bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immediate Improvements in Patellofemoral Pain Are Associated With Sagittal Plane Movement Training to Improve Use of Gluteus Maximus Muscle During Single Limb Landing
Authors: Atkins Lee T , James C Roger , Yang Hyung Suk , Sizer Phillip S , Brismée Jean-Michel , Sawyer Steven F , Powers Christopher M 
Published: June 2021

Abstract

Objective
The authors sought to examine the immediate effects of movement training aimed at improving use of gluteus maximus (GMAX) in the sagittal plane on hip internal rotation and self-reported patellofemoral pain (PFP) during single-limb landing.

Methods
Seventeen females with PFP participated. Lower extremity kinematics and kinetics, GMAX activation, and self-reported PFP were obtained before and after a single-session movement training program aimed at increasing the use of GMAX. Dependent variables of interest included self-reported PFP, average GMAX activation, average hip extensor moment, and peak hip internal rotation. Post-training changes were evaluated using paired t tests and Wilcoxon signed rank tests.

Results
Following movement training, self-reported PFP decreased significantly (mean [standard deviation]) (3.9 [1.1] vs 0.8 [1.3] on a 0–10 scale). Additionally, significant increases were observed for the average hip extensor moment (0.6 [0.3] vs 1.8 [0.4] Nm/kg) and average GMAX activation (41.0% [18.3] vs 51.6% [25.7] maximum voluntary isometric contraction), whereas peak hip internal rotation decreased significantly (8.5 degrees [5.8] vs 6.0 degrees [5.3]).

Conclusion
Movement training aimed at improving the use of GMAX in the sagittal plane resulted in clinically relevant changes in self-reported pain, GMAX activation, and hip kinetics and kinematics. Improving the use of GMAX during movement merits consideration when designing rehabilitation programs for females with PFP.

Impact
The current study highlights the clinical utility of movement training for persons with PFP and provides a biomechanical rationale for its use as a potential intervention in this population.
A clinical perspective on lifelong deglutition: What do we do when it does not work?
Authors: Skoretz Stacey A. 
Published: June 2021

Swallowing and breathing are two vital processes necessary to sustain human life. These acts require precise coordination given their biomechanical interdependence as characterized by their shared anatomy, neurophysiological regulation and function (Miller, Bieger, & Conklin, 1997; Shaw & Martino, 2013). Whether or not a swallow is competent is governed not only by the integrity of its anatomy but also by multiple factors including those that are: systemically mediated, part of the external environment or any combination thereof. As a result, the traditional swallowing phases, as they evolve over the lifespan of an individual, are best understood by taking a cross‐systems perspective (Martin‐Harris, Brodsky, et al., 2005; Matsuo & Palmer, 2009). This approach is the cornerstone of innovative assessment and management techniques for oropharyngeal dysphagia (or disordered swallowing), which supports subdivisions of the swallowing phases. This modern perspective affords the opportunity to ascertain the subtleties of the swallow's anatomical symbiosis with other processes, its intricate physiology all while opening the door to novel dysphagia intervention. This session will: 1) outline the anatomical and physiological differences between reflexive and volitional swallows, 2) explore a cross‐systems approach to understanding swallowing anatomy and physiology across the lifespan, and 3) review clinical cases that highlight the importance of anatomical and biomechanical integrity during swallowing.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Neovascularization in Pancreatic Cancer is Dependent on Neuropilin 2
Authors: Destin Orlane , Niclou Benoit , Li Xiaoran , Levonyak Nicholas , Jia Amy , Watnick Randy S. , Adam Rosalyn M. , Bielenberg Diane R. 
Published: June 2021

Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate due to lack of detection, tendency to metastasize to the liver, and the absence of effective treatments. Consequently, there is an urgent need to understand the biology of this devastating disease in order to develop drugs to inhibit PDAC progression. Neuropilin‐2 (Nrp2) is a transmembrane receptor that binds competitively to either the angiogenic ligand, Vascular Endothelial Growth Factor (VEGF), or the inhibitory protein, Semaphorin‐3F (SEMA3F). Nrp2 expression is quiescent in the normal adult blood vasculature, however the expression of Nrp2 is strongly upregulated in tumor‐associated neovessels in human and mouse xenograft models of PDAC. Nrp2‐deficient mice in the C57BL/6J background are viable with no obvious defects in the blood vascular system or signs of edema. Using immunohistochemistry to CD31, we compared the blood microvascular density (MVD) in the adult mouse pancreas of Nrp2+/+ wildtype mice and Nrp2−/− knockout (KO) mice and found no significant difference. However, when luciferase‐labeled syngeneic PDAC cells were injected orthotopically into the pancreas of Nrp2‐mutant mice, subsequent PDAC tumor growth was impeded in mice lacking Nrp2 compared to wildtype littermates. Additionally, PDAC tumors showed reduced tumor MVD in Nrp2‐deficient mice compared to PDAC tumors in Nrp2 wildtype littermates. Correspondingly, the incidence of liver metastasis was inhibited in mice lacking Nrp2 suggesting that tumor angiogenesis and metastasis is dependent on endothelial expression of Nrp2 in this PDAC model. Lastly, PDAC tumor cells do not express the VEGF Receptor 2 tyrosine kinase and therefore do not respond in vitro to VEGF stimulation. However, the Nrp2 inhibitory ligand, SEMA3F, was able to directly inhibit the migration of PDAC tumor cells in vitro. Taken together, our data suggests that Nrp2 may be an important receptor to target in both tumor cells and endothelial cells in PDAC. Our results suggest that targeted therapy to the NRP2 axis could be a potential treatment strategy to inhibit the growth and metastasis of pancreatic tumors.Support or Funding InformationNIH CA155728 (DRB)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
RAGE and SAGE: Ameliorating COPD Pathogenesis via RAGE Abrogation
Authors: Hirschi Kelsey M , Tsai K YF , Davis T , Llavina S , Stitton B , Clark C , Plothow E , Aanderlund‐Tanner H , Mella N , Arroyo J A , Reynolds P R 
Published: June 2021

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease involving chronic airway inflammation and emphysema. While primary smoke poses the greatest risk, evidence suggests nearly half of the US population is also at risk due to exposure to second hand smoke (SHS). In the present study, we used control, RAGE null, and lung‐specific RAGE overexpressing transgenic (TG) mice to study the role of RAGE during responses to SHS. We evaluated inflammatory effects of SHS in these mice with and without the administration of semi‐synthetic glycosaminoglycan ethers (SAGEs), a family of anionic, partially lipophilic sulfated polysaccharide derivatives known to inhibit RAGE signaling. Mice were weaned and fed doxycycline to induce RAGE in TG mice at PN30. Select mice were exposed to SHS from three Kentucky 3R4F research cigarettes via a nose‐only delivery system (Sireq Scientific, Montreal, Canada) five days a week and ip injections of PBS or SAGE (a 30mg/kg body weight) occurred three times per week from PN40‐70 before all mice were sacrificed on PN70. RAGE mRNA and protein expression was elevated following SHS exposure of control and TG mice and no expression was detected in RAGE null mice. Bronchoalveolar lavage fluid (BALF) analysis revealed RAGE‐mediated influence of inflammatory cell diapedesis and BALF protein abundance. A multiplex cytokine array was performed in order to precisely determine the secretion of pro‐inflammatory modulators into BALF. Lung histological assessment revealed indistinguishable morphological changes following exposure, yet apoptosis was increased in lung parenchyma. Thematically, inflammatory signaling intermediates and downstream responses induced by SHS exposure were influenced by the availability of RAGE, as evidenced by RAGE nulls and SAGE treatment. These data reveal fascinating data suggesting therapeutic potential for the use of RAGE inhibitors in lungs exposed to SHS smoke.Support or Funding InformationThis work was supported by a grant from the Flight Attendant's Medical Research Institute (FAMRI, PRR and JAA) and a BYU Mentoring Environment Grant (JAA and PRR).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
What can trabecular bone tell us about activity levels and self‐domestication?
Authors: Chirchir Habiba 
Published: June 2021

Various studies have compared trabecular bone fraction (i.e., TBF both volumetric and areal) among modern humans, great apes and fossil hominins and found that modern humans have gracile skeletons in having low TBF. This has been observed even among populations engaging in greater levels of activity such as foraging compared to farming. These findings raise questions about when and why the gracile human skeleton emerged. Although, sedentism has been proposed to explain this phenomenon, another hypothesis that may explain the unusually gracile modern human skeleton is the human self‐domestication (HSD) hypothesis. This hypothesis proposes that selection for prosociality among mammals with increased cognition resulted in changes in morphological features e.g., having a slight reduction in cranial capacity, a globular cranium, and thin cranial bones. In fact, other mammals thought to have undergone self‐domestication such as bonobos vs. chimpanzees, domestic dogs vs. wolves exhibit this trend in prosociality, and display differences in morphological traits such as feminization of the skull, and a reduction in cranial capacity among others. Thus, these observations provide an opportunity to test the HSD hypothesis. The present study tests this hypothesis first, by examining whether domestic dogs have low TBF (gracile skeletons) compared to their wild relatives: the wolves, foxes, and coyotes based on the understanding that domestic dogs are prosocial relative to their wild counterparts and therefore, would exhibit low TBF as a by‐product of selection for prosociality. Secondly, by estimating TBF in the human fossil record comparing hominins from the Pleistocene (early Homo and upper Paleolithic Homo), and recent modern humans from the Holocene. MicroCT and pQCT scanning were used to image proximal femora and humeri, which were then analyzed using Quant3D to quantify TBF. One‐way ANOVA with Tukey post‐hoc correction was used to identify differences among species. Results show that, indeed the domestic dogs across breeds studied exhibit low TBF compared to wolves and other canids. Secondly, that recent modern humans have low TBF compared to Pleistocene hominins. These results suggest that it is plausible that apart from sedentism, selection for prosociality may have had an effect on gracility, however, more work on other prosocial species that underwent self‐domestication needs to be done to further test this hypothesis and better understand the mechanisms responsible for it. These findings indicate that the highly gracile skeletons of modern humans and the increased risks of bone fracture associated with a decline in bone mass have evolutionary underpinnings‐ albeit relatively recent‐ than has been considered before.Support or Funding InformationNASA WV Space ConsortiumThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Connexin Gap Junction Proteins in Development and Disease
Authors: Laird Dale W 
Published: June 2021

