bluuebunny/crossref_metadata_2025_split huggingface dataset:
A science mapping and scientometric study on the application of botanical agents to the research on testosterone
Authors: Sohn Eunsoo , Sohn Eun-Hwa 
Published: April 2020

Many physiological and pharmacological studies on testosterone(TS), the major male sex hormone, have been carried out over the past decades. This study aimed to quantify the research trend based on TS scientific publications in a 23‐yr period, and provide the quantitative estimates of the TS research associated with botanical agents(BA) using scientometric methods. Total 2,279 bibliographic records retrieved from the SCOPUS database from 1996 to 2018 were analyzed with Knowledge Matrix Plus, VOS viewer and Gephi software. We obtained science map derived from co‐word network analysis and identified TS research area related to BA. The results revealed that TS studies related to BA have concentrated on the modulating effect of BA on TS and TS metabolite levels in environmental, medical, and toxicological research field. The findings report that TS is highly related to risk assessment factors such as endocrine disruption exposed to pollution and wastewater in industrial, agricultural and livestock environments. In medical studies, spermatogenesis, testis, erectile dysfunction, and fertility studies have been observed in TS research involving BA. Research on the development of 5‐alpha‐reductase inhibitor for alopecia, and the regulation of bcl‐2 for carcinogenesis were also revealed. In toxicological studies, side effects of TS therapy for prostate cancer, hyperplasia, hepatotoxicity (cytochrome p450), and lipid peroxidation were investigated in a relatively higher frequency.Support or Funding InformationThis research was supported by Korea Institute of Science and Technology Information (KISTI) under the research program “Development of Future Technology Analysis System Based on Open Data”.
Urine metabolomics and proteomics for bladder cancer prediction by LC/MS based strategy
Authors: Tang Xiaoyue , Guo Zhengguang , Sun Haidan , Liu Xiaoyan , Liu Xiang , Li Jing , Lian Xiaoxiao , Zheng Shuxin 
Published: April 2020

Early diagnosis and life‐long surveillance are clinically important to improve the long‐term survival of bladder cancer (BCa) patients. Cystoscopy is considered the gold standard for the clinical diagnosis of human BCa. However, it is expensive and invasive. The objective of this study was to discover novel biomarkers to distinguish BCa from healthy controls, urothelium carcinoma and benign bladder lesions by LC‐MS based metabolomics and proteomics. We also tried to differentiate high‐grade and low‐grade BCa. A total of 234 subjects were enrolled, including 80 healthy adults, 22 benign patients, 26 urothelium carcinoma patients and 106 BCa patients (63 high‐grade BCa, 43 low‐grade BCa). The results showed that both urine metabolites and urine proteins could distinguish the BCa group from the healthy group, urothelium carcinoma group and benign bladder lesions group. And the combination of metabolites and proteins could achieve higher accuracy. Similarly, BCa clinical stages (high‐ vs. low‐grade BCa) could be better separated with a panel consisting of metabolites and proteins than either the metabolite panel or the protein panel alone. In conclusion, this study showed that urine proteomic and metabolic profiling were able to assist in the detection of BCa and grading distinguish.Support or Funding InformationNational Basic Research Program of China (No. 2013CB530805, 2014CBA02005)
An Initial Preparation for Cadaveric Dissection Ameliorates the Associated Mental distress of Human Cadaveric Dissection
Authors: Shaik Mustafa vali 
Published: April 2020

