Miracle-dz/UniFAR-FTUs huggingface dataset:
Differentiation of equine induced pluripotent stem cells into mesenchymal lineage for therapeutic use

ABSTRACT In previous work, we established an equine induced pluripotent stem cell line (E-iPSCs) from equine adipose-derived stem cells (ASCs) using a lentiviral vector encoding four transcription factors: Oct4, Sox2, Klf4, and c-Myc. In the current study, we attempted to differentiate these established E-iPSCs into mesenchymal stem cells (MSCs) by serial passaging using MSC-defined media for stem cell expansion. Differentiation of the MSCs was confirmed by analyzing expression levels of the MSC surface markers CD44 and CD29, and the pluripotency markers Nanog and Oct4. Results indicated that the E-iPSC-derived MSCs (E-iPSC-MSCs) retained the characteristics of MSCs, including the ability to differentiate into chondrogenic, osteogenic, or myogenic lineages. E-iPSC-MSCs were rendered suitable for therapeutic use by inhibiting immune rejection through exposure to transforming growth factor beta 2 (TGF-β2) in culture, which down-regulated the expression of major histocompatibility complex class I (MHC class I) proteins that cause immune rejection if they are incompatible with the MHC antigen of the recipient. We reported 16 cases of E-iPSC-MSC transplantations into injured horses with generally positive effects, such as reduced lameness and fraction lines. Our findings indicate that E-iPSC-MSCs can demonstrate MSC characteristics and be safely and practically used in the treatment of musculoskeletal injuries in horses.
Prospective Health Professions Students’ Misperceptions About Pharmacists

Public misperceptions about the pharmacy profession have the potential to impact pharmacy education, practice, and the health of those who pharmacists serve. Student misperceptions of the profession can lead to fewer applicants to pharmacy schools and frustration among pharmacy students and faculty members. With the recent decline in applicants to Doctor of Pharmacy (PharmD) programs, professional pharmacy organizations, colleges and schools of pharmacy, and individual pharmacists must implement strategies that mitigate these misperceptions. This commentary discusses the potential impact of prospective health students’ (ie, students pursuing admission to health professional programs) misperceptions on the supply of quality candidates to PharmD programs. Strategies to elevate the image of the profession at the individual and collegiate level are discussed.
Sweet Cherry Extract Targets the Hallmarks of Cancer in Prostate Cells: Diminished Viability, Increased Apoptosis and Suppressed Glycolytic Metabolism

Abstract The present work evaluated the anticancer properties of sweet cherry (Prunus avium) extract on human prostate cells. Several sweet cherry cultivars from Fundão (Portugal) were methanol-extracted and their phytochemical composition characterized. The Saco “late harvest” extract was highly-enriched in anthocyanins and selected for use in biological assays. Non-neoplastic (PNT1A) and neoplastic (LNCaP and PC3) human prostate cells were treated with 0–2,000 μg/ml of extract for 48–96 h. Cell viability was evaluated by the MTT assay. Apoptosis, oxidative stress, and glycolytic metabolism were assessed by Western blotting and enzymatic assays. Glucose consumption and lactate production were measured spectrophotometrically. Saco cherry extract diminished the viability of neoplastic and non-neoplastic cells, whereas enhancing apoptosis in LNCaP. Cherry extract-treatment also diminished oxidative damage and suppressed glycolytic metabolism in LNCaP cells. These findings widened the knowledge on the mechanisms by which cherry extract modulate cell physiology, demonstrating their broad action over the hallmarks of cancer.
Size‐Dependent Vulnerability of Lumbar Motor Neuron Dendritic Degeneration in SOD1G93A Mice

