bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three‐dimensional functional capacity of the intrinsic hand musculature in humans and chimpanzees
Authors: Fields Mara G. , Mackereth Eden M. , Sullivan Spiro P. , McGechie Faye R. , Middleton Kevin M. , Holliday Casey A. , Ward Carol V. 
Published: May 2022

Accurately interpreting the functional significance of variation in hand morphology has been central to discussions of the evolution of in hominoids, especially humans. Although there is an extensive literature on bony morphology, muscle size and strength, kinematics, and use of the hand, to date it has not been possible to visualize and quantify the mechanics of the of the hand in situ.This study compared the intrinsic hand muscles of Homo sapiens and Pan troglodytes in 3D. Each specimen was fixed, stained with Lugol’s iodine, and microCT scanned [<61 µm resolution]. Bones, muscles and the flexor retinaculum were segmented using Avizo. Avizo Xfiber was used to visualize and quantify fascicle orientation within muscles, which permits quantification of both whole muscle and within muscle fascicle orientations. Fascicle length, pennation angles and muscle volume were used to calculate PCSA and estimate force output of each muscle. Together, these data are used to compare functional capability of muscles individually and in aggregate.Data reveal differences in force‐generating capacity and force orientations of muscles, and with finer‐scale variation of within‐muscle fascicle orientations. The most significant differences were found in the adductor pollicis and opponens pollicis, which are larger and more transversely oriented in humans than in chimpanzees. Data also reveal differences in other thenar and hypothenar muscles, affecting the capacity to effect different grips.Our approach and results highlight the importance of evaluating of the musculoskeletal system of the hand in 3D which can then be used to compare to bone form across hominoids.
SIRT1 Mutation Impairs Ca2+ Buffering in Coronary Smooth Muscle Cells of Ossabaw Miniature Swine
Authors: Reed John , Thamba Aish , Strobel John , Byrd James , Alloosh Mouhamad , Coutts Alex , Sturek Michael 
Published: May 2022

BackgroundMetabolic syndrome (MetS) impairs sarco‐endoplasmic reticulum Ca2+ ATPase (SERCA) activity in coronary smooth muscle (CSM) and is implicated in coronary atherosclerosis in Ossabaw miniature swine. Sirtuin 1 (SIRT1) is a deacetylase that has diverse roles in intracellular Ca2+ signaling, metabolism, and cardiovascular disease. SIRT1 impairment exacerbates MetS and vascular disease, including calcification. After Ca2+ is increased in CSM by Ca2+ influx or release from the sarcoplasmic reticulum (SR), the Ca2+ is then buffered by either Ca2+ efflux from the cell by the plasmalemmal Ca2+ ATPase or sequestration back into the SR via SERCA. SIRT1 inhibition hyper‐acetylates SERCA and decreases activity, thereby impairing the Ca2+ buffering capacity of the cell.HypothesisMetS and SIRT1 mutation will impair Ca2+ buffering in CSM.MethodsUsing CRISPR/Cas9 methodology a point mutation (SIRT1L100P) was made in Ossabaw miniature swine to mimic the naturally occurring mutation in humans and decrease SIRT1 activity, thereby resulting in hyperacetylation of Ca2+transporters and impaired function. Four groups of pigs were used to analyze genotype and diet interactions: wild type lean, SIRT1 lean, wild type MetS, and SIRT1 MetS. Pigs were age 4 months at the start and fed normal chow (lean) or atherogenic diet (MetS) for 7 months. CSM cells were enzymatically dispersed and Ca2+ was measured with fura‐2. The main Ca2+ regulation protocol was the maximal release of Ca2+ from the SR by 5 mM caffeine and then assessment of Ca2+ efflux and sequestration. Time to half recovery of Ca2+ to baseline during caffeine exposure was measured to assess Ca2+ efflux (rapid phase Ca2+buffering) and deviation from baseline was measured to assess SERCA function (slow phase Ca2+buffering).ResultsThere was no effect of MetS or SIRT1 mutation on Ca2+ efflux. Two‐way ANOVA showed SIRT1 mutation alone inhibits SERCA buffering of Ca2+ in CSM (p=0.0005). There was no effect of MetS diet (p=0.184) and no interactions of SIRT1 genotype and MetS diet (p=0.113) on SERCA activity.ConclusionSIRT1L100P mutation is likely to contribute to coronary atherosclerosis and SIRT1 activators may be effective therapies.
Providing effective feedback with soaring class sizes: It’s still possible
Authors: Hart Orla M. 
Published: May 2022