IntroductionIt is universally recognized that cadaveric dissection is an essential part of training in anatomy. However, it has also been reported to lead to mental distress in some students and can even impair their intrinsic motivation to study. One of the postulated reasons for this behavior is the lack of adequate information and preparation for cadaveric dissection. Hence it is hypothesized that providing relevant information prior to cadaveric dissection will ameliorate the mental distress of students, and improve in their academic performance.MethodsA cohort of Masters of Occupational Therapy students enrolled in an Anatomy course were provided with a curated list of journal articles and videos related to cadaveric dissection, prior to the start of the course. All students were also required to attend an oral presentation related to cadaveric dissection, immediately before commencing of dissection. The control group consisted of students who had not been provided any information or prepared for cadaveric dissection.ResultsWhen compared to the control group, students who had been prepared for cadaveric dissection reported a lesser degree of mental distress. In addition, they also demonstrated greater intrinsic motivation, and better quality of cadaveric dissection. Moreover, students reported the oral presentation to be most relevant and journal articles to be least useful in this regard.ConclusionHence preparation for cadaveric dissection is a valuable approach in the amelioration of mental distress and improvement of academic performance in anatomy students. Therefore, it is suggested that this approach could be a requisite in human anatomy.Support or Funding InformationJoydeep D Chaudhuri Joydeep D Chaudhuri, MD Associate Professor, School of Occupational Therapy 314 Commons Husson University, 1 College Circle Bangor, ME 04401 Tel: 207 8528747 Email:
chaudhurij@husson.edu
Improved Sonic Hedgehog Protein Autoprocessing Assay in Cells Using Luciferase Reporter System
Authors: Ciulla Daniel , Mancusi Rebecca , Psaras Alexandra , Ghotra Sahib , Callahan Brian 
Published: April 2020

Dysregulated cell signaling by Sonic hedgehog (Hh) proteins is implicated in developmental malformations and sporadic tumor growth. Biosynthesis of Sonic Hh requires cholesterolysis, a specialized autoprocessing event involving peptide‐bond cleavage and subsequent cholesterol modification. Cholesterolysis provides a potential site for targeted therapy. We are pursuing an in‐cell assay to monitor cholesterolysis activation and inhibition in multi‐well plates to improve on conventional techniques such as the Western Blot. Our chimeric reporter construct that fuses luciferase to human Sonic hedgehog cholesterolysis‐active domain (nLuc‐SHhC) appears to provide sensitive and quantitative measurement of cholesterolysis in HEK293 cells. Construct function was initially assessed by transient transfection. We are now preparing stable cell lines using CRISPR‐Cas9 system as a means for targeted gene insertion. Transient transfections demonstrate 5–10 fold difference in luciferase luminescence between catalytically active Sonic Hh and cholesterolysis‐defective mutant constructs. Wildtype construct yields a stronger luminescence in the supernatant, while the mutant Hh constructs show signal predominately in cell lysate. Additionally, stable cell lines show an even greater fold difference based on preliminary results. We intend to apply the reporter system introduced here for structure/function studies of cholesterolysis and for assessment of potential inhibitors targeting cholesterolysis.Support or Funding InformationFunding for this research has been graciously provided by National Cancer Institute (Grant R01 CA206592) and Department of Defense (Grant W81XWH‐14‐1‐0155).
High‐Throughput Matrix Synergy Screening Identifies Novel Therapeutic Combinations for Merkel Cell Carcinoma
Authors: Garman Khalid Ammar , Gelb Tara , Urban Daniel , Hall Matthew David , Brownell Isaac Franklin 
Published: April 2020

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer. The majority of MCC tumors are virus‐positive (VP‐MCC) with Merkel cell polyomavirus integrated into the host genome, whereas virus‐negative (VN‐MCC) tumors are associated with mutations induced by ultraviolet light exposure. Primary MCC is treated by surgical resection and radiotherapy. For metastatic MCC, conventional chemotherapy is ineffective, and although immune checkpoint inhibitors (ICI) can produce durable responses in some cases, many MCC patients cannot receive ICI and others have disease progression despite immunotherapy. To identify novel treatments for MCC, we performed high‐throughput small molecule screening of ~4,000 FDA‐approved and experimental drugs for their ability to reduce MCC viability in VP‐MCC and VN‐MCC cell lines relative to immortalized control cell lines. Drugs were grouped by target and ranked according to area under dose‐response curve (AUC). We identified navitoclax as selectively efficacious against VP‐MCC cell lines compared to VN‐MCC and controls. However, navitoclax use in the clinic is limited by a dose‐dependent thrombocytopenia. To identify drug combinations that will lower the effective dose of navitoclax and thereby decrease the risk of thrombocytopenia, we performed a synergy screen combining navitoclax with each of the 1912 clinically relevant compounds in the NCATS Mechanism Interrogation PlatE (MIPE) library. This combination study revealed synergistic effects between navitoclax and multiple drug categories. We are now testing high priority drug combinations for toxicity and efficacy in pre‐clinical xenograft models of MCC. Collectively, our study has identified novel therapeutic drug combinations for MCC with the potential for enhanced efficacy and lower side effect profiles. By focusing on repurposing approved drugs, these combinations will be immediately available to patients who fail ICI therapy.Support or Funding InformationNIH Intramural Research Program
Interactions of Estrogen and TRPM5 Channels in Fat Taste and Metabolism
Authors: Dahir Naima , Calder Ashley , Gilbertson Timothy A. 
Published: April 2020