Connexins form tightly‐regulated large‐pore channels that facilitate the passage of various ions, metabolites, and signaling molecules directly between cells, or in some cases and/or pathologies, to the extracellular milieu. The human connexin encoding gene family consists of 21 members and mutations in half of these genes leads to over two dozen diseases ranging in severity from manageable developmental abnormalities to life‐shortening organ failure. Developmentally, connexin expression and gap junctional intercellular communication begins at the 8 cell stage and persists throughout organogenesis resulting in most adult cells expressing two or more connexin subtypes. Connexin genes are exquisitely regulated during all developmental processes before birth, and in many tissues like the skin, after birth. Connexins regulate their function by channel gating processes and notably through their turnover owing to their short half‐life of only a few hours. Given their ubiquitous distribution it is not at all surprising that gene mutations lead to disease. In fact, it is probably more surprising that patients harbouring connexin gene mutations do not present with more clinical morbidities. Our laboratory has used tissue‐relevant cells, primary cells, organotypic cultures, mouse models of human diseases, and induced pluripotent stem cells from connexin‐linked disease patients to uncover ten distinct mechanisms by which connexin gene mutations cause disease. Collectively, connexin‐disease linked mutants have been classified into distinct gain‐ and loss‐of function molecular mechanisms of action. Our long‐term goals include developing strategies to compensate or overcome the cellular and tissue defects triggered by these mutants. This presentation will discuss how connexins have emerged as therapeutic targets in disease and in injury repair. We anticipate that once it is better understood how connexin gene mutations cause disease and abnormalities, which often present more acutely during aging, these findings could be translated into pre‐clinical studies leading to possible treatments for gap junction‐linked diseases.Support or Funding InformationSupported by the Canadian Institutes of Health Research.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Human cortical organoids from single iPSC‐derived neural rosettes for studying human cortical development and disorders
Authors: Shcheglovitov Alex , Wang Yueqi , Bell Laura , Russell Chad , Armstrong Celeste , Spampanato Jay 
Published: June 2021

Human cerebral cortex is the most complex brain structure implicated in many human‐specific behaviors and disorders. Genes important for the development and wiring of human cortex have often been found mutated in individuals with neurodevelopment disorders. Cerebral organoids generated from human embryonic and induced pluripotent stem cells have been used for modeling human‐specific aspects of cortical development; however, some variability‐ and maturation‐related issues prohibit the widespread use of these approach for disease modeling. We developed a new protocol for growing human cortical organoids from single stem cell‐derived neural rosettes and demonstrated that single‐rosette‐derived cortical organoids grow large in suspension culture, reaching 4–5 mm in diameter by 4 months, and consist of different types of properly organized neuronal cells, including cortical neural progenitors, deep and superficial cortical excitatory neurons, inhibitory neurons, and astrocytes. Using slice patch‐clamp electrophysiology, we show that many neurons in slices from single‐rosette‐derived cortical organoids fire repetitive action potentials, receive excitatory and inhibitory synaptic inputs, exhibit typical pyramidal‐like morphologies, and have dendritic spines. Our results indicate that single‐rosette‐derived cortical organoids can be used as a more robust experimental system for modeling human cortical development and disorders.Support or Funding InformationUtah Neuroscience Initiative Seed Grant, Whitehall Foundation, Brain Research Foundation, Brain and Behavior Research Foundation, NIMH, NINDSThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Discovery of Novel Mechanisms for Idiopathic Pain Disorders Through Genome Wide Approaches
Authors: Smith Shad B. 
Published: June 2021

