bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging: a proof of principle study
Authors: Bowman Gene L. , Quinn Joseph F. , Shannon Jackilen , Dodge Hiroko , Frei Balz , Kaye Jeffrey , Howieson Diane 
Published: June 2021

Clinical trials of single or few nutrients to slow the progression or delay the onset of Alzheimer's disease have been unsuccessful. One explanation may be related to more minimal effects that nutrients have in isolation. However, rigorous methods to define the ideal set of nutrients to inform this view have remained elusive. We applied a data driven method to generate distinct nutrient patterns derived from biological markers of diet and tested their relationship with cognitive and neuroimaging outcomes.Thirty plasma nutrients were measured in 104 elders at risk for dementia. These nutrient biomarkers were selected on the basis of existing knowledge of association with neurodegeneration. Principle component analysis generated distinct nutrient biomarker patterns. Regression analysis tested cross sectional and longitudinal relationship with cognitive and MRI measures of brain aging.Mean age was 87 (SD±10) and 62% were women. Eight nutrient biomarker patterns met out inclusion criteria (eigenvalue > 1.0). Three NBPs (NBP1, NBP5, NBP8) were associated with cognitive and neuroimaging outcomes in cross sectional analysis. Two NBPs, one favorable (NBP1) and another unfavorable (NBP8) explained significant variance in rates of change in Clinical Dementia Rating – sum of box score over a mean of 1.8 years.Three distinct nutrient biomarker patterns were internally consistent. These may represent a successful formula of nutrition more capable of promoting cognitive health in people at high risk for Alzheimer's disease.
PROTEOMIC PROFILES OF DESMOID TUMORS AND OSTEOSARCOMA OF BONE AND SOMATIC SOFT TISSUE
Authors: RAO UMA N , CONRADS TOM P , HOOD BRIAN 
Published: June 2021

DESMOID TUMORS AND HIGH GRADE OSTEOSARCOMAS OF BONE AND SOMATIC SOFT TISSUE HAVE DISTINCT PROTEOMIC PROFILESProteomic analysis of recurrent but non metastasizing desmoid tumors, and osteosarcoma (OS) with known metastatic potential occurring in older individuals was performed to identify potential predictive marker proteins for drug resistance and prognosis. Archived samples from nineteen desmoid tumors and fourteen primary osteosarcoma occurring in soft tissue, bone were collected following IRB approval. Five micron thick sections were obtained from paraffin blocks of tumor and scraped, digested and analyzed by mass spectrometry. Protein abundances determined by spectral counting and used for hierarchical cluster analysis. Increase in HSP70, clusterin, emelin, creatine kinase B and carbonic anhydrase noted predominantly in OS. Results were validated for myoglobin and clusterin by immunohistochemical stains.. Proteins at higher abundance in OS relate to oxidative stress and hypoxia. HSP90 and clusterin may be markers of aggressive extraosseous osteosarcoma and may be indicative of drug resistance. The absence of these proteins in desmoids support their being considered benign locally recurrent tumors.
DepoFoam® Bupivacaine (EXPARELTM) is Compatible Following Lidocaine: Pharmacokinetic Study in Mini‐pigs
Authors: Richard Brigitte M , Rickert Doug E , Doolittle Danette , Mize Amy , Liu Jason , Lawson Charles F 
Published: June 2021

DepoFoam bupivacaine (DB; bupivacaine extended‐release liposome injection) is in development for prolonged postsurgical analgesia via wound infiltration (WI). Lidocaine with epinephrine (lido/epi) is commonly used for WI prior to surgery. DepoFoam product, DepoDur® can exchange its drug load with lido (ref. DepoDur® USPI) and we explored this potential with DB. Sixty (60) male Yucatan Swine were randomized into 20 groups (N=3/group). DB (2 or 4 mg/kg) and/or lidocaine HCl solution 1% or 2% (with epinephrine 1:200,000) were injected subcutaneously along a 5‐cm virtual incision line. Time intervals (5, 10, 20 or 40 minutes) between administration of lido/epi and DB were tested. Plasma concentrations of bupivacaine (bup) and lido were measured simultaneously by a LC‐MS/MS assay. Systemic exposure to lido was increased (AUC0–24hr by 48%; Cmax by 1,640%) when lido (4 mg/kg) was followed 5 minutes later by DB (4 mg/kg) compared to lido/epi alone. The systemic exposure to bup was increased (AUC0–24hr by 50 – 95%; Cmax by 67 – 1000%) when lido (4 mg/kg) was followed 5 or 10 minutes later by DB (4 mg/kg) compared to DB alone. While DB should not be admixed with lidocaine, this study shows that DB may be locally administered after at least 20 minutes following local administration of lido with minimal potential for a clinically relevant interaction. Source of ResearchSupport: Pacira Pharmaceuticals, Inc.
A STUDY ON CLINICAL PROFILE OF THE PATIENT PRESENTED WITH CEREBRAL VENOUS THROMBOSIS
Authors: nagarajan elanagan 
Published: June 2021

