bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementing MR‐PRESSO and GCTA‐GSMR for pleiotropy assessment in Mendelian randomization studies from a practitioner's perspective
Authors: Ong Jue‐Sheng , MacGregor Stuart 
Published: May 2019

AbstractWith the advent of very large scale genome‐wide association studies (GWASs), the promise of Mendelian randomization (MR) has begun to be fulfilled. However, whilst GWASs have provided essential information on the single nucleotide polymorphisms (SNPs) associated with modifiable risk factors needed for MR, the availability of large numbers of SNP instruments raises issues of how best to use this information and how to deal with potential problems such as pleiotropy. Here we provide commentary on some of the recent advances in the MR analysis, including an overview of the different genetic architectures that are being uncovered for a variety of modifiable risk factors and how users ought to take that into consideration when designing MR studies.
Ultramafic–mafic and granitoids supra‐subduction magmatism in the southern Ashanti volcanic belt, Ghana: Evidence from geochemistry and Nd isotopes
Authors: Dampare Samuel B. , Shibata Tsugio , Asiedu Daniel K. , Okano Osamu , Osae Shiloh K.D. , Atta‐Peters David , Sakyi Patrick A. 
Published: May 2019

Geochemical and Nd isotope data are presented for Palaeoproterozoic ultramafic to mafic rocks and granitoids which are associated with volcanic rocks in the southern part of the Ashanti greenstone belts of Ghana. The Prince's Town granitoids display subduction‐zone geochemical features, with some showing signatures similar to high‐SiO2 adakites (HSA). Their initial εNd (2.1 Ga) values range from −1.01 to +2.92, and they have TDM2 of 2.17–2.51 Ga. The gabbros show slightly LREE‐depleted and ‐enriched patterns, Th–U troughs, negative Nb, Zr–Hf and Ti anomalies, spikes in Sr and Pb, have εNd (2.1 Ga) values ranging from −1.23 to +5.23, and TDM2 values from 2.08 to 2.57 Ga. The Ahama ultramafic body is characterized by two groups of pyroxenites. Both groups show LREE enrichment patterns, display Th–U and Nb–Ta troughs, minor or pronounced negative Zr–Hf and Ti anomalies. However, the Group I pyroxenites exhibit minor Ce anomalies and lower total REE contents (28.1–32.8 ppm) whereas Group II pyroxenites show significant negative Ce anomalies and relatively higher total REE contents of 57.1–124 ppm. The pyroxenites show negative initial εNd (2.1 Ga) values (−0.58 to −5.68) and have TDM2 values of 2.52 to 2.75 Ga. The pyroxenitic and gabbroic rocks were most likely originated from a subduction‐related lithospheric mantle. The Aketakyi ultramafic–mafic complex is made up of mainly cumulate dunite, harzburgite, pyroxenites, and gabbro. The rocks display LREE‐depleted to flat patterns with low total REE contents (1.71 to 22.3 ppm) and demonstrate a supra‐subduction affinity. They show high positive initial εNd (2.1 Ga) values (+3.69 to +4.93), and TDM2 values of 1.99 to 2.04 Ga, which suggest that they were derived from depleted mantle magmas and were juvenile at their time of formation. The Nd isotopic data provides evidence for a possible contamination of the juvenile Birimian crust of the southern Ashanti belt by some amount of a pre‐Birimian (or Archaean?) crustal material. The trace element and isotopic signatures as well as the field relations of the studied granitoids and mafic–ultramafic rocks show they were derived through supra‐subduction‐related magmatism during the Palaeoproterozoic.
The demand for season of birth
Authors: Clarke Damian , Oreffice Sonia , Quintana‐Domeque Climent 
Published: May 2019

SummaryWe study the determinants of season of birth for married women aged 20–45 in the USA, using birth certificate and Census data. We also elicit the willingness to pay for season of birth through discrete‐choice experiments implemented on the Amazon Mechanical Turk platform. We document that the probability of a spring first birth is significantly related to mother's age, education, race, ethnicity, smoking status during pregnancy, receiving WIC (Women, Infants & Children) food benefits during pregnancy, prepregnancy obesity, and the mother working in “education, training, and library” occupations; whereas among unmarried women without a father acknowledged on their child's birth certificate, all our findings are muted. A summer first birth does not depend on socioeconomic characteristics, although it is the most common birth season in the USA. Among married women aged 20–45, we estimate the average marginal willingness to pay (WTP) for a spring birth to be 877 USD. This implies a willingness to trade‐off 560 grams of birth weight in the normal range to achieve a spring birth. Finally, we estimate that an increase of 1,000 USD in the predicted marginal WTP for a spring birth is associated with a 15 pp (percentage points) increase in the probability of obtaining an actual spring birth.
Identification of potential microRNA markers related to Crimean‐Congo hemorrhagic fever disease
Authors: Arslan Serdal , Engin Aynur , Aydemir Eylem Itir , Sahin Nil Ozbilum , Bayyurt Burcu , Sari Ismail , Cosgun Yasemin , Bakir Mehmet 
Published: May 2019

