bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cadaveric Clinical Integration: Integration of Basic Science and Medical Science
Authors: Day Leslie , Greene Ericka , Patham Bhargavi 
Published: May 2022

IntroductionCadaveric dissection is an integral part of many medical schools and provides an opportunity for students to visualize anatomical structures through active learning and critical thinking. Often during dissection, several pathological features and medical interventions can be identified, but are not regularly explored due to time or knowledge constraints. To encourage horizontal integration of content, a self‐directed learning (SDL) activity was implemented across four concurrent courses, gross anatomy (MGA), Foundations of Medicine which includes histology and physiology (FOM), Practice of Medicine that includes physical examination (POM) and Engineering Innovation (ENG). The goal of this longitudinal experience was to foster integration of basic science with clinical science thereby increasing metacognitive and lifelong learning skills.Methods49 students enrolled in the Engineering‐Medicine dual degree program at Texas A&M College of Medicine were divided into 7 groups, based on the cadaveric dissection assignments in MGA. Over the 16‐week MGA course, students documented the medical interventions and pathology found during dissection. During most dissection labs, a surgeon related to the field was present to answer questions. In addition, at three time points in the semester an anatomical pathologist performed a modified autopsy on the cadavers based on students request. This self‐directed, problem‐based learning (PBL) activity culminated in a forensic clinical summary, reconstructed comprehensive patient encounter 1 year prior to death, and 15‐minute oral presentation of their findings of their assigned cadaver. To assess potential changes in learning behavior, students completed a 46‐question, 8 subcategory modified Motivated Strategies for Learning Questionnaire (MSLQ) related to the activity. In addition, student’s provided verbal and written feedback on their perceptions of the project.Results47 out of 49 students successfully completed all aspects of the project. The was a positive trend and strong correlation in 7 out of 8 MSLQ categories, including intrinsic motivation, metacognition, task value, critical thinking, self‐efficacy, peer learning and help seeking. A paired t‐test showed a decrease in student's extrinsic motivation (t(46) = 1.831, p = 0.037) as related to the project. Students reported an overall high satisfaction with the project. The student presentations demonstrated high level of integration of basic science with clinical medicine.Conclusion/ImplicationThis innovative multi‐disciplinary activity increased the value of cadaveric dissection, integration of content across courses, and promoted self‐directed learning of integrated clinicopathology material.
Subarcuate Fossa Anatomy as an Indicator of Future Locomotor Behavior in Newborn Primates
Authors: Militello Molly L. , Bryson Emily R. , Smith Timothy D. , DeLeon Valerie B. 
Published: May 2022

Previous studies have demonstrated a link between subarcuate fossa size and locomotor behavior in primates. This fossa contains the petrosal portion of the paraflocculus, a portion of the brain associated with mobility and motor control. Studies have determined that the size of the fossa is larger in primate species that have more complex forms of locomotion. This study tested whether size of the subarcuate fossa in newborns predicts adult locomotor behavior. The sample included adult and newborn individuals of species representing strepsirrhine, tarsier, and platyrrhine primates. MicroCT images were used to create virtual endocasts in 3DSlicer software. The subarcuate fossa was isolated, and the volume was measured for each specimen.Results demonstrated that newborns from species with higher levels of locomotor agility exhibit a larger subarcuate fossa at the time of birth than newborns from species with lower levels of locomotor agility. This confirms that the subarcuate fossa is an indicator of the future locomotion of the primate. Comparison of subarcuate fossa volume between newborn and adult scans from the same species indicated that there is little growth in the fossa from birth to adulthood in most primates. These results are consistent with an expectation that the size of the subarcuate fossa is highly constrained by the semicircular canals, which are not expected to increase in size through growth. The possibility exists that the size of the semicircular canals is the object of selection, and the size of the subarcuate fossa is a secondary effect. These findings show that this aspect of a newborn primate’s anatomy expresses information about its future behavior prior to any experience with locomotor action.
Essential oil metabolites can regulate adrenal androgen production by inhibition of CYP17A1 activities
Authors: Sharma Katyayani , Lanzilotto Angelo , Pandey Amit V. 
Published: May 2022

