal anomalies were detected in 94% of cases, the most frequent being aneuploidy and polyploidy. Cytogenetic studies carried out on tissue fragments taken from aborted products of conception revealed the presence of a genetic cause in 57% of cases, an abnormal chromosome number being the most common (36%). The analysis of microdeletions of the long arm of the Y chromosome indicated that 5.5% of men with infertility are affected by this condition. Conclusions: Although genetic tests are considered complex and expensive laboratory investigations, they are crucial in identifying the etiology of over 40% of infertility cases associated with genetic factors, as well as in the correct and effective management of infertility.
Evaluation of a new series of pyrazole derivatives as a potent epidermal growth factor receptor inhibitory activity: QSAR modeling using quantum‐chemical descriptors

Pyrazole derivatives correspond to a family of heterocycle molecules with important pharmacological and physiological applications. At present, we perform a density functional theory (DFT) calculations and a quantitative structure–activity relationship (QSAR) evaluation on a series of 1‐(4,5‐dihydro‐1H‐pyrazol‐1‐yl) ethan‐1‐one and 4,5‐dihydro‐1H‐pyrazole‐1‐carbothioamide derivatives as an epidermal growth factor receptor (EGFR) inhibitory activity. We thus propose a virtual screening protocol based on a machine‐learning study. This theoretical model relates the studied compounds' biological activity to their calculated physicochemical descriptors. Moreover, the linear regression function is used to validate the model via the evaluation of Q2ext and Q2cv parameters for external and internal validations, respectively. Our QSAR model shows a good correlation between observed activities IC50 and predicted ones. Our model allows us to mitigate time‐consuming problems and waste chemical and biological products in the preclinical phases.
AI in nuclear medicine – what, why and how?

There have been various attempts to define artificial intelligence (AI), and none is sufficiently precise but at the same time universally applicable. However, in the context of medical imaging, the term machine learning (ML), which is generally considered a subset of AI [1], may describe most applications more appropriately. Here, “learning” relates to the capability of systems to identify complex relationships between data and to predict outcomes in new and unknown data with similar characteristics. With the computing power available today, ML has advanced from classical ML methods, such as decision trees or support vector machines, to more complex architectures, such as deep learning. This uses “deep” artificial neural networks, which are characterized by multiple layers of artificial neurons [2]. In several applications in medical imaging, deep learning has been found to be equivalent or superior to classical ML methods [3, 4, 5], and it is now the most commonly used ML approach for such tasks. Deep neural networks, and especially convolutional neural networks (yet another subset), are inherently useful for the numerous “visual tasks” involved in image analysis.
Prior Acoustic Trauma Alters Type II Afferent Activity in the Mouse Cochlea

Abstract Auditory stimuli travel from the cochlea to the brainstem through type I and type II cochlear afferents. While type I afferents convey information about the frequency, intensity, and timing of sounds, the role of type II afferents remains unresolved. Limited recordings of type II afferents from cochlear apex of prehearing rats reveal they are activated by widespread outer hair cell stimulation, ATP, and by the rupture of nearby outer hair cells. Altogether, these lines of evidence suggest that type II afferents sense loud, potentially damaging levels of sound. To explore this hypothesis further, calcium imaging was used to determine the impact of acoustic trauma on the activity of type II cochlear afferents of young adult mice of both sexes. Two known marker genes (Th, Drd2) and one new marker gene (Tac1), expressed in type II afferents and some other cochlear cell types, drove GCaMP6f expression to reveal calcium transients in response to focal damage in the organ of Corti in all turns of the cochlea. Mature type II afferents responded to acute photoablation damage less often but at greater length compared with prehearing neurons. In addition, days after acoustic trauma, acute photoablation triggered a novel response pattern in type II afferents and surrounding epithelial cells, delayed bursts of activity occurring minutes after the initial response subsided. Overall, calcium imaging can report type II afferent responses to damage even in mature and noise-exposed animals and reveals previously unknown tissue hyperactivity subsequent to acoustic trauma.
A review on chemistry and biological activities of Laurus nobilis L. essential oil

Laurus nobilis L. commonly known as bay belonging to the family Lauraceae is one of the most useful essential oil and is an industrial plant used in foods, drugs and cosmetics. Bay is cultivated throughout the world mainly in tropical and sub-tropical Asia, Australia, Pacific region and South Asia. Bay essential oil can be extracted from various parts of plant and chiefly consisted of 1, 8 Cineole, sabinene, α-pinene and p-Cymene. Due to presence of various chemical constituents in bay, various biological and pharmacological properties have been reported such as antibacterial, antifungal, antioxidant, insecticidal and nematicidal activities. This review highlighted chemical composition and biological activities of Laurus nobilis which will be useful to the researcher for further study.
Gradient H‐Bonding Binder Enables Stable High‐Areal‐Capacity Si‐Based Anodes in Pouch Cells