Transient Receptor Potential channel type Melastatin 5 (TRPM5) is a nonselective cation channel that is activated by an increase in cytosolic calcium. TRPM5 channels are highly expressed in Type II taste receptor cells that transduce bitter, sweet, umami, and fatty acid compounds. While the function of TRPM5 channels is well‐defined in these cells, the effects of hormones such as estrogen on TRPM5‐mediated signaling that impact the taste system are not well known. We investigated TRPM5 channel activation in fatty acid‐sensing cells and the physiological impact in long‐term fat intake in males and females. This study followed from our earlier work where we showed a sex difference in TRPM5‐deficient (TRPM5−/−) animals and their wild type (WT) counterparts on a 60% high‐fat diet. We showed TRPM5−/− male mice were obese‐resistant compared to their WT counterparts. In comparison, TRPM5−/− females showed no drastic change in caloric intake but gained less body weight and body fat compared to the WT females. We found that removing the secretion of estrogen via ovariectomy in the TRPM5−/− females changed their weight status; they gained the same amount of weight and body fat as the WT females while not altering their caloric intake. At the taste cell level, we found that estrogen increased fatty acid‐induced Ca2+ responses in both TRPM5−/− and their WT counterparts. Interestingly, this difference was papillae‐specific in the TRPM5−/− females; circumvallate taste cells showed no increase in fatty acid responses when estrogen was present. Fungiform taste cells displayed a striking increase in cytosolic calcium in TRPM5−/− but not in WT females. Together, these results demonstrate a link between estrogen and TRPM5‐mediated signaling in feeding behavior and taste cells that is both sex and papillae‐specific. We are conducting additional experiments to better understand the mechanistic interactions between estrogen receptor activation and taste signaling via TRPM5 channels.Support or Funding InformationSupported by NIH DC013194 and DC013318 (tag)
ASIC1a plays a key role in evoking the metabolic component of the exercise pressor reflex in rats
Authors: Ducrocq Guillaume P. , Kim Joyce S. , Estrada Juan A. , Kaufman Marc P. 
Published: April 2020

The role of the acid‐sensing ion channel 1a (ASIC1a) in evoking the exercise pressor reflex is unknown despite the fact that ASIC1a is opened by decreases in pH in the physiological range. This fact prompted us to test the hypothesis that ASIC1a plays an important role in evoking the exercise pressor reflex in decerebrated rats with freely perfused hindlimb muscles. To test this hypothesis, we measured the effect of injecting two ASIC1a blockers into the arterial supply of the triceps surae muscles on the reflex pressor responses to four maneuvers, namely (1) static contraction of the triceps surae muscles (i.e., the exercise pressor reflex), (2) calcaneal tendon stretch, and (3) intra‐arterial injection of lactic acid and (4) diprotonated phosphate. We found that the two ASIC1a blockers, psalmotoxin‐1 (200 ng kg−1) and mambalgin‐1 (6.5 μg −1), decreased the pressor responses to static contraction as well as the peak pressor responses to injection of lactic acid and diprotonated phosphate. In contrast, neither ASIC1a blocker had any effect on the pressor responses to tendon stretch. Importantly, we found that ASIC1a blockade significantly decreased the pressor response to static contraction after a latency of at least 8 s. Our results support the hypothesis that ASIC1a plays a key role in evoking the metabolic component of the exercise pressor reflexSupport or Funding Information Funding for this study was provided by the National Institute of Arthritis and Muskuloskeletal and Skin Diseases (Grant R01‐AR‐059397) and National Heart, Lung, and Blood Institute (Grant P01‐HL‐134609).
HYPOXEMIA PREVENTS RECOVERY FOLLOWING FENTANYL OVERDOSE IN AWAKE AND SEDATED RATS
Authors: Guck Daniel , McCann Marissa , Tubbs Nicole , Haouzi Philippe 
Published: April 2020

