bluuebunny/crossref_metadata_2025_split huggingface dataset:
PDB‐101: Molecular Explorations through Biology and Medicine
Authors: Zardecki Christine , Goodsell David S. , Dutta Shuchismita , Voigt Maria , Burley Stephen K. 
Published: May 2022

PDB‐101 is an online portal for teachers, students, and the general public to promote exploration of the structural biology of proteins and nucleic acids (pdb101.rcsb.org). Learning about the diverse shapes and functions of these biological macromolecules helps to understand all aspects of biomedicine and agriculture, from protein synthesis to health and disease to biological energy.Why PDB‐101? Researchers around the world are studying these molecules at the atomic level. These 3D structures are freely available at the Protein Data Bank (PDB), the central storehouse of biomolecular structures. This website builds introductory materials to help beginners get started in the basics of biomolecular structure and function (“101”, as in an entry level course) as well as resources for extended learning.Since 2011, PDB‐101 has been developed by the RCSB PDB, a global resource for the advancement of research and education in biology and medicine. Along with our Worldwide PDB collaborators, RCSB PDB curates, annotates, and makes publicly available the PDB data deposited by scientists around the globe. The RCSB PDB then provides a window to these data through a rich online resource with powerful searching, reporting, and visualization tools for researchers. This information is then streamlined for students and teachers at PDB‐101.Features include the ongoing Molecule of the Month series, educational materials such as paper models, posters, molecular animations, educational curricula and more. The section “Guide to Understanding PDB Data” is a primer for detailed PDB‐specific information: PDB Data, Visualizing Structures, Reading Coordinate Files, scientific methods for structure determination, and more.PDB‐101 also runs annual Video Challenges for high school students. Participants create short videos that tell molecular stories that connect structural biology and medicine. Previous topics have included HIV/AIDS, diabetes, and antimicrobial resistance. The 2022 challenge will focus on Molecular Mechanisms of Cancer.PDB‐101 activities are evaluated using user surveys, feedback from in‐person activities, and website analytics. In 2020, PDB‐101 hosted >850,000 users and >2.6 million page views.
Radiography Suggests a Fibrous Tubular Sleeve Distal to a Cartilaginous Anlage in a Limb with ‘Absent Fibula’ Represents a Traction
Authors: Krisch Maria , Levinsohn Mark , Hootnick David , Ogden Kent , Katzman Philip 
Published: May 2022

BackgroundDissections of congenitally shortened limbs displaying congenital fibular deficiency have revealed pathologic cartilaginous bodies and fragments along the course of the “absent” fibula consistent with remnants of a fibular anlage (Wagstaffe, 1875; Freund, 1936; Harmon & Fahey, 1937; Thompson et al., 1957). Bands distal to the anlagen have traditionally been reported as fibular calcaneal collateral ligaments.ObjectiveThis project reinterprets the composition of the posterolateral ankle band frequently found in patients with congenital shortened limb (CSL) with fibular deficiency based on advanced radiographic criteria.Patient and MethodBilateral thin slice computed tomography (TSCT) imaging was performed on the distal lower extremities of a 43‐year‐old female patient with unilateral congenital shortened limb with fibular “absence” for operative planning. The images were imported into virtual modeling system 3D Slicer and various tissues in the region were measured and compared for attenuation using the Hounsfield unit (HU) scale.ResultsThe radiological study of the posterolateral ankle band in the presence of a limb with a diminutive fibular anlage exhibiting a normal medullary density revealed a tubular structure sharing attenuation readings with nearby adipose tissue at its core and fibrous tissue at its periphery.ConclusionThe tubular structure of the posterolateral ankle band with an adipose core, surrounded by fibrous tissue in the presence of a retained primitive fibular anlage, supports the assertion that fibular absence in this congenitally shorted limb is a radiographic misnomer, since a dystrophic anlage persists in its place. Additionally, previously identified fibulocalcaneal structures (or bands) may actually represent a stretched periosteal sleeve caused by traction exerted on the anlage by the paired lower tibia.These findings support the hypothesis that this “ligament” structure is the distalmost tubular remnant of an otherwise normally formed cartilaginous scaffold of the fibular anlage. The anlage has failed to ossify to form a normal fibular long bone structure, due to embryonic arterial dysgenesis and failed vascular invasion during the sixth‐seventh weeks of embryonic development.
