bluuebunny/crossref_metadata_2025_split huggingface dataset:
Student created quizzes to reinforce critical information and highlight deficits for both the students and instructor
Authors: Patenaude Bart , Scott Joanna 
Published: May 2022

IntroductionMedical students use passive strategies to study even though evidence shows the benefits of active learning. Having students work in groups and write quiz questions is an effective way to engage the students in active learning.MethodsStudents in a dental head and neck anatomy course worked in groups of 7‐11 and created review quizzes for extra credit. The quizzes covered the material in the module and were posted a week before the module’s exam. In addition to the posted quiz, they posted the correct answers and a justification for why they were asking the question.Results104/109 (95%) students agreed to be part of the educational research. The majority of students thought that the writing of questions and course structure improved their educational experience (81%). The strength of this opinion increased from the first exam to the final (p<0.001).DiscussionUsing a small amount of extra credit points to motivate students to create quizzes was impactful on the students learning. It also was appreciated by them. It could be added to a course without any additional resources and without removing any material from the course. Finally, it gave the instructor a valuable window into the students’ understanding of the material taught.
Treatment of Sleep Disordered Breathing with Leptin Loaded Extracellular Vesicles
Authors: Freire Carla , Pho Huy , Ramsey Jacob D. , Zhao Yuling , Kim Lenise J. , Berger Slava , Anokye‐Danso Frederick , Sennes Luiz U. , Ahima Rexford S. , Batrakova Elena V. , Kabanov Alexander V. , Polotsky Vsevolod Y. 
Published: May 2022

IntroductionObstructive sleep apnea (OSA) is the most common type of sleep disordered breathing (SDB), characterized by recurrent periods of upper airway obstruction during sleep leading to increase in morbidity and mortality. The prevalence of OSA exceeds 50% in individuals with obesity and 10‐20% also develop hypercapnia and hypoventilation during sleep which characterizes obesity hypoventilation syndrome (OHS). There is no effective pharmacotherapy for SDB. Leptin, an adipocyte derived hormone, can stimulate breathing and is a potential therapeutic candidate. However, diet‐induced obesity is associated with impairment of leptin transport across the blood‐brain barrier. Previous studies have shown that extracellular vesicles (EVs) naturally derived from macrophages can penetrate the BBB and be used for drug delivery. The objective of this study was to determine if EVs overcome the BBB and treat SDB in DIO mice.MethodsTo examine the ability of EVs to cross the BBB, lean (n=5) and DIO (n=5) C57BL/6J mice were injected with fluorescent EVs or saline into the lateral tail vein. After 4h EV biodistribution was evaluated by Bioimaging and Infrared Spectroscopy (IVIS). Sleep studies were performed in a plethysmography chamber in a separate subgroup of male, DIO (n=10) and lean (n=10) mice. Mice received saline, empty exosomes, free leptin, or leptin‐loaded exosomes in a crossover manner. Similar design was used to determine energy expenditure in a Comprehensive Laboratory Animal Monitoring System (CLAMS).ResultsWe demonstrated that EVs accumulated in the brain and the transport across the BBB was 2‐times more efficient in DIO when compared to lean mice (p<0.005). In DIO mice, leptin EVs induced 1.7‐2.2‐fold increases in minute ventilation and 1.5‐2.0‐fold increases in maximal inspiratory flow during flow‐limited and non‐flow limited breaths (p<0.05). In contrast, free leptin had no effect. There was no effect of leptin EVs on metabolism. These findings suggest that leptin EVs mitigated upper airway obstruction and improved control of breathing in DIO mice. Lean mice did not present significant sleep disordered breathing and no differences were observed between groups.ConclusionWe demonstrated that EVs overcome the BBB and that leptin loaded EVs treat SDB in DIO mice.
Mother with Obesity Induced by High‐Fat Diet Impaired Autophagic Process and Induced Renal Lipid Accumulation in the Offspring
Authors: Phengpol Nichakorn , Promsan Sasivimon , Sutthasupha Prempree , Lungkaphin Anusorn 
Published: May 2022

