Miracle-dz/UniFAR-FTUs huggingface dataset:
Factors Associated with Student Pharmacists’ Academic Progression and Performance on the National Licensure Examination

Objective. To examine predictors of Doctor of Pharmacy (PharmD) students’ on-time graduation, dismissal from pharmacy school, and scores on their first attempt at taking the North American Pharmacist Licensure Examination (NAPLEX). Methods. A retrospective review of student records for the graduating classes of 2015-2018 at a college of pharmacy was performed. Data on the following were collected: student demographics/characteristics (age, gender, race/ethnicity, financial need), having an undergraduate degree, undergraduate science grade point average (GPA), Pharmacy College Admission Test composite score percentile, pharmacy school GPAs for the didactic portion of the curriculum, Pre-NAPLEX score, on-time graduation from pharmacy school, dismissal from pharmacy school, and outcome (pass/fail) of first-attempt at taking the NAPLEX. Binary logistic regression analysis was conducted. Results. Of the 657 students whose records were included in the study, the majority were female (60%) and non-Hispanic white (70%). Higher first-year GPA was associated with increased likelihood of on-time graduation, while increased age and having an undergraduate degree were associated with a decreased likelihood of on-time graduation. A higher first-year GPA was associated with decreased likelihood of being dismissed from pharmacy school. Appearing before the Academic Standing and Promotion Review Committee for unsatisfactory academic performance was associated with decreased likelihood of passing the NAPLEX. Conclusion. First-year pharmacy school GPA is a critical predictor for student pharmacists in terms of on-time graduation and dismissal, and may have consequences for later NAPLEX outcome. Pharmacy schools should closely monitor students’ performance during the first year and provide support to students experiencing academic difficulties.
Interactions of Glycerol, Diglycerol, and Water Studied Using Attenuated Total Reflection Infrared Spectroscopy

In order to examine the mixing properties of glycerol–water and diglycerol–water solutions, these solutions were measured using attenuated total reflection infrared spectroscopy. The absorbance spectra corrected for 1 µm thickness were subtracted by pure polyols for obtaining water spectra, and by pure water for polyol spectra. Both asymmetric and symmetric CH2 stretching vibration bands (around 2940, 2885 cm−1) shifted about 10 cm−1 to lower wavenumber side (redshifts) with increasing polyol concentrations, especially at higher concentrations. Redshifts of C–O–H rocking bands (around 1335 cm−1) with increasing polyol concentrations are slightly larger for diglycerol–water (10 > 6 cm−1) than glycerol–water solutions. C–O stretching bands of CHOH groups (1125 and 1112 cm−1) shift slightly but in opposite sides for glycerol and diglycerol at highest polyol concentrations (90–100 wt%). These shifts of CH2 stretching, COH rocking, and CO stretching of CHOH at higher polyol concentrations suggest interactions of outer CH2 with inner CHOH groups of surrounding polyols. The normalized band area changes with polyol concentrations could be fitted by quadratic polynomials possibly due to mixtures of different interactions between water–water, polyol–water, and polyol–polyol molecules. The OH stretching band for diglycerol 90 wt% shows three humps indicating at least three OH components: long, medium, and short H bond water molecules. Short H bond water molecules are the major component possibly between inner CHOH and outer side CH2OH groups, while the long H component might loosely bind to outer CH2OH groups.
Role of Hepatitis B virus capsid phosphorylation in nucleocapsid disassembly and covalently closed circular DNA formation