High Sodium Intake Differentially Impacts Brachial Artery Flow Mediated Dilation When Evaluated with Reactive Versus Active Hyperemia
Authors: Decker Kevin , Weggen Jennifer , Hogwood Austin , Darling Ashley , Chiu Alex , Richardson Jacob , Garten Ryan 
Published: May 2022

OBJECTIVEThis study sought to determine if a high sodium (HS) intake attenuates upper limb flow mediated dilation in response to reactive (RH‐FMD) and sustained (SS‐FMD) hyperemia, and the role of oxidative stress in this response. Our hypothesis is HS intake will similarly impair upper limb vascular function when assessed as both RH‐FMD and SS‐FMD, and that this dysfunction will be reversed following acute antioxidant consumption.METHODSTen young, salt resistant participants (9 Males, 1 Female) consumed a 7‐day HS (6,900 mg/day) or a 7‐day low sodium (LS: 2,300 mg/day) diet in a randomized order. On the last day of the diet, brachial artery RH‐FMD (evaluated after 5 minutes of cuff occlusion) and SS‐FMD (handgrip exercise) were performed following consumption of placebo (PL) and repeated two hours after the consumption of antioxidants [AO; (1000 mg of vitamin C, 800 IU of vitamin E, and 400 mg of alpha lipoic acid]. Handgrip exercise (HG) was performed in 3‐minute workloads, increasing by 8 kg until failure, at a rate of one contraction per second. RH‐FMD responses were evaluated as percentage change from baseline and SS‐FMD was evaluated as brachial artery shear‐to‐dilation slopes assessed across all HG workloads achieved.RESULTSBetween diets, sodium consumption and excretion were significantly greater in the HS condition (p < 0.05 for both), but mean arterial blood pressure was unchanged (LS 85 ± 5; HS 84 ± 7 mmHg; p = 0.5). RH‐FMD was significantly lower during HS compared to LS (p = 0.01), in the placebo condition but not during the AO condition (p = 0.7), with a significant interaction present (HS+PL: 5.9 ± 3.4; HS+AO: 8.2 ± 2.7; LS+PL: 8.8 ± 4.7; LS+AO: 7.0 ± 2.1 %; p = 0.01) due to a significant increase in the HS+AO condition. A comparison of shear‐dilation slopes during SS‐FMD revealed no differences between sodium interventions (p = 0.3), AO condition (p = 0.1), or any interaction effect (p = 0.7) [HS+PL: 0.0031 ± 0.0013; HS+AO: 0.0026 ± 0.0012; LS+PL: 0.0028 ± 0.0012; LS+AO: 0.0022 ± 0.0010; mm.seconds‐1.kg‐1].CONCLUSIONIndependent of changes in MAP, a HS intake impaired peripheral vascular function when assessed via RH‐FMD, which was restored with AO consumption, potentially implicating elevated oxidative stress as a contributor to this dysfunction. However, SS‐FMD, evaluated via HG exercise, was not altered by a HS intake or AO consumption. In conclusion, 7‐days of a HS intake appears to have disparate effects between the two peripheral vascular function techniques, implicating an inability of HS intake to impact exercise‐induced BA dilation.
The Dissection Experience of Orthopedic Resident: A Comparison between Soft‐Preservation and Formalin‐Fixation Embalming Techniques
Authors: Arce Jazmin E. , Contreras Erik , Vaghani Parth , Goyal Kanu , Balta Joy Y. 