Endocrine‐disrupting chemicals (EDCs) can affect human steroid metabolism. Previous clinical case reports have shown that some Essential Oils (EOs) like lavender oil and tea tree oil may act as potential EDCs and are linked to prepubertal gynecomastia in boys and premature thelarche in girls due to regular exposure to lavender based fragrances among Hispanic population. These studies suggested role of EOs in steroid metabolism in humans. We have screened a range of EO metabolites for effects on androgen production by CYP17A1.For preliminary screening, human adrenal NCI H295R cells were treated with 10 µM of test compounds for 24 hours. The test compounds had been extracted and purified from natural resources and are found as major components in EOs. For CYP17A1 activity, the conversion of radiolabelled substrate, 17‐Hydroxy‐pregnenolone to Dehydroepiandrosterone was determined using tritiated water release assay.Eucalyptol, Dihydro‐β‐Ionone, (‐)‐α‐pinene were extracted from eucalyptus, rose and pine resin. Out of about 50 test compounds, eucalyptol, Dihydro‐β‐Ionone & (‐)‐α‐pinene showed 20% to 40% inhibition of DHEA production. Rest of the compounds showed either no or low inhibition. Some compounds were also tested for effects on CYP19A1 (aromatase) activity where upto 30% inhibition was observed.EOs are often used in various beauty and hygiene products as they have few known side‐effects. However, prolonged exposure to these products may result in steroid imbalance. Due to their anti‐androgenic activity, these compounds should be studied further as chemical leads for the treatment of hyperandrogenic disorders such as Prostate cancer and Polycystic ovary syndrome.
Brain Shape Provides a Structural Mechanism for Postorbital Septation in Primates
Authors: DeLeon Valerie B. , Franklin Katheryn P. , Cunningham Andreana S. , Summers Siobhan A. , Bryson Emily R. , Vinyard Christopher J. , Smith Timothy D. 
Published: May 2022

Postorbital septation is a character that unites haplorhine primates. As a result, evidence of postorbital septation is expected for fossil primates that may be ancestral to both modern tarsiers and modern anthropoids. Our previous work on newborn primates has indicated that postorbital septation in tarsiers is secondary to growth of their large eyes. If this is the case, postorbital septation is convergent in tarsiers and anthropoids, and therefore should not be expected in their fossil ancestors. Here, we used morphometric analysis of the cranium and endocast of newborn and adult primates to show that postorbital septation in the order Primates may be explained by shape of the brain.We used a sample of over thirty species of modern primates representing all major clades, with individuals representing both newborn and adult stages. The newborn stage is most informative for understanding spatial relationships of soft tissues during formation of the skull. MicroCT image data were used to create virtual reconstructions of the cranium and endocast as an estimate of brain shape. Fixed landmarks were used to capture the shape of the cranium, and sliding semilandmarks represented the contour of frontal and temporal lobes on the endocast. As expected, morphometric analysis showed a significant effect of phylogeny on cranial and endocast shape in both newborns and adults. Notably, the phylogenetic effect was apparent in only the contours of the frontal and temporal lobes, independent of cranial shape. We present 3D models of the endocast and cranium of newborn primates to illustrate the spatial relationship of brain and facial structures as a mechanism for postorbital septation in anthropoid primates.
Stratification by Race Reveals Disparate Vascular Toxicity in Response to Anti‐Cancer Therapies
Authors: Hader Shelby N. , Terwoord Janée D. , Norwood Toro Laura E. , Gutterman David D. , Beyer Andreas M. 
Published: May 2022