“Do more with less”, is a message that many of us are likely used to hearing, whether explicitly, or implicitly. We consolidate resources, streamline processes etc, in the name of economy. Sometimes streamlining grading and feedback means grading with minimal or no feedback, and/or eliminating intensive writing assignments that take a lot of time to grade. However, in upper‐level, discipline‐specific classes, automated grading and feedback do not always do what we need it to do for formative assessment. Writing assignments are a critical component of students demonstrating learning outcomes, and thoughtful, specific feedback accompanying the grading, is just as important. But how we do this in a class of 20 students just isn’t scalable. Does that mean the feedback component is lost? Not necessarily. My hypothesis is that the feedback that students require on higher Bloom’s level assignments can be consolidated by topic/question, and effectively delivered to large classes via video feedback.ResultsIn studying the errors made in different types of questions/topics of a particular assignment over multiple semesters, it appeared that between 3‐5 specific errors accounted for more than 95% of the errors in each question on the assignment. When the protocol was implemented, grading was completed expeditiously, without any direct written feedback other than number grades. Subsequently, a feedback video was released to the class discussing the assignment and going through each question/topic. Common errors, and how to avoid them, were covered in the video feedback. In a class of 68 students, 186 video plays were recorded for a single remediation assignment. And although some of the engagement durations were highly variable, that is the engagement model that was suggested to students by encouraging them to only watch those parts of the video feedback they felt was necessary.ConclusionsIn concert with other types of feedback including peer feedback, and immediate in‐class feedback, video feedback for common misconceptions/errors provides an efficient way to engage students in formative learning. Despite this, it is clear that alternative (or traditional) access to feedback must be provided for those students who fall outside these so‐called normal thresholds. However, streamlining the feedback process for >90% of students will allow more time to be spent with non‐typical learners, or other students who require alternate resources. In this way, it is hoped that learners from marginalized communities and neuroatypical learners, who may benefit from increased guidance, can still get what they need, while the greater majority have opportunities to refine and tailor the feedback they most need.
Biocompatible and biodegradable nanoparticles for enhancing solubility and bioavailability of trans‐resveratrol
Authors: Hu Qiaobin , Zhou Fang , Wang Shu 
Published: May 2022

ObjectivesTrans‐resveratrol (R) is a natural polyphenolic compound found in red grapes, mulberries, and other berries. Cell and animal studies indicate that it can improve metabolic health through its anti‐inflammation, anti‐obesity, anti‐oxidant properties. However, the evidence is inconclusive in human studies regarding its effectiveness in improving metabolic health, most likely due to its low aqueous solubility, and trivial bioavailability. The objectives of this study are to encapsulate R into biocompatible and biodegradable nanoparticles (R‐NPs), and measure their characteristics and oral bioavailability in C57BL/6J mice.MethodsThe R‐NPs were made of soy phosphatidylcholine, vitamin E, Tween 80, and R. Their size, polydispersity index and zeta potential were measured using Zetasizer Pro. R‐NPs were stored in dark at 4°C, 22°C and 37°C, and their physical and chemical stability was measured every day. The physical stability was determined using Zetasizer Pro. The encapsulation efficiency and chemical stability were determined using an Agilent 1290 Infinity II UHPLC system. After oral administration of R‐NPs and free R at R concentration 50 mg/kg body weight in C57BL/6J mice, their oral bioavailability was determined by measuring blood R concentrations using the UHPLC system.ResultsNanoencapsulation significantly increased aqueous solubility of R by more than 140 times. The mean particle size of freshly made R‐NPs was around 70 nm. The polydispersity index was less than 0.3. The zeta potential of R‐NPs was around −13 mV. R’s encapsulation efficiency was more than 95%. The size, polydispersity index, zeta potential, and R concentrations of R‐NPs did not change significantly at 4°C, 22°C and 37°C for 3 days. The encapsulation efficiency of R‐NPs remained above 94% after storage for 3 days at three tested temperatures. These data indicated good chemical and physical stability of R‐NPs. As compared to free R, R‐NPs had higher oral bioavailability in C57BL/6J mice.ConclusionsNanoencapsulation increased the aqueous solubility and stability of R, and improved R’s oral bioavailability in mice.
A Theoretical Model of the Mechanism by which Dietary Lipid Variance and Increased Oxysterols Allow Increased Formation of Soluble Endoglin in Preeclampsia
Authors: Hart Nancy R. 
Published: May 2022

