bluuebunny/crossref_metadata_2025_split huggingface dataset:
CT Visualization of Vasculature Channels in Modern and Fossil Sloth Ungual Claws
Authors: Jones Jade , Grass Andy 
Published: May 2022

One of the interesting features of modern sloths is the vasculature patterns of their upper and lower limbs. Even though sloths are endothermic like other mammals, their mean body temperature tends to be lower, more variable, and more linked to the ambient temperature than other placental mammals. Like some other mammals from environments with temperature extremes, they possess rete arteriovenous bundles, which work as an effective heat exchange mechanism, where heat from distally flowing arterial blood is transferred to proximally flowing venous blood. This minimizes the heat loss from the extremities while still maintaining blood flow. The temperature gradient increases in the rete system when the animal’s core temperature decreases, which cools the limbs and preserves core body heat. When the body temperature rises the flow through the superficial venous system increases, which promotes heat loss and body cooling.This begs the question of how this complex vasculature system may or may not extend to the distal phalanges and claws of the sloth, perhaps their most distinctive feature. One possibility could be that to work with the limb cooling function of the rete system, the distal phalanx and claw may be poorly vascularized so as not to increase chances for heat loss. However, considering the extensive and important use of their claws, they may require extensive vascularization to withstand the large amount of stress they are often under. This study uses Micro CT scans of sloth ungual phalanges to visualize their vascular channels. In both modern and extinct giant ground sloths, vascular networks through the bone of the ungual phalanx are quite extensive, and are very clearly linked to externally visible channels and impressions left by the proper digital arteries. In ground sloths these internal vascular channels quickly branch on either side and continue distally, letting off smaller branches as they go. These channels are rather large, even appearing to be artificial drill holes on one specimen that has the distal end broken off. Modern sloths show a similar pattern, but their vascular channels take up proportionally less space in the bone than in the giant ground sloths. This difference may be due extinct giant ground sloths’ more varied use of their claws. These complex patterns show that sloth claws require a significant blood supply, and may indicate that the rete system is effective enough that by the time the arterial blood gets to the distal phalanx it has been sufficiently cooled to not be a significant source of heat loss.
Anatomical variations of the maxillary sinus and their relationship with pathologies of surrounding structures: A literature review
Authors: Orellana Mathias I. , Ávila Roberto H. , Gold Marjorie H. , Cariseo Carolina , Valenzuela Juan J. 
Published: May 2022

IntroductionAnatomically, the maxillary sinus (MS) and maxillary bone is a complex structure to study, due to its walls and its communication with different structures such as the respiratory system, upper teeth and the orbital cavity, specifically the floor of this cavity and the inferomedial region. The MS is a pneumatic cavity housed within the body of the mandible that communicates with the nasal cavity through the ostium at the middle nasal meatus.MethodsThis literature review seeks to describe the characteristics of the anatomical variations of the region of the maxillary sinus, The search process was carried out in the following databases; MEDLINE, SCIELO, WOS, CINHAL, SCOPUS and GOOGLE SCHOLAR, using as search terms; “Maxillary bone”, “Maxillary sinus”, “Paranasal sinus”, “Anatomical variations”, “Sinusitis” and “Clinical anatomy”.ResultsDifferent anatomical variations of the sinus and maxillary bone were found, being mainly the anterior and medial maxillary regions, those that presented the greatest number of variations in their walls or external and internal structures, from the clinical point of view, there are variations that can cause sinusitis, some types of tumors or affect neighboring structures that can be compromised by this variation.ConclusionThe results obtained in this review show that MS is a complex anatomical structure for its study, which is why it is also certainly complex to be able to distinguish the presence of anatomical variations or pathological abnormalities. Therefore, the knowing the different variations and the possible clinical relationship of these can be very useful for the clinical practice of medical personnel who are dedicated to this region.
Are Surface Models Obtained Using Different Methodologies Comparable?
Authors: Russell C. Kinley 
Published: May 2022