IntroductionCardiovascular toxicity is the primary reason for halting anti‐cancer therapy (CTx) or limiting the dose, and cardiovascular side effects of CTx represent a major clinical problem with implications for survival and quality of life. Ongoing work in our laboratory suggests that CTx induces microvascular endothelial dysfunction, which is a well‐established predictor of future CV events. CV disease in general and CTx‐induced adverse events are significantly more prevalent in Black patients (B) relative to non‐Hispanic White patients (NHW). Despite clinical evidence of these health disparities, little to no data exist to explain the underlying causes. Therefore, we tested the novel hypothesis that CTx‐induced microvascular dysfunction is augmented in B, which may explain the increase in cardiotoxic events in this population compared to NHW.MethodsFresh human tissues were obtained as de‐identified surgical discard specimens. Peripheral adipose arterioles (100–200 µm) from healthy B and NHW were incubated ex vivowith the CTx agents, doxorubicin (Dox), trastuzumab (TZM), or paclitaxel (PTX) for 16–20 h and used for isolated arteriole preparations. Endothelium‐dependent vasodilation in response to flow (Flow‐Mediated Dilation, FMD; 5–100 cmH2O pressure gradient) or acetylcholine (ACh; 10−9 to 10−5 M) and smooth muscle‐dependent dilation to papaverine (100 µM) were evaluated. Data are presented as % max. diameter ± SEM, N. Statistical significance was established with two‐way ANOVA RM.ResultsUnder control conditions, there was no difference in microvascular FMD in healthy B (ACh: 89.8±4.0%, n=5; 85.8±1.8%, n=6) vs. NHW (ACh: 86.2±3.2%, n=6; 78.7±5.9%, n=8). Ex vivo exposure to Dox impaired endothelial function in arterioles from both B and NHW (ACh: 45.0±10.5%, n=4 and 34.2±9.8%, n=7; FMD: Figure 1A). TZM impaired endothelial function to a greater extent in arterioles from B (ACh: 36.1±7.1%, n=3; FMD: Figure 1B) compared to NHW (ACh: 44.4±8.6%, n=8; FMD: Figure 1B). Interestingly, PTX did not affect endothelial function in NHW (ACh: 91.5±1.6%, n=4; FMD: Figure 1C), but impaired endothelial function in arterioles from B (ACh: 54.7±12.9%, n=3; FMD: Figure 1C). Max dilator capacity to the endothelium‐independent dilator papaverine was not changed in either group (not shown).ConclusionOur findings reveal disparate effects of CTx agents on microvascular endothelial function from B and NHW patients. This raises the possibility that microvascular dysfunction may contribute to the known disparities in adverse CV clinical outcomes of cancer patients and potentially other CV pathologies (e.g., disparities in adverse events associated with PTX‐eluting stents.) Future work should differentiate between biological/genetic vs. social/environmental contribution to observed microvascular responses to CTx.
Comparative Growth of the Tympanic Cavity in Primates
Authors: Franklin Katheryn P. , Haynes Laura K. , Smith Timothy D. , DeLeon Valerie B. 
Published: May 2022

Primate auditory structures are morphologically indicative of taxonomy and phylogeny. The tympanic cavity houses the three articulating ear ossicles: malleus, incus, and stapes. The ossicles amplify sound waves from mechanical vibrations to the cochlea, a sensory organ, where it can then be interpreted by the organism. All primates are characterized by a petrous bulla, but the extent of the tympanic cavity varies across taxa.Our sample of newborn and adult individuals representing strepsirrhines (e.g., Galago moholi and Nycticebus pygmaeus) and haplorhines (e.g., Aotus nancymaae and Cebuella pygmaea) allowed us to study the comparative growth of these structures. Using a combination of conventional CT data and diffusion iodine contrast‐enhanced CT (diceCT) data, we created 3D models of auditory structures using 3DSlicer. Metric data included angles between ear ossicles, surface area of the tympanic membrane, surface area of the stapes footplate, and overall tympanic cavity volume. Many differences among major clades are already evident at the newborn stages in this sample. The pneumatization of accessory cavities in newborns has been initiated. For example, in the newborn Galago moholi, pneumatization of accessory cavities is most pronounced posteriorly. In contrast, in the newborn Aotus nancymaae, we see early evidence of the anterior accessory cavity. Mesh‐to‐mesh comparisons of endocasts of the cavity indicate structural changes through ontogeny. Additionally, the surface area of the tympanic membrane remains consistent through growth.This research allows for a better understanding of the relationship between the functional morphology of the auditory system and audible frequency levels. Haplorhines are adapted to lower frequencies than strepsirrhines. This adaptation is discernable at birth, and key spatial relationships of ossicles are maintained through ontogeny even as spatial configuration of the cranium as a whole undergoes profound change due to pneumatic expansion of sinus cavities and growth of soft tissue structures.
Effects of contraction and feeding on skeletal muscle protein synthesis during the initiation of cachexia
Authors: Counts Brittany , Halle Jessica , Carson James 
Published: May 2022

