bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioinformatic analysis identifies potentially key differentially expressed genes in oncogenesis and progression of clear cell renal cell carcinoma
Authors: Zhang Haiping , Zou Jian , Yin Ying , Zhang Bo , Hu Yaling , Wang Jingjing , Mu Huijun
Published: November 2019

Clear cell renal cell carcinoma (ccRCC) is one of the most common and lethal types of cancer within the urinary system. Great efforts have been made to elucidate the pathogeny. However, the molecular mechanism of ccRCC is still not well understood. The aim of this study is to identify key genes in the carcinogenesis and progression of ccRCC. The mRNA microarray dataset GSE53757 was downloaded from the Gene Expression Omnibus database. The GSE53757 dataset contains tumor and matched paracancerous specimens from 72 ccRCC patients with clinical stage I to IV. The linear model of microarray data (limma) package in R language was used to identify differentially expressed genes (DEGs). The protein–protein interaction (PPI) network of the DEGs was constructed using the search tool for the retrieval of interacting genes (STRING). Subsequently, we visualized molecular interaction networks by Cytoscape software and analyzed modules with MCODE. A total of 1,284, 1,416, 1,610 and 1,185 up-regulated genes, and 932, 1,236, 1,006 and 929 down-regulated genes were identified from clinical stage I to IV ccRCC patients, respectively. The overlapping DEGs among the four clinical stages contain 870 up-regulated and 645 down-regulated genes. The enrichment analysis of DEGs in the top module was carried out with DAVID. The results showed the DEGs of the top module were mainly enriched in microtubule-based movement, mitotic cytokinesis and mitotic chromosome condensation. Eleven up-regulated genes and one down-regulated gene were identified as hub genes. Survival analysis showed the high expression of CENPE, KIF20A, KIF4A, MELK, NCAPG, NDC80, NUF2, TOP2A, TPX2 and UBE2C, and low expression of ACADM gene could be involved in the carcinogenesis, invasion or recurrence of ccRCC. Literature retrieval results showed the hub gene NDC80, CENPE and ACADM might be novel targets for the diagnosis, clinical treatment and prognosis of ccRCC. In conclusion, the findings of present study may help us understand the molecular mechanisms underlying the carcinogenesis and progression of ccRCC, and provide potential diagnostic, therapeutic and prognostic biomarkers.
Navigating oxygen deprivation: liver transcriptomic responses of the red eared slider turtle to environmental anoxia
Authors: Biggar Kyle K. , Zhang Jing , Storey Kenneth B.
Published: November 2019

The best facultative anaerobes among vertebrates are members of the generaTrachemys(pond slider turtles) andChrysemys(painted turtles), and are able to survive without oxygen for up to 12 to 18 weeks at ∼3 °C. In this study, we utilized RNAseq to profile the transcriptomic changes that take place in response to 20 hrs of anoxia at 5 °C in the liver of the red eared slide turtle (Trachemys scripta elegans). Sequencing reads were obtained from at least 18,169 different genes and represented a minimum 49x coverage of theC. picta belliiexome. A total of 3,105 genes showed statistically significant changes in gene expression between the two animal groups, of which 971 also exhibited a fold change equal to or greater than 50% of control normoxic values. This study also highlights a number of anoxia-responsive molecular pathways that are may be important to navigating anoxia survival. These pathways were enriched in mRNA found to significantly increase in response to anoxia and included molecular processes such as DNA damage repair and metabolic reprogramming. For example, our results indicate that the anoxic turtle may utilize succinate metabolism to yield a molecule of GTP in addition to the two molecules that results from lactate production, and agrees with other established models of anoxia tolerance. Collectively, our analysis provides a snapshot of the molecular landscape of the anoxic turtle and may provide hints into the how this animal is capable of surviving this extreme environmental stress.
Effects of the Interation of Metformin and Vernonia amygdalina (Bitter Leaf) On Steptozotocin-Induced Diabetic Rats
Authors: Oluwayemi A. T. , Nwachuku E. O. , Holy B.
Published: November 2019

The effects of Vernonia amygdalina and metformin in lowering glucose in streptozotocin-induced diabetic rats were evaluated. A total of 120 Wistar albino males and females rats weighing approximately 200 g were used for the study. Diabetes was induced in the rats using 50 mg/kg of streptozotocin, and it was confirmed by checking the glucose levels of the rats. Rats with glucose level greater than 10 mmol/L were considered diabetic. The extract, metformin and a combination of the extract and metformin were given orally to different groups of diabetic rats daily for 10 weeks. Four rats were sacrificed every 2 weeks, and blood samples were collected from all the groups to estimate glucose, total protein and liver enzymes. The data obtained were compared using analysis of variance (ANOVA) and the differences between groups were established using Dunnets. The extract and metformin produced significant (P<0.05) decrease in plasma glucose concentrations in the diabetic rats. There was also a reduction in the plasma glucose of the rats that received a combination of the extract and metformin. The decrease in the blood glucose concentrations of the diabetic rats following the administration of the extract suggests that it possesses hypoglycemic effects on streptozotocin-induced diabetic rats. The presence of flavonoids, saponins and other phytochemicals in the extract must have acted to potentiate the hypoglycemic role of the extract.
Molecular Characterization of Global Finger Millet (Eleusine coracana, L. Gaertn) germplasm Reaction to Striga in Kenya
Authors: Nyongesa Sirengo Peter , Simiyu Wamalwa Dennis , Chrispus Oduor , Achieng Odeny Damaris , George Dangasuk Otto
Published: November 2019

