bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is MTHFD1 polymorphism rs 2236225 (c.1958G>A) associated with the susceptibility of NSCL/P? A systematic review and meta-analysis
Authors: Zhao Huaxiang , Zhang Jieni , Zhang Mengqi , Deng Feng , Zheng Leilei , Zheng Hui , Chen Feng , Lin Jiuxiang 
Published: January 2016

Aims: To investigate the association between the methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) polymorphism rs 2236225 (c.1958G>A) and susceptibility to non-syndromic cleft of the lip and/or palate (NSCL/P).Methods: An extensive literature review has been conducted using PubMed, Web of Science, Cochrane Library, Google Scholar, the China National Knowledge Infrastructure (CNKI), and Wanfang Database for eligible researches. The terms for searching were “cleft lip OR cleft palate OR CLP OR CL/P OR oral facial cleft OR OFC” AND “methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1 OR methenyltetrahydrofolate cyclohydrolase formyltetrahydrofolate synthetase OR MTHFD1 OR MTHFD”. Two independent researchers screened, evaluated and extracted the data of included studies. The pooled odds ratios (OR) with 95% confidence intervals (95% CI) were calculated by random effects model under five gene models. Subgroup, sensitivity analysis and publication bias were also assessed.Results: Ten case-control studies have been included in the systematic review and eight studies have been considered for the meta-analysis. Overall, the MTHFD1 polymorphism rs2236225 and the risk of NSCL/P showed pooled OR (95% CI) of 1.02 (0.86-1.21) under allelic model. A higher degree of heterogeneity was observed in Asian countries (I2 = 75.6%) compared to non-Asian countries (I2 = 48.9%). Similar consequence appeared in the subgroup of children (I2 = 78.6%) compared with that of mothers (I2 = 0.0%). There was no significant difference in the publication bias by the Begg’s funnel plot (P = 0.711) and Egger’s regression test (P = 0.746).Conclusion: Our assessment suggested there was no significant association between the MTHFD1 polymorphism rs 2236225 (c.1958G>A) and the susceptibility to NSCL/P. Further investigations using a large sample size and a more advanced technique should be adopted to reach a more precise conclusion in the future.
Is IT Enough? Evidence from a Natural Experiment in India’s Agriculture Markets
Authors: Parker Chris , Ramdas Kamalini , Savva Nicos 
Published: January 2016

Access to information and communication technologies (ICTs) such as mobile phone networks is widely known to improve market efficiency. In this paper, we examine whether access to timely and accurate information provided through ICT applications has any additional impact. Using a detailed data set from Reuters Market Light (RML), a text message service in India that provides daily price information to market participants, we find that this information reduces the geographic price dispersion of crops in rural communities by an average of 12%, over and above access to mobile phone technology and other means of communication. To identify the effect of information on price dispersion, we exploit a natural experiment where bulk text messages were banned unexpectedly across India for 12 days in 2010. We find that besides reducing geographic price dispersion, RML also increases the rate at which prices converge across India over time. We discuss the implications of this for development organizations and information providers. This paper was accepted by Lorin Hitt, information systems.
On the Nonexclusivity of Loan Contracts: An Empirical Investigation
Authors: Degryse Hans , Ioannidou Vasso , von Schedvin Erik 
Published: January 2016

We study how a bank’s willingness to lend to a previously exclusive firm changes once the firm obtains a loan from another bank (“outside loan”) and breaks an exclusive relationship. Using a difference-in-difference analysis and a setting where outside loans are observable, we document that an outside loan triggers a decrease in the initial bank’s willingness to lend to the firm, i.e., outside loans are strategic substitutes. Consistent with concerns about coordination problems and higher indebtedness, we find that this reaction is more pronounced the larger the outside loan and it is muted if the initial bank’s existing and future loans retain seniority and are protected with valuable collateral. Our results give a benevolent role to transparency enabling banks to mitigate adverse effects from outside loans. The resulting substitute behavior may also act as a stabilizing force in credit markets limiting positive comovements between lenders, decreasing the possibility of credit freezes and financial crises. This paper was accepted by Itay Goldstein, finance.
Ectopic overexpression of Nanog induces tumorigenesis in non-tumorous fibroblasts
Authors: Park Yo Seph , Nemeño Judee Grace E. , Choi Na Young , Lee Jeong Ik , Ko Kisung , Choi Seung-Cheol , Kim Wan Seop , Han Dong Wook , Tapia Natalia , Ko Kinarm 
Published: January 2016