AbstractCrimean‐Congo hemorrhagic fever (CCHF) is a tick‐borne disease caused by the arbovirus Crimean‐Congo hemorrhagic fever virus (CCHFV). The CCHFV has a single‐stranded RNA genome of negative sense. MicroRNAs (miRNAs) are key players in virus‐host interactions and viral pathogenesis. We investigated the miRNA gene expression profiles in patients with CCHF using microarray for the first time in the world. Microarray analysis was performed using mirBase Ver 21 (Agilent Technologies, Santa Clara, CA). All statistical analyses were performed across the case‐control, fatal‐control, and fatal‐nonfatal case groups using Genespring (Ver 3.0). Fifteen miRNAs were statistical significant in patients with CCHF compared with the controls (5 were upregulated, 10 were downregulated). Seventy‐five and sixty‐six miRNAs are in fatal compared with control and nonfatal case, respectively (fold change ([FC] ≥50) were statistically significant. In this study, the target genes of important miRNAs were identified and Gene Ontology analyses were performed across all groups. As a result of this study, we propose that the detection of miRNAs in patients with CCHF will allow the determination of therapeutic targets in diseases. CCHF is an important public health problem that can often be fatal. In this study, we investigated miRNA expression in case‐control, fatal‐control, and fatal‐nonfatal case groups. Significant miRNAs associated with fatality were detected in CCHF. This study will serve as a source of data for the development of an antagomir‐based therapy against CCHF using miRNAs in the future.
Exploring the relationship between sense of community and vigor in workplace community: The role of needs satisfaction and physical activity
Authors: Scotto di Luzio Silvia , Isoard‐Gautheur Sandrine , Ginoux Clément , Sarrazin Philippe 
Published: May 2019

AbstractThe present study aimed to increase understanding of well‐being in workplace community by examining a moderated mediated model including the test of the mediating effect of needs satisfaction, and the moderating effect of physical activity on the sense of community—vigor relationship, in a longitudinal perspective. The sample was composed of 95 workers (63.6% females) who completed an online survey three times during a 4‐month period. Results showed that the indirect effect of sense of community on vigor 4 months later, through satisfaction of need for relatedness, is significant among employees who practice a high level of moderate to vigorous physical activity. The ﬁndings suggest that (a) sense of community—conceived as a job resource—is responsible for needs satisfaction and may be considered an important component of the vigor process, and (b) that positive effects of physical activity can enhance employees' resource gains and recovery, favoring the experience of vigor in workplace community.
Tuftelin's involvement in embryonic development
Authors: Shilo Dekel , Blumenfeld Anat , Haze Amir , Sharon Shay , Goren Koby , Hanhan Salem , Gruenbaum‐Cohen Yael , Ornoy Asher , Deutsch Dan 
Published: May 2019

AbstractLittle is known about tuftelin expression in the developing embryo, previously it was thought to play a role in tooth enamel mineralization. In this study we show tuftelin's spatio‐temporal expression in mineralizing and nonmineralizing tissues of the craniofacial complex in the developing mouse embryo. Embryos aged E10.5−E18.5 and newborns aged P3 were used in this study. Polymerase chain reaction (PCR), Real‐time PCR, sequencing, and in‐situ hybridization were used to detect and quantify messenger RNA (mRNA) expression in different developmental stages. We applied indirect immunohistochemistry and western‐blot analyses to investigate protein expression. Two tuftelin mRNA transcripts and a single 64KDa protein were detected throughout embryonic development. Tuftelin was detected in tissues which develop from different embryonic origins; ectoderm, ectomesenchyme, and mesoderm. Tuftelin mRNA and protein were expressed already at E10.5, before the initiation of tooth formation and earlier than previously described. The expression pattern of tuftelin mRNA and protein exhibits dynamic spatio‐temporal changes in various tissues. Tuftelin is expressed in neuronal tissues, thus fitting with its described correlation to nerve growth factor. A shift between cytoplasmatic and perinuclear/nuclear expression implies a possible role in regulation of transcription. Recent studies showed tuftelin is induced under hypoxic conditions in‐vitro and in‐vivo, through the hypoxia‐inducible factor 1‐α pathway. These results led to the hypothesis that tuftelin is involved in adaptation to hypoxic conditions. The fact that much of mammalian embryogenesis occurs at O
2 concentrations of 1–5%, raises the possibility that tuftelin expression throughout development is due to its role in the adaptive mechanisms in response to hypoxia.
The p53 gene family in vertebrates: Evolutionary considerations
Authors: Biscotti Maria Assunta , Barucca Marco , Carducci Federica , Forconi Mariko , Canapa Adriana 
Published: May 2019