Finger millet (Eleusine coracana, L. Gaertn) is an important food crop in Africa and Asia. The parasitic weed Striga hermonthica (Del.) Benth limits finger millet production through reduced yield in agro-ecologies where they exist. The damage of Striga to cereal crops is more severe under drought and low soil fertility. This study aims to determine genetic basis for reaction to Striga hermonthica among the selected germplasm of finger millets through genotyping by sequencing (GBS). One hundred finger millet genotypes were evaluated for reaction to Striga hermonthica infestation under field conditions at Alupe and Kibos in Western Kenya. The experiment was laid out in a randomized complete block design (RCBD) consisting of 10 x 10 square (triple lattice) under Striga (inoculated) and no Striga conditions and plant growth monitored to maturity after 110 days. All genotypes were genotyped by genotyping by sequencing (GBS) and data analyzed using the non-reference based Universal Network Enabled Analysis Kit (UNEAK) pipeline. Genome wide association studies (GWAS) were done to establish the association of detected Single Nucleotide Polymorphisms (SNPs) with Striga reaction based on field results. In molecular analysis 117,542 SNPs from raw GBS data used in GWAS revealed that markers TP 85424 and TP 88244 were associated with Striga resistance in the 95 genotypes. Principal Component Analysis revealed that the first and third component axes accounted for 2.5 and 8% of total variance respectively and the genotypes were distributed according to their reaction to Striga weed. Genetic diversity analysis grouped the 95 accessions into three major clusters containing; 32 (A), 56 (B), and 7 (C) genotypes.  All finger millet genotypes that showed high resistance to Striga in the field were from cluster B while the most susceptible genotypes were from clusters A and C. Results revealed genetic variation for Striga resistance in cultivated finger millet genotypes and hence the possibility of marker –assisted breeding for resistance to Striga.
Dose-Dependent Chemopreventive Effect of Methanol Extract of Carica papaya Seed on Potassium Bromate- Induced Nephrotoxicity in Rats
Authors: Kanadi M. A. , Wudil A. M. , Alhassan A. J. , Ngwen A. L. , Yaradua A. I. , Nasir A.
Published: November 2019

Aim: To investigate the effect of Carica papaya seed extract on KBrO3 - induced nephrotoxicity in rats. Renal toxicity was induced by a single oral dose of 100 mg/kg body weight of KBrO3.

Study Design: Thirty (30) male albino rats were divided into six groups, five rats per group; normal control, KBrO3 control, papaya control and KBrO3 group administered with methanol seed extract of 200 mg/kg, 400 mg/kg and 600 mg/kg body weight for 48 hours.

Place and Duration of Study: Department of Biochemistry Laboratory, Faculty of Basic Medical Sciences, Bayero University Kano, Nigeria, from April 2018 to August 2018.

Methodology: Serum urea, creatinine, uric acid and electrolytes were determined using kits from randox laboratories. Furthermore, activities of renal brush border membrane marker enzymes namely γ-glutamyltransferase (GGT), alkaline phosphatase (ALP), maltase (Mal) and leucine aminopeptidase (LAP) and some parameters of oxidative stress including catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH) and malondialdehyde (MDA) were determined in homogenates prepared from renal cortex and medulla of the kidney of rats using colorimetric methods.

Results: Administration of KBrO3 significantly (P<0.05) increases the serum levels of urea, creatinine, uric acid and all electrolytes studied in a dose-dependent fashion from 200mg/kg to 400mg/kg and 600mg/kg in that order. Furthermore, the activities of GGT, ALP, Mal and LAP decrease in renal homogenates with KBrO3 administration. Also the activities of CAT, SOD, GPx and level of GSH decreases while the level of MDA significantly (P<0.05) increases however concurrent administration of Carica papaya seed extract prevented all the KBrO3- induced changes in the biochemical parameters studied .

Conclusion: It was suggested that methanol seed extract of Carica papaya possess nephroprotective effect against KBrO3 –induced renal toxicity and oxidative stress, and the most effective dose was 600 mg/kg body weight.
Cytotoxicity of N-(P-chlorophenyl)-7-hydroxycoumarin -3-yl carboxamide and Ethyl 7-hydroxycoumarin-3-yl Ester
Authors: Tmamm A. S. , Mohammed F. Z. , El-Deen I. M.
Published: November 2019

Background: Coumarins (2H-1-benzopyran-2-one), an important class of heterocyclic compounds, and its derivatives can be found in many natural or synthetic drug molecules and possess versatile bioactivities making them important molecules for medical practitioners and medicinal chemists.

Aims and Objective: Our study aims to evaluate cytotoxicity of new Coumarin derivatives: N-(P-chlorophenyl)-7-hydroxycoumarin-3-yl carboxamide (comp-3) and Ethyl 7-hydroxycoumarin-3-yl ester (comp-2) against four human cell lines such as human breast cancer (MCF-7), human liver cancer (HEPG-2), human colon cancer (HCT) and human prostate cancer cell (PC-3).

Methodology: The ethyl-7-hydroxycoumarin-3-ylester (comp-2) was prepared via cyclocon-densation of 2, 4-dihydroxybenzaldhyde with diethylmalonate in the presence of piperidine under fusion followed by Amonolyses with 4-chloro-aniline in the presence of acid medium under fusion produced the N-(4-chlorophenyl)-7-hydroxycoumarin-3-yl carboxamide (comp-3).

Result: The synthesized compounds have potent cytotoxicity against different tumor cell lines (MCF-7, HEPG-2, HCT, and PC-3).

Discussion: The compound N-(P-chlorophenyl)-7-hydroxycoumarin-3-yl carboxamide (comp-3) is better than Ethyl 7-hydroxycoumarin-3-yl ester (comp-2) because of the nature of the halogen atom (a chlorine or a bromine atom) in the ‘meta’ position of the phenyl ring relative to the ester oxygen atom of 2-oxo-2H-1-benzopyran- 3-carboxylate led to a better anti-tumor effect than that observed in the absence of any substituent.
Expression of PDCD1 (PD-1) Gene among Non-small Cell Lung Cancer (NSCLC) Patients with Real-Time PCR Application
Authors: Ahmadpanah Seyed Mohammad Amin , Ghanbari Mohammadreza , Janani Seyed Alireza , Nemati Fahimeh
Published: November 2019

Background: PD-L1 is the main ligand is expressed on many tumors including lung cancer and is expressed in hematopoietic cells and various leukemia. The aim of this study was to evaluate the expression of PD-1 gene and the evaluation of cancerous grades of NSCLC and its subclasses from lung cancer patients in Tehran hospitals using Real-Time PCR.