This presentation will introduce an overview of recent findings of genetic variants associated with chronic pain, focusing on recent discoveries from a large cohort study of painful temporomandibular disorders (TMD), the leading cause of orofacial pain. The Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study was designed to identify risk factors for development of TMD. Recognized as a complex condition with biological and psychosocial risk factors, TMD has also been shown to have a substantial genetic component. Dr. Smith will discuss genome‐wide and bioinformatics approaches that have revealed etiological mechanisms underlying TMD, representing novel pathways of vulnerability. This work has implicated genetic variation associated with the presence of chronic pain, as well as polymorphisms associated with intermediate phenotypes known to be major risk factors for TMD development. Data from stratified analyses indicate certain pathways may be distinct between sexes. To understand the functional significance of these novel discoveries, additional behavioral and bioinformatics studies have been performed that show convergent lines of evidence pointing to immunological as well as neurological mechanisms. The state of knowledge about genetic contributors to orofacial pain and its management will be summarized with an emphasis on how these findings may be applied for personalized and targeted treatment of pain.Support or Funding InformationThis work was supported by the National Institute of Dental and Craniofacial Research (NIDCR) grant number U01DE017018, and by a K12 Biomedical Researcher Development Scholarship in TMJD and Orofacial Pain (K12DE022793).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Populations from under‐represented backgrounds are not adequately represented in clinical databases
Authors: Barnes Kathleen 
Published: June 2021

Personalized medicine (PM) is a field in medicine that leverages information about a patient's genes, environment and behavior to prevent, diagnose, and treat disease. Health care providers rely on publicly available genetic databases for recommendations for implementing PM. For example, the Clinical Pharmacogenetics Implementation Consortium (CPIC) makes recommendations for clinical implementation of pharmacogenetics tests by creating, curating, and sharing peer‐reviewed, evidence‐based and updated drug‐gene pair clinical practice guidelines. While most drugs with CPIC guidelines have at least some evidence based off of non‐European data, none have been exclusively developed for a specific ancestral group. Similarly, ClinVar, an NIH supported, freely accessible archive, reports relationships between genetic variation and disease phenotypes. However, these databases reflect a measurable bias toward genetic data based on European ancestry, owed in large part to the underrepresentation of non‐white populations in federally funded and published research programs, including genome wide association (GWAS) and whole genome sequencing studies, which in turn limits the ability to identify variants associated with disease and response to certain therapeutics. Inadequate representation further exacerbates existing health disparities. After over a decade of GWAS, non‐European, non‐Asian groups combined account for <4% of individuals represented in the international GWAS catalog. Previously the role that ancestry plays in variant prioritization approaches often implemented in genomic medicine (e.g., Human Gene Mutation Database, ClinVar) was explored and it was determined these databases are missing considerable African‐specific pathogenicity data. Recent developments through national and international initiatives have provided an opportunity to classify new genetic variants and reassess prior variant classifications and deposit this information into public databases. Approximately half of the NHLBI supported Trans‐Omics for Precision Medicine (TOPMed) program's samples represent non‐European samples. Similarly, the NHGRI Population Architecture using Genomics and Epidemiology (PAGE) study aims to better characterize how genetic factors influence susceptibility to disease in a multi‐ethnic dataset. Researchers representing both TOPMed and PAGE previously designed a commercially available multi‐ethnic genotyping array that was enriched with genetic variants representing underrepresented minority populations, which is being widely used, including institutional biobanks. Together, these developments promise to improve genomic diversity and subsequently benefit underrepresented minorities through personalized medicine.Support or Funding InformationNIH grant #HL104608This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
To Code or Not to Code: What Is the Linc?
Authors: Flavell Richard 
Published: June 2021

The annotation of the mammalian protein coding genome is incomplete. Arbitrary open reading frame (ORF) size restriction and the absolute requirement for a methionine codon as the sole initiator of translation, have constrained identification of potentially important transcripts with non‐canonical protein coding potential. Using unbiased transcriptomic approaches in macrophages responding to bacterial infection, we show widespread ribosome association with a large number of RNAs that were previously annotated as “non‐protein coding”. Although the ability of such non‐canonical ORFs to encode functional protein is controversial, we identify a plethora of novel short and non‐ATG initiated ORFs with the ability to generate stable and spatially distinct proteins. Importantly, we show that the translation of a novel ORF ‘hidden’ within the long non‐coding RNA Aw112010 is essential for the orchestration of mucosal immunity during both bacterial infection and colitis. Together this work expands our interpretation of the protein coding genome and demonstrates the critical nature of proteinaceous products generated from non‐canonical ORFs to the immune response in vivo. We therefore propose that the misannotation of non‐canonical ORF‐containing genes as non‐coding RNAs may obscure the essential role of a multitude of previously undiscovered protein coding genes in immunity and disease.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.