Endoglin (TGF‐β receptor III), an accessory receptor necessary for transforming growth factor‐β (TGF‐β) signaling, is essential during angiogenesis. Cleavage of endoglin by matrix metalloproteinase‐14 (MMP‐14) creates a soluble receptor (sEng) which is elevated in the sera of people with preeclampsia. Similarly to sflts which bind VEGF, sEng binds TGF‐β and impairs functions ranging from endothelial nitric oxide synthesis, vasodilation, and modulation of vascular permeability, to regulation of immune homeostasis, trophoblastic invasion and differentiation.Cleavage of endoglin to form sEng is upregulated in the presence of oxysterols. Initially, oxysterols were believed to upregulate MMP‐14 and down regulate its inhibiter TIMP3. However, in placental explants, expression MMP14 and TIMP3 mRNA were not altered by oxysterols and pravastatin did not decrease oxysterol‐induced upregulation of sEng. Membrane raft domains negatively regulate TGF‐β signaling, and aspirin, which disperses membrane rafts, induces TGF‐β signaling.This perspective considers the known changes in dietary lipids over the last 100 years, the possible effects of these changes on membrane raft formation, oxidative stress, and oxysterol formation, as well as the known effects of oxysterols on membrane thickness and fluidity and proposes an alternate mechanism by which oxysterols might increase sEng formation.
Assessing Racial Consciousness in Anatomy Educators
Authors: Anand Shreya 
Published: May 2022

Anatomy teaching faculty have the ability to affect how race is discussed and portrayed in the curriculum, such as choosing which images to use, which textbooks to assign and reference, and whether to include race or other social determinants of health in discussions of clinical correlates of anatomy. Inclusive learning materials can impact medical students’ self‐perception and either reinforce or dismantle implicit and explicit biases that may be held toward future patients and colleagues. Using a mixed methods approach, we surveyed faculty teaching anatomy at a variety of levels in order to assess the materials, resources, and concepts that are currently taught in anatomy classrooms, and the barriers that anatomy faculty face in creating diverse and inclusive teaching materials.Survey results show that of 162 total respondents, only 17.86% of anatomy faculty are satisfied with the diversity represented in their anatomy textbook, while 50.89% are not satisfied. Overall, it appears that while race is at least sometimes discussed in the majority of curricula surveyed here (39.69 % “sometimes”, 17.46% “often,” 3.05% “always”), it appears to be less frequently discussed in the anatomy classroom (37.40% “sometimes,” 6.11% “often,” 0.0% “always”).Qualitative data collected from survey participants suggests that some anatomy faculty (18) feel that race is outside of the scope of discussion in an anatomy course. However, 17 educators felt that discussion of race is within scope for an anatomy course. Interestingly, describing race as a social construct was used both to justify its exclusion in the anatomy curriculum (2 respondents) as well as its inclusion (4 respondents).Our preliminary data that most educators desire to be more inclusive in their instructional materials, however, they feel restricted by the lack of diverse resources at their disposable. We hope the insights from this study will help us understand information gaps and create a more racially conscious anatomy curriculum.
ST segment elevation: the lost measure of early ischemic preconditioning in the landmark study of Murry et al. 1986
Authors: Sturek Michael , Byrd James , Alloosh Mouhamad 
Published: May 2022