Abstract
Key regulatory genes in pluripotent stem cells are of interest not only as reprogramming factors but also as regulators driving tumorigenesis. Nanog is a transcription factor involved in the maintenance of embryonic stem cells and is one of the reprogramming factors along with Oct4, Sox2, and Lin28. Nanog expression has been detected in different types of tumors, and its expression is a poor prognosis for cancer patients. However, there is no clear evidence that Nanog is functionally involved in tumorigenesis. In this study, we induced overexpression of Nanog in mouse embryonic fibroblast cells and subsequently assessed their morphological changes, proliferation rate, and tumor formation ability. We found that Nanog overexpression induced immortalization of mouse embryonic fibroblast cells (MEFs) and increased their proliferation rate in vitro. We also found that formation of tumors after subcutaneous injection of retroviral-Nanog infected MEFs (N-MEFs) into athymic mouse. Cancer-related genes such as Bmi1 were expressed at high levels in N-MEFs. Hence, our results demonstrate that Nanog is able to transform normal somatic cells into tumor cells.
Caveolin-1 in Tumour Cells is Predominately Expressed in the Basal Subtype of Triple-Negative Breast Carcinoma
Authors: Popovska Savelina L. , Ivanov Ivan N. , Ooi Akishi 
Published: January 2016

Abstract
Triple-negative breast cancer (TNBC) is a subtype of breast cancer which is clinically negative for expression of steroid hormones and HER2 protein. According to DNA microarray profiling, breast cancer was divided into several molecular subgroups, including Luminal A and Luminal B; HER2 overexpressing; normal breast- like and basal-like subtype. TNBC comprises tumours that express heterogeneous molecular and immunohistochemical phenotype, thus determining different prognosis. The majority of TNBC carry the “basal-like” molecular profile on gene expression arrays. Basal-like carcinomas of the breast associated with poor prognosis often correlate with expression of Caveolin-1. The study aimed to investigate the expression of caveolin-1 in the tumour cells and in the stromal component of the tumour among the group of TNBC and compare it to the expression of caveolin-1 in a control group with non-TN breast cancer. Whole tissue sections were used. Formalin fixed, paraffin embedded tissue materials from 101 patients diagnosed with invasive breast cancer during the period 2004-2007 were investigated in a retrospective study. A multistep approach was used to separate the different subtypes of breast cancer. During the first step the breast tumours were separated according to their ER, PgR, HER 2 and proliferative activity, using the Ki-67 index. The triple- negative tumours were additionally tested for EGFR and CK5/6. The basal breast cancer group was finally subdivided into basal and baso-luminal according to the type of expression of basal cytokeratins. caveolin-1 expression was examined in the tumour parenchyma and stroma. According to our results, caveolin-1 expression in breast cancer was significantly associated with basal biomarkers expression (basal and baso-luminal type of BC) χ2= 33.4; p<0.0001. Caveolin-1 can be used as a potential marker to examine the presence of basal phenotype in breast cancer.
Assessment of the Impact of Oxidative Stress on Frozen Seminal Plasma in Fertile and Infertile Men by Examining the Total Antioxidant Capacity
Authors: Rilcheva Violeta S. , Ayvazova Nina P. , Martinov Danail I. , Ivanov Cvetomir I. , Konova Emiliana I. 
Published: January 2016

AbstractThe aim of the study was to explore the impact of oxidative stress on frozen seminal plasma in fertile and infertile men by examining the total antioxidant capacity. Patients: Infertile patients from male infertility clinic with various diagnoses and fertile men. Design: Seminal plasma from proven fertile men [n=50] and infertile patients [n=50] were examined for total antioxidant capacity (TAC) level, semen parameters such as morphology, motility and concentration, and DNA integrity test. Interventions: Seminal plasma TAC measurement by luminometric assay using the TAC assay kit, semen analysis parameters, DNA integrity test. Fertile men showed higher TAC values (median and SD): 1201µM (SD±548), as compared with the infertile patients: 831μM (SD±343). The result from sperm morphology of fertile patients showed a mean percentage of 4.8 % (SD±1.68) whereas the percentage in the infertile group was 2.68% (SD ±1.68). The same group of samples, analyzed for DNA damage showed a mean of DFI 10.38% (SD±5.17%) in fertile men and a mean of DFI 17.22% (SD±7.22%) in infertile men. Total antioxidant capacity of the seminal plasma as measured by the luminоmetric assay is a reliable and simple test for diagnosing and management of male infertility.
Uterine Angiomyolipoma: A Case Report, Differential Diagnosis with Pecoma and Review of the Literature
Authors: Totev Tihomir P. , Mateva Svetlana A. , Nikolova Margarita R. , Gorchev Grigor A. 
Published: January 2016