Materials and Methods: A total of 35 clinical samples were collected from patients with NSCLC-derived lung cancer from three hospitals in Tehran (Khatam Hospital, Athiyah Hospital, and Masih Hospital). Of the 35 samples collected in 2017, 20% of the patients were women and 80% of them were male. The range of patients’ age spectrum was 37 - 80 years. The disease grade of the patients in this study was varied and 22 different grades among them. To investigate the PDCD-1 gene expression level, after extraction of RNA and cDNA synthesis the Real-Time PCR was done and the expression of the gene was investigated.

Results: The highest grade was IIIa which contained 6 patients (17.1%). 74% of adenocarcinoma cases were in T-categories of lung cancer and 25% of patients were in grade IIIa. Patients with the grade of T3 were observed in 4 samples, 2 had adenocarcinoma and 2 with SCC with age range of 55 -62 years. The results showed that the expression of PDCD-1 increased 2.46 Fold more in patients with lung cancer than NSCLC.

Conclusion: The results of this study showed that there is a significant relationship between the PDCD1 or PD-1 expression of NSCLC-type lung cancer compared with healthy individuals, and using the RT-PCR for ease and rapidity it can be proved.
Extraction, Purification and Kinetic Study of Lactate Dehydrogenase of Male Chicken from Ebocha-oil Exploration Area, Nigeria
Authors: E. Esonu Chimdi , C. Onyeze G. O. , M. E. Iheanacho Kizito , N. Nwaogu Linus , Odirichukwu Simon-Peter
Published: November 2019

Aim: This study focused on the extraction, purification and kinetic studies of lactate dehydrogenase of male chickens from Ebocha oil exploration area, Imo state, Nigeria.

Methods: Twenty-one apparently healthy mature (6-9 months) male chickens (Gallus domesticus) from Ebocha oil exploration area, Imo State, Nigeria were screened for lactate dehydrogenase activity, thus accessing the level of chronic cell exposure to gas flaring. Their thigh muscle tissues were severed and investigated for lactate dehydrogenase activity using the standard method and sodium pyruvate as the substrate. Lactate dehydrogenase was isolated and purified by ammonium sulphate precipitation, desalted by dialysis and then gel filtration.

Results: The enzyme activity increased with advancement in the purification steps and was maximum using dialysis. The values for the lactate dehydrogenase activities were 103.43±3.27 U/L, 279.50±5.38 U/L, 318.16±13.08 U/L, 100.47±2.59 U/L, with a purification fold of 1, 3.7, 6.24 and 2.55 for the purification steps respectively. Also, the values of the protein concentrations were 0.071 mg/ml, 0.050 mg/ml, 0.035 mg/ml and 0.027 mg/ml (values for the crude enzyme, ammonium sulphate precipitation, dialysis and gel filtration respectively). The enzyme showed optimal activity at pH range of 5.5-6.5 and temperature of 30ºC-40ºC. Using sodium pyruvate as the substrate, with a fixed enzyme volume, an increase in the concentration of substrate resulted in increase in enzyme activity until a saturation point 0.3mM was reached. The apparent Km and Vmax values obtained were 0.01 mM and 0.12 U/mg/min. The Lineweaver-burk plot of the partially purified enzyme gave real Km and Vmax values of 0.20 mM and 0.16 U/mg/min respectively.

Conclusion: Partial purification procedures and biochemical properties of lactate dehydrogenase, from the muscle tissues of male chickens of Ebocha origin, gives room for more investigation on the metabolic shift caused by chronic exposure of the environment, humans and livestock to gas flaring and petroleum exploration.
Effects of Powdered Stem Bark of Terminalia avicennioides Made as Dietary Feed Fed to Mice Infected with Plasmodium berghei, on Liver Function
Authors: Owoloye Afolabi , Akanbi Olusegun Matthew , Bakare Oluwafemi Shittu
Published: November 2019

Aim: This study aimed to investigate the antiplasmodial activity and effect of stem bark of Terminalia avicennioides made as dietary feed fed to mice infected with Plasmodium berghei, on some serum biochemistry.

Methodology: Twenty (20) mice were divided into four groups. Group 1 was not infected with Plasmodium berghei (normal control), Group 2 was infected with P. berghei but not treated (negative control). Group 3 was infected and treated with 5.0 mg/kg of Arthemeter-Lumefantrine (positive control). Groups 4 was infected and fed with treated feed (T. avicennioides). Treatments were carried out for five days. Blood was taken daily from the tail of the mice before treatment for the assessment of parasitaemia. The animals were sacrificed on the fifth day and the whole blood was collected into EDTA bottle. Serum obtained was used to assay for biochemical parameters.

Results: Parasitaemia count was significantly lower (p<0.05) in all the treated groups when compared with the negative control group. The high-density lipoprotein was significantly higher (P<0.05) in the normal control (123.14±3.19) when compared with the positive control (99.18±2.76), negative control (85.29±0.85) and the group treated with T avicennioides (86.14±3.21). The serum alanine aminotransferase, alkaline phosphatase and aspartate aminotransferase level in the group treated with T. avicennioides (167.90±4.13, 15.87±1.32 and 17.50±1.95) respectively were significantly reduced (p<0.05) when compared with the negative control (197.25±5.44, 20.01±1.32 and 26.71±0.45) respectively. The mean bilirubin and albumin level in the negative control showed no significant difference when compared with the group fed with T. avicennioides.