IntroductionThe prevalence of obesity has increased worldwide, and more women are entering obese pregnancy. The offspring born to maternal obesity have an increased risk of obesity and insulin resistance in later life and could affect offspring’s kidney injury. The abnormal renal lipid metabolism leads to renal lipid accumulation and these suggested to be the importance mechanism to develop and progress of chronic kidney disease (CKD). Lipophagy is the autophagic process to hydrolyze lipid droplet into free fatty acid for preserve energy and prevent an excess of lipid accumulation. The defect in lipophagy regulation is associated with renal lipid accumulation and contribute to kidney injury. Therefore, we hypothesized that maternal obesity induced by high‐fat diet programmed to increase offspring renal lipid accumulation via dysregulation of autophagic process and abnormal renal lipid metabolism leading to offspring’s kidney injury.MethodsFemale C57BL/6 mice were divided into two groups, control lean mother and maternal obesity groups, fed with standard and high‐fat diet, respectively, for 8 weeks. After that, female mice were mated with normal male mice and were housed and maintain each diet throughout gestation and lactation periods. After weaning, male offspring from each mother were sacrificed and blood samples and kidney were collected to evaluate autophagic and lipid metabolism.ResultsMaternal obesity was significantly increased body weight, fat weight, blood glucose and HOMA‐IR in the offspring. The increasing in renal cholesterol and triglyceride together with upregulated FAS, Srebp1, ADFP and CD36 protein expression indicating increased renal lipid synthesis and renal lipid uptake were observed in the offspring born to maternal obesity. Meanwhile, maternal obesity affected to downregulated PPARα and CPT1A demonstrating decreased renal lipolysis leading to exacerbated renal lipid accumulation in the offspring born to maternal obesity. The significant increase in mTOR, decrease in AMPK, Beclin‐1, LC3B and LAMP2 protein expression were shown in offspring’s kidney born to maternal obesity. These represented the inhibition of autophagic process, impaired autophagosome formation along with aberrant lysosome formation.ConclusionMaternal obesity affected to program offspring obese‐insulin resistance and increased the risk of kidney injury. The stimulation of renal lipogenesis and the suppression of renal lipolysis led to increased renal lipid accumulation. Moreover, maternal obesity induced impaired autophagic process by decreasing autophagosome formation and impaired lysosome formation. These alterations reduced the hydrolyzation of lipid droplet in the offspring’s kidney leading to more severity of renal lipid accumulation and resulting in offspring’s kidney injury.
Crotonate sensitizes IAPi in the disruption of latent HIV by modulating the ncNF‐κB signaling pathway at the step of p100 cleavage into p52
Authors: Jiang Guochun , Li Dajiang , Falcinelli Shane D. , Wong Lilly M. , Tang Yuyang , Browne Edward P. , Archin Nancie M. , Margolis David M. 
Published: May 2022