Hepatitis B virus (HBV) delivers a partially double-stranded, relaxed circular (RC) DNA genome in complete virions to the host cell nucleus for conversion to the covalently closed circular (CCC) DNA, which establishes and sustains viral infection. An overlength pregenomic RNA (pgRNA) is then transcribed from CCC DNA and packaged into immature nucleocapsids (NCs) by the viral core (HBc) protein. pgRNA is reverse transcribed to produce RC DNA in mature NCs, which are then enveloped and secreted as complete virions, or delivered to the nucleus to replenish the nuclear CCC DNA pool. RC DNA, whether originating from extracellular virions or intracellular mature NCs, must be released upon NC disassembly (uncoating) for CCC DNA formation. HBc is known to undergo dynamic phosphorylation and dephosphorylation at its C-terminal domain (CTD) to facilitate pgRNA packaging and reverse transcription. Here, two putative phosphorylation sites in the HBc N-terminal domain (NTD), S44 and S49, were targeted for genetic and biochemical analysis to assess their potential roles in viral replication. The NTD mutant that mimics the non-phosphorylated state (N2A) was competent in all steps of viral replication tested from capsid assembly, pgRNA packaging, reverse transcription, to virion secretion, except for a decrease in CCC DNA formation. On the other hand, the phosphor-mimetic mutant N2E showed a defect in the early step of pgRNA packaging but enhanced the late step of mature NC uncoating and consequently, increased CCC DNA formation. N2E also enhanced phosphorylation in CTD and possibly elsewhere in HBc. Furthermore, inhibition of the cyclin-dependent kinase 2 (CDK2), which is packaged into viral capsids, could block CCC DNA formation. These results prompted us to propose a model whereby rephosphorylation of HBc at both NTD and CTD by the packaged CDK2, following CTD dephosphorylation during NC maturation, facilitates uncoating and CCC DNA formation by destabilizing mature NCs.
Dynamical model of the CLC-2 ion channel reveals conformational changes associated with selectivity-filter gating

This work reports a dynamical Markov state model of CLC-2 “fast” (pore) gating, based on 600 microseconds of molecular dynamics (MD) simulation. In the starting conformation of our CLC-2 model, both outer and inner channel gates are closed. The first conformational change in our dataset involves rotation of the inner-gate backbone along residues S168-G169-I170. This change is strikingly similar to that observed in the cryo-EM structure of the bovine CLC-K channel, though the volume of the intracellular (inner) region of the ion conduction pathway is further expanded in our model. From this state (inner gate open and outer gate closed), two additional states are observed, each involving a unique rotameric flip of the outer-gate residue GLUex. Both additional states involve conformational changes that orient GLUex away from the extracellular (outer) region of the ion conduction pathway. In the first additional state, the rotameric flip of GLUex results in an open, or near-open, channel pore. The equilibrium population of this state is low (∼1%), consistent with the low open probability of CLC-2 observed experimentally in the absence of a membrane potential stimulus (0 mV). In the second additional state, GLUex rotates to occlude the channel pore. This state, which has a low equilibrium population (∼1%), is only accessible when GLUex is protonated. Together, these pathways model the opening of both an inner and outer gate within the CLC-2 selectivity filter, as a function of GLUex protonation. Collectively, our findings are consistent with published experimental analyses of CLC-2 gating and provide a high-resolution structural model to guide future investigations.
An improved animal model for herpesvirus encephalitis in humans

Herpesviral encephalitis caused by Herpes Simplex Virus 1 (HSV-1) is one of the most devastating diseases in humans. Patients present with fever, mental status changes or seizures and when untreated, sequelae can be fatal. Herpes Simplex Encephalitis (HSE) is characterized by mainly unilateral necrotizing inflammation effacing the frontal and mesiotemporal lobes with rare involvement of the brainstem. HSV-1 is hypothesized to invade the CNS via the trigeminal or olfactory nerve, but viral tropism and the exact route of infection remain unclear. Several mouse models for HSE have been developed, but they mimic natural infection only inadequately. The porcine alphaherpesvirus Pseudorabies virus (PrV) is closely related to HSV-1 and Varicella Zoster Virus (VZV). While pigs can control productive infection, it is lethal in other susceptible animals associated with severe pruritus leading to automutilation. Here, we describe the first mutant PrV establishing productive infection in mice that the animals are able to control. After intranasal inoculation with a PrV mutant lacking tegument protein pUL21 and pUS3 kinase activity (PrV-ΔUL21/US3Δkin), nearly all mice survived despite extensive infection of the central nervous system. Neuroinvasion mainly occurred along the trigeminal pathway. Whereas trigeminal first and second order neurons and autonomic ganglia were positive early after intranasal infection, PrV-specific antigen was mainly detectable in the frontal, mesiotemporal and parietal lobes at later times, accompanied by a long lasting lymphohistiocytic meningoencephalitis. Despite this extensive infection, mice showed only mild to moderate clinical signs, developed alopecic skin lesions, or remained asymptomatic. Interestingly, most mice exhibited abnormalities in behavior and activity levels including slow movements, akinesia and stargazing. In summary, clinical signs, distribution of viral antigen and inflammatory pattern show striking analogies to human encephalitis caused by HSV-1 or VZV not observed in other animal models of disease.
CK1α-targeting inhibits primary and metastatic colorectal cancer in vitro, ex vivo, in cell-line-derived and patient-derived tumor xenograft mice models