Surface models are used to quantify differences in form in a variety of anatomical analyses. Different methods for obtaining surface models are used across studies and multiple methodologies may be used within a single study. The number of methodologies available for the collection of surface data has multiplied in recent years. Though this presents an opportunity, it also presents a potential problem. Are surface models obtained using different methodologies comparable? Here I quantify surface distances between aligned surface models obtained using a blue light scanner and photogrammetry.Proximal tibiae from ten individuals were mounted to a rotating stand and scanned using an Artec Space Spider; surface models were automatically reconstructed using the real‐time fusion setting in Artec Studio 16. The same tibiae were photographed from 65 angles using a Canon Coolpix camera set to the macro setting. Photographs for each individual were masked and aligned to build a surface mesh using Agisoft Metashape. Artec scanner and photogrammetry surface models for each individual were imported into Avizo Lite. The photogrammetry model for each individual was scaled and aligned to the Artec model by iteratively minimizing surface distance between the models. Once surface alignment reached a stable configuration, surface distances from the Artec model to the photogrammetry model were calculated. Surface distances were also calculated between aligned pairs of individuals obtained using the Artec scanner.Surface distances between different individuals obtained using the same methodology were 73 times larger than those between models of the same individual obtained using different methodologies (p<0.001). Mean surface distance between models of the same individual was 0.020 mm and mean surface distance between models of different individuals was 1.477 mm. While surface distances exceeded 0.5 mm for approximately 75% of vertices in between individual comparisons, surface distances never exceeded 0.5 mm in comparisons of Artec scanner and photogrammetry derived models. These results suggest that surface models obtained using different methodologies are comparable, at least in this case.
Exercise‐induced Bronchoconstriction does not Change the Configuration of the Maximal Expiratory Flow‐Volume Curve in Adults with Asthma
Authors: Luu Peter , Klimenko Oksana , Klansky Andrew , Noggle Nathan , Petrics Greg , Haverkamp Hans C. 
Published: May 2022

BackgroundSeveral indices of airflow and volume derived from the maximal expiratory flow volume (MEFV) curve are used to identify and diagnose the severity of respiratory disease. In addition to the objective measures of expiratory airflow and volume, the shape of the MEFV curve is thought to provide information on pulmonary (patho)physiology. In the asthmatic, the MEFV curve is often convex relative to the volume axis (“scooped”). This “scooped” curve is thought to indicate heterogeneous airway emptying during the forced exhalation. The effect of exercise‐induced airway narrowing on the shape of the MEFV curve is not known. The purpose of this study was to determine the effect of exercise‐induced bronchoconstriction (EIB) on the shape of the MEFV curve in asthmatic adults. We hypothesized that the slope‐ratio (SR) index, and thus the overall shape of the MEFV curve would not be affected by EIB.MethodsAdult male and female asthmatics (n=9; age, 26.8 ± 8.4 yrs; BMI, 27.4 ± 4.3 kg/m2) and non‐asthmatics (n=9; age, 25.4 ± 7.8 yrs; BMI, 21.9 ± 2.0 kg/m2) completed a high‐intensity cycle ergometry bout for six minutes at 85% of peak power. Maximal forced exhalations (MFE) were performed before exercise. Following exercise cessation, subjects remained on the ergometer and performed a MFE every two‐minutes for a total 20 minutes. In each MEFV curve, the SR index was calculated in 1% volume increments between 20% and 80% of the vital capacity. To calculate SR, the tangent and chord slope were generated at each point of interest, and the tangent slope was divided by the chord slope.ResultsPulmonary function at baseline was lower in asthmatics compared to the control group (FEV1% predicted, 84.9 ± 11.0 vs. 96.5 ± 12.2% in asthmatics vs. control, respectively; P<0.05). In asthmatic subjects, post‐exercise nadir FEV1 decreased by 29.1 ± 13.7% from baseline (3.40 ± 0.74 to 2.47 ± 0.7 L for baseline and nadir, respectively; P<0.001), whereas FEV1 did not change after exercise in control subjects (3.84 ± 0.9 to 3.70 ± 0.8 L for baseline and nadir, respectively). At all time points, the average SR between 20 and 80% of vital capacity was significantly larger in asthmatic than control subjects (1.49 ± 0.02 vs. 1.23 ± 0.02 [SD] for asthma vs. control; P<0.005). However, in both control and asthmatic subjects, post‐exercise SR was not different from baseline at any time point. In asthmatic subjects, average SR between 20 and 80% of vital capacity was 1.49 ± 0.13 at baseline and averaged 1.49 ± 0.02 across all post‐exercise time points (range = 1.48 to 1.53).ConclusionIn this group of adults with asthma, EIB did not influence the SR index, indicating no change to the overall shape of the MEFV curve. Thus, these findings suggest that inhomogeneities in airway caliber and lung emptying are not magnified during an episode of EIB.
Fractionated Lichen Parmelia vagansExtract Exhibits Two distinct Antiproliferative Activities Against Human Cancer Cells
Authors: Bondarenko Vladimir , Kelley Laura , Argyle Daniel 
Published: May 2022