BackgroundAntiretroviral therapy (ART) effectively suppresses HIV‐1 (HIV) replication to an undetectable level in the periphery; however, the treatment is life‐long and HIV reservoirs cannot be eliminated by ART alone in people living with HIV (PLWH). The major obstacle that impedes HIV eradication in ART‐treated PLWH is the latent viral reservoir harbors in the resting CD4+ T cells. Recently, the activation of non‐canonical (nc) NF‐κB pathway via IAP inhibitor (IAPi) or the SMAC mimetic (SMACm) compounds has raised as an attractive mechanism to disrupt HIV from latency. IAPi/SMACm targets IAPs to activate NF‐κB inducing kinase (NIK) followed by phosphorylation of IkappaB kinase (IKK), leading to the cleavage of p100 into p52. The latter forms a complex with RelB to stimulate transcription of its target genes after translocation into the nucleus. Previously, we discovered that crotonylation stimulates HIV latency reversal that elicited by PKC/NF‐κB agonist. We hypothesize that there may exist a functional interaction between protein crotonylation and ncNF‐κB signaling, which may enhance IAPi‐induced latency reversal to optiomally disrupt HIV latency for a cure of HIV.MethodsMultiple HIV latency models were used, including Jurkat cell derived HIV latency models, the U1 promonocytic model of latency, the primary CD4+ T cell model of HIV latency and the resting CD4+ T cells isolated from ART‐suppressed PLWH. HIV expression was determined by flow cytometry and/or real‐time PCR. Protein expression and cleavage was determined by Western blot.ResultsWe found that IAPi/SMACm can disrupt latent HIV. However, its ability to reactivate latent HIV varied among different HIV latency models, with a lowest efficacy in the primary CD4+ T cell model of latency. Interestingly, IAPi/SMACm‐induced disruption of latent HIV was greatly enhanced in the presence of crotonate in all these in vitro and ex vivo models. This was possibly mediated by the enhancement of p100 cleavage into p52 in the ncNF‐κB signaling pathway.ConclusionsWe propose that a blockage of p100 cleavage prevents an efficient activation of ncNF‐κB signaling pathway in the latently infected CD4+ T cells in PLWH, which could be relieved by targeting IAP proteins to induce p100 cleavage for the activation of ncNF‐κB signaling. Crotonylation, which was recently defined by us as a new epigenetic mark for the active HIV transcription, potentiates the reactivation of HIV from latency by further releasing the blockage at the p100 cleavage step, thereby enhancing ncNF‐κB activation to disrupt HIV latency. These data indicate that crotonylation could be exploited to develop novel strategies for HIV cure or remission in the future.
T Cells Contribute to Lipid Deposition in Male and Female Dahl Rats Fed a High Saturated Fat Diet
Authors: Ramirez Lindsey A. , Snyder Elizabeth E. , Mattson David , Abais‐Battad Justine , Dasinger John Henry , Sullivan Jennifer C. 
Published: May 2022

BackgroundThe Dahl rat has been used as a model of high fat diet (HFD)‐induced hypertension and adiposity. Genetic deletion of T cells blunts HFD‐induced hypertension. However, it is not clear if deletion of T cells can also reduce the adiposity caused by the HFD. T cells have been shown to play a role in many inflammatory conditions which are characterized by dyslipidemia. Therefore, the goal of the current study was to test the hypothesis that deletion of T cells prevents lipid deposits in the liver and adipose tissue.Methods5‐week‐old male and female wildtype Dahl (WT; n=9‐19/group) or Dahl rats lacking T cells (CD247 knock out [KO] rats; n=3‐7/group) were randomized to either a control normal fat diet (NF; 7.2% calories from fat) or a high fat diet (HF; 36% calories from saturated fat) for 10 weeks. Following treatment, a subset of livers were processed for hematoxylin and eosin staining and liver steatosis was scored. Gonadal adipose tissue was extracted and weighed.ResultsTen weeks of HFD increased liver steatosis in WT males and females (PInteraction=0.84, PDiet=0.01, Psex=0.75, Table 1), but not in T cell deficient animals (PInteraction=0.35, PDiet=0.29, Psex=0.04). While HFD increased gonadal adipose tissue weight in both males and females, this weight was increased more in the females (PInteraction=0.006, PDiet<0.0001, Psex<0.0001). T cell deletion abolished the HFD‐induced weight gain in gonadal adipose tissue (PInteraction=0.98, PDiet=0.14, Psex=0.01).DiscussionThese data confirm the hypothesis that T cell KO prevents the HFD‐induced increases in adiposity in the liver and gonadal adipose tissue. Lipid deposits in these areas are detrimental for cardiovascular health. Lipid deposition in the liver is a strong predictor of insulin resistance. Furthermore, chronic ingestion of a HFD increases adipose tissue expansion, which promotes inflammation and oxidative stress. Since the majority of Americans are consuming large amounts of fat, investigating the mechanisms underlying HFD‐induced adiposity will help identify targets to improve cardiovascular health.
How Useful Was That Critical Reflection? Technology Enhanced Learning in Physiology Skill Lab
Authors: Malik Samina 
Published: May 2022