Background Colorectal cancer (CRC) remains a leading cause of cancer-related deaths globally. Despite improved understanding of its initiation and progression, and advances in diagnostic or therapeutic strategies, the treatment of metastatic CRC remains a clinical challenge, necessitating identification of novel efficacious therapeutics with little/no toxicity to non-tumor colorectal cells. The present study investigated the effect of Epiblastin A, an adenosine triphosphate (ATP)-mediated competitive inhibitor of casein kinase 1α (CK1α) on the viability, proliferation, and oncogenicity of CRC cells. Methods Comparative evaluation of the effect of Epiblastin A on CK1α in fetal human normal colonic mucosa (FHC) and CRC (HCT116, HT29, DLD1) cell lines, using western blot, immunohistochemical staining, real-time polymerase chain reaction (RT-PCR), and sulforhodamine B (SRB) cytotoxicity assays. Primary culture cells, patient-derived xenograft (PDX), and tumor xenograft mice CRC models were also employed. Kaplan-Meier plots were used for survival analysis of our CRC cohort. Results CRC cells aberrantly express CK1α at mRNA and protein levels. This overexpression of CK1α is strongly associated with worse 5-year overall survival (OS) in patients with CRC. Epiblastin A inhibits CK1α and compared to its apparent non-effect on FHC cells regardless of concentration, it elicits significant dose-dependent inhibition of the viability of HT29, HCT116, and DLD1 cells with a 48 h IC50 of 6.8, 5.0, and 3.2 μM, respectively. The expression of CK1α in CRC primary cultures and PDX samples, significantly correlated with Ki-67 expression, and both were attenuated by Epiblastin A. We also observed that the effect of 5 mg/kg Epiblastin A on tumor volume, and body weight in the CRC PDX mice models, was similar to that of 5 mg/kg Cetuximab over the time-course of our in vivo study. In DLD1-derived tumor xenograft mice, Epiblastin A with very mild effect on mice body weight, suppressed tumor volume and tumor weight in a CK1α-dependent manner (P=0.024). Conclusions Our results demonstrate the efficacy of Epiblastin A in CRC and its potential as a putative small-molecule inhibitor of CK1α and Ki-67 signaling, which are relevant in the CRC initiation, progression and prognosis.
Binding Kinetics of Ruthenium Pyrithione Chemotherapeutic Candidates to Human Serum Proteins Studied by HPLC-ICP-MS

The development of ruthenium-based complexes for cancer treatment requires a variety of pharmacological studies, one of them being a drug’s binding kinetics to serum proteins. In this work, speciation analysis was used to study kinetics of ruthenium-based drug candidates with human serum proteins. Two ruthenium (Ru) complexes, namely [(η6-p-cymene)Ru(1-hydroxypyridine-2(1H)-thionato)Cl] (1) and [(η6-p-cymene)Ru(1-hydroxypyridine-2(1H)-thionato)pta]PF6 (2) (where pta = 1,3,5-triaza-7-phosphaadamantane), were selected. Before a kinetics study, their stability in relevant media was confirmed by nuclear magnetic resonance (NMR). Conjoint liquid chromatography (CLC) monolithic column, assembling convective interaction media (CIM) protein G and diethylamino (DEAE) disks, was used for separation of unbound Ru species from those bound to human serum transferrin (Tf), albumin (HSA) and immunoglobulins G (IgG). Eluted proteins were monitored by UV spectrometry (278 nm), while Ru species were quantified by post-column isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS). Binding kinetics of chlorido (1) and pta complex (2) to serum proteins was followed from 5 min up to 48 h after incubation with human serum. Both Ru complexes interacted mainly with HSA. Complex (1) exhibited faster and more extensive interaction with HSA than complex (2). The equilibrium concentration for complex (1) was obtained 6 h after incubation, when about 70% of compound was bound to HSA, 5% was associated with IgG, whereas 25% remained unbound. In contrast, the rate of interaction of complex (2) with HSA was much slower and less extensive and the equilibrium concentration was obtained 24 h after incubation, when about 50% of complex (2) was bound to HSA and 50% remained unbound.
Weight suppression and weight maintenance following treatment of anorexia nervosa.