Conclusion: The study concluded that T. avicennioides have antiplasmodial activity with a mild adverse effect on liver function.
Studies on the Phytochemical Compounds in the Ethanolic Leaf Extract (ELE), Ethanolic Bark Extract (EBE) and Ethanolic Root Extract (ERE) of Bridelia ferruginea Benth (Euphorbiaceae)
Authors: Attah Alfa Abdullahi , Ayodeji Orukotan Abimbola , Donatus Teru Goji Anthony , Bajeh Tijani Kokori
Published: November 2019

The phytochemical compounds of Bridelia ferruginea plant parts was carried out using qualitative method to determine the bioactive compounds present in the plant leave, stem bark and root extracts. The samples was weighed, of which 100 g each of the powder were extracted in solvents (ethanol) 1000 ml macerated and stand for 72 hours. The solvents contained in the maceration bottle was decanted and filtered using a filter paper, the filtration was aided using a suction pump. The filtrate was concentrated using a rotary evaporator and then transferred into thermostatic water cabinet (Temperature was set at 45oC), allowed to dry completely. The plant parts extracts were separately kept in a screw capped bottle for further research. The bioactive compound in the plant parts were detected. The result revealed that Carbohydrates, Saponins, Flavonoids, Tannins, Cardiac Glycosides, fats and oils were present. Alkaloid present in Dragendoff’s test in all plant parts extract but absent in Mayer’s test in only leaf extract. Terpenoids/Steroids present in Liebermann-Burchard’s test in all plant parts extract but absent in Salkowski’s test in only leaf extract. Anthraquinones were absent in all plant parts extracts using Bontrager’s test. Therefore, the presence of these phyto-pharmacological compounds is an indicative that the plant is medicinal and it can be used for the treatment of bacterial and other microbial infections. Further study can be done to separate the individual metabolites to test their antimicrobial activity against some pathogenic bacteria like bacterial meningitis, tuberculosis and syphilis to determine their potency.
Exomorphic Characters of Seeds of Some Species of Capparaceae Family in Taif, KSA
Authors: Al-Yasi Hatim M.
Published: November 2019

Seed exomorphic characters of six species belonging to four genera of family Capparaceae were studied using light microscope (LM) and scanning electron microscopy (SEM) in order to determine the importance of seed features as taxonomic evidence. These species are Cadaba farinosa Forssk, Capparis decidua (Forssk). Edgew, Capparis cartilaginea Decne, Dipterygium glaucum Decne, Maerua crassifolia Forssk and Maerua oblongifolia (Forssk.) A. Rich. The diagnostic characters at level of the general and specific level are shape of seed, size, color, texture and seed coat surface. There is a wide range of variations of seed shape among the studied species. LM revealed that the studied seeds are mostly varying from ovate to globose or cardiac- shape. All of the seeds lack wings except Dipterygium glaucum Decne. and most of the seed is coarse texture. There are six main types of seed surface sculptures revealed by SEM investigation at higher magnifications; reticulate, rugose-striate, winding undulate, ribbed and papillate.
Ginkgo Biloba as a New Medication for Resisting Dementia: A New Proposal
Authors: Lin Jyh-Woei
Published: November 2019

Ginkgo biloba has been used in traditional medicine, by which memory in the brain could be improved. In this study, a dementia patient has taken Ginkgo biloba during the time period of a year as a case study. He has taken a pill with 665 mg for a year from 08 November 2018 to 08 November 2019 (Taiwan Standard Time, TST). Later, the brain waves were largely different. However, he could only know his family name, the long term memory (LTM) could showed only a small recovery. The treatment outcome has been limited. Focusing on synapses in the brain can be a good way of interpreting the results. For future research, some new medications containing Ginkgo biloba can be devised for keeping a normal converting long-term potentiation (LTP) for healthy persons and for resisting dementia. The new proposal contributes to this study. Ginkgo biloba should be necessary as a pharmaceutical ingredient.
Protein structure determination using a Riemannian approach
Authors: Wei Xian , Li Zhi‐Cheng , Li Shi‐Jian , Peng Xu‐Biao , Zhao Qing
Published: November 2019

Protein NMR structure determination is one of the most extensively studied problems. Here, we adopt a novel method based on a matrix completion technique – the Riemannian approach – to rebuild the protein structure from the nuclear Overhauser effect distance restraints and the dihedral angle restraints. In comparison with the cyana method, the results generated via the Riemannian approach are more similar to the standard X‐ray crystallographic structures as a result of the simple but powerful internal calculation processing function. In addition, our results demonstrate that the Riemannian approach has a comparable or even better performance than the cyana method on other structural assessment metrics, including the stereochemical quality and restraint violations. The Riemannian approach software is available at: https://github.com/xubiaopeng/Protein_Recon_MCRiemman.
Smart Wide‐Bandgap Omnidirectional Reflector as an Effective Hole‐Injection Electrode for Deep‐UV Light‐Emitting Diodes
Authors: Lee Tae Ho , Park Tae Hoon , Shin Hee Woong , Maeda Noritoshi , Jo Masafumi , Hirayama Hideki , Kim Bo‐Hyun , Kim Tae Geun
Published: November 2019