IntroductionPurpose of this study was to evaluate the clinical profile of the patients with cerebral venous thrombosis and to assess the risk factors involved.MethodsThis study was a retrospective study performed at Sri Ramachandra Medical Centre, Porur, Chennai and a total of 25 patients were reviewed. Clinical features, mode of onset, predisposing factors and CT/MRI findings were noted. All patients who were diagnosed to be having cerebral venous thrombosis were included in this study.ResultsMean age was 35.7 years (range, 15 to 70 years) with a male to female ratio of 13:12. Headache (84%) and convulsions (47%) were the most common clinical features. 44% of the patients had altered sensorium and 9.1% were comatose at the time of presentation. Focal neurological deficits were observed in 60% of the patients and hemiparesis was the common deficit, seen in 28% of the cases. Subacute presentation (52%) was the most common mode of onset followed by acute presentation (40%). Predisposing factors were identified in 72% of patients. Infection was identified as a risk factor in 28% cases. CT scans showed hemorrhagic infarcts in 32% of the patients. Superior sagittal sinus was the most frequent sinus involved, 68% had partial or complete occlusion of the superior sagittal sinus. There was no mortality in the present series.ConclusionThis study reports that cerebral venous thrombosis in developing countries particularly in rural area are no different from developed countries and needs to follow similar prevention and management.
Nerve Growth Factor (NGF) and Its Receptors in Skeletal Muscle Signaling
Authors: Ettinger Keren , Mizrachi Shlomit , Marcinkiewicz Cezary , Nevo Yoram , Lazarovici Philip 
Published: June 2021

The role of nerve growth factor (NGF) and its receptors in physiology of skeletal muscles has not been extensively studied. However, anti‐NGF transgenic mice expressed skeletal muscle damage resembling myopathy, implying that NGF plays an important role in muscle physiology. Our aim is to evaluate the role of NGF and its receptors in muscle, using C2C12 skeletal muscle cell line and wild type (WT) and homozygote dystrophic dy2J mice muscles.A similar mRNA expression for NGF and it receptors p75NTR and α9β1 integrin was found in C2C12 myoblasts and myotubes, while mRNA for trkA receptor was absent. In addition, C2C12 myoblasts secreted NGF to the media in an amount of 60pg/ml/24h, while NGF was not secreted by C2C12 myotubes. NGF treatment induced ERK1/2 stimulation in C2C12, an effect blocked by VLO5 (a disintegrin with relative selectivity towards α9 integrin). We also characterized mRNA expression of NGF, p75NTR, trkA and α9β1 integrin in WT and dy2J mice. We propose that NGF induced signaling in muscle cells is mediated by coupling of p75NTR and α9β1 integrin, as previously reported for glioma cells. Clarification of the role of NGF in muscle pathophysiology may provide novel understanding on the interaction between neurotrophins receptors and integrins towards possible development of novel drugs for muscle diseases.
Characterization of D3 dopamine receptor signaling in a PD mouse model
Authors: Cote Samantha Rae , Kuzhikandathil Eldo V 
Published: June 2021

The dopamine D3 receptor is known to couple to many signal transduction pathways and has been implicated in Parkinson's disease (PD). The D3 receptor exhibits a tolerance property wherein repeated stimulation elicits a progressively decreasing response. In vitro studies have shown that among others, the tolerance is observed in the D3 receptor‐Mitogen Activated Protein Kinase (MAPK) signal transduction pathway. PD patients on chronic levodopa treatment develop Levodopa Induced Dyskinesia (LID). In this study our objective was to test whether the D3 tolerance property exists in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) mouse model of PD. Drd3‐EGFP mice that report the expression of endogenous D3 receptor were used in this study. D3 receptor induced activation of the MAPK kinase pathway was determined in the striatum of control mice or mice treated chronically with levodopa, MPTP or MPTP + levodopa. MPTP treated mice exhibited increased MAPK phosphorylation when challenged with a D3 selective dose of PD128907. However, the MPTP group chronically treated with L‐dopa showed a decrease in phospho‐MAPK after administration of PD128907. These results suggest that in the mouse PD model chronically treated with levodopa, the tolerance property of D3 receptor might be involved.Supported by: Parkinson's Disease Foundation, NIH (MH82376) and the FM Kirby foundation grants
Mitochondrial respiratory capacity is decreased in muscle fibers from tumor‐bearing mice
Authors: Gilliam Laura A. A. , Cathey Brook , Lin Chien‐Te , Pittman H. Keith , Verbanac Kathryn M. , Neufer P. Darrell 
Published: June 2021