OBJECTIVE The value of weight suppression (WS) in predicting the course of anorexia nervosa (AN) is uncertain. The objective of this study was to determine, using data from a previously published study, whether patients who remain weight suppressed following restoration to a minimally normal weight are at greater risk for relapse. METHOD Following weight restoration, 93 women with AN were randomly assigned to receive fluoxetine or placebo along with cognitive behavioral therapy for 1 year. WS (highest adult weight minus current weight), body mass index (BMI), and their interaction were assessed as predictors of change in weight over the first 28 days, of successful weight maintenance at 6 and 12 months, and of time to relapse. RESULTS Neither WS nor its interaction with BMI predicted successful weight maintenance at 6 and 12 months, time to relapse, or weight change over the first 28 days following discharge. DISCUSSION This study found that WS does not substantially impact the likelihood of successful weight maintenance or time to relapse following restoration to a minimally normal weight in AN.
Extrinsic Calibration of Multiple Two-Dimensional Laser Rangefinders Based on a Trihedron

Multiple two-dimensional laser rangefinders (LRFs) are applied in many applications like mobile robotics, autonomous vehicles, and three-dimensional reconstruction. The extrinsic calibration between LRFs is the first step to perform data fusion and practical application. In this paper, we proposed a simple method to calibrate LRFs based on a corner composed of three mutually perpendicular planes. In contrast to other methods that require a special pattern or assistance from other sensors, the trihedron corner needed in this method is common in daily environments. In practice, we can adjust the position of the LRFs to observe the corner until the laser scanning plane intersects with three planes of the corner. Then, we formed a Perspective-Three-Point problem to solve the position and orientation of each LRF at the common corner coordinate system. The method was validated with synthetic and real experiments, showing better performance than existing methods.
The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2

Abstract A new type of pneumonia caused by a novel coronavirus SARS-CoV-2 outbreaks recently in China and spreads into many other countries. This disease, named as COVID-19, is similar to patients infected by SARS-CoV and MERS-CoV, and nearly 20% of patients developed severe condition. Cardiac injury is a prevalent complication of severe patients, exacerbating the disease severity in coronavirus disease 2019 (COVID-19) patients. Angiotensin-converting enzyme 2 (ACE2), the key host cellular receptor of SARS-CoV-2, has been identified in multiple organs, but its cellular distribution in human heart is not illuminated clearly. This study performed the first state-of-art single cell atlas of adult human heart, and revealed that pericytes with high expression of ACE2 might act as the target cardiac cell of SARS-CoV-2. The pericytes injury due to virus infection may result in capillary endothelial cells dysfunction, inducing microvascular dysfunction. And patients with basic heart failure disease showed increased ACE2 expression at both mRNA and protein levels, meaning that if infected by the virus these patients may have higher risk of heart attack and critically ill condition. The finding of this study explains the high rate of severe cases among COVID-19 patients with basic cardiovascular disease; and these results also perhaps provide important reference to clinical treatment of cardiac injury among severe patients infected by SARS-CoV-2.
Gastrocnemius Medialis and Vastus Lateralis in vivo muscle‐tendon behavior during running at increasing speeds