BackgroundAs severe acute hypoxemia produces a rapid inhibition of the respiratory neuronal activity through a non‐opioid mechanism, we have investigated in adult rats the effects of hypoxemia following fentanyl overdose‐induced apnea on 1‐ auto‐resuscitation and 2‐ the antidotal effects of naloxone.MethodsIn unsedated rats, the breath‐by‐breath ventilatory and pulmonary gas exchange response to fentanyl overdose (300 mg.kg−1.min−1 iv in one minute) was determined in an open flow plethysmograph. The effects of inhaling air (9 rats) or a hypoxic mixture (FIO2 between 7.3 amd 11.3%, 8 rats) on the ability to recover a spontaneous breathing rhythm and on the effects of naloxone (2 mg/kg) were investigated. In addition, arterial blood gases, arterial blood pressure, ventilation and pulmonary gas exchange were determined in spontaneously breathing tracheostomized urethane‐anesthetized rats in response to 1‐ fentanyl induced hypoventilation (7 rats), 2‐ fentanyl induced apnea (10 rats) in air and hyperoxia, and 3‐ isolated anoxic exposure (6 rats).ResultsData are expressed as median and range. In the unsedated rat model, bolus fentanyl injection in air breathing produced an apnea within 14 seconds (12 – 29 seconds). A spontaneous rhythmic activity resumed after 85.4 s (33–141 seconds) consisting in a persistent low tidal volume and slow frequency rhythmic activity that rescued all animals. Naloxone at 10 minutes immediately restored the baseline level of ventilation. At FIO2 below 10%, fentanyl induced apnea was irreversible despite a transient gasping pattern, the administration of naloxone had no effects. In sedated rats, no spontaneous recovery of breathing occurred following fentanyl‐induced apnea, when PaO2 was lower than 16 mmHg, akin to the effects of hypoxemia alone. Naloxone had no rescuing effect on fentanyl‐induced apnea despite circulation being maintained.ConclusionHypoxia‐induced ventilatory depression during fentanyl induced apnea 1) opposes the spontaneous emergence of a respiratory rhythm, which would have rescued the animals otherwise, 2) prevents the effects of high dose naloxone.Support or Funding InformationNone
Interferon‐γ Induces PD‐L1 Expression in Ovarian Cancer Cells by JAK/STAT1 Signaling
Authors: Padmanabhan Sveta , Gaire Bijaya , de Leon Daniel , Vancura Ales , Vancurova Ivana 
Published: April 2020

Interferon‐γ (IFNγ) is a pleiotropic cytokine critical for immune functions and tumor immunity. Although IFNγ has been used in the treatment of different types of cancer, including ovarian cancer (OC), most clinical trials using IFNγ to treat solid tumors have produced mixed or disappointing results. Recent studies have shown that IFNγ induces expression of the immune checkpoint PD‐L1 in OC cells, resulting in their increased proliferation and tumor growth. However, the mechanisms that regulate the PD‐L1 expression in OC remain poorly understood. Since one of the main pathways induced by IFNγ is the JAK/STAT pathway, we investigated whether the IFNγ‐induced PD‐L1 expression in OC cells is regulated by JAK/STAT signaling. Here, we show that IFNγ induces STAT1 expression and STAT1 phosphorylation on Tyr‐701 and Ser‐727 in OC cells. In addition, JAK1 suppression significantly decreases the IFNγ‐induced PD‐L1 mRNA and protein levels in OC cells, demonstrating that the IFNγ‐induced PD‐L1 expression in OC cells is dependent on JAK1 activity. Together, our results indicate that the IFNγ‐induced PD‐L1 expression in OC cells is regulated by JAK/STAT1 signaling. Understanding the mechanisms of how IFNγ induces the PD‐L1 expression in OC cells will contribute to the development of therapeutic strategies aimed to increase the anti‐tumor effects of IFNγ, and modulate the levels of PD‐L1 in ovarian cancer.Support or Funding InformationNIH CA202775 grant
Choice of Hunting Method Influenced Human‐Carnivore Competition in Late Pleistocene Southeast Asia
Authors: Zachwieja Alexandra J , Bacon Anne-Marie , Nguyen Thi Mai Huong , Nguyen Anh Tuan , Sichanthongtip Phonephanh , Sayavongkhamdy Thongsa , Demeter Fabrice , Shackelford Laura L 
Published: April 2020