BackgroundIn their landmark study Murry et al. (Circulation 74:1124, 1986) showed dramatic ST segment elevation of the ECG during the first occlusion of a dog coronary artery. They made the insightful observation that “… in subsequent occlusions, these changes were slower to develop and frequently did not reach the magnitude seen during the first occlusion.” This electrophysiological preconditioning has been almost completely dismissed as irrelevant to ischemic preconditioning in animal models. We found in the Ossabaw miniature swine model of metabolic syndrome that brief coronary occlusion often led to ST elevation that quickly progressed to ventricular tachycardia and fibrillation.HypothesisAn AMPKγ3 mutation in Ossabaw swine will explain the extreme ST elevation and provide evidence for the relevance of ST segment ischemic preconditioning.Methods and ResultsLean mutants had impaired glucose tolerance compared to wild type Ossabaw swine. Myocardial ischemia induced by balloon occlusion of the circumflex artery elicited profound electrocardiographic ST elevation in lean mutant compared to wild type swine. Infusion of an AMPK agonist, AICAR (0.5 mM), prior to occlusion significantly reduced ST elevation in lean mutants, while completely preventing ST segment elevation in wild type. Ischemic preconditioning of the ST segment changes occurred in wild type pigs during the course of 5 occlusions, but only occurred in mutant pigs with AICAR infusion. Infusion of compound C (30 μM), an AMPK antagonist, prior to occlusion blocked the AICAR‐induced attenuation of ST elevation in lean mutants. The KATP channel agonist pinacidil increased ST elevation and the antagonist glibenclamide attenuated ST elevation during occlusion. While the degree of diet‐induced MetS (obesity, further impaired glucose tolerance, insulin resistance, and hypertension) was not different between mutant and wild type swine, except for greater plasma lipids in mutants, there was no difference in ST elevation during myocardial occlusion.ConclusionsLean Ossabaw swine with the V199l AMPK mutation have impaired glucose tolerance and exacerbated KATP channel‐mediated ST elevation during myocardial ischemia. Excess calorie diet induces MetS and abolishes cardioprotection in wild type AMPK swine. ST segment changes are an excellent measure of ischemic preconditioning in this model, thus showing the relevance of Murry’s landmark discovery.
Histopathology of Dermatologic Complications of Tattoos
Authors: Torre-Castro Juan , Nájera Laura , Suárez Dolores , García-Fresnadillo Diego , Freites-Martínez Azael , Briz Angel Santos , Rodríguez Peralto Jose Luis , Requena Luis 
Published: May 2022

Abstract:
Tattoos are characterized by the introduction of exogenous pigments into the dermis. Tattoos usually serve cosmetic purposes, although they may have other causes, such as traumatic pigment implants in accidents or medical-related tattoos in the context of radiotherapy. Dermatologic adverse reactions are relatively uncommon, and they include infections, immune-mediated reactions, cutaneous lesions secondary to the Koebner phenomenon, exacerbation of preexisting dermatosis, benign and malignant neoplasms, and a miscellaneous group of dermatologic conditions that may appear in a preexisting tattoo. The aim of this study is to review the types of histopathologic reactions that may appear in a preexisting permanent tattoo.
Spindle Cell/Pleomorphic Lipoma With Trichodiscoma-like Epithelial Hyperplasia Mimicking Atypical Fibroxanthoma/Pleomorphic Dermal Sarcoma
Authors: Aghighi Maryam , Andea Aleodor A. , Patel Rajiv M. , Fullen Douglas R. , Bresler Scott C. 
Published: May 2022

Abstract:
A 58-year-old man presented with a lesion on the nose suspicious for basal cell carcinoma. An initial biopsy specimen reviewed at an outside institution showed a cytologically atypical spindle cell proliferation that lacked expression of cytokeratins or melanocytic markers. The resulting differential diagnosis included atypical fibroxanthoma and pleomorphic dermal sarcoma. Histopathologic examination of the excision specimen at our institution revealed an intradermal pleomorphic and spindle cell tumor which extended into underlying skeletal muscle. The tumor was associated with a fibromyxoid stroma, scattered adipocytes, and hyperplastic folliculosebaceous epithelium at the periphery. The pleomorphic tumor cells showed hyperchromatic nuclei with smudgy chromatin, and no mitotic activity was detected. Overall, the cellularity was less than would be expected for atypical fibroxanthoma/pleomorphic dermal sarcoma. Furthermore, the tumor cells were strongly positive for CD34 and showed diffuse loss of retinoblastoma protein by immunohistochemistry. Consequently, a diagnosis of benign CD34-positive pleomorphic spindle cell tumor was rendered, with features overlapping between spindle cell/pleomorphic lipoma and trichodiscoma. Subsequent single-nucleotide pleomorphism array testing revealed heterozygous loss of chromosome 13q in a region that spanned the RB1 locus and copy number loss at 16q, favoring that the proliferation in fact represents a spindle cell/pleomorphic lipoma with trichodiscoma-like epithelial induction. This case highlights an important diagnostic pitfall that may be avoided by recognizing characteristic architectural and cytologic features of this spectrum of lesions.
PRAME Expression Correlates With Genomic Aberration and Malignant Diagnosis of Spitzoid Melanocytic Neoplasms
Authors: Gerami Pedram , Benton Sarah , Zhao Jeffrey , Zhang Bin , Lampley Nathaniel , Roth Andrew , Boutko Anastasiya , Olivares Shantel , Busam Klaus J. 
Published: May 2022