IntroductionCritical reflection blended with technology is essential to gain insight into one’s action leading to enhanced learning & performance in Objectively Structured Clinical Evaluation (OSCE). However, it is still being under‐utilized by teachers and students in most second year undergraduate clinical physiology curricula of Pakistan including University College of Medicine and Dentistry.Aims and objectivesTo evaluate the usefulness of critical reflection blended with technology as a learning enhancement tool.Subjects and methodologyTeachers and second year physiology students of University College of Medicine and Dentistry, University of Lahore mutually planned an experimental study of QUAL‐quan design, using critical reflection as a tool to enhance learning and performance in cranial nerve examination. The technological stimulus or intervention involved student engagement by video‐presentation of role‐play conducted by class‐fellows on cranial nerves examination. Each of the three randomized groups (n=50) experienced conventional practical demonstration by a standardized common demonstrator followed by hands‐on‐practice by common tutors. Group B was additionally involved in video recording of role‐play, with one student as examiner, second student as a subject, and the third as the examiner who marked the structured key. The remaining students observed the entire activity. Group C additionally watched recorded video followed by reflective group discussion analyzing examination against structured key and tutor’s performance and corrected the mistakes presented in the video through critique and collaborative feedback. Open and closed ended feedback was obtained from students and tutors. Qualitative analysis was conducted on piloted and peer‐reviewed feedback questionnaires whereas quantitative analysis was done on surprise formative assessment scores after couple of months to see the behavioral change as per Kirkpatrick’s model.ResultsComparatively significant quantitative and qualitative responses were obtained from group C on ANOVA, including enjoyable learning environment, enhanced memory, critical thinking, clarity of concepts, time‐management & confident performance.ConclusionCritical reflection blended with technology may enhance learning and performance.
Epigenetics: A Gatekeeper to DNA Amplification and Replication Control
Authors: Whetstine Johnathan R. 
Published: May 2022

DNA amplification is associated with pathological states such as neurological disorders, cardiac disease and cancer. At least 50% of the amplifications in cancer are transient extrachromosomal DNA (ecDNA). The transient behavior contributes to copy number plasticity, results in heterogeneous oncogene expression and alters therapeutic response. The unanswered question remains as to whether distinct mechanisms control ecDNA copy gains within cells and how they impact copy gain events associated with disease. Our laboratory aims to define the principles regulating selective DNA amplification and the associated plasticity, so we may control these events in disease. By resolving general mechanisms governing selective DNA amplifications, we will build a framework to further understand the molecular basis by which copy gains occur in neoplasia and other diseases.Recent studies have begun to uncover the importance of epigenetic states and histone lysine methyltransferases (KMTs) and demethylases (KDMs) in regulating extrachromosomal transient site‐specific DNA copy number gains (TSSGs). In fact, our laboratory discovered the first chromatin factor promoting TSSGs in the human genome. We have revealed a critical interplay between a myriad of KMTs and KDMs in modulating methylation balance in order to control rereplication and extrachromosomal amplification events. The methyl‐lysine modifier networks that control site‐specific DNA amplification were resolved through genetic and chemical treatments coupled to cytological approaches, epigenomic profiling and 3D genome organizational analyses. While interrogating their role in controlling DNA amplification, we have also begun to appreciate their impact on chromatin modification dynamics and global DNA replication timing. We have established that enhancers coupled to methylation changes in broad methylation domains strongly predicts replication timing changes when perturbed by specific lysine modifiers. Taken together, we have established that methyl‐lysine modifiers are key regulators promoting or preventing DNA amplification and play instrumental roles in regulating replication timing control through the combined regulation of methylation states. The most recent studies addressing these observations will be presented at the meeting.
The vital landmarks of human body (Marma) according to TCAM and its application in Physical medicine and Rehabilitation
Authors: Kumar Madan , Meshram Akashdeep A. 
Published: May 2022