Published: May 2022

ObjectiveIn a recent study, it was found that residents will feel more confidence, independence and fluency in the operational procedures presented to them throughout their career if introduced to the learning first on a human donor (James et al., 2020). This study is a comparison of alcohol preserved to standard formalin preserved through regional‐based donor dissection completed by orthopedic residents. The results from this study will help inform orthopedic residencies to consider different preservation techniques of human donors in teaching their future students through dissection for better learning outcomes.MethodsOrthopedic Residents filled out a dissection survey after they had dissected for each week over a course of six weeks. Residents were expected to perform at least one dissection on a formalin‐based donor and one on an alcohol persevered donor for accurate comparison in data collection. The survey used a likert scale format ranging from 1 to 5. The survey questions range from bone, tendon, muscle, ligament, nerve, vessel quality; ease of dissection; similarity to in vivo tissue, ease of finding specific structures, etc. Descriptive statistics were used to describe the differences in resident opinion/experience between the two types of donors.ResultsA total of 24 residents participated in the dissector survey over the six weeks. Residents compared ease of dissection, ease of identification, odor of chemical, skills acquired, joint range of motion, tissue elasticity, donor comparability to live patients, time spent and overall learning preferences. 88.3% of residents in the dissections stated that overall they favored dissecting from alcohol preserved donors. When residents were asked to evaluate the differences in the donor preservations, residents favored alcohol preservation as a better way to stimulate their learning to in vivo tissue.Conclusions/ImplicationsOrthopedic Residents ultimately agree that the alcohol preserved donors are more effective when it comes to identifying the human body framework through dissection. The results suggest that orthopedic residency programs should take into consideration the preservation techniques when teaching their students anatomy from human donors.
Dopamine‐driven Increase in IL‐1β in Myeloid Cells is Mediated by Differential Dopamine Receptor Expression and Exacerbated by HIV
Authors: Matt Stephanie , Nolan Rachel , Manikandan Samyuktha , Agarwal Yash , Channer Breana , Canagarajah Joanna , Runner Kaitlyn , Nickoloff‐Bybel Emily , Gaskill Peter J. 
Published: May 2022

The neurological complications of HIV infection, known as neuroHIV, remain prevalent even in individuals on antiretroviral therapy (ART). Although the mechanism(s) underlying neuroHIV remain undefined, current data suggest that neuroinflammation is central to the development of HIV neuropathogenesis. Neuroinflammation can be exacerbated by substance use disorders, which are highly comorbid with HIV infection and substantively worsen clinical outcomes. Despite distinct mechanisms of action, all substances of abuse increase central nervous system (CNS) dopamine, suggesting that dopamine is a common mechanism by which addictive drugs potentiate neuroHIV. Our published data show that dopamine increases the production of inflammatory cytokines such as IL‐1β in human microglia and macrophages, but the mechanisms by which dopamine drives inflammation are not clear. Studies indicate that D1‐like dopamine receptors (DRD1, DRD5) mediate inflammatory activity while D2‐like dopamine receptors (DRD2, DRD3, and DRD4) mediate anti‐inflammatory activity, and we have shown that human macrophages and microglia have higher expression of D1‐like receptors. Therefore, we hypothesize that dopamine‐mediated production of IL‐1β in CNS myeloid cells is regulated by the ratio of different dopamine receptor expression levels and can be exacerbated by HIV infection. Our data in primary macrophages indicate that DRD1 expression is necessary for dopamine‐mediated increases in IL‐1β, but that changes in DRD2 expression can alter the magnitude of the dopamine‐mediated increase in IL‐1β. We confirm this in human microglia cell lines, showing that dopamine only increases IL‐1β gene and protein expression in microglia with a high ratio of D1‐like receptors to D2‐like receptors. Further, antagonizing dopamine receptor expression with the pan‐dopamine receptor antagonist flupentixol or decreasing the D1‐like/D2‐like ratio by overexpressing DRD2 diminishes the dopamine‐mediated increase of IL‐1β. We also show that the effects of dopamine on IL‐1β are potentiated in the presence of HIV infection in both microglial cell lines and iPSC‐derived microglia. Ongoing studies are examining the role of epigenetic regulation in the effects of dopamine and HIV on inflammation in these myeloid systems.Due to the prevalence of both substance use disorders and the increasing use of dopamine‐modulating therapeutics, a detailed understanding of dopamine‐mediated changes in inflammation will be critical to effectively tailor ART regimens to HIV‐infected individuals using these drugs.