Abstract:
Spitzoid melanocytic neoplasms are a diagnostically challenging class of lesions in dermatopathology. Recently, molecular assays and immunohistochemical markers have been explored as ancillary methods to assist in the diagnostic workup. Specifically, preferentially expressed antigen in melanoma (PRAME) immunohistochemistry is a nuclear stain commonly positive in melanomas, but not in nevi. This study investigates PRAME immunoreactivity (≥75% positive nuclear staining in tumor cells) in a set of 59 spitzoid melanocytic neoplasms with known clinical outcomes. We compared PRAME status with (1) the clinical outcomes, (2) the morphologic diagnoses, and (3) the status of TERT promoter mutation. Regarding clinical outcomes, 3 cases developed metastatic disease, of which 2 expressed diffusely positive PRAME staining. Of the 56 cases that did not show evidence of metastasis, 6 expressed diffusely positive PRAME staining. Morphologically, diffusely positive PRAME staining was seen in 7 of 21 cases (33.3%) diagnosed as melanoma and only 1 benign tumor 1 of 38 (2.6%). There were 4 of 8 cases with a TERT promoter mutation which were diffusely PRAME-positive compared with 4 of 51 cases without TERT promoter mutation (P = 0.001). Our results show a statistically significant correlation between PRAME expression and the diagnosis, outcome, and TERT promoter mutation status of atypical spitzoid melanocytic neoplasms, suggesting immunohistochemistry for PRAME can help support a suspected diagnosis. However, because of occasional false-positive and negative test results, correlation with the clinical and histologic findings as well as results from other tests is needed for the interpretation of diagnostically challenging spitzoid melanocytic neoplasms.
Proposals for a standardized procedure of validation of DNA extraction and allelic discrimination assays in pharmacogenomics according to ISO15189 requirements
Authors: Imbert Laurent , Lagoutte-Renosi Jennifer , Wils Julien , Lamoureux Fabien 
Published: May 2022

Objectives
In the era of quality management in clinical laboratories, method validation can be a challenge without appropriate guidelines, such as in the field of pharmacogenetics. The present work describes a method validation for DNA extraction and CYP3A5*3 genotyping, which would meet ISO15189:2012 requirements.

Methods
DNA extraction was performed using a QIAamp DSP DNA Blood kit, DNA purity and concentration were determined using a Nanodrop, and the genotyping assay was a real-rime PCR using TaqMan reagents. Validation criteria were similar to those usually verified when validating methods in the analytical field: specificity, sensitivity, cross-over contamination, stability of reagents, robustness, lower and upper limits of detection, and between-run and within-run precisions. A comparison to alternate or reference methods was also performed (i.e. QiAamp kit versus DNA extractor and TaqMan genotyping versus Sanger sequencing). Each validation step is described from the pharmacogenetic point of view, as well as acceptance criteria for both DNA extraction [i.e. concentration relative SD (RSD) below 25%, verified purity, and no DNA in blank samples] and genotyping assay (i.e. specificity and diagnostic sensitivity, RSD of mean threshold cycle below 15%, no amplification in blank samples).

Results
Concerning CYP3A5 genotyping following a DNA extraction described as an example, validation criteria were met, allowing routine use of this analytical process. Cost estimation of the overall validation procedure was approximately 290 euros, concerning reagents and consumables.

Conclusion
This work aims to provide a reference for method validation for pharmacogenetic analysis using real-time PCR to detect single nucleotide polymorphisms, in accordance with ISO15189:2012.