Debilitating muscle weakness and fatigue are common symptoms in cancer patients, the underlying cause of which is unknown. Compromised mitochondrial function can lead to persistent weakness in skeletal muscle. To determine if cancer alters skeletal muscle mitochondrial respiratory control/capacity and/or reactive oxygen species (ROS) production, C57BL6 male mice were injected with syngeneic Lewis lung carcinoma cells subcutaneously. Permeabilized fibers were prepared from the red gastrocnemius muscle 30 days post‐injection. Compared to controls, TB mice showed a significant (p<0.05) reduction in both complex I‐linked (mM: 5 glutamate/2 malate) basal (state 4) respiration (−54 ± 8 % change, mean ± SE) and maximal ADP‐stimulated (State 3) respiration (−51 ± 6 %, n=5). To examine the kinetics of complex I mediated respiration, we titrated in glutamate under maximal state 3 conditions. Surprisingly, the Km for glutamate was slightly decreased in TB mice (TB: 2 ± 9, CTRL: 4 ± 1, p<0.05), indicating improved sensitivity. In response to succinate titration during state 4 conditions supported by glutamate, preliminary data suggests mitochondrial H2O2 emitting potential is elevated in skeletal muscle from TB mice (+58 ± 23 %, n=4). Our findings suggest cancer compromises metabolic function in skeletal muscle, leading to a mitochondrial environment that increases the potential for electron leak and ROS generation.Supported by DK 073488
High throughput identification of compounds targeting influenza RNA dependent RNA polymerase activity
Authors: Su Ching-Yao , Wong Chi-Huey 
Published: June 2021

We developed an antiinfluenza screening strategy for a HTS campaign against a large compound library. The screening of a large library resulted in the identification of several classes of unique compounds that appear to inhibit influenza at different targets. Two of the identified antiinfluenza compounds inhibit influenza RdRP activities by targeting different subunit proteins. The compound 3061 (FA‐2) interacts with the NP, while the other antiinfluenza inhibitor, 367, prevents PB1 functions. It is conceivable that RdRP could be targeted at many different sites. Optimization of these compounds could result in the development of new antiinfluenza agents.Grant Funding Source: Academia Sinica
Effect of calcium intake on premenstrual symptoms
Authors: Ko Catherine , Burns-Whitmore B. , Spalding Thomas W. , Bidlack Wayne R. 
Published: June 2021

Reports suggest an association of calcium supplementation and reduced severity of premenstrual symptoms. The aims of our study were to: 1) evaluate the association between dietary calcium intake and the level of premenstrual stress 2) determine whether an intake of calcium above the Dietary Reference Intake would reduce premenstrual symptoms.Healthy, premenopausal women (19–45 years) were recruited. In the assessment phase (AP), premenstrual symptoms were documented over two menstrual cycles using a validated daily symptoms report, and five food records per person were collected.Calcium was provided in increments of 250mg to all participants with the intent to reach 1200mg/d. During the calcium supplementation phase (SP), participants recorded symptoms for two cycles. A median split was used to divide participants into either a high‐ or low‐symptom group. Mean affective scores (MAS) and mean somatic scores (MSS) were used to conduct regression analyses.Mean calcium intake increased from 614±195mg/d in AP to 1133±246mg/d in SP. No association was found between dietary calcium intake and level of affective or somatic premenstrual stress. After SP, a decrease of MAS was observed (p=0.07). The MSS was significantly lower after SP in the high symptom group (p=0.01). Calcium intakes slightly above the DRIs may be beneficial for women who experience mild to moderate premenstrual somatic symptoms.Grant Funding Source: none
Stunting rates in young children aged 6 to 23 months in infants and toddlers born in metropolitan Quetzaltenango, Guatemala
Authors: Reurings Marieke , Doak Colleen M , Vossenaar Marieke , Solomons Noel W 
Published: June 2021