The New Faculty Myth‐busters: Pharmacology Educators and Curators of Information
Authors: Hernandez Mark , MacGregor Gordon G. , Parker Robert W. , Helms Kristen 
Published: May 2022

IntroductionAs we move towards completion of a second year of remote medical pharmacology instruction due to the Covid‐19 global pandemic, osteopathic medical students are also dealing with changes in the USMLE Step‐1 and/or COMLEX Level‐1 with the new Pass/Fail System in 2022. Unlike previous generations, Gen Z are inundated with an abundance of digital information that is readily and freely available, including professional advice from external sources which are not part of the formal curriculum (unspecified social networks, handed down Anki cards, etc.). Misinformation and/or misconstrued or unqualified advice for rapidly mastering pharmacology material over time can lead to development of myths which can be found in comments provided within the student evaluation of faculty. Identifying trends and/or myths in the feedback provided by the students can serve as a meaningful tool for faculty self‐reflection and will also help faculty steer students away from common misinformation as well.MethodsThe aggregate data reported in Medical School Year Two Questionnaire All Schools Summary Reportpublished by the AAMC at the end of the second year of medical education (Years 2014‐2021) was used to develop a construct of trends in medical student usage of YouTube and/or Wikipedia as a source for medical information. Faculty involved in the instruction of pharmacology at the Alabama College of Osteopathic Medicine convened to review student feedback of pharmacology faculty collected between 2020 and 2021. Student feedback was examined to identify facts and myths, and these were further categorized to develop approaches to address these concerns in the future.ResultsThe use of Wikipedia has continually declined and the reliance on YouTube has increased as a resource of medical knowledge. Although this was already happening before the pandemic, the shift to other unspecified resources for medical knowledge during remote learning is of concern. In our institution, the review of pharmacology specific feedback demonstrated common myths within the following categories: 1) A lack of consistency in instructor and resources used (formal and informal), 2) perceived misconceptions on what is relevant (basic science versus clinical), 3) expectations for learning only what is perceived to be high yield. Approaches to preventing misperceptions for the future were identified for each category.ConclusionsPharmacology educators are curators of information. Evidence‐based clinical pharmacology information is changing faster than it can be updated in texts and the sanctioned board preparation resources that our students utilize. In the same manner, misinformation can rapidly spread via online forums and/or from handed down outdated resources from past students. Therefore, when pharmacology educators re‐engage medical students in‐person in the classroom, they will also have to more diligently serve as myth busters to combat misinformation and misperceptions.
Individualized Estrogen Dosing in Women Undergoing Premenopausal Bilateral Oophorectomy
Authors: Harvey Ronee E. , Baker Sarah E. , Kapoor Ekta 
Published: May 2022

Early menopause (prior to age 46 years) due to bilateral oophorectomy results in an abrupt loss of estrogen and other ovarian hormones and an increased risk of cardiovascular disease (CVD). Administration of estrogen partially mitigates this increased CVD risk; however, optimal dosing strategies for lowering CVD risk have not been studied. Current standard care is to use a dose of estrogen higher than that used for vasomotor symptom treatment in women after natural menopause in order to approximate the physiologic estradiol levels in premenopausal women (standard care); however, estradiol levels are not generally measured. An individualized approach that titrates estradiol levels to premenopausal hormone levels (individualized dosing) may be better for CVD risk mitigation in this younger population.The goal of this study was to compare the effect of estradiol dosing strategies (standard care vs. individualized dosing) on subclinical predictors of CVD in women with early menopause due to bilateral oophorectomy.We