AbstractThe origin of the p53 gene family predates multicellular life since TP53 members of this gene family have been found in unicellular eukaryotes. In invertebrates one or two genes attributable to a TP53‐like or TP63/73‐like gene are present. The radiation into three genes, TP53, TP63, and TP73, has been reported as a vertebrate invention. TP53 is considered the “guardian of the genome” given its role in protecting cells against the DNA damage and cellular stressors. TP63 and TP73 play a role in epithelial development and neurogenesis, respectively. The evolution of the p53 gene family has been the subject of considerable analyses even if several questions remain still open. In this study we addressed the evolutionary history of the p53 gene family in vertebrates performing an extended microsyntenic investigation coupled with a phylogenetic analysis, together with protein domain organization and structure assessment. On the basis of our results we discussed a possible evolutionary scenario according to which a TP53/63/73 ancestor form gave rise to the current TP53 and a TP63/73 form, which in turn independently duplicated into two genes in agnathe and gnathostome lineages.
Reptile enamel matrix proteins: Selection, divergence, and functional constraint
Authors: Alazem Omar , Abramyan John 
Published: May 2019

AbstractThe three major enamel matrix proteins (EMPs): amelogenin (AMEL), ameloblastin (AMBN), and enamelin (ENAM), are intrinsically linked to tooth development in tetrapods. However, reptiles and mammals exhibit significant differences in dental patterning and development, potentially affecting how EMPs evolve in each group. In most reptiles, teeth are replaced continuously throughout life, while mammals have reduced replacement to only one or two generations. Reptiles also form structurally simple, aprismatic enamel while mammalian enamel is composed of highly organized hydroxyapatite prisms. These differences, combined with reported low sequence homology in reptiles, led us to predict that reptiles may experience lower selection pressure on their EMPs as compared with mammals. However, we found that like mammals, reptile EMPs are under moderate purifying selection, with some differences evident between AMEL, AMBN, and ENAM. We also demonstrate that sequence homology in reptile EMPs is closely associated with divergence times, with more recently diverged lineages exhibiting high homology, along with strong phylogenetic signal. Lastly, despite sequence divergence, none of the reptile species in our study exhibited mutations consistent with diseases that cause degeneration of enamel (e.g. amelogenesis imperfecta). Despite short tooth retention time and simplicity in enamel structure, reptile EMPs still exhibit purifying selection required to form durable enamel.
The characteristics of the ancient cell death suppressor, TMBIM6, and its related signaling pathways after endoplasmic reticulum stress
Authors: Doycheva Desislava , Kaur Harpreet , Tang Jiping , Zhang John H. 
Published: May 2019

AbstractActivation of the unfolded protein response in combination with generation of reactive oxygen species, from cytochrome P450 members and NADPH‐P450 reductases, are two major consequences of Endoplasmic Reticulum (ER) stress that cause oxidative damage and cell death. Herein, we reviewed the role of Bax Inhibitor‐1 (BI‐1), an evolutionarily conserved protein encoded by the Transmembrane Bax inhibitor Motif Containing 6 gene, in protection from ER stress. As BI‐1 has multimodal properties that can target a wide array of pathophysiological consequences after injury, our main objective was to explore BI‐1's protective role in ER stress and its potential signaling pathways.
Epigenetic mechanisms related to cognitive decline during aging
Authors: Harman María F. , Martín Mauricio G. 
Published: May 2019

