bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initiation of medications for Parkinson's disease: a qualitative description
Authors: Shin Ju Young , Habermann Barbara 
Published: September 2015

Aims and objectivesTo understand experiences of people with Parkinson's disease to initiate medication therapy for Parkinson's disease.BackgroundNonadherence to medication regimens and reluctance to initiate medication therapy among people with Parkinson's disease has been documented in previous research. However, little is known about experiences and decisions of people with Parkinson's disease to initiate antiparkinsonian medications and their beliefs or levels of understanding of antiparkinsonian medications in the USA.DesignAn exploratory, descriptive qualitative study was employed.MethodsSemi‐structured interviews were conducted with 16 community‐dwelling individuals with Parkinson's disease (69% male) and five family caregivers (40% male). Data analysis was performed using content analysis.ResultsTwo domains emerged from the data: decision‐making to initiate antiparkinsonian medications as prescribed and reasons to delay initiation of levodopa to a later stage of Parkinson's disease.ConclusionsAcceptance of antiparkinsonian medications at the early stage of Parkinson's disease was influenced by the trusting relationship between participants and their health care provider. Fear of levodopa's long‐term side effects led to acceptance of non‐levodopa therapies first. Complementary and Alternative Medicine was used to manage Parkinson's disease symptoms among participants who delayed antiparkinsonian medication therapy.Relevance to clinical practiceNurses may have a role to assess individuals’ beliefs and concerns about antiparkinsonian medication therapy and to provide adequate information to assist with the decision about Parkinson's disease symptom management.
Intrapartum fetal heart rate patterns preceding terminal bradycardia in infants (>34 weeks) with poor neurological outcome: A regional population‐based study in Japan
Authors: Kodama Yuki , Sameshima Hiroshi , Yamashita Rie , Oohashi Masanao , Ikenoue Tsuyomu 
Published: September 2015

AbstractAimIntrapartum fetal bradycardia necessitates immediate operative delivery. Our aim was to investigate the hypothesis that some non‐reassuring fetal heart rate (FHR) patterns were present before the onset of terminal bradycardia in infants who developed subsequent brain damage.Material and MethodsFrom a population‐based study of 65 197 deliveries, 190 stillbirths, 115 neonatal deaths, and 136 neurologically high‐risk infants were registered by the Miyazaki Perinatal Conference. There were 15 cases of neurologically high‐risk infants born at >34 weeks of gestation exhibiting intrapartum terminal bradycardia. Focusing on the brain‐damaged infants, we retrospectively analyzed FHR patterns for at least 1 h prior to the bradycardia.ResultsBrain damage (cerebral palsy [n = 11] and mental retardation [n = 2]) was diagnosed at 2 years old in 13 out of 15 neurologically high‐risk infants. Two infants had bradycardia on admission. In the remaining 11 infants, FHR patterns were reassuring in six (55%) and non‐reassuring in five (45%), including late decelerations (n = 4) and variable decelerations (n = 2). Clinically relevant factors in the non‐reassuring group included intrauterine infection (n = 3), malpresentation with umbilical cord coiling (n = 1), and unknown causes (n = 1). Clinically relevant features in the reassuring group included cord prolapse (n = 1), vaginal breech delivery (n = 1), shoulder dystocia (n = 1), rupture of membranes (n = 1), and unknown causes (n = 2).ConclusionMore than half of the brain‐damaged infants born at >34 weeks of gestation who exhibited intrapartum terminal bradycardia had unremarkable FHR patterns before abrupt‐onset bradycardia. For those with non‐reassuring patterns preceding bradycardia, intrauterine infection was the major sentinel event.
Mandibular Overdentures Retained by Two Mini‐Implants: A Seven‐Year Retention and Satisfaction Study
Authors: Catalán Alfonso , Martínez Alejandra , Marchesani Francisco , González Urcesino 
Published: September 2015