studied a total of 18 women at baseline and 6 months following surgical and medical intervention: 6 women underwent bilateral oophorectomy and were treated with standard care (age 41±2 years), 7 women underwent bilateral oophorectomy followed by estrogen therapy dosage based on individualized dosing (39±2 years), and 5 women served as time controls (did not undergo bilateral oophorectomy and were studied during the early‐follicular phase of the menstrual cycle at both visits; 34±3 years). At each time point, we assessed parameters of subclinical CVD including resting aortic blood pressure, carotid‐femoral pulse wave velocity, and blood pressure changes during a handgrip test and a cold pressor test.At baseline, serum estradiol levels were similar amongst groups (p>0.05). After 6 months, women who received individualized dosing of estrogen therapy had higher serum estradiol levels (179±23 pg/ml) than women who received standard care (53±25 pg/ml, p=0.01) and women in the control group (78±27 pg/ml, p=0.03). Systolic and diastolic aortic blood pressures did not change between baseline and 6 months, nor did they differ amongst groups at any time point (p>0.05 for all). There were no group or time differences in the change in mean blood pressure during the handgrip exercise or cold pressor test across 6 months (p>0.05 for all).Over a 6‐month follow‐up, despite differences in serum estradiol levels following two different estradiol dosing strategies after bilateral oophorectomy, there were no group differences or detrimental changes in subclinical CVD parameters across time. It is yet to be seen if differences in these parameters will be apparent following a longer duration after bilateral oophorectomy.
The Effect of Lipolysis Inhibitor Acipimox on Brown Adipose Tissue Bioenergetics and Uncoupling Protein Abundance in Severely Burned Rats
Authors: Rontoyanni Victoria G. , El Ayadi Amina , Prasai Anesh , Wang Ye , Bhattarai Nisha , Vardarli Emre , Porter Craig , Murton Andrew J. 
Published: May 2022

IntroductionUncoupling protein 1 (UCP1) activation in brown adipose tissue (BAT) contributes to the hypermetabolic stress response to burn trauma. Strategies that target BAT UCP1 could be beneficial in controlling burn‐induced hypermetabolism. Acipimox, an inhibitor of adipose tissue lipolysis, has been shown to be effective at blunting burn‐induced lipolysis and expression of UCP1 protein in rodent white adipose tissue. The impact of acipimox on BAT bioenergetics and uncoupling protein abundance is currently unknown. We hypothesized that acipimox would blunt burn‐induced UCP‐1 dependent respiration and UCP‐1 protein levels in BAT.MethodsSixty‐four male Sprague‐Dawley rats received a 60% TBSA scald burn (n=32) or sham procedure (n=32) and were subsequently randomized to receive either acipimox (n=16/group; 50 mg/kg/day i.p.) or vehicle (n=16/group) daily for 7d. BAT was harvested from the interscapular fat pad on day 7 after burn and mitochondrial respiratory function assessed by high‐resolution respirometry. GDP‐sensitive respiration was assayed as a direct measure of UCP1 function. UCP1 and adenine nucleotide translocator (ANT2) protein levels were determined by western blot.ResultsUCP1‐dependent and UCP1‐independent uncoupled respiration in BAT was reduced at 7d after severe burn, independent of treatment (injury effect, P<0.01). Post‐burn, UCP1‐dependent respiration accounted for 65% of total uncoupled respiration compared to 59% in sham rats (injury effect, P<0.05), independent of treatment. Acipimox appeared to exert a lowering effect on UCP1‐dependent respiration (treatment effect, P=0.07) but not on UCP1‐independent respiration. Neither burn nor treatment with acipimox had a significant effect on UCP1 protein levels. Protein levels of ANT2, a carrier protein involved in fatty acid‐induced uncoupling, were greater in response to acipimox (treatment effect, P<0.05).ConclusionBAT UCP1 function than UCP1 protein content is greater in severely burned rats. Acipimox appears to reduce UCP1‐dependent respiration, independent of UCP1 protein levels. The effect of acipimox on BAT ANT2 protein content may partly explain the absence of an effect on UCP1‐independent respiration, but this warrants further investigation.The protocol was approved by the University of Texas Medical Branch IACUC.