AbstractCognitive decline is a hallmark of the aging nervous system, characterized by increasing memory loss and a deterioration of mental capacity, which in turn creates a favorable context for the development of neurodegenerative diseases. One of the most detrimental alterations that occur at the molecular level in the brain during aging is the modification of the epigenetic mechanisms that control gene expression. As a result of these epigenetic‐driven changes in the transcriptome most of the functions of the brain including synaptic plasticity, learning, and memory decline with aging. The epigenetic mechanisms altered during aging include DNA methylation, histone modifications, nucleosome remodeling, and microRNA‐mediated gene regulation. In this review, we examine the current evidence concerning the changes of epigenetic modifications together with the molecular mechanisms underlying impaired neuronal gene transcription during aging. Herein, we discuss the alterations of DNA methylation pattern that occur in old neurons. We will also describe the most prominent age‐related histone posttranslational modifications in the brain since changes in acetylation and methylation of specific lysine residues on H3 and H4 are associated to functional decline in the old. In addition, we discuss the role that changes in the levels of certain miRNAs would play in cognitive decline with aging. Finally, we provide an overview about the mechanisms either extrinsic or intrinsic that would trigger epigenetic changes in the aging brain, and the consequences of these changes, i.e., altered transcriptional profile and reactivation of transposable elements in old brain.
Supra‐optimal growth temperature exacerbates adverse effects of low Zn supply in wheat
Authors: Rehman Abdul , Farooq Muhammad , Asif Muhammad , Ozturk Levent 
Published: May 2019

AbstractRising temperatures are a major threat to global wheat production, particularly when accompanied by other abiotic stressors such as mineral nutrient deficiencies. This study aimed to quantify the effects of supra‐optimal temperature on growth, photosynthetic performance, and antioxidative responses in bread wheat cultivars grown under varied zinc (Zn) supply. Two bread wheat cultivars (Triticum aestivum L., cvs. Lasani‐2008 and Faisalabad‐2008) with varied responsiveness to Zn supply and drought tolerance were cultured in nutrient solution with low (0.1 µM) or adequate (1.0 µM) Zn under optimal (25/20°C day/night) or supra‐optimal (36/28°C day/night) temperature regimes. Supra‐optimal temperature severely reduced root but not shoot biomass, whereas low Zn reduced shoot as well as root biomass. Shoot‐to‐root biomass ratio was reduced under low Zn but increased under supra‐optimal temperature. Supra‐optimal temperature inhibited root elongation and volume particularly in plants supplied with low Zn. In both cultivars, Zn efficiency index was reduced by supra‐optimal temperature, whereas heat tolerance index was reduced by low Zn supply. Supra‐optimal temperature decreased photosynthesis, quantum yield, and chlorophyll density in low‐Zn but not in adequate‐Zn plants. In comparison, low Zn decreased specific activities of superoxide dismutase (SOD) and ascorbate peroxidase (APX) and increased glutathione reductase (GR), where supra‐optimal temperature increased SOD, decreased GR and did not change APX activity in leaves and roots. Moreover, supra‐optimal temperature severely reduced shoot Zn concentration and Zn uptake per plant specifically under adequate Zn supply. Overall, supra‐optimal temperature exacerbated adverse effects of low Zn supply, resulting in severe reductions in growth traits viz. shoot and root biomass, root length and volume, and consequently impeded Zn uptake, enhanced oxidative stress and impaired photosynthetic performance. Adequate Zn nutrition is crucial to prevent yield loss in wheat cultivated under supra‐optimal temperatures.
Postbiliary drainage rates of cholangitis are impacted by procedural technique for patients with supra‐ampullary cholangiocarcinoma: A SEER‐Medicare analysis
Authors: Kariya Christine M. , Wach Michael M. , Ruff Samantha M. , Ayabe Reed I. , Lo Winifred M. , Torres Madeline B. , Petrick Jessica L. , McNeel Timothy S. , Davis Jeremy L. , McGlynn Katherine A. , Hernandez Jonathan M. 
Published: May 2019

AbstractBackgroundThe optimal approach to biliary drainage for patients with supra‐ampullary cholangiocarcinoma remains undetermined. Violation of sphincter of Oddi results in bacterial colonization of bile ducts and may increase postdrainage infectious complications. We sought to determine if rates of cholangitis are affected by the type of drainage procedure.MethodsWe examined the Surveillance, Epidemiology, and End Results‐Medicare linked database from 1991 to 2013 for cholangiocarcinoma. Biliary drainage procedures were categorized as sphincter of Oddi violating (SOV) or sphincter of Oddi preserving (SOP). Patients were stratified by resection.ResultsA total of 1914 patients were included in the final analysis. A total of 1264 patients did not undergo a postdrainage resection (SOP 83, SOV 1181) while 650 did undergo a postdrainage resection (SOP 26, SOV 624). For those patients not undergoing a postdrainage resection, the rate of cholangitis 90 days after an SOP procedure was 19% compared with 34% in the SOV cohort (P = 0.007). For those patients undergoing a postdrainage resection, the rate of cholangitis 90 days after an SOP procedure was less than 42.3% compared with 30% in the SOV cohort (P = 0.66).ConclusionFor patients with supra‐ampullary cholangiocarcinoma that did not undergo resection, biliary drainage procedures that violated the sphincter of Oddi were associated with increased rates of cholangitis.
Trigeminocardiac reflex in pediatric adenotonsillectomy: A report of two cases with literature review
Authors: Li Lilun , Lin Connie , Peña Maria , Challa Chaitanya 
Published: May 2019