Muscle contraction and feeding are potent regulators of skeletal muscle protein synthesis. Cancer cachexia can suppress muscle protein synthesis through Akt/mTORC1 signaling suppression. Cachexia also suppresses acute contraction‐induced muscle protein synthesis. However, the cancer environment’s impact on the combined feeding and contraction activation of protein synthesis during the initiation of cachexia is not well understood. Therefore, we examined the cancer environment’s effect on the muscle protein synthesis response to an acute bout of muscle contraction with and without feeding.METHODSMale C57BL/6J (B6; N=36) were injected with 1 x 106 Lewis Lung Carcinoma (LLC) cells or PBS subcutaneously in the right flank and were monitored for up to 30 days. Following an overnight 12hr fast, mice were given ad libitum access to a food pellet for 1hr (fed) or fasted for an additional hour (fast). Subsequently, mice were subjected to low‐frequency electrical stimulation (LFES) for 30 minutes and sacrificed 3hrs post. Puromycin was injected 30min before sacrifice for protein synthesis measurements. Gastrocnemius muscle was examined for protein expression and values normalized to the contralateral limb.RESULTSIn PBS mice, LFES induced rpS6 (9.5‐fold) and protein synthesis (4.7‐fold). LFES induced rpS6 (1.7‐fold) and protein synthesis (0.9‐fold) in LLC mice. Overall, rpS6 and protein synthesis were lower in the LLC mice compared to PBS. Feeding increased muscle rpS6 and protein synthesis in PBS mice (p<0.001) but not in LLC (p=0.821 and p=0.642) mice. Feeding and LFES synergistically induce rpS6 and protein synthesis in PBS mice; however, this was not present in LLC mice.CONCLUSIONWe report that contraction’s ability to increase muscle protein synthesis is suppressed in mice initiating cachexia. The ability for feeding to increase muscle protein synthesis is also suppressed in mice initiating cachexia. Notably, the combined effects of feeding and contraction were insufficient to synergistically improve muscle protein synthesis as in healthy mice. Future studies should determine why feeding was not sufficient to induce muscle protein synthesis in mice initiating cachexia.
Regulation of the Nuclear Bile Acid Receptor, Farnesoid X Receptor, by the Omega‐3 Polyunsaturated Fatty Acid, Alpha‐Linolenic Acid, in Colonic Epithelial Cells
Authors: Smyth Jessica S. , Fallon Ciara M. , Keely Stephen J. 
Published: May 2022

Introduction and AimsThe intestinal epithelium forms the interface between the body and the luminal contents, facilitating fluid and electrolyte transport, while also acting as a barrier to harmful pathogens. Dysregulation of barrier and transport function is associated with the pathogenesis of a number of conditions, including chronic diarrhoeal and inflammatory bowel diseases (IBD). Previous studies from ours, and other laboratories, have identified the nuclear bile acid receptor, farnesoid x receptor (FXR), as an excellent target for the development of new anti‐diarrhoeal and anti‐inflammatory therapeutics. Polyunsaturated fatty acids (PUFAs), such as alpha‐linolenic acid (ALA), are a group of bioactive phytochemicals, which have been shown in other systems to modulate FXR activity. PUFAs are also thought to be ligands for another group of nuclear receptors, known as the peroxisome proliferator‐activated receptors (PPARs), which have been recently shown to modulate FXR expression. Here, we set out to investigate a possible role for ALA in regulating farnesoid x receptor signalling in colonic epithelial cells.MethodsT84 human colonic epithelial cells were cultured as polarised monolayers on permeable supports and treated bilaterally with alpha‐linolenic acid (ALA) (100 µM) for 1 – 24 hours, in the presence or absence of the FXR agonist, GW4064 (5 µM), or the PPARg antagonist, GW9662 (20 µM). Levels of FXR, FGF19, an index of FXR activation, and ANGPTL4, a PPAR target gene, were measured by qRT‐PCR, western blotting, or ELISA.ResultsTreatment of T84 cells with ALA increased FXR expression in a time dependent fashion. Maximal effects of ALA occurred after 6 hrs when increases in FXR mRNA and protein were 8.65 ± 0.80 fold (n = 4; p < 0.01) and 4.44 ± 0.85 fold (n = 4) of untreated controls, respectively. Moreover, treatment of the cells with ALA potentiated GW4064‐induced expression of the FXR target gene, FGF‐19, at both mRNA and protein levels by 2.66 ± 0.56 (n = 4) and 5.52 ± 1.52 (n = 6), respectively. The effects of ALA on FXR expression and activity were mimicked by the PPARg agonist, rosiglitazone (1 mM). Treatment with ALA also significantly increased mRNA expression of the PPAR target gene, ANGPTL4, by 56.69 ± 5.7 (n = 4; p < 0.01), while the PPARg antagonist, GW9662 (20 µM; 1 hr), inhibited ALA‐induced FXR mRNA expression by 0.44 ± 0.12 fold (n =4) and protein by 0.23 ± 0.06 fold (n = 3).ConclusionThe dietary PUFA, ALA, regulates colonic epithelial FXR expression through mechanisms that involve activation of PPARγ. By virtue of their ability to upregulate FXR expression and activity, PUFAs, such as ALA, have excellent potential for development as FXR‐targeted nutraceuticals for the treatment and prevention of intestinal disease.
Immunoelectron Microscopy of Trace Amine‐Associate Receptor 1 Intracellular Localization
Authors: Huey Julia , Shi Xiao , Janowsky Aaron 
Published: May 2022