IntroductionApproximately one quarter of all prescription drugs contain active ingredients of plant origins. Lichens have been historically used to treat a multitude of ailments, ranging from headaches during the Middle Ages to dressing wounds before colonial times and much of the potency of lichen relies on the secondary metabolites they produce. The purpose of this project is to analyze antiproliferative properties of the secondary metabolites of lichen Parmelia vagans.MethodsLichen extracts were prepared using different organic solvents and further fractionated either by preparative TLC or by reverse‐phase chromatography. We assessed the antiproliferative activity of the fraction using human cancer cell lines. The same number of cells of different cell lines were plated into a 96‐well plate and allowed to adhere overnight. Next day, different dilutions of the enriched fractions were added to the adhered cells and the plate was placed in CO2 incubator for 24 hours. By the end of the incubation time a picture of each well was taken to assess cell confluency and morphology followed by Resazurin assay to analyze the effect of the lichen extract on cell growth and proliferation. After Resazurin assay, the cells in each well were treated with trypsin, suspended in growth medium and counted using Bio‐Rad cell counter to evaluate a percent of live cells.ResultsAssessment of antiproliferative activity of the TLC and reverse‐phase chromatography fractions revealed two separate peaks of inhibitory activity against cancer cell. The fraction obtained from P.vagans extract significantly suppress (30% ‐ 80%) the growth of human lung carcinoma A549. We also found that cancer cells treated by the lichen extracts results in their morphological changes that resemble an activation of apoptosis.DiscussionOur findings indicate that from P.vagans produces secondary metabolites that slow cancer cells growth and proliferation. Future experiments will be focused on isolation and identification of the compounds from P.vagans that are responsible for the inhibition of cancer cells growth. Another important aspect of the future research is to identify the cellular target(s) of the antiproliferative compound(s) and its molecular mechanism of action. I summary, the lichen’s secondary metabolites may hold a vast medicinal potential and could be a viable source of a novel of anticancer drugs.
Intestinal epithelial specific AhR deficient mice exhibit increased severity of experimentally induced chronic colitis
Authors: Qazi Aisha , Kumar Anoop , Sharma Anchal , Calzadilla Nathan , Weber Christopher R. , Mongan Kai , Saksena Seema , Dudeja Pradeep K. , Alrefai Waddah A. , Gill Ravinder K. 
Published: May 2022

Inflammatory Bowel Diseases (IBD), including Crohn’s Disease (CD) and ulcerative colitis (UC), are associated with chronic inflammation of the gastrointestinal tract. While it is a multifactorial disease, recently the aryl hydrocarbon receptor (AhR) has been identified as a susceptibility gene for IBD. AhR is a ubiquitously expressed transcription factor and its activation results in xenobiotic detoxification by CYP1A1 and CYP1B1, as well as induction of anti‐inflammatory pathways such as IL‐10 and IL‐22. In the gut, AhR is vital in maintaining immune cell populations, proliferation, and motility. Previous studies utilizing constitutive knock out of AhR in IECs showed exacerbated inflammation in acute DSS model. How intestinal epithelial cell (IEC) AhR deficiency impacts chronic colitis resembling human IBD is not yet known. Here, we investigated the effect of removing of IEC AhR in an inducible manner utilizing DSS induced chronic colitis (resembling Th1/Th17 and Th2 infiltration as seen in CD patients) and elucidated underlying mechanisms.MethodsAhRfl/fl x Villin‐CreERT mice received intraperitoneal injections of Tamoxifen (AhRΔIECKO) to induce knockout or the vehicle (WT) for 5 days. The mice were given water or 1.0% DSS for 5 weeks, alternating weekly with water. Distal colon tissue samples were taken for myeloperoxidase (MPO) assay, immunostaining, and histology to assess severity of inflammation. Additionally, distal colon mucosa samples were collected for mRNA and protein expression. Serum was used to assess levels of LPS through ELISA.ResultsAhRΔIECKOmice given DSS had increased severity of colitis as evidenced by i) a significant decrease in the colon length when compared to the WT given DSS; ii) an increase in mRNA expression of pro‐inflammatory cytokines, IFN‐ γ and IL‐1□; iii) an increase in MPO activity in the distal colon; iv) a significant increase in the spleen to body weight ratio; and v) a significant increase in histological scores. Interestingly, DSS treatment caused an increase in lipopolysaccharide (LPS) in the serum that was significantly higher in AhRΔIECKO as compared to WT indicative of increased paracellular permeability. There were no significant differences observed in the protein expression of Occludin, Claudin‐2, and ZO‐1 between AhRΔIECKO and WT DSS groups, however AhR KO mice given DSS had significantly increased phosphorylated ERK1/2 (pERK normalized to total ERK) levels which may contribute to the increased permeability and severity of inflammation.ConclusionDeletion of AhR from intestinal epithelial cells increases severity of chronic colitis associated with increased permeability possibly through ERK1/2 dependent mechanisms.
Preconditioning Exercise Protects Against Tumor‐Mediated Muscle Dysfunction in the Male Mouse
Authors: Parry Traci L. , Brantley Jason (TJ) , Tichy Louisa 
Published: May 2022