The motor neuron (MN) soma surface area is correlated with motor unit type. Larger MNs innervate fast fatigue‐intermediate (FInt) or fast‐fatiguable (FF) muscle fibers in type FInt and FF motor units, respectively. Smaller MNs innervate slow‐twitch fatigue‐resistant (S) or fast fatigue‐resistant (FR) muscle fibers in type S and FR motor units, respectively. In amyotrophic lateral sclerosis (ALS), FInt and FF motor units are more vulnerable, with denervation and MN death occurring for these units before the more resilient S and FR units. Abnormal MN dendritic arbors have been observed in ALS in humans and rodent models. We used a Golgi‐Cox impregnation protocol to examine soma size‐dependent changes in the dendritic morphology of lumbar MNs in SOD1G93A mice, a model of ALS, at pre‐symptomatic, onset and mid‐disease stages. In wildtype control mice, the relationship between MN soma surface area and dendritic length or dendritic spine number was highly linear (i.e., increased MN soma size correlated with increased dendritic length and spines). By contrast, in SOD1G93A mice, this linear relationship was lost and dendritic length reduction and spine loss were observed in larger MNs, from pre‐symptomatic stages onward. These changes correlated with the neuromotor symptoms of ALS in rodent models. At presymptomatic ages, changes were restricted to the larger MNs, likely to comprise vulnerable FInt and FF motor units. Our results suggest morphological changes of MN dendrites and dendritic spines are likely to contribute ALS pathogenesis, not compensate for it. Anat Rec, 303:1455–1471, 2020. © 2019 American Association for Anatomy
mTOR-regulated U2af1 tandem exon splicing specifies transcriptome features for translational control

Abstract U2 auxiliary factor 1 (U2AF1) functions in 3′-splice site selection during pre-mRNA processing. Alternative usage of duplicated tandem exons in U2AF1 produces two isoforms, U2AF1a and U2AF1b, but their functional differences are unappreciated due to their homology. Through integrative approaches of genome editing, customized-transcriptome profiling and crosslinking-mediated interactome analyses, we discovered that the expression of U2AF1 isoforms is controlled by mTOR and they exhibit a distinctive molecular profile for the splice site and protein interactomes. Mechanistic dissection of mutually exclusive alternative splicing events revealed that U2AF1 isoforms’ inherent differential preferences of nucleotide sequences and their stoichiometry determine the 3′-splice site. Importantly, U2AF1a-driven transcriptomes feature alternative splicing events in the 5′-untranslated region (5′-UTR) that are favorable for translation. These findings unveil distinct roles of duplicated tandem exon-derived U2AF1 isoforms in the regulation of the transcriptome and suggest U2AF1a-driven 5′-UTR alternative splicing as a molecular mechanism of mTOR-regulated translational control.
Is it safe to SCUBA dive with asthma?

ABSTRACT Introduction: Internationally it is estimated that six million people participate in self-contained underwater breathing apparatus (SCUBA) diving each year. Registries suggest a significant proportion of divers have a current or historical diagnosis of asthma. Previously individuals with asthma were prohibited from diving, however, several contemporary guidelines suggest a select population of patients with asthma may be able to dive with an acceptable degree of risk. Areas covered: Divers with asthma may be at an increased risk of a variety of diving-related medical injuries including; pulmonary barotrauma (PBT), pneumothorax, pneumomediastinum, arterial gas embolism (AGE), reduction in pulmonary function, bronchospasm and decompression sickness (DCS). This article will discuss the latest evidence on the incidence of adverse events in diving with a focus on those caused by asthma. Expert opinion: Physicians can be faced with the difficult task of counseling patients with asthma who wish to dive. This review article will aim to explore the current guidelines which can assist a physician in providing a comprehensive dive safety assessment.
In the Literature.

Nicolai and colleagues in Brescia, Italy, describe their experience with 160 patients with fungus balls of the paranasal sinuses, all of whom underwent endoscopic surgery. The maxillary sinus was involved in 135 patients (84.4%), the sphenoid was involved in 23 (14.4%), and 1 patient had simultaneous sphenoid and ethmoid disease. Although computed tomography detected an area of “metal density” in 71.9% of maxillary cases, this was seen in only 1 patient with sphenoid involvement; heterogeneous hyperdensity with microcalcifications was seen in 16.3% and 42.9%, respectively, and abnormalities of the osseous sinus wall were seen in 37.8% and 52.4%. Magnet resonance imaging, which was performed for 10 patients with sphenoid mycetoma, demonstrated a lesion of reduced intensity surrounded by a hyperintense T2-weighted image and mucosal enhancement; a central signal void was seen in 5 of the 10. Histological examination of the endoscopically obtained specimens revealed fungal elements in each, but fungal growth in culture was detected in only 24 (20.3%) of 118 cases, with Aspergillus fumigatus and Alternaria species being most frequently identified fungi. No disease recurrence was observed after follow-up conducted 18–195 months after surgery. No mention is made of antifungal chemotherapy. A review of 24 cases of sphenoid fungus balls seen at the Hôpital Lariboisière in Paris, France, over a 10-year period found that symptoms were variably present. Only 62% of patients had headache, and its localization varied widely. Computerized tomography, which was available for review in 12 cases, revealed sphenoid opacity in 11, intracavitary hyperdensity in 10, osteogenesis or sclerosis in 15, and osteolysis in 5. All patients were treated endoscopically. Culture results were not reported (these seem to have not been routinely performed), but branched hyphae were seen on histological examination in each case. Mycetoma of the paranasal sinuses is infrequently encountered. By definition, it is noninvasive and, as a consequence, systemically administered antifungal therapy may be of little or no value, although there appears to be little data available addressing this issue. Although imaging may provide clues to the diagnosis, diagnosis ultimately depends on demonstration of fungus ball on endoscopic or open surgical exploration, and these procedures are likely to be curative in the absence of invasive disease.
Mediterranean Diet Adherence Modulates Anthropometric Measures by TCF7L2 Genotypes among Puerto Rican Adults.