Trace amine‐associated receptor 1 (TAAR1) is a G protein‐coupled receptor (GPCR) in brain regions that are critical to reward and habit formation. TAAR1 is activated by a variety of substituted phenethylamines (e.g. methamphetamine, MA), and is uniquely involved in the mechanism of action of amphetamine‐like psychostimulants. Pharmacological manipulation of TAAR1 alters the spontaneous firing rate of neurons in the ventral tegmental area, and psychiatric disorders characterized by dysregulated dopaminergic neurotransmission, including schizophrenia and substance use disorders, have been associated with altered trace amine levels or TAAR1 polymorphisms.Unlike many GPCRs, TAAR1 is an intracellular receptor; rather than localizing to the plasma membrane, TAAR1 is associated with unidentified membranous compartments within the cell. Previous efforts to identify the intracellular localization of TAAR1 have had limited success due to difficulty with heterologous expression systems and a lack of sufficiently specific antibodies, as well as inherent spatial resolution limits of light‐based microscopic techniques. In order to determine the precise subcellular localization of TAAR1, immunoelectron microscopy was performed in HEK293T cells stably expressing human TAAR1 with a C‐terminal EGFP tag. Preliminary results suggest that TAAR1 localizes to the endoplasmic reticulum and mitochondria. Future experiments using similar techniques will explore TAAR1 localization in primary neurons. Together, these results will further elucidate the molecular mechanisms by which TAAR1 signals within neurons and ultimately alters neurotransmission.
Role of the High‐Conductance Calcium‐Activated Potassium Chanel in first order mesenteric artery of hypercaloric diet rat model
Authors: Hernandez‐Garcia Ana P. 
Published: May 2022

Obesity has been identified like as a risk factor of metabolic syndrome. The High‐Conductance Calcium‐Activated Potassium Channel (BKCa) in vascular smooth muscle cells regulates membrane potential and control myogenic tone.Objectiveevaluated the role of the BKCa channel in first order mesenteric arteries of rats feed with a hypercaloric diet for 18 and 28 weeks.MethodologyWe performed isometric tension experiments in first and second order mesenteric arteries rings and Patch Clamp recordings of vascular smooth muscle cells isolated of the same vascular bed.ResultsThe rats feed with a hypercaloric diet for 18 weeks shows an augmented un percentage of adipose tissue, triglycerides, glucose tolerance curve, blood pressure and more relaxation to BKCa channel activator NS11021 un rings precontracted with phenylephrine. At 28 weeks of evolution, an increase in percentage of adipose tissue with respect to body weight was observed, as well as an increase in blood pressure, Regarding BKCa channel function, an increase in current density was observed in the experimental group with respect to the control group.ConclusionChanges have been developed at the metabolic level in the groups of the hypercaloric diet, with changes in the BKCa channels, a gain of function in first order mesenteric rings of the 18 weeks group and in cells isolated from these arteries at 28 weeks group. Nevertheless, at 28 weeks of evolution, first order mesenteric artery rings no longer showed the gain in function observed in the previous group, which suggest a compensatory mechanism maybe associated to aging.