Alleviating large stress is critical for high‐energy batteries with large volume change upon cycling, yet this still presents a challenge. Here, a gradient hydrogen‐bonding binder is reported for high‐capacity silicon‐based anodes that are highly desirable for the next‐generation lithium‐ion batteries. The well‐defined gradient hydrogen bonds, with a successive bond energy of −2.88– −10.04 kcal mol−1, can effectively release the large stress of silicon via the sequential bonding cleavage. This can avoid recurrently abrupt structure fracture of traditional binder due to lack of gradient energy dissipation. Certainly, this regulated binder endows stable high‐areal‐capacity silicon‐based electrodes >4 mAh cm−2. Beyond proof of concept, this work demonstrates a 2 Ah silicon‐based pouch cell with an impressive capacity retention of 80.2% after 700 cycles (0.028% decay/cycle) based on this gradient hydrogen‐bonding binder, making it more promising for practical application.
Probiotic lactobacilli in formulas and hygiene products for the health of the urogenital tract

Lactobacilli are the predominant microorganisms of the healthy human vagina. A novel alternative for the prevention and treatment of female urogenital tract infections (UGTI) is the inclusion of these microorganisms as active pharmaceutical ingredients in probiotic formulas, and more recently in female hygienic products. Probiotics are defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. ” A list of requirements must be considered during the development of probiotic product/formula for the female urogenital tract (UGT). This review aims to resume the requirements, probiotic characteristics, and clinical trial applied to determine the effect of probiotic and potentially probiotic strains on different woman’s physiological and pathological conditions, and in preterm birth prevention. A revision of female hygienic products available in the world market is included, together with novel studies applying nanotechnology for Lactobacillus incorporation in hygienic products. Further studies and well‐designed clinical trials are urgently required to complement the current knowledge and applications of probiotics in the female UGT. The use of probiotic formulas and products will improve and restore the ecological equilibrium of the UGT microbiome to prevent and treat UGTI in women under different conditions.
Telemedicine for preanesthesia evaluation: review of current literature and recommendations for future implementation

Purpose of review The in-person preanesthesia visit serves multiple purposes including identification and optimization of comorbid conditions as well as patient education. However, it imposes a significant burden on patients and healthcare providers. In this review, we define the scope of telemedicine and present the most up-to-date literature supporting its role for the preanesthesia evaluation. The opportunities and challenges are discussed and approaches to implementation of telemedicine in preanesthesia care are offered. Finally, the future of telemedicine as it pertains to preanesthesia care is examined. Recent findings Although telemedicine for preanesthesia practice was proposed almost two decades ago, the COVID-19 pandemic has accelerated its implementation. The potential benefits of telemedicine include improved patient satisfaction as well as the ability to provide cost-effective specialty services while reducing the burden on healthcare providers. Limitations to telemedicine include lack of technology, training, regulatory barriers, and an inability to perform a physical exam. Summary Telemedicine will continue to expand and its application to the preanesthesia evaluation is a clear example of how technology will revolutionize anesthesia practice. In order for telemedicine to continue to expand in the postpandemic period, steps must be taken to ensure that healthcare facilities and providers keep up with the times.
Students’ perspective on wellness intervention programs

We read with great interest the article by Waechter et al. (2021) on mitigating medical student stress and as final year medical students we applaud their initiative in addressing such an important topic. We hope to further this discussion and offer some of our views on the topic. One aspect that we believe needs to be further considered relates to the complex nature of stress particularly in medicine. As acknowledged by the authors, medical students tend to experience higher levels of stress and anxiety compared to peers in a similar age group (Waechter et al. 2021). Studies have shown that multiple major stressors contribute varying from the constant pressure of academic excellence and lack of work-life balance through to the distress associated with exposure to patient suffering (Hill et al. 2018). Indeed, many of these are carried by medical professionals throughout their careers and so the aim should be long-term change instead of a more short-term solution. We envision that integrating mandatory wellbeing intervention into the curriculum will reduce it to simply another module or rotation in medical school and produce only short-term benefits in reducing stress and so should be supplemented with further adjustments to the curriculum. By introducing a formal and more extensive program of learning, teaching and assessment around stress that involves normalising discussions about self-care and wellbeing as part of student support programs, you are more likely to change the mindset of students in managing stress and will consequently provide continued benefits later in our careers. As part of this, as mentioned earlier, stress amongst medical students is complex and so focus should be on a holistic approach to these individual factors. For example, our medical school has employed the use of a version of Balint groups for students to discuss distressing scenarios they may have had whilst on their Psychology rotations. This was often a useful time to unpack emotions and our thoughts allowing support and advice to be offered from both peers and supervisors. We propose that introducing similar sessions for all rotations that run throughout the year offers just one of the ways to supplement wellbeing intervention programs. We have no doubt that wellbeing interventions are effective in decreasing levels of perceived stress and burnout, but we believe that encouraging personal development and initiative towards this instead of solely enforcing mandatory wellbeing activities is more likely to be well received by students.