Abstract
Angiomyolipomas are benign mesenchymal neoplasms, presenting with a variable mixture of adipose tissue, smooth muscle and vascular component. Although they are typically found in the kidneys, many cases of extrarenal angiomyolipomas have been reported. They are extremely rarely present in the uterus. We describe a case of a 56-year-old woman, operated on for leiomyoma. Total laparohysterectomy and bilateral adnexectomy was performed. After histological and immunohistochemical examination, the final diagnosis of uterine angiomyolipoma was made. Renal and extrarenal angiomyolipomas are compared in regard to clinical and morphological aspect and their difference from PEComas is dicussed. PEComas have been defined during the last decade and there are still issues regarding terminological clarity and overlapping.
A Case of “Rayism”- Tropical Stingray Intoxication with a Favorable Outcome
Authors: Iliev Yanko T. , Bozhilov Vladimir V. 
Published: January 2016

Abstract
Tropical fresh water stingrays have become quite popular among amateur and professional aquarists due to their attractive appearance. However, the species may have a high life-threatening potential. Stingray intoxication is rare in Eastern Europe and there is no specific antivenin available. We present the first case of “rayism” - envenomation caused by sp. Reticulatus in Eastern Europe. The patient was a 63-year-old amateur aquarist, with a history of ischaemic heart disease and allergy to NSAIDs. He got stung while cleaning a stingray fish tank and was admitted to the department of clinical toxicology 40min following the incident, with symptoms of moderate intoxication: accentuated local toxic syndrome - mild bleeding at the sting site, worsening and excruciating (8- 9/10) pain in his left hand and forearm, feeling of “burning” in the arm, accompanying toxic symptoms - vertigo, malaise, fatigue, sweating and tightness in the chest. No antitoxin was available and the treatment plan included local aseptic treatment of the wound, anti- tetanus prophylaxis, fluoroquinolone-type antibiotic prophylaxis, antihistamine, a corticosteroid and i.v. infusions. Thermal therapy (immersing the arm in hot, 45℃ tap water) completely reduced the pain within 5 hours. Full recovery was achieved on the 3rd day after the exposure. A toxicologist should react adequately in the setting of a rare intoxication even when a specific antidote is not available. Thermal therapy proved to be effective in the case of stingray envenomation.
Extra-Abdominal Musculo-Aponeurotic Fibromatosis: A Case with Metachronous Multicentric Lesions of the Right Thigh
Authors: Popovska Savelina L. , Betova Tatyana M. , Petrov Кrasimir T. 
Published: January 2016

Abstract
Fibromatoses are a group of benign proliferations of fibrous tissue with clinical behaviour ranging from that of truly malignant tumours to that of benign reactive fibrous proliferations. Some of the superficial fibromatoses are fairly common but deep ones, also known as desmoid tumours or musculoaponeurotic fibromatoses, are rare. We describe a case of extra-abdominal musculo- aponeurotic fibromatosis in a 22-years old male. He underwent 14 operations for a period of 9 years for fibromatosis of the posterior surface of the right lower limb. The histological findings of the lesions were similar consistent across surgeries and consistent with a diagnosis of aggressive extra-abdominal fibromatosis.
Human iPS Cell-Derived Neurons Uncover the Impact of Increased Ras Signaling in Costello Syndrome
Authors: Rooney Gemma E. , Goodwin Alice F. , Depeille Philippe , Sharir Amnon , Schofield Claude M. , Yeh Erika , Roose Jeroen P. , Klein Ophir D. , Rauen Katherine A. , Weiss Lauren A. , Ullian Erik M. 
Published: January 2016