BackgroundCancer is associated with cardiac and skeletal muscle wasting. While exercise has been shown to be myoprotective, less is known about the most effective “dose” of exercise in terms of intensity, timing, and duration. Therefore, the purpose of this study was to determine the effects of preconditioning exercise – exercise completedJ before tumor bearing ‐ as a protective measure for tumor‐mediated muscle wasting.MethodsMale mice were randomly separated into four groups: sedentary non‐tumor bearing (SED+NT), sedentary tumor bearing (SED+T), treadmill exercise non‐tumor bearing (TM+NT), and treadmill exercise tumor bearing (TM+T). Mice underwent an 8‐week progressive treadmill exercise training protocol (TM) or remained sedentary (SED). At the end of the preconditioning treadmill training protocol, mice remained sedentary for 4 weeks. During this 4 week sedentary period, mice were implanted with tumor cells (T group; 1x105 LLC cells in flank) or remained non‐tumor (NT). To determine whether 8 weeks of exercise preconditioning could preserve cardiac and skeletal muscle function, mice underwent echocardiogram and grip strength analyses at baseline, 8‐week, and 12‐week time points.ResultsTumor bearing resulted in significant muscle dysfunction. SED+T showed a significant decrease in fractional shortening (p<0.05) and grip strength (p<0.05) when compared to all other groups. This coincided with SED+T’s significantly smaller heart masses and skeletal masses (p<0.05 vs to all other groups). Interestingly, preconditioning exercise (exercise prior to tumor bearing) appeared to offer myoprotection since TM groups were not significantly different from SED+NT for fractional shortening and grip strength (p>0.05). This data was in step with preserved heart mass and skeletal muscle mass in TM+T (p>0.05 vs SED+NT).ConclusionThese data indicate that exercise initiated prior to tumor bearing can protect the musculature from tumor‐mediated muscle dysfunction. This may be attributed to slowed muscle wasting as evidenced by maintenance of muscle mass in TM+T groups. These data make an important case for the long‐term benefits of an active lifestyle that last even after exercise is stopped (i.e., upon diagnosis and treatment). Such information is critical in elucidating the most effective “dose” of exercise for cancer survivors.
Keratinocyte‐associated Protein 3May Participate in the Stress Response to Impact Adiposity
Authors: Szalanczy Alexandria M. , Giorgio Gina , Goff Emily , Seshie Osborne , Grzybowski Michael , Klotz Jason , Roberts Mackenzie , Geurts Aron M. , Redei Eva E. , Solberg Woods Leah C. 
Published: May 2022