BackgroundThe Guatemalan national prevalence of stunting (chronic undernutrition) in children up to 60 months is 54%, which is the fifth highest in the world. As the stunting process continues out through the third year, stunting rates through 24 mo would expected to be lower.ObjectiveTo describe the rate of stunting in a sample of infants and toddlers recruited in Metropolitan Quetzaltenango.MethodsA total of 300 young children (150 boys), ranging in age from 6 to 23 mo, equalized for months of life, were recruited at 2 public health clinics in metropolitan Quetzaltenango. Recumbent spine length and weight were measured according to standardized procedures and height‐for‐age (HAZ) were calculated. HAZ ≤2 SD of the WHO 2006 Growth Standards was considered stunting.ResultsThe overall mean HAZ‐score was −1.89±1.11 and 135 (45%) children were stunted. Children of women classified of Mayan ascent were significantly (p<0.001) shorter (HAZ‐score −2.20±1.03, and 54% stunted) than others (HAZ‐score −1.71±1.11, and 40% stunted).The age‐specific HAZ‐scores were −1.71±1.13, − 2.07±1.16 and −1.94±0.99 for the 6–11 mo, 12–17 mo and 18–23 mo old age groups, respectively and stunting rates were 36%, 54% and 48%, respectively.ConclusionStunting rates are high, progressing with aging through the first 2 years of life.Funded by Sight and Life, Switzerland
Obesity and Sedentary Life Style are not associated with increasing risk of Colorectal Cancer in Jordan
Authors: Waly Mostafa , Arafa Mostafa , Jriesat Sahar , Sallam Sunny , Al-Kafajei Ahmed 
Published: June 2021

MethodsA case‐control study included 440 Jordanian subjects (220 recently diagnosed CRC patients and 220 age and gender matched healthy subjects as a control group). The body mass index (BMI) was calculated for all study participants. The physical activity levels (low, moderate or high) were determined according to World Health Organization (Global Physical Activity Questionnaire) (WHO, Physical activity/GPAQ v2.0).ResultsThere were 220 (118 males and 102 females) CRC cases and 220 matched controls for age and gender. The CRC cases and controls were similar in age (56.3 ± 12.3 years for males and 53.7 ± 6.8 years for females) and gender (53.6 % males & 46.4% females). The mean BMI for all study participants was similar (ranged from 28 to 29.5). The CRC female and male patients and their matched controls had no significant difference with regards to BMI (P>0.05). CRC patients and controls had comparable low to moderate physical activity levels. All study subjects were not maintaining a routine exercise practice.ConclusionInconsistent with the reported studies at developed nations, our study indicated that obesity (BMI<30) and a trend of decreased physical activity were prevalent among the study subjects (patients and controls) with no significance differences.
Glucagon synthesizing alpha‐cells secret Islet Homeostasis protein (IHoP) for regulation of hormone synthesis and proliferation of insulin producing beta‐cells
Authors: Oh Seh-Hoon , Petersen Bryon E 
Published: June 2021

ObjectiveWe have identified a novel protein in bone marrow‐derived insulin‐producing cells. We now characterize a role for this protein, termed Islet Homeostasis Protein (IHoP), in the pancreatic islet.MethodsDetection of IHoP was performed using RT‐PCR, immunocytochemistry and in‐situ hybridization. IHoP functions were utilizing proliferation, insulin secretion by in vitro assays, and following siRNA protocols for suppression of IHoP.ResultsIHoP did not homologue with known pancreatic hormones. IHoP expression was seen in both BM‐derived IPCs and isolated pancreatic islets. Immunohistochemistry on pancreatic islet revealed that IHoP localized to the glucagon synthesizing alpha‐cells. Inhibition of IHoP by siRNA resulted in the loss of glucagon expression, which induced low blood glucose levels (63–85mg/dL). IHoP is secreted from the glucagon synthesizing α‐cells, and that it has a role in regulating cellular proliferation of beta‐cell under high glucose conditions. Subsequently, cellular apoptosis was observed throughout the islet, including the insulin‐producing beta‐cells. Islets of pre‐onset diabetic patients showed normal expression of IHoP and glucagon; however IHoP was lost upon onset of the disease.ConclusionThese data suggest that IHoP could be a new functional protein required in the homeostasis of the islet and it may also play a role in our understanding of T1D progression.
Impaired mTOR/S6 signaling pathway contributes to neurodegeneration in early postnatal Nbs1‐deficient mouse cerebral cortex
Authors: Liu Bo , Tong Wei-Min 
Published: June 2021