Trigeminocardiac reflex (TCR) is a physiological response that occurs due to stimulation of the trigeminal nerve, resulting in vagus nerve activation, parasympathetic dysrhythmia, and sympathetic hypotension. The pediatric population is vulnerable to TCR due to higher resting vagal tone, which can result in ischemia and death. This study reports two cases of TCR during adenotonsillectomy. Placement and rapid opening of a Crowe‐Davis retractor led to immediate bradycardia and hypotension in two children undergoing adenotonsillectomy, which resolved upon release of the retractor. Early intraoperative recognition of TCR with removal of mechanical stimulation can resolve vital instability without need for chemical intervention.Laryngoscope, 130:803–805, 2020
Preparation and Characterization of Novel Low‐Temperature/pH Dual‐Responsive Poly(N‐isopropylacrylamide‐co‐1H‐benzimidazolyl‐ethyl acrylate) Copolymers
Authors: Zhang Shu‐Gui , Ju Xiao‐Jie , Zhou Xing‐Long , Pu Xing‐Qun , Peng Han‐Yu , Wang Wei , Xie Rui , Liu Zhuang , Chu Liang‐Yin 
Published: May 2019

AbstractStimuli‐responsive polymers in response to both low temperature and pH are of great potential for designing drug carriers to obtain a better therapeutic effect during cryotherapy of tumors. In this work, novel low‐temperature and pH dual‐responsive poly(N‐isopropylacrylamide‐co‐1H‐benzimidazolyl‐ethyl acrylate) (PNBM) linear copolymers are developed, which can undergo stretching/shrinking conformational transition at low temperature and mildly acidic conditions. The dual‐responsive properties of PNBM copolymers can be affected and regulated by the host–guest inclusion action between benzimidazole and hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) molecules. The critical response temperature of the copolymers can be flexibly adjusted when the benzimidazole groups in copolymer chains are captured by HP‐β‐CD. And the PNBM copolymers present a pH‐responsive stretching‐to‐shrinking‐to‐stretching conformational transition in a narrow pH range in HP‐β‐CD solution. The results provide valuable guidance for designing and applying PNBM‐based smart materials in biomedical applications.
A familial case of pseudohypoaldosteronism type II (PHA2) with a novel mutation (D564N) in the acidic motif in WNK4
Authors: Sakoh Takashi , Sekine Akinari , Mori Takayasu , Mizuno Hiroki , Kawada Masahiro , Hiramatsu Rikako , Hasegawa Eiko , Hayami Noriko , Yamanouchi Masayuki , Suwabe Tatsuya , Sawa Naoki , Ubara Yoshifumi , Fujimaru Takuya , Sohara Eisei , Shinichi Uchida , Hoshino Junichi , Takaichi Kenmei 
Published: May 2019

AbstractBackgroundThere have been still few case reports of pseudohypoaldosteronism type II (PHA2), also known as Gordon's syndrome, genetically diagnosed, and this is the first report of familial PHA2 case in Japan with a novel D564N mutation in WNK4.MethodsA 29‐year‐old woman was admitted to our hospital due to hyperkalemia (serum potassium: 6.4 mmol/L). She had mild hypertension (135/91 mm Hg), a bicarbonate level at the lower limit of the normal range (HCO3: 22 mmol/L) with a normal anion gap, low plasma renin activity (0.2 ng ml‐1 hr‐1), and high urinary calcium excretion (505.4 mg/g Cre). A hereditary condition was suspected because her mother also had the same symptoms. We performed a comprehensive genetic analysis for major inherited kidney diseases with next‐generation sequencing including the genes responsible for PHA2 (WNK1, WNK4, KLHL3, and CUL3).ResultsGenetic analysis revealed that the patient and her mother had a novel missense mutation (D564N) in the acidic motif in WNK4, which leads to the diagnosis of PHA2. Administration of trichlormethiazide (1 mg/day) effectively ameliorated her blood pressure (114/69 mm Hg), plasma bicarbonate (25 mmol/L), serum potassium (4.3 mmol/L), and urinary calcium excretion (27.2 mg/g Cre).ConclusionWe report the first Japanese familial case of PHA2 with WNK4 mutation. D564N mutation in WNK4 is a novel genetic cause of PHA2 with a relatively mild phenotype.