BACKGROUND Transcription factor 7-like 2 (TCF7L2) genetic variants that predispose individuals to type 2 diabetes (T2D) show inconsistent associations with anthropometric traits. Interaction between TCF7L2 genotypes and dietary factors may help explain these observations. OBJECTIVE We aimed to examine the potential modulation of TCF7L2-rs7903146 and rs12255372 on anthropometric markers by a Mediterranean diet (MedDiet). METHODS Cross-sectional analysis was conducted in 1120 participants (aged 45-75 y) of the Boston Puerto Rican Health Study. Anthropometric variables were measured, and polymorphisms were genotyped using standardized protocols. Diet was assessed using a validated FFQ. The MedDiet was defined based on adherence to 9 food and nutrient components using sex-specific population-based median cut-offs; high adherence was defined as meeting ≥4 components. Haplotypes were tested for association with obesity traits, independently and via interaction with the MedDiet. RESULTS TCF7L2-rs7903146 showed significant interaction with the MedDiet influencing BMI, weight, and waist circumference. The T risk-allele carriers (CT + TT) with a high MedDiet score had lower weight (77.3 ± 1.0 compared with CC 80.9 ± 1.0 kg; P = 0.013) and waist circumference (99.2 ± 0.9 compared with CC 102.2 ± 0.9 cm; P = 0.021), when compared with CC participants. A low MedDiet score resulted in no significant differences between genotypes. For TCF7L2-rs12255372, we found significant interactions with the MedDiet for weight (P-interaction = 0.034) and BMI (P-interaction = 0.036). The T allele carriers with a higher MedDiet score showed a trend of lower but no significant differences when compared with CC participants for BMI (P = 0.19), weight (P = 0.09), and waist circumference (P = 0.11). We found significant interactions between the 2 risk-carrying haplotypes and the MedDiet compared with the common haplotype (GC), with lower BMI (β ± SE, TT: -1.53 ± 0.68; P-interaction = 0.024), weight (TT: -4.16 ± 1.77; P-interaction = 0.019), and waist circumference (GT: -5.07 ± 2.50; P-interaction = 0.042) at a high MedDiet score. CONCLUSION Puerto Ricans with the TCF7L2-rs7903146 and rs12255372 T2D risk genotypes, although still high, had better anthropometric profiles when adhering to a MedDiet, suggesting that this diet may offset unfavorable genetic predisposition.
Follicular Helper T Cells Are Major Human Immunodeficiency Virus-2 Reservoirs and Support Productive Infection

Abstract Follicular helper T cells (Tfh), CD4 lymphocytes critical for efficient antibody responses, have been shown to be key human immunodeficiency virus (HIV)-1 reservoirs. Human immunodeficiency virus-2 infection represents a unique naturally occurring model for investigating Tfh role in HIV/acquired immune deficiency syndrome, given its slow rate of CD4 decline, low to undetectable viremia, and high neutralizing antibody titers throughout the disease course. In this study, we investigated, for the first time, Tfh susceptibility to HIV-2 infection by combining in vitro infection of tonsillar Tfh with the ex vivo study of circulating Tfh from HIV-2-infected patients. We reveal that Tfh support productive HIV-2 infection and are preferential viral targets in HIV-2-infected individuals.
High penetrance and similar disease progression in probands and in family members with arrhythmogenic cardiomyopathy