Although obesity rates have been steadily climbing the last few decades, the genetics underlying the disease are poorly understood. Previous work in our lab identified Keratinocyte‐associated protein 3(Krtcap3) as a candidate gene for adiposity. To characterize the role of Krtcap3in adiposity, we developed an in vivowhole‐body knock‐out (KO) rat model of Krtcap3,hypothesizing that KO rats would have greater adiposity compared to wild‐type (WT) rats.In our first in vivostudy, primarily occurring before the COVID‐19 shut down, we found that female KO rats have significantly increased food intake and fat mass compared to WT rats, supporting a role of Krtcap3in adiposity. We conducted a second study in 2020‐2021, when traffic in the vivarium was lighter due to COVID‐19, and were unable to replicate the initial differences in food intake or fat mass between WT and KO rats. Compared to Study 1, WT rats ate more and had a corresponding increase in adiposity, with no corresponding change in KO rats. We hypothesized that with decreased traffic the environment in Study 2 became less stressful for the WT rats, who then began to eat more. KO rats appeared to be resistant to the effects of chronic stress, and thus ate similar amounts between the two studies. Supporting this difference, measurements of corticosterone (CORT) in rats between Study 1 and Study 2 revealed that WT rats had increased CORT in Study 1 relative to Study 2, with no differences in CORT between the studies for the KO rats.To determine if Krtcap3may be responsive to stress, we measured Krtcap3expression in key stress response tissues between unstressed rats and rats injected with a high dose of CORT (40 mg/kg). We found that Krtcap3is highly expressed in the pituitary gland, with expression significantly decreased following the CORT injection. Although expression of Krtcap3is very low in blood, we also saw a significant decrease in Krtcap3expression in the blood after the CORT injection. In contrast, Krtcap3has low expression in the adrenal glands, with no change after the CORT injection. These results indicate that Krtcap3may play a role in the negative feedback regulation of the HPA axis, potentially explaining the differences in food intake and fat mass between studies 1 and 2 discussed above. Future studies will seek to confirm that decreased Krtcap3expression is protective against chronic stress, and that this can impact feeding behavior to influence adiposity.
Low‐Dose 6β‐Naltrexol Prevents Opioid Dependence Without Affecting Antinociception
Authors: Sadee Wolfgang , Oberdick John 
Published: May 2022

We asked whether opioid dependence can be prevented during opioid pain therapy or maintenance therapy of opioid use disorder. We hypothesize that 6β‐naltrexol (6BN) binds to the basally activated μ opioid receptor (MOR) prevalent in dependence and gradually reverts it to its resting state, proposing a novel MOR model (1). Clinical utility of opioid analgesics is compromised by adverse effects and addiction liability, largely mediated by MOR, which displays spontaneous basal activity. It’s upregulation by opioid agonists can contribute to opioid dependence. Acting as inverse MOR antagonists in the dependent state, naltrexone and naloxone cause withdrawal at exceedingly low doses. We had identified 6β‐naltrexol (6BN) as a neutral MOR antagonist, which blocks antinociception and causes withdrawal only at much higher doses, even though its MOR affinity equals that of naltrexone. Weak antagonist potency of 6BN is due to both its neutral antagonism and peripheral selectivity because of slow entry into the brain. Nevertheless, low‐dose 6BN (LD‐6BN; <0.1 mg/kg) potently prevents the development of dependence in adult guinea pigs treated with methadone (6BN IC50=~0.01 mg/kg), presumably a central effect (2). To test whether LD‐6BN establishes meaningful 6BN levels in the brain, we measure blood and brain levels with a highly sensitive mass spectrometry assay. Following an s.c. 6BN dose of 0.02 mg/kg in guinea pigs, blood levels initially exceed brain levels tenfold, consistent with its peripheral selectivity, followed by rapid elimination from blood (t1/2 ~1h). In contrast, 6BN levels increased over 2h and persisted in brain for 8h at 1‐2 nM levels (t1/2 ~5h). Co‐administration of a saturating naloxone dose reduced 6BN brain levels by ~70% at 1‐3h, indicating saturable high affinity binding. The results show that LD‐6BN reaches central opioid receptor sites by slow penetration and long retention in the brain, enabling a possible gradually reversal of upregulated basal MOR activity. LD‐6BN appears to act as a dependence modulator rather than a typical opioid antagonist, accounting for its prevention of opioid dependence during agonist treatment, and possibly other aspects of opioid addiction.1. W. Sadee, J. Oberdick, Z. Wang. Biased Opioid Antagonists as Modulators of Opioid Dependence: Opportunities to Improve Pain Therapy and Opioid Use Management. Molecules 25, 4163; doi:10.3390/molecules25184163 (2020)2. A. Safa, A.R. Lau, S., Aten, K. Schilling, K.L. Bales, V. Miller, J. Fitzgerald, M. Chen, K. Hill, K. Dzwigalski, K. Obrietan, M.A. Phelps, W. Sadee, J. Oberdick. Pharmacological prevention of neonatal opioid withdrawal in a pregnant guinea pig model. Front. Pharmacol, DOI: 10.3389/fphar.2020.613328 (2021)