Deep‐ultraviolet light‐emitting diodes (DUV‐LEDs) find widespread applications in various industries and are a focus area in environmental and life science research. However, the quantum efficiency of DUV‐LEDs is still low because of the unbalanced hole injection, high operation voltage, and low reflectivity of the p‐electrode. In this study, a smart wide‐bandgap omnidirectional reflector (ODR), which simultaneously acts as an effective hole‐injection electrode, is demonstrated for a flip‐chip DUV‐LED. The smart ODR is composed of p‐type AlGaN (p‐AlGaN)/Ni:AlN/Al with a high reflectivity of 94.2% at 280 nm, in which AlN with a theoretically calculated thickness of 40 nm is Ni‐doped using the pulsed electrical breakdown (PEBD) method. The smart ODR‐mounted AlGaN‐multiquantum‐well‐based DUV‐LED exhibits a remarkable wall‐plug efficiency (4.8%) and high external quantum efficiency (8.5%) at a low operation voltage of 9.75 V owing to the fused layer of Ni3N and Ga vacancies formed in the interfacial region of the p‐AlGaN and AlN layers, through the mutual diffusion of Ni and Ga during PEBD. The interface‐mediated Ohmic contact leads to an effective hole injection without reducing the reflectivity, yielding increased optical output and electric input powers. The proposed smart ODR can provide an innovative route for the manipulation of DUV light.
Selenenate Anions (PhSeO−) as Organocatalyst: Synthesis of trans‐Stilbenes and a PPV Derivative
Authors: Zheng Zhipeng , Trofymchuk Oleksandra S. , Kurogi Takashi , Varela Elena , Mindiola Daniel J. , Walsh Patrick J.
Published: November 2019

The selenenate anion (RSeO−) is introduced as an active organocatalyst for the dehydrohalogen coupling of benzyl halides to form trans‐stilbenes. It is shown that RSeO− is a more reactive catalyst than the previously reported sulfur analogues (sulfenate anion, RSO−) and selenolate anions (RSe−) in the aforementioned reaction. This catalytic system was also applied to the benzylic‐chloromethyl‐coupling polymerization (BCCP) of a bis‐chloromethyl arene to form ppv (poly(p‐phenylene vinylene))‐type polymers with high yields, Mn (average molecular weight) up to 13,000 and Đ (dispersity) of 1.15.

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The Keyword Effect: A Grounded Theory Study Exploring the Role of Keywords in Clinical Communication
Authors: Chan Michael W. , Eppich Walter J.
Published: November 2019

Objectives

Keywords, also known as “buzzwords” or “trigger words,” serve as memorable descriptors to associate physical findings with specific diagnoses. These terms, such as “target lesion” and “steeple sign,” liken a physical or radiographic finding to a nonmedical comparator as a means to elicit an associated diagnosis. Keywords permeate medical literature and clinical conversations. However, the potential for miscommunicating critical information exists and the impact of keywords on communication‐related medical error is unknown. We explored the use of keywords and how physicians perceive their use in their clinical communication as part of patient care.

Methods

With a grounded theory approach, semistructured interviews were completed in 2016 to 2017 with a purposive sample of 15 resident and attending physicians working in one pediatric emergency department, where clinical conversations occur frequently between providers of different specialties and levels of training. Constant comparative analysis for emergent themes was conducted. We identified key themes and examined their relationships to theorize how keywords affect clinical communication.

Results

We identified three major aspects: 1) keywords belong to the culture of medicine, by which providers connect with each other using specialized terms that imply a shared experience and knowledge base. This culture encourages keyword use. 2) By encapsulating a pattern of clinical findings into one word or short phrases, keywords allow for convenient, efficient communication of both diagnoses and of thought processes between providers. 3) Keywords, however, may mislead; if incorrectly applied to a given clinical situation, they may be misinterpreted by the receiver, or they may introduce bias to diagnostic decision making.

Conclusions

More than simple descriptors, keywords can communicate entire diagnoses and activate illness scripts between providers. Also, keywords are integral to the culture and language of medicine. However, providers should be aware of the potential negative effects of keywords in clinical conversations and must balance the demands of efficient and accurate communication with the potential for miscommunication and error.
TGDS pathogenic variants cause Catel‐Manzke syndrome without hyperphalangy
Authors: Boschann Felix , Stuurman Kyra E. , de Bruin Christiaan , van Slegtenhorst Marjon , van Duyvenvoorde Hermine A. , Kant Sarina G. , Ehmke Nadja
Published: November 2019

Catel‐Manzke syndrome, also known as micrognathia‐digital‐syndrome, is a rare autosomal recessive disorder characterized by the combination of the two cardinal features Pierre‐Robin sequence and bilateral hyperphalangy leading to ulnar clinodactyly (ulnar curvature of the phalanges) and radial deviation (radial angulation at the metacarpophalangeal joint) of the index fingers. Individuals without one of these major hallmarks or with additional hand malformations have been described as atypical or Catel‐Manzke‐like syndrome. Biallelic TGDS pathogenic variants have thus far been detected in eight individuals with typical Catel‐Manzke syndrome and in one fetus with additional features. Here we report on two individuals with TGDS pathogenic variants who presented with mild radial deviation and ulnar clinodactyly of the index fingers but without radiologic signs of hyperphalangy. Furthermore, both individuals have disproportionate short stature, a feature that has not yet been associated with Catel‐Manzke syndrome. Our data broaden the phenotypic spectrum of TGDS‐associated Catel‐Manzke syndrome and expand the indication for diagnostic testing.
Person‐reference in autism spectrum disorder: Developmental trends and the role of linguistic input
Authors: Barokova Mihaela , Tager‐Flusberg Helen
Published: November 2019

Past research has provided mixed evidence of the nature and difficulty with personal pronouns of children with autism spectrum disorder. No study to date has examined the nature of person‐reference in autism, more broadly, by looking at referential language both in terms of who is being referred to (self vs. other) and how (words with shifting reference: personal pronouns, vs. fixed reference: names and nouns). Furthermore, the role of linguistic input specifically in the domain of referential language in autism has not been investigated before. We collected natural language samples from parent–child interactions from children with autism (N = 38; 7 female) at three time points (age 2, 3, and 4 years) and administered a battery of standardized assessments to evaluate their language ability. The samples were transcribed and coded for person‐referential language. Children with autism used increasingly more pronouns both when referring to themselves and to their parent, but pronoun reversals were extremely rare. Their person‐reference use was associated with language ability only at age 2. Parental input was also characterized by an increase in pronoun use but only when referring to their child. Parents' and children's person‐reference were not associated across time, but they were concurrently related at age 3. Autism Res 2020, 13: 959‐969. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