Abstract Aims We aimed to assess structural progression in arrhythmogenic cardiomyopathy (AC) patients and mutation-positive family members and its impact on arrhythmic outcome in a longitudinal cohort study. Methods and results Structural progression was defined as the development of new Task Force imaging criteria from inclusion to follow-up and progression rates as annual changes in imaging parameters. We included 144 AC patients and family members (48% female, 47% probands, 40 ± 16 years old). At genetic diagnosis and inclusion, 58% of family members had penetrant AC disease. During 7.0 [inter-quartile range (IQR) 4.5–9.4] years of follow-up, 47% of family members without AC at inclusion developed AC criteria, resulting in a yearly new AC penetrance of 8%. Probands and family members had a similar progression rate of right ventricular outflow tract diameter (0.5 mm/year vs. 0.6 mm/year, P = 0.28) by mixed model analysis of 598 echocardiographic examinations. Right ventricular fractional area change progression rate was even higher in family members (−0.6%/year vs. −0.8%/year, P < 0.01). Among 86 patients without overt structural disease or arrhythmic history at inclusion, a first severe ventricular arrhythmic event occurred in 8 (9%), of which 7 (88%) had concomitant structural progression. Structural progression was associated with higher incidence of severe ventricular arrhythmic events adjusted for age, sex, and proband status (HR 21.24, 95% CI 2.47–182.81, P < 0.01). Conclusion More than half of family members had AC criteria at genetic diagnosis and yearly AC penetrance was 8%. Structural progression was similar in probands and family members and was associated with higher incidence of severe ventricular arrhythmic events.
CBE1 is a manchette and mitochondria associated protein with a potential role in somatic cell proliferation.

Ciliated bronchial epithelium 1 (CBE1) is a microtubule-associated protein localized to the manchette and developing flagellum during spermiogenesis, and associated with sperm maturation arrest in humans. It was hypothesized that CBE1 functions in microtubule-mediated transport mechanisms and sperm tail formation. To test this hypothesis, we analysed Cbe1 expression and localization during spermiogenesis, and in mouse IMCD3 cells as a model of ciliogenesis. Further, we generated and analysed the fertility of a Cbe1 mutant mouse line. Mice containing a homozygous deletion in the long forms of Cbe1 were born at a lower frequency than predicted by Mendelian inheritance, however, adult male mice were fertile. An in-depth analysis of the Cbe1 gene revealed alternative transcript variants, which were not affected by the exon 2 mutation. To assess whether short variants compensate for the loss of long variants, exons 2 and 4 (which affect all variants) were individually mutated in IMCD3 cells and the effect on cell proliferation and ciliogenesis analysed. In wild type IMCD3 cells, both variants were upregulated during cilia assembly. CBE1 protein was not a structural component of cilia, rather, CBE1 localised to the mitochondria and the contractile ring of dividing IMCD3 cells. While IMCD3 cells carrying the mutation in long variants showed no phenotypic alterations, the mutation in exon 4 resulted in a significantly decreased proliferation rate. This study reveals that long isoforms of CBE1 are not essential for male fertility. Data, however, suggests that CBE1 is associated to intra-manchette transport and mid-piece formation of the sperm tail.
Racial/ethnic disparities in renal cell carcinoma: Increased risk of early‐onset and variation in histologic subtypes

Racial/ethnic minority groups have a higher burden of renal cell carcinoma (RCC), but RCC among Hispanic Americans (HAs) and American Indians and Alaska Natives (AIs/ANs) are clinically not well characterized. We explored variations in age at diagnosis and frequencies of RCC histologic subtypes across racial/ethnic groups and Hispanic subgroups using National Cancer Database (NCDB) and Arizona Cancer Registry Data.
Thermal niche predictors of alpine plant species.