AbstractPurposePatients with atrophic edentulous ridges generally have problems with retention, therapeutic satisfaction, and comfort with their complete dentures. An alternative treatment to assist in improving retention and stability involves the use of mini‐implants. The aim of this study was to evaluate the retention of mandibular overdentures connected to two mini‐implants and overall patient satisfaction with them.Materials and MethodsSeven patients with atrophic mandibular ridges (Type 4D Misch classification), aged 62 to 74 years old were rehabilitated with complete dentures. In each patient, two mini‐implants measuring 15 or 13 mm in length and 1.8 mm in diameter were placed. After 15 days, overdentures were connected to the mini‐implants with O‐ring attachments. In each patient, retention of the overdentures was measured, and a survey of therapeutic satisfaction before and after connection to the mini‐implants was administered. Prosthesis retention was measured with a digital dynamometer at 1 month, 6 months, and 2, 3, 5, and 7 years after mini‐implant placement. Patient satisfaction was assessed with a survey. Data were analyzed with Student's t‐test (satisfaction survey) and the Friedman test (retention measurements and satisfaction survey).ResultsThe initial retention values (0.34 to 0.63 N without mini‐implants) varied significantly (p ≤ 0.050). These values were less than the subsequent measurements of 3.92 to 9.64 N, taken after placement of the mini‐implants and connecting them to the dentures. Satisfaction was good to very good over the 7‐year observation period. Mucosa and peri‐implant bone showed no pathological changes.ConclusionsIn this limited sample size clinical study the results indicated that after connecting mandibular overdentures to two mini‐implants, patient satisfaction significantly increased and retention significantly improved during the 7‐year observation period.
Frontal metabolic activity contributes to individual differences in vulnerability toward total sleep deprivation‐induced changes in cognitive function
Authors: Xu Junling , Zhu Yuanqiang , Fu Chang , Sun Jinbo , Li Huiqiang , Yang Xuejuan , Li Weiling , Qin Wei , Shi Dapeng , Tian Jie 
Published: September 2015

SummarySubstantial individual differences characterize the changes induced by total sleep deprivation on cognitive functions. Despite some progress having been achieved, the mechanisms of individual differences in response to total sleep deprivation have not been clearly elucidated. Cerebral metabolism in the resting state is among the key physiological processes supporting the daily function of the brain, and may play an important role in these individual differences. Twenty‐two right‐handed participants (nine females and 13 males) between 20 and 26 years old completed a mathematical processing task both in resting wakefulness and after 24 h of total sleep deprivation. Fluorine‐18 fluorodeoxyglucose positron emission tomography‐computed tomography was used to investigate brain metabolism changes. The mathematical task was performed after the positron emission tomography scans were completed. Correlation analysis was used to investigate the correlations between cognitive performance changes and brain metabolism changes. Large inter‐individual differences were found in the throughput changes, but these inter‐individual differences were not associated with baseline or post‐deprivation performance levels. Specifically, deterioration of throughput on the mathematical processing task was significantly correlated with metabolism changes in the superior frontal medial gyrus. These findings suggested that frontal metabolic activity contributes to individual differences in waking‐induced impairment of cognitive performance.
Yeast nitrogen catabolite repression is sustained by signals distinct from glutamine and glutamate reservoirs
Authors: Fayyad‐Kazan Mohammad , Feller A. , Bodo E. , Boeckstaens M. , Marini A. M. , Dubois E. , Georis I. 
Published: September 2015

SummaryNitrogen catabolite repression (NCR) is a wide transcriptional regulation program enabling baker's yeast to downregulate genes involved in the utilization of poor nitrogen sources when preferred ones are available. Nowadays, glutamine and glutamate, the major nitrogen donors for biosyntheses, are assumed to be key metabolic signals regulating NCR. NCR is controlled by the conserved TORC1 complex, which integrates nitrogen signals among others to regulate cell growth. However, accumulating evidence indicate that the TORC1‐mediated control of NCR is only partial, arguing for the existence of supplementary regulatory processes to be discovered. In this work, we developed a genetic screen to search for new players involved in NCR signaling. Our data reveal that the NADP‐glutamate dehydrogenase activity of Gdh1 negatively regulates NCR‐sensitive gene transcription. By determining the total, cytoplasmic and vacuolar pools of amino acids, we show that there is no positive correlation between glutamine/glutamate reservoirs and the extent of NCR. While our data indicate that glutamine could serve as initial trigger of NCR, they show that it is not a sufficient signal to sustain repression and point to the existence of yet unknown signals. Providing additional evidence uncoupling TORC1 activity and NCR, our work revisits the dogmas underlying NCR regulation.
Ammonia activates pacC and patulin accumulation in an acidic environment during apple colonization by Penicillium expansum
Authors: Barad Shiri , Espeso Eduardo A. , Sherman Amir , Prusky Dov 
Published: September 2015

SummaryPenicillium expansum, the causal agent of blue mould rot, causes severe post‐harvest fruit maceration simultaneously with the secretion of d‐gluconic acid (GLA) and the mycotoxin patulin in colonized tissue. The factor(s) inducing patulin biosynthesis during colonization of the host acidic environment is unclear. During the colonization of apple fruit in vivo and growth in culture, P. expansum secretes pH‐modulating GLA and ammonia. Although patulin and its possible opportunistic precursor GLA accumulate together during fungal development, ammonia is detected on the colonized tissue's leading edge and after extended culture, close to patulin accumulation. Here, we demonstrate ammonia‐induced transcript activation of the global pH modulator PacC and patulin accumulation in the presence of GLA by: (i) direct exogenous treatment of P. expansum growing on solid medium; (ii) direct exogenous treatment on colonized apple tissue; (iii) growth under self‐ammonia production conditions with limited carbon; and (iv) analysis of the transcriptional response to ammonia of the patulin biosynthesis cluster. Ammonia induced patulin accumulation concurrently with the transcript activation of pacC and patulin biosynthesis cluster genes, indicating the regulatory effect of ammonia on pacC transcript expression under acidic conditions. Electrophoretic mobility shift assays using P. expansum PacC and antibodies to the different cleaved proteins showed that PacC is not protected against proteolytic signalling at pH 4.5 relative to pH 7.0, but NH4 addition did not further enhance its proteolytic cleavage. Ammonia enhanced the activation of palF transcript in the Pal pathway under acidic conditions. Ammonia accumulation in the host environment by the pathogen under acidic pH may be a regulatory cue for pacC activation, towards the accumulation of secondary metabolites, such as patulin.
A descriptive review of cardiac tumours in dogs and cats
Authors: Treggiari E. , Pedro B. , Dukes‐McEwan J. , Gelzer A. R. , Blackwood L. 
Published: September 2015

AbstractCardiac tumours are uncommon in the canine and feline population and often an incidental finding. Common types include haemangiosarcoma (HSA), aortic body tumours (chemodectoma and paraganglioma) and lymphoma. These neoplasms can cause mild to severe, life‐threatening clinical signs that are independent of the histological type and may be related to altered cardiovascular function or local haemorrhage/effusion into the pericardial space. Cardiac tumours may require symptomatic treatment aimed at controlling tumour bleeding and potential arrhythmias, and other signs caused by the mass effect. Additional treatment options include surgery, chemotherapy and radiotherapy. For all medical therapies, complete remission is unlikely and medical management, beyond adjunctive chemotherapy inHSA, requires further investigation but combination chemotherapy is recommended for lymphoma. The aim of this report is to summarize and critically appraise the current literature in a descriptive review. However, interpretation is limited by the lack of definitive diagnosis and retrospective nature of most studies.
Innervating sympathetic neurons regulate heart size and the timing of cardiomyocyte cell cycle withdrawal
Authors: Kreipke R. E. , Birren S. J. 
Published: September 2015

Key points
Cardiomyocytes withdraw from the cell cycle late in prenatal and early in postnatal life and subsequent heart growth occurs via cellular hypertrophy. The signals regulating this transition remain unknown.
Lesion of the neonatal sympathetic nervous system results in decreased heart size.
In vitro investigations show that sympathetic neurons delay cardiomyocyte maturation and cell cycle withdrawal.
Early sympathetic innervation may contribute to the determination of adult heart size by regulating the total number of cardiomyocytes via regulation of the proliferative/hypertrophic transition.
Early perturbations of sympathetic structure or function could have long‐term effects on adult heart function.
AbstractSympathetic drive to the heart is a key modulator of cardiac function and interactions between heart tissue and innervating sympathetic fibres are established early in development. Significant innervation takes place during postnatal heart development, a period when cardiomyocytes undergo a rapid transition from proliferative to hypertrophic growth. The question of whether these innervating sympathetic fibres play a role in regulating the modes of cardiomyocyte growth was investigated using 6‐hydroxydopamine (6‐OHDA) to abolish early sympathetic innervation of the heart. Postnatal chemical sympathectomy resulted in rats with smaller hearts, indicating that heart growth is regulated by innervating sympathetic fibres during the postnatal period. In vitro experiments showed that sympathetic interactions resulted in delays in markers of cardiomyocyte maturation, suggesting that changes in the timing of the transition from hyperplastic to hypertrophic growth of cardiomyocytes could underlie changes in heart size in the sympathectomized animals. There was also an increase in the expression of Meis1, which has been linked to cardiomyocyte cell cycle withdrawal, suggesting that sympathetic signalling suppresses cell cycle withdrawal. This signalling involves β‐adrenergic activation, which was necessary for sympathetic regulation of cardiomyocyte proliferation and hypertrophy. The effect of β‐adrenergic signalling on cardiomyocyte hypertrophy underwent a developmental transition. While young postnatal cardiomyocytes responded to isoproterenol (isoprenaline) with a decrease in cell size, mature cardiomyocytes showed an increase in cell size in response to the drug. Together, these results suggest that early sympathetic effects on proliferation modulate a key transition between proliferative and hypertrophic growth of the heart and contribute to the sympathetic regulation of adult heart size.
Application of a Three-Dimensional Immersed Boundary Method for Free Convection From Single Spheres and Aggregates
Authors: Musong Samuel G. , Feng Zhi-Gang , Michaelides Efstathios E. , Mao Shaolin 
Published: September 2015

AbstractA three-dimensional immersed boundary method (IBM) is applied for the solution of the thermal interactions between spherical particles in a viscous Newtonian fluid. At first, the free convection of an isolated isothermal sphere immersed in a viscous fluid is analyzed as a function of the Grashof number. A new correlation for the heat transfer rate from a single sphere is obtained, which is valid in the ranges 0.5 ≤ Pr ≤ 200 and 0 ≤ Gr ≤ 500. Second, the free convection heat transfer rate from pairs of spheres (bispheres) and from small spherical clusters immersed in air (Pr = 0.72) is investigated using this numerical technique. For bispheres, their orientation and the thermal plume interactions within a range of interparticle distances may cause the enhancement of the heat transfer rate above the values observed for two isolated spheres. For the simple triangular particle clusters, where the particles are in contact, it was observed that the average heat transfer rate per sphere decreases with the increased number of spheres in the cluster.
Gallstone is correlated with an increased risk of idiopathic sudden sensorineural hearing loss: a retrospective cohort study
Authors: Chiu Chong-Chi , Lee Kuan-Ji , Weng Shih-Feng , Yang Yuan-Ming , Lin Yung-Song 
Published: September 2015

ObjectivesThis study aims to test the hypothesis that gallstone disease (GSD) is a risk factor for the development of idiopathic sudden sensorineural hearing loss (ISSNHL). Research has shown risks of cardiovascular and cerebrovascular events in patients with GSD; however, well-conducted English studies on the association between GSD and the development of ISSNHL are lacking.Design and settingRetrospective cohort study using the Taiwan Longitudinal Health Insurance Database.ParticipantsWe compared 26 449 patients diagnosed with GSD between 1 January 2001 and 31 December 2007, with 52 898 age-matched, gender-matched and comorbidities propensity scores-matched controls.Outcome measuredWe followed each patient until the end of 2011 and evaluated the incidence of ISSNHL for at least 4 years after the initial GSD diagnosis.ResultsThe incidence of ISSNHL was 1.42 times higher in the GS cohort than in the non-GS cohort (9.27 vs 6.52/10 000 person-years). Using Cox proportional hazard regressions, the adjusted HR was 1.44 (95% CI 1.19 to 1.74). In the cohort of patients with GSD who needed a cholecystectomy, 37 patients suffered from ISSNHL. Among those patients, 31 (83.7%) patients sustained ISSNHL before cholecystectomy and 6 (16.2%) patients sustained ISSNHL after cholecystectomy.ConclusionsA diagnosis of GSD may be an independent risk for ISSNHL. This finding suggests that an underlying vascular and inflammatory mechanism may contribute to the development of ISSNHL. Physicians may want to counsel patients with GSD to seek medical attention if they have hearing impairments, because patients may be at an increased risk of developing ISSNHL.
The importance of tissue handling of surgically removed breast cancer for an accurate assessment of the Ki-67 index
Authors: Arima Nobuyuki , Nishimura Reiki , Osako Tomofumi , Nishiyama Yasuyuki , Fujisue Mamiko , Okumura Yasuhiro , Nakano Masahiro , Tashima Rumiko , Toyozumi Yasuo 
Published: September 2015

AimInsufficient attention for the Ki-67 immunohistochemistry has been given to the importance of tissue handling for surgical breast cancer specimens. We sought to investigate the effect of fixation status on the Ki-67.MethodsWe examined the effect of fixative, time to and duration of fixation using surgical specimens, and finally, compared the paired Ki-67 index in the tumour between core needle and surgical specimen.ResultsThe Ki-67 was significantly higher when 10% neutral buffered formalin was used (p=0.0276). Insufficient fixation caused a drastic reduction in the Ki-67 index (p=0.0177), but not significant in oestrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). Sixteen hours delayed time to fixation also caused a reduction of the Ki-67 (p=0.0284), but not significant in ER. Prolonged fixation significantly led to a gradual reduction in the Ki-67 in a time-dependent manner, but not in both ER and HER2. Finally, cutting the tumour before fixation improved fixation status and consequently caused an increased level of the Ki-67 index (p=0.0181), which resulted in a strong correlation of the Ki-67 between core needle and surgical specimen (r=0.8595).ConclusionsTissue handling of surgical specimen is critical for assessing the Ki-67 compared with ER and HER2. We should pay more attention to tissue fixation status for the standard assessment of the Ki-67 index.
The PKC/NF-κB Signaling Pathway Induces APOBEC3B Expression in Multiple Human Cancers
Authors: Leonard Brandon , McCann Jennifer L. , Starrett Gabriel J. , Kosyakovsky Leah , Luengas Elizabeth M. , Molan Amy M. , Burns Michael B. , McDougle Rebecca M. , Parker Peter J. , Brown William L. , Harris Reuben S. 
Published: September 2015

Abstract
Overexpression of the antiviral DNA cytosine deaminase APOBEC3B has been linked to somatic mutagenesis in many cancers. Human papillomavirus infection accounts for APOBEC3B upregulation in cervical and head/neck cancers, but the mechanisms underlying nonviral malignancies are unclear. In this study, we investigated the signal transduction pathways responsible for APOBEC3B upregulation. Activation of protein kinase C (PKC) by the diacylglycerol mimic phorbol-myristic acid resulted in specific and dose-responsive increases in APOBEC3B expression and activity, which could then be strongly suppressed by PKC or NF-κB inhibition. PKC activation caused the recruitment of RELB, but not RELA, to the APOBEC3B promoter, implicating noncanonical NF-κB signaling. Notably, PKC was required for APOBEC3B upregulation in cancer cell lines derived from multiple tumor types. By revealing how APOBEC3B is upregulated in many cancers, our findings suggest that PKC and NF-κB inhibitors may be repositioned to suppress cancer mutagenesis, dampen tumor evolution, and decrease the probability of adverse outcomes, such as drug resistance and metastasis. Cancer Res; 75(21); 4538–47. ©2015 AACR.
Extent and Location of Tumor-Infiltrating Lymphocytes in Microsatellite-Stable Colon Cancer Predict Outcome to Adjuvant Active Specific Immunotherapy
Authors: Turksma Annelies W. , Coupé Veerle M.H. , Shamier Marc C. , Lam Kevin L.H. , de Weger Vincent A. , Belien Jeroen A.M. , van den Eertwegh Alfons J. , Meijer