In this study, we found that as children with autism grew older, they used more and more personal pronouns to refer both to themselves and their parents. Furthermore, they very rarely reversed their pronouns (used I instead of you) with only 1 child out of 38 making a pronoun error. This lack of pronoun errors suggests that pronoun difficulty in autism might not occur for long periods of time throughout development and might not be as prevalent in autism as previously thought.
Gender differences in combined homicide‐suicide with consideration of female terrorist bombers
Authors: Felthous Alan R. , Samantarai Sadhna , Mukhtar Assad
Published: November 2019

Combined homicide‐suicide (H‐S) is a phenomenon described as an offender committing a homicidal act followed by their suicide. Current literature on H‐S is dominated by a focus on men and their particular set of motivations and actions, primarily because females constitute only a small fraction of the cases of completed H‐S. This review begins by analyzing this data and integrating females within two subclassifications of H‐S: the psychopathology of the actor (or perpetrator), and the actor's relationship to her homicide victims. Within the relational subcategory of H‐S, females are: (1) underrepresented when victims are their spouses or intimate partners (consortial H‐S); (2) more prevalent when victims are their own children (filial H‐S); and (3) with rare exceptions, not represented in extrafamilial, adversarial and pseudo‐commando H‐S perpetrators. This review includes female bombers in this gender comparison.
CCN1 stimulated the osteoblasts via PTEN/AKT/GSK3β/cyclinD1 signal pathway in Myeloma Bone Disease
Authors: Yan Siyang , Liu Hui , Liu Zhaoyun , Peng Fengping , Jiang Fengjuan , Li Lijuan , Fu Rong
Published: November 2019

Backgrounds

Myeloma‐related bone disease (MBD) is a common complication of multiple myeloma (MM), which can both decrease life quality and influence the prognosis of the patients. We have found that CCN1 stimulated proliferation and differentiation of osteoblasts in MM in vitro and in vivo, while its mechanism still remains unknown.

Method

Bone marrow mononuclear cells were collected from MM patients and differentiated into the osteoblasts. After co‐culture with CCN1 in vitro, the intracellular signaling antibody array and western blot were performed to explore the signaling pathway. Furthermore, GSK3β inhibitor TWS119 was used to check the pathway of CCN1 might have on osteoblasts in vitro.

Results

For the protein array kit, the expressions of GSK3β, 4E‐BP1, and PTEN are decreased in CCN1 group. For western blots, the CCN1 group also has lower expression comparing to the control group in PTEN (P = .031). Meanwhile p‐AKT and cyclinD1 levels have increased in the CCN1 group (P = .002, P = .039). After adding TWS119 as another group, western blot was performed again to verify the pathway. For upstream proteins PTEN and p‐AKT, TWS119 group has higher expression level compared to that in CCN1 group (P = .003, P = .001). And for downstream protein cyclinD1, TWS119 group also presented higher level than the control group (P = .02). CCN1 could have almost the same effect on GSK3β as the specific inhibitor TWS119 had.

Conclusions

CCN1 can stimulate osteoblasts through PTEN/AKT/GSK3β/cyclinD1 pathway in MBD, which has the potential to be a novel therapy of MBD.
LncRNA MBNL1‐AS1 represses cell proliferation and enhances cell apoptosis via targeting miR‐135a‐5p/PHLPP2/FOXO1 axis in bladder cancer
Authors: Wei Xiaosong , Yang Xiaoming , Wang Beibei , Yang Yang , Fang Zhiwei , Yi Chengzhi , Shi Lei , Song Dongkui
Published: November 2019

LncRNAs have been shown to play essential roles in bladder cancer (BC) progress. Our microarrays of clinical samples firstly screened that lncRNA muscleblind‐like 1 antisense RNA 1 (MBNL1‐AS1) was poorly expressed in BC tissues. However, its biological function in BC remains not well understood. Here we examined the clinical correlations with MBNL1‐AS1 in BC patients. Then, 5673 and T24 cell lines were employed to investigate the role of MBNL1‐AS1 in the proliferation and apoptosis of BC cells in vitro and in vivo. Furthermore, miR‐135a‐5p (miR‐135a)/PHLPP2/FOXO1 axis was focused to explore its regulatory mechanism in BC. The results showed that MBNL1‐AS1 was significantly downregulated in bladder tumor tissues, and associated with BC progression. In vitro, MBNL1‐AS1 knockdown increased the number of viable cells and bromodeoxyuridine‐positive cells, accelerated cell cycle, and dysregulated proliferative regulators (Ki67, p21, p27, and Cyclin D1) in BC cells. The apoptotic cells and the cleavages of caspase‐3/9 were reduced in MBNL1‐AS1‐silenced BC cells. Overexpression of MBNL1‐AS1 had opposite effects on BC cell proliferation and apoptosis. Moreover miR‐135a was demonstrated to interact with MBNL1‐AS1, and inhibiting miR‐135a reversed the effects of shMBNL1‐AS1 on BC cells. The downstream effectors (PHLPP2 and FOXO1) were positively regulated by MBNL1‐AS1, but negatively regulated by miR‐135a. Similar results were also observed in xenograft tumors. In conclusion, this study firstly suggests that MBNL1‐AS1 acts as a tumor suppressor of BC by targeting miR‐135a/PHLPP2/FOXO1 axis, providing a novel insight for BC diagnosis and treatment.
Patterns of germline and somatic mutations in 16 genes associated with mismatch repair function or containing tandem repeat sequences
Authors: Chang Shih‐Ching , Lan Yuan‐Tzu , Lin Pei‐Ching , Yang Shung‐Haur , Lin Chien‐Hsing , Liang Wen‐Yi , Chen Wei‐Shone , Jiang Jeng‐Kai , Lin Jen‐Kou
Published: November 2019

Background

We assumed that targeted next‐generation sequencing (NGS) of mismatch repair‐associated genes could improve the detection of driving mutations in colorectal cancers (CRC) with microsatellite instability (MSI) and microsatellite alterations at selected tetranucleotide repeats (EMAST) and clarify the somatic mutation patterns of CRC subtypes.