Within the context of species distribution models, scrutiny arises from the choice of meaningful environmental predictors. Thermal conditions are not the sole driver but are the most widely acknowledged abiotic driver of plant life within alpine ecosystems. We linked long-term measurements of direct, plant-relevant, near-surface temperatures to plant species frequency. Across 47 sites located along environmental gradients within the Scandinavian mountain chain, the thermal preferences of 26 focal species of vascular plants, lichens, and bryophytes were explored. Based on partial least squares regression (PLSR), we applied a relative importance analysis to inductively derive the thermal variables that were best related to a species' frequency. To discover potential seasonal variability of thermal controls, analyses were both differentiated according to meteorological season and integrated across the entire year. The pronounced inter-species and temporal variability of thermal constraints revealed the thermal niches were much more nuanced and variable than they have commonly been represented. This finding challenges us to generally better present, interrogate, and interpret data representing these thermal niches, which seem to be a prerequisite for moving beyond purely probabilistic and correlative descriptions of species' range limits. Thus, this information will help improve predictions of species distributions in complex arctic-alpine landscapes.
Ten-Day Concomitant, 10-Day Sequential, and 7-Day Triple Therapy as First-Line Treatment for Helicobacter pylori Infection: A Nationwide Randomized Trial in Korea

Background/Aims This nationwide, multicenter prospective randomized controlled trial aimed to compare the efficacy and safety of 10-day concomitant therapy (CT) and 10-day sequential therapy (ST) with 7-day clarithromycin-containing triple therapy (TT) as first-line treatment for Helicobacter pylori infection in the Korean population. Methods Patients with H. pylori infection were assigned randomly to 7d-TT (lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg twice daily for 7 days), 10d-ST (lansoprazole 30 mg and amoxicillin 1 g twice daily for the first 5 days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 500 mg twice daily for the remaining 5 days), or 10d-CT (lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily for 10 days). The primary endpoint was eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. Results A total of 1,141 patients were included. The 10d-CT protocol achieved a markedly higher eradication rate than the 7d-TT protocol in both the ITT (81.2% vs 63.9%) and PP analyses (90.6% vs 71.4%). The eradication rate of the 10d-ST protocol was superior to that of the 7d-TT protocol (76.3% vs 63.9%, ITT analysis; 85.0% vs 71.4%, PP analysis). No significant differences in adherence or serious side effects were found among the three treatment arms. Conclusions The 10d-CT and 10d-ST regimens were superior to the 7d-TT regimen as standard first-line treatment in Korea.
Anti-inflammatory and hemostatic effects of Linaria reflexa Desf

Abstract The work presented here was aimed to investigate the in vivo anti-inflammatory and in vitro hemostatic activities of Linaria reflexa extract and to establish the relationship between its bioactivity and chemical composition. Twenty-three secondary metabolites were identified, most of them are good anti-inflammatory agents, in line with data by carrageenin-induced rat paw edema assays of the n-butanol extract showing high anti-inflammatory inhibition (63.90%) of edema swelling in the rat paw at the dose 200 mg/kg after 4 h. Furthermore, both extent of inflammatory response and tissue injury were prevented keeping the levels of rate myeloperoxidase (60.16%) and of malondialdehyde, which is the final product of lipid peroxidation generated by free radicals (58.58%). The same extract showed also a remarkable hemostatic effect established by measuring the coagulation time of decalcified plasma (45 s), related to its flavonoid glycosides content. Graphical Abstract
The Ontogeny of Masticatory Muscle Architecture in Microcebus murinus

The masticatory apparatus has been the focus of many studies in comparative anatomy—especially analyses of skulls and teeth, but also of the mandibular adductor muscles which are responsible for the production of bite force and the movements of the mandible during food processing and transport. The fiber architecture of these muscles has been correlated to specific diets (e.g., prey size in felids) and modes of foraging (e.g., tree gouging in marmosets). Despite the well‐elucidated functional implications of this architecture, little is known about its ontogeny. To characterize age‐related myological changes, we studied the masticatory muscles in a large (n = 33) intraspecific sample of a small, Malagasy primate, Microcebus murinus including neonatal through geriatric individuals. We removed each of the mandibular adductors and recorded its mass as well as other linear measurements. We then chemically dissected each muscle to study its architecture—fascicle length and physiological cross‐sectional area (PCSA) which relate to stretch (gape) and force capabilities, respectively. We observed PCSA and muscle mass to increase rapidly and plateau in adulthood through senescence. Fascicle lengths remained relatively constant once maximal length was reached, which occurred early in life, suggesting that subsequent changes in PCSA are driven by changes in muscle mass. Quadratic curvilinear models of each of the architectural variables of all adductors combined as well as individual muscles regressed against age were all significant. Anat Rec, 303:1364–1373, 2020. © 2019 American Association for Anatomy