Competition has been investigated as a source of dispersal pressure in animal species both past and present. Particularly in Southeast Asia, where the Pleistocene carnivore guild remains largely intact to this day, there is a unique opportunity to assess the effects of competition on both dietary and spatial (dispersal) niche partitioning behavior in humans. Here, we investigate the relationship of early modern humans to local carnivores during their likely period of dispersal through Laos and Vietnam (~80‐50ka) to – for the first time – assess humans as a member of a local carnivore guild. By using the Competition Index (CI), a method which has shown success in predicting competitive pressure in island Southeast Asian paleontological communities on a scale of 0 (no competition) to 1 (full prey overlap, maximum competition). We approach this research with a purposeful desire to remove the “bias of human exceptionalism” from our analysis, treating humans as another medium size animal. We find that humans definitively were subject to competitive pressure from concurrent carnivores, particularly medium‐size prey specialists like hyenas, dholes, and leopards (Max CI: 0.6, 0.5, 0.66 respectively). Additionally, we find that the estimated competitive pressure on humans changes accounting for hunting method (solo ambush vs. group hunting), with group hunting practices reducing competitive pressure for medium‐size prey, particularly from leopards. We suggest that hunting behavior may have been used along with dietary and spatial partitioning as a strategy to reduce competitive pressure during initial human dispersal in Southeast Asia and that biotic interactions should not be overlooked in studies of human dispersal in this region.Support or Funding InformationFunding for this work was provided by: National Geographic Early Career Grant #EC‐378R‐18, Wenner‐Gren Foundation Dissertation Fieldwork Grant, UIUC Anthropology Department, UIUC Graduate College, The Explorer’s Club Exploration Fund, and the Beckman Institute CS/AI Award.
Knockdown and Inhibition of SYK Tyrosine Kinase Decreases mTORC1 Activity and Enhances Lysosomal Biogenesis and Autolysosomal Maturation in Pancreatic Cancer Cell Lines
Authors: Pan Michelle , Hua Kevin , Villait Akash , Zuger Angelina , Rafati Minoo , Chen Ryan , Liu Sherry , Singh Anurag 
Published: April 2020

In cancer, oncogene dependency is a phenomenon where a dominant driver oncogene promotes tumor cell proliferation and survival, and loss of this oncogene results in tumor cell death and, eventually, tumor regression. KRAS, a GTPase that regulates cell growth and proliferation, is an oncogene constitutively activated in over 90% of pancreatic cancer. However, clinically effective inhibitors of KRAS have been unsuccessful so efforts have been focused on identifying other potential targets associated with the KRAS signaling network. Spleen tyrosine kinase (SYK), expressed at high levels in KRAS‐dependent pancreatic cancer cell lines, may be one of these targets. Our data indicate that SYK activates the mechanistic target of rapamycin kinase complex 1 (mTORC1), which promotes protein translation and cell growth. SYK activation also leads to decreased autolysosome count. In connecting SYK activation with increase mTORC1 activity and decrease autolysosome count, we hypothesis that the MiT/TFE transcription factors are involved. We propose that SYK inhibition in pancreatic cancer cells leads to reduced mTORC1 activity, which reduces phosphorylation of MiT/TFE transcription factors. The unphosphorylated MiT/TFE transcription factors are then allowed into the nucleus to activate genes for lysosomal biogenesis and autophagy. Autophagy is a process that recycles cellular macromolecules during nutrient deprivation by fusing autophagosomes and lysosomes, produced from lysosomal biogenesis, to generate autolysosomes. From our experiments, we were able to show that SYK inhibition blocks mTORC1‐dependent phosphorylation of MITF and TFEB transcription factors, members of the MiT/TFE family. MITF and TFEB activation leads to increased autophagy due to autolysosomal biogenesis and accumulation. In summary, our studies of the SYK‐mTORC1‐autophagy pathway provide support to investigate SYK as a candidate, therapeutic target for pancreatic cancer treatment.Support or Funding InformationNIH/NCI K99/R00 ‐ Anurag Singh (PI); Boston University Dahod Breast Cancer Pilot Award ‐ Anurag Singh (PI); Boston University's Undergraduate Research Opportunities Program ‐ Michelle Pan