Material and methods

DNAs from tumors and white blood cells were obtained from 81 patients with EMAST(+)/MSI‐high (MSI‐H), 78 patients with EMAST(+)/microsatellite stable (MSS), and 72 patients with EMAST(−)/MSI‐H. The germline and somatic mutations were analyzed with a 16‐genes NGS panel.

Results

In total, 284 germline mutations were identified in 161 patients. The most common mutations were in EPCAM (24.8%), MSH6 (24.2%), MLH1 (21.7%), and AXIN2 (21.7%). Germline mutations of AXIN2, POLE, POLD1, and TGFBR2 also resulted in EMAST and MSI. EMAST(+)/MSI‐H tumors had a significant higher mutation number (205.9 ± 95.2 mut/MB) than tumors that were only EMAST(+) or MSI‐H (118.6 ± 64.2 and 106.2 ± 54.5 mut/MB, respectively; both P < .001). In patients with AXIN2 germline mutations, the number of pathological somatic mutations in the tumors was significantly higher than those without AXIN2 germline mutations (176.7 ± 94.2 mut/MB vs 139.6 ± 85.0 mut/MB, P = .002).

Conclusion

Next‐generation sequencing could enhance the detection of familial CRC. The somatic mutation burden might result from not only the affected genes in germline mutations but also through the dysfunction of downstream effectors. The AXIN2 gene might associate with hypermutation in tumors. Further in vitro experiments to confirm the causal relationship is deserved.
The fallopian tube as origin of ovarian cancer: Change of diagnostic and preventive strategies
Authors: Kyo Satoru , Ishikawa Noriyoshi , Nakamura Kohei , Nakayama Kentaro
Published: November 2019

Ovarian cancer is the leading cause of gynecologic cancer death in the world, and its prevention and early diagnosis remain the key to its treatment, especially for high‐grade serous carcinoma (HGSC). Accumulating epidemiological and molecular evidence has shown that HGSC originates from fallopian tube secretory cells through serous tubal intraepithelial carcinoma. Comprehensive molecular analyses and mouse studies have uncovered the key driver events for serous carcinogenesis, providing novel molecular targets. Risk‐reducing bilateral salpingo‐oophorectomy (RRSO) has been proposed to reduce the subsequent occurrence of serous carcinoma in high‐risk patients with BRCA mutations. However, there is no management strategy for isolated precursors detected at RRSO, and the role of subsequent surgery or chemotherapy in preventing serous carcinoma remains unclear. Surgical menopause due to RRSO provides a variety of problems related to patients’ quality of life, and the risks and benefits of hormone replacement are under investigation, especially for women without a previous history of breast cancer. An additional surgical option, salpingectomy with delayed oophorectomy, has been proposed to prevent surgical menopause. The number of opportunistic salpingectomies at the time of surgery for benign disease to prevent the future occurrence of HGSC has increased worldwide. Thus, the changing concept of the origin of serous carcinoma has provided us a great opportunity to develop novel diagnostic and therapeutic approaches.
New Borrelidins from Onchidium sp. Associated Streptomyces olivaceus SCSIO LO13
Authors: Zhou Zhenbin , Wu Qiaoling , Xie Qing , Ling Chunyao , Zhang Hua , Sun Changli , Ju Jianhua
Published: November 2019

Borrelidins M−O (1–3), along with four previously known family members (4–7), were isolated from marine pulmonated mollusks Onchidium sp. associated Streptomyces olivaceus SCSIO LO13. The structures of 1–3 were elucidated by extensive spectral analyses of HR‐ESI‐MS, 1D and 2D NMR data. In addition, the cytotoxic and antibacterial activities of 1–7 were evaluated enabling us to propose some tentative structure‐activity relationships (SARs), especially those involving modifications at C(22) and the moieties at C(7) and C(8) of the borrelidin scaffold.
In silico and in vitro effects of the I30T mutation on myelin protein zero instability in the cell membrane
Authors: Ghanavatinejad Fatemeh , Pourteymourfard‐Tabrizi Zahra , Mahnam Karim , Doosti Abbas , Mehri‐Ghahfarrokhi Ameneh , Pourhadi Masoumeh , Azimeh Hosseini Sayedeh , Hashemzadeh Chaleshtori Morteza , Soltanzadeh Payam , Jami Mohammad‐Saeid
Published: November 2019

Charcot‐Marie‐Tooth (CMT) diseases are a heterogeneous group of genetic peripheral neuropathies caused by mutations in a variety of genes, which are involved in the development and maintenance of peripheral nerves. Myelin protein zero (MPZ) is expressed by Schwann cells, and MPZ mutations can lead to primarily demyelinating polyneuropathies including CMT type 1B. Different mutations demonstrate various forms of disease pathomechanisms, which may be beneficial in understanding the disease cellular pathology. Our molecular dynamics simulation study on the possible impacts of I30T mutation on the MPZ protein structure suggested a higher hydrophobicity and thus lower stability in the membranous structures. A study was also conducted to predict native/mutant MPZ interactions. To validate the results of the simulation study, the native and mutant forms of the MPZ protein were separately expressed in a cellular model, and the protein trafficking was chased down in a time course pattern. In vitro studies provided more evidence on the instability of the MPZ protein due to the mutation. In this study, qualitative and quantitative approaches were adopted to confirm the instability of mutant MPZ in cellular membranes.
Nicotinamide‐induced silencing of SIRT1 by miR‐22‐3p increases periodontal ligament stem cell proliferation and differentiation
Authors: Zheng Minqian , Guo Jianbin
Published: November 2019