Increasing evidence implicates abnormal Ras signaling as a major contributor in neurodevelopmental disorders, yet how such signaling causes cortical pathogenesis is unknown. We examined the consequences of aberrant Ras signaling in the developing mouse brain and uncovered several critical phenotypes, including increased production of cortical neurons and morphological deficits. To determine whether these phenotypes are recapitulated in humans, we generated induced pluripotent stem (iPS) cell lines from patients with Costello syndrome (CS), a developmental disorder caused by abnormal Ras signaling and characterized by neurodevelopmental abnormalities, such as cognitive impairment and autism. Directed differentiation toward a neuroectodermal fate revealed an extended progenitor phase and subsequent increased production of cortical neurons. Morphological analysis of mature neurons revealed significantly altered neurite length and soma size in CS patients. This study demonstrates the synergy between mouse and human models and validates the use of iPS cells as a platform to study the underlying cellular pathologies resulting from signaling deficits.SIGNIFICANCE STATEMENTIncreasing evidence implicates Ras signaling dysfunction as a major contributor in psychiatric and neurodevelopmental disorders, such as cognitive impairment and autism, but the underlying cortical cellular pathogenesis remains unclear. This study is the first to reveal human neuronal pathogenesis resulting from abnormal Ras signaling and provides insights into how these phenotypic abnormalities likely contribute to neurodevelopmental disorders. We also demonstrate the synergy between mouse and human models, thereby validating the use of iPS cells as a platform to study underlying cellular pathologies resulting from signaling deficits. Recapitulating human cellular pathologiesin vitrofacilitates the future high throughput screening of potential therapeutic agents that may reverse phenotypic and behavioral deficits.
Sustained Suppression of Hyperalgesia during Latent Sensitization by μ-, δ-, and κ-opioid receptors and α2AAdrenergic Receptors: Role of Constitutive Activity
Authors: Walwyn Wendy M. , Chen Wenling , Kim Hyeyoung , Minasyan Ani , Ennes Helena S. , McRoberts James A. , Marvizón Juan Carlos G. 
Published: January 2016

Many chronic pain disorders alternate between bouts of pain and periods of remission. The latent sensitization model reproduces this in rodents by showing that the apparent recovery (“remission”) from inflammatory or neuropathic pain can be reversed by opioid antagonists. Therefore, this remission represents an opioid receptor-mediated suppression of a sustained hyperalgesic state. To identify the receptors involved, we induced latent sensitization in mice and rats by injecting complete Freund's adjuvant (CFA) in the hindpaw. In WT mice, responses to mechanical stimulation returned to baseline 3 weeks after CFA. In μ-opioid receptor (MOR) knock-out (KO) mice, responses did not return to baseline but partially recovered from peak hyperalgesia. Antagonists of α2A-adrenergic and δ-opioid receptors reinstated hyperalgesia in WT mice and abolished the partial recovery from hyperalgesia in MOR KO mice. In rats, antagonists of α2Aadrenergic and μ-, δ-, and κ-opioid receptors reinstated hyperalgesia during remission from CFA-induced hyperalgesia. Therefore, these four receptors suppress hyperalgesia in latent sensitization. We further demonstrated that suppression of hyperalgesia by MORs was due to their constitutive activity because of the following: (1) CFA-induced hyperalgesia was reinstated by the MOR inverse agonist naltrexone (NTX), but not by its neutral antagonist 6β-naltrexol; (2) pro-enkephalin, pro-opiomelanocortin, and pro-dynorphin KO mice showed recovery from hyperalgesia and reinstatement by NTX; (3) there was no MOR internalization during remission; (4) MORs immunoprecipitated from the spinal cord during remission had increased Ser375phosphorylation; and (5) electrophysiology recordings from dorsal root ganglion neurons collected during remission showed constitutive MOR inhibition of calcium channels.SIGNIFICANCE STATEMENTChronic pain causes extreme suffering to millions of people, but its mechanisms remain to be unraveled. Latent sensitization is a phenomenon studied in rodents that has many key features of chronic pain: it is initiated by a variety of noxious stimuli, has indefinite duration, and pain appears in episodes that can be triggered by stress. Here, we show that, during latent sensitization, there is a sustained state of pain hypersensitivity that is continuously suppressed by the activation of μ-, δ-, and κ-opioid receptors and by adrenergic α2Areceptors in the spinal cord. Furthermore, we show that the activation of μ-opioid receptors is not due to the release of endogenous opioids, but rather to its ligand-independent constitutive activity.
Saccadic Corollary Discharge Underlies Stable Visual Perception
Authors: Cavanaugh James , Berman Rebecca A. , Joiner Wilsaan M. , Wurtz Robert H. 
Published: January 2016