This study combines in vivo ultrasound measurements of the Vastus Lateralis (VL) and Gastrocnemius Medialis (GM) muscles with electromyographic, kinematic, and kinetic measurements during treadmill running at different speeds (10, 13, and 16 km/h) to better understand the role of muscle and tendon behavior in two functionally different muscle‐tendon units. In addition, the force‐length and force‐velocity relationships of VL and GM were experimentally assessed by combining dynamometry and EMG data with ultrasound measurements. With increasing running speed, the operating length of the fascicles in the stance phase shifted toward smaller lengths in the GM (P < .05; moving down the ascending limb of the F‐L relationship) and longer lengths in the VL (P < .05; moving down the descending limb) at all speeds; however, both muscles contracted close to their optimal length L0, where isometric force is maximal. Whereas the length of VL SEE did not change as a function of speed, GM SEE lengthened and shortened more at higher speeds. With increasing running speed, the contribution of elastic strain energy to the positive power generated by the MTU increased more for GM (from 0.75 to 1.56 W/kg) than for VL (from 0.62 to 1.02 W/kg). Notwithstanding these differences, these results indicate that, at increasing running speeds, both the VL and GM muscles produce high forces at low contraction velocities, and that the primary function of both muscle‐tendon units is to enhance the storage and recovery of elastic strain energy.
Perceived changes in psychological and physical symptoms after hospital clown performances in a cancer setting

ABSTRACT Background: The therapeutic role of humor and hospital clowns has become a focus of interest in recent decades. Most of the research in the area has focused on children; here, we explore the influence of clown performances on adult cancer patients, their companions, and health-care staff. Methods: Ninety-nine cancer patients and 113 companions were assessed pre- and post-interventions performed by professional clowns; 31 health professionals were asked about the possible influence of the presence of clowns in hospital on their work. Results: Patients felt that clowning performances helped to reduce their level of psychological symptoms, but not their physical symptoms. Companions reported improvements in all the psychological symptoms explored. Health professionals reported that the presence of clowns in the workplace improved their well-being. Conclusions: Clowning performances helped to improve psychological functioning in all the populations studied, especially in companions. Adult hospitals should consider promoting clowning interventions to improve general well-being.
The effects on the quality of poultry meat of supplementing feed with zinc-methionine complex.

BACKGROUND Recently, an increase in the consumption of poultry meat has been observed Worldwide. This is related to the growing production of this kind of meat. Intensive poultry meat production affects the level of bird welfare and meat quality. The meat industry is looking for new solutions that can reduce meat quality defects. One of them may undoubtedly be a feed reformulation, of which a supplementation with zinc can be taken into consideration. The aim of this study was to evaluate the impact of Zn supplementation of chicken feed on the technological and sensory quality of meat. METHODS The research was carried out on material taken from 60 carcasses. Half of the group (30 pieces) was fed with Zn in the form of nonorganic compounds (zinc oxide) and the other 30 chickens were fed zinc in its organic form, and amino acids (ratio 1:1). After the broilers were slaughtered, the meat quality was evaluated in the breast muscle, and was based on pH value, color parameters, natural drip loss, cooking loss, microbiological status, sensory quality, instrumental shear force and lipid oxidation status. RESULTS The obtained results show that lower levels (p ≤ 0.01) of drip loss (1.04%), and higher amounts (p ≤ 0.01) of glucose (4.61 mmol/l) and protein (0.7%) were found in the meat from the group fed with zinc in organic form as an additive. Moreover, the meat from this group was less red (a* value = –0.46 vs. 0.11) and less yellow (b* value 8.41 vs. 10.16) at the same time (p ≤ 0.01). There were no significant differences between the examined groups for cooking loss, microbiological status, lipid oxidation and sensory quality. CONCLUSIONS It should be stated that Zn supplementation in a form with amino acids has a beneficial effect on the quality of poultry meat as far as drip loss reduction is concerned.
Interdependence of physical and psychological morbidity among patients with cancer and family caregivers: Review of the literature

Caregivers for patients with cancer have an integral role in maintaining patients' health. Although patients and caregivers experience the impact of cancer individually, studies suggest their health is interdependent. The objective of this review was to synthesize the literature on interdependent physical and psychological morbidity in patient‐caregiver dyads published since 2016.