According to Traditional Complementary and Alternative Medicine (TCAM), the universe as well as the human body, is grossly and subtly comprised of five elements. The five elements namely space, air, fire, water and earth. These are the prime factors for origin of life. Among the five elements, space is related with mind, air with body movements, fire with thermodynamics of the body, water with structural integrity of the body and earth with gross body. The Indian System of Medical science has contributed various insights into the understanding of human body using various philosophical, analytical, experimental and spiritual modalities. Marma sastra and varma sastraare two nomenclatures given for the same type of human anatomical body landmarks, which strongly works on the principles of anatomy and physiology and energy principles. Varma/marma is air (vayu). Varma is also referred to as energy. Thirteen energy locations, grouped into three categories has been explained in detail. In order to understand the varma techniques, an additional knowledge regarding the basic Indian philosophy, is also needed.Experts have given various classifications of marma. Among them the most practical system is based on method of application. It illustrates the following: 1) Thodu Varmam (stimulated by touching), 2) Padu Varmam (activate other regions), 3) Thattu Varmam (stimulated by gentle tap), 4) Enai Varmam (unified activation of two points can relieve symptoms), 5) Pakka Varmam (action of adjacent varmas), 6) Ellidai Varmam (points related in between joints), 7) Oothu Varmam (stimulation by blowing; for children), 8) Nakku Varmam (stimulation by licking; for children), 9) Naal Varmam (associated with astrological stars), 10) Griha Varma (associated with astrological planets), 11) Patchi Varmam (points related to internal organs), 12) Vaatha Varmam, 13) Pitha Varmam, 14) Sleshma Varmam, (12, 13 and 14 areregulated by bodily humor 15) Nokku Varmam (stimulated by looking). More than fifty manuscripts have been published in the Nation Workshop on Manuscriptology, India, 1999. The present session is a representation of the major varma/marma landmarks of human body and its utility based on connecting this physical landmarks to improve the mobility standards of human body. These principles will be detailed using most recent photographs from eminent resources followed by detailed diagrammatic representation of their practical applications. Though based on ancient knowledge, the matter detailed in this session is based on current practice of these methods in India. The topic gives a new dimension and scope in using the Varma/Marma as a anatomico‐physiological landmarks for medical students as well as practitioners of physical medicine and rehabilitation (PMR).
Effects of tooth loss on anxiety‐like behaviors in Heterocephalus glaber
Authors: Hite Natalee J. , Sarko Diana K. 
Published: May 2022

Tooth loss is an ailment affecting a large percentage of the population, particularly individuals of lower socioeconomic status and the elderly. Extensive tooth loss is known to result in anatomical changes in the face, including atrophy of masticatory muscles and decreases in mandibular and maxillary bone density, as well as volumetric changes within the brain. Human studies have reported strong correlations between tooth loss and levels of both anxiety and depression. However, little has been reported to date regarding the effect of dental health on emotional states, with only sparse information available from animal models regarding the psychiatric effects of tooth loss.Our study investigated the short‐term effects of tooth loss on anxiety‐like behaviors using Heterocephalus glaber, an animal with extensive sensory dedication to and behavioral reliance on its incisors. Adult naked mole‐rats underwent either tooth extraction or sham surgeries, followed by testing in both an open field maze and elevated plus maze in the weeks following. As there are no known studies to date that have utilized this animal model in behavioral tests of anxiety, our study provides critical information about the methodologies and modifications necessary to ascertain these important translational behavioral states so that future researchers can apply similar tests in other fields such as neurodegeneration, aging, and oncology.We hypothesized that tooth extraction will result in greater anxiety‐like behaviors, manifesting in various ways: greater defecation in the mazes, more time spent in the outer regions of the open field maze, and less time in the open arms of the elevated plus maze. The study demonstrated a trend towards tooth extraction increasing anxiety‐like behaviors in naked mole‐rats when investigated using the open field maze paradigm. There is evidence that, with an increase in sample sizes, this research will make evident the causal relationship of tooth loss and anxiety. Future research will investigate the long‐term behavioral changes associated with extensive tooth loss and the neurocircuitry associated with these behavioral alterations. Uncovering these details will provide potential therapeutic targets for negating the mental health difficulties associated with deficits in dental health.