Saccadic eye movements direct the high-resolution foveae of our retinas toward objects of interest. With each saccade, the image jumps on the retina, causing a discontinuity in visual input. Our visual perception, however, remains stable. Philosophers and scientists over centuries have proposed that visual stability depends upon an internal neuronal signal that is a copy of the neuronal signal driving the eye movement, now referred to as a corollary discharge (CD) or efference copy. In the old world monkey, such a CD circuit for saccades has been identified extending from superior colliculus through MD thalamus to frontal cortex, but there is little evidence that this circuit actually contributes to visual perception. We tested the influence of this CD circuit on visual perception by first training macaque monkeys to report their perceived eye direction, and then reversibly inactivating the CD as it passes through the thalamus. We found that the monkey's perception changed; during CD inactivation, there was a difference between where the monkey perceived its eyes to be directed and where they were actually directed. Perception and saccade were decoupled. We established that the perceived eye direction at the end of the saccade was not derived from proprioceptive input from eye muscles, and was not altered by contextual visual information. We conclude that the CD provides internal information contributing to the brain's creation of perceived visual stability. More specifically, the CD might provide the internal saccade vector used to unite separate retinal images into a stable visual scene.SIGNIFICANCE STATEMENTVisual stability is one of the most remarkable aspects of human vision. The eyes move rapidly several times per second, displacing the retinal image each time. The brain compensates for this disruption, keeping our visual perception stable. A major hypothesis explaining this stability invokes a signal within the brain, a corollary discharge, that informs visual regions of the brain when and where the eyes are about to move. Such a corollary discharge circuit for eye movements has been identified in macaque monkey. We now show that selectively inactivating this brain circuit alters the monkey's visual perception. We conclude that this corollary discharge provides a critical signal that can be used to unite jumping retinal images into a consistent visual scene.
Mild Perceptual Categorization Deficits Follow Bilateral Removal of Anterior Inferior Temporal Cortex in Rhesus Monkeys
Authors: Matsumoto Narihisa , Eldridge Mark A.G. , Saunders Richard C. , Reoli Rachel , Richmond Barry J. 
Published: January 2016

In primates, visual recognition of complex objects depends on the inferior temporal lobe. By extension, categorizing visual stimuli based on similarity ought to depend on the integrity of the same area. We tested three monkeys before and after bilateral anterior inferior temporal cortex (area TE) removal. Although mildly impaired after the removals, they retained the ability to assign stimuli to previously learned categories, e.g., cats versus dogs, and human versus monkey faces, even with trial-unique exemplars. After the TE removals, they learned in one session to classify members from a new pair of categories, cars versus trucks, as quickly as they had learned the cats versus dogs before the removals. As with the dogs and cats, they generalized across trial-unique exemplars of cars and trucks. However, as seen in earlier studies, these monkeys with TE removals had difficulty learning to discriminate between two simple black and white stimuli. These results raise the possibility that TE is needed for memory of simple conjunctions of basic features, but that it plays only a small role in generalizing overall configural similarity across a large set of stimuli, such as would be needed for perceptual categorical assignment.SIGNIFICANCE STATEMENTThe process of seeing and recognizing objects is attributed to a set of sequentially connected brain regions stretching forward from the primary visual cortex through the temporal lobe to the anterior inferior temporal cortex, a region designated area TE. Area TE is considered the final stage for recognizing complex visual objects, e.g., faces. It has been assumed, but not tested directly, that this area would be critical for visual generalization, i.e., the ability to place objects such as cats and dogs into their correct categories. Here, we demonstrate that monkeys rapidly and seemingly effortlessly categorize large sets of complex images (cats vs dogs, cars vs trucks), surprisingly, even after removal of area TE, leaving a puzzle about how this generalization is done.