Nijmegen breakage syndrome (NBS) is a genomic instability disease caused by hypomorphic mutations of NBS1 gene encoding Nbs1 protein. The Nbs1 protein is a component of the Mre11/Rad50/Nbs1 (MRN) complex that acts as a DNA double‐strand break sensor and functions in response to DNA damage. We have generated a mouse model (termed as NbnCNS‐del mice) by inactivating Nbn gene in the mouse central nervous system (CNS) with nestin‐Cre system. Our previous study has indicated that the neurons in the cerebral cortex, hippocampus and thalamus of NbnCNS‐del mice displayed neurodegeneration changes that consist of size reduction, numerical decreasing and disorganization. However, the molecular mechanisms of the phenotype remain unknown. In the present study, we report that in cerebral cortical neurons, Nbs1 deficiency affects glial cell function, for the reduced expression level of nerve growth factor (NGF) mRNA and protein. In turn, altered glial cell function results in the down‐regulation of neuronal mTOR and S6 ribosomal protein expression in postnatal NbnCNS‐del mice. This result demonstrates that the interplay between neuron and glia contributes to the neurodegeneration, and implies an important role of DNA damage response in neuron.This work is supported in part by National Novel Drug Development Fund (2009ZX09303‐008), and by 111 project (B08007).
Adaptive Single Neuron Hypertensive Gene Expression Programs in the Nucleus Tractus Solitarius
Authors: Brureau Anthony Yannick Bernard , Vadigepalli Rajanikanth , Paton Julian , Schwaber James 
Published: June 2021

We describe the initial adaptive response process of single neurons following elevation of the blood pressure that identify processes that may evolve over time to alter central blood pressure set point control in neurogenic hypertension. Our initial approach is to study single A2 neurons in the nucleus tractus solitarius NTS. We then study the network of NTS A2 neurons with central amygdale (CeA) and ventrolateral medulla (VLM) by injecting Retrobeads in CeA and VLM in order to identify NTS A2 neurons with projections in this network. We lift NTS A2 neurons by Laser capture Microdissection while mapping their origin in the 3‐ dimensional NTS structure to assay several hundred neurons per brain. Our 96 qPCR gene expression assays are refined from previous global gene expression studies to select a cohort that appear co‐regulated and coordinated in response to blood pressure and relevant to the A2 phenotype and to the angiotensin II AT1R receptor activated responses. Analysis of the resulting high‐dimensional dataset reveals a remarkable complexity in the response to an increase of blood pressure. These results demonstrate differential expression programs for each anatomically distinct neuronal group and neuronal type.Research Support: NIH GM 083108
The Role of Brain Derived Neurotrophic Factor in Depression In a Mouse Model
Authors: Overacre Abigail , Sakata Kazuko 
Published: June 2021

BackgroundBrain derived neurotrophic factor(BDNF) levels have been thought to be a link to depression. It is not clear in which brain region BDNF mRNA levels are reduced in BDNF‐KIV mice. While BDNF gene expression is regulated by at least 9 promoters, promoter IV is of interest because it is suggested to be decreased in depressed patients.ObjectiveIn our research, we generated mutant mice that lack promoter IV‐driven BDNF expression and show depression‐like behavior (BDNF‐KIV). We aimed to determine 1) which brain regions show substantially decreased total BDNF mRNA levels, and 2) whether there is a correlation between brain and blood BDNF levels using the mouse model of depression. We also screened for what gene expression was affected by lack of promoter IV‐driven BDNF expression.MethodsMouse RNA was extracted from various neuroanatomical structures of the brain as well as PBMC cells in the blood using QIA‐Shredder and RNeasy column systems. A cDNA was prepared using the Transcriptor First Strand cDNA Synthesis Kit and a sample was preamplified using PreAmp Master Mix. A primer‐probe plate was designed to express genes, focusing on the BDNF exons. Gene expression was calculated with a reference gene, Cyclophilin D. The Biomark HD system by Fluidigm expressed the genes using qRT‐PCR, comparing BDNF levels with other genes in WT versus BDNF‐KIV mice.ResultsGene expression showed BDNF levels were lower in brain tissues of KIV mice than in WT mice, especially in the prefrontal cortex and hippocampus. BDNF levels were higher in PBMC cells of KIV mice in comparison with WT mice. The results were calculated directly from the gene expression in Exon IX.ConclusionBDNF levels are linked to depression and are found to be lower in KIV mice, especially in the PFC and the HIP. However, BDNF levels are reversed in PBMC cells, suggesting that BDNF levels in PBMC do not correlate to those in the brain and cannot be used as a biomarker of depression.