Dental stem cell proliferation and osteoblast differentiation are key cellular processes involved in periodontitis diseases. Researchers have found that SIRT1 (sirtuin 1, silent mating type information regulation 2 homolog 1) and microRNAs play a pivotal role in the process, but a clear underlying mechanism has not been determined. In this study, the has‐miR‐22‐3p that target SIRT1 was predicted by TargetScan. Luciferase reporter assay was used to confirm that SIRT1 is the direct target of miR‐22‐3p. Importantly, miR‐22‐3p was revealed to control SIRT1 in periodontal ligament stem cell (PDLSC) and to regulate the proliferation and differentiation of PDLSC by SIRT1 silencing. Furthermore, we detected the induction of miR‐22‐3p expression by nicotinamide treatment on PDLSC. Induction of PDLSC proliferation and differentiation by nicotinamide treatment was blocked by miR‐22‐3p knockdown. These results suggested that the effect of nicotinamide on PDLSC is through miR‐22‐3p. In addition, miR‐22‐3p also upregulated the expression levels of the inflammatory cytokines tumor necrosis factor‐α, interleukin‐1β (IL‐1β), and IL‐8 in PDLSC through SIRT1 pathway and downregulated the expression of TLR‐2 and TLR‐4. miR‐22‐3p is a new target either for the treatment of periodontitis or the improvement of inflammation caused by orthodontics.
A One‐Pot Method to Synthesize a Co‐Based Graphene‐Like Structure Doped Carbon Material for the Oxygen Reduction Reaction
Authors: Peng Hongliang , Duan Diancheng , Tan Xiyou , Hu Fang , Ma Jiaojun , Zhang Kexiang , Xu Fen , Li Bin , Sun Lixian
Published: November 2019

The performance of the oxygen reduction reaction (ORR) is a core issue in of fuel cells. ORR is a slow kinetic process; platinum normally is used to accelerate the reaction. This is a bottleneck for further development of fuel cells. Transition metal and heteroatom co‐doped carbon materials have great potential in ORR catalysis. However, one‐step synthesis of high activity and stability transition metal and heteroatom co‐doped electrocatalysts is still a challenge. In this work, nitrogen, fluorine, and cobalt co‐doped carbon catalyst, MPCo‐950‐5, is prepared from melamine, polytetrafluoroethylene, and cobalt acetate by a one‐step method. MPCo‐950‐5 with a graphene‐like structure and its specific surface area is 642 m2 g−1. The ORR half‐wave potential of MPCo‐950‐5 is positively shifted by 35 mV compared to that of commercial Pt/C. In addition, MPCo‐950‐5 also shows excellent stability and methanol tolerance. This work serves as a simple and feasible method for preparing high ORR active transition metal and heteroatom co‐doped carbon materials.
Somatosensory corticospinal tract axons sprout within the cervical cord following a dorsal root/dorsal column spinal injury in the rat
Authors: McCann Margaret M. , Fisher Karen M. , Ahloy‐Dallaire Jamie , Darian‐Smith Corinna
Published: November 2019

The corticospinal tract (CST) is the major descending pathway controlling voluntary hand function in primates, and though less dominant, it mediates voluntary paw movements in rats. As with primates, the CST in rats originates from multiple (albeit fewer) cortical sites, and functionally different motor and somatosensory subcomponents terminate in different regions of the spinal gray matter. We recently reported in monkeys that following a combined cervical dorsal root/dorsal column lesion (DRL/DCL), both motor and S1 CSTs sprout well beyond their normal terminal range. The S1 CST sprouting response is particularly dramatic, indicating an important, if poorly understood, somatosensory role in the recovery process. As rats are used extensively to model spinal cord injury, we asked if the S1 CST response is conserved in rodents. Rats were divided into sham controls, and two groups surviving post‐lesion for ~6 and 10 weeks. A DRL/DCL was made to partially deafferent one paw. Behavioral testing showed a post‐lesion deficit and recovery over several weeks. Three weeks prior to ending the experiment, S1 cortex was mapped electrophysiologically, for tracer injection placement to determine S1 CST termination patterns within the cord. Synaptogenesis was also assessed for labeled S1 CST terminals within the dorsal horn. Our findings show that the affected S1 CST sprouts well beyond its normal range in response to a DRL/DCL, much as it does in macaque monkeys. This, along with evidence for increased synaptogenesis post‐lesion, indicates that CST terminal sprouting following a central sensory lesion, is a robust and conserved response.
AR CAPTCHA: Recognizing robot by augmented reality
Authors: Jin Xin , Han Rui , Duan Yuwei , Ning Ning , Li Xiaodong
Published: November 2019

We propose a novel AR CAPTCHA that first uses Augmented Reality to design CAPTCHA. Users should use their cameras on mobile devices to capture a marker in the 3D physical world or PC screens to find the appropriate angle to recognize each 3D character rendered on the marker in a 3D registration manner, which is very hard for machines or robots to do the same thing. Besides, we add many random 2D characters on the marker to make the state‐of‐the‐art scene text recognition methods fail to recognize the target 3D characters. To ensure availability, we design dual‐channel scenario setting (mobile phone and physical world) that enhances the security level of CAPTCHA and single‐channel scenario setting (mobile phone only) that the gyroscope could be used for our CAPTCHA. The experimental results reveal that the recognition accuracy of machines is nearly 0%, while a human could recognize AR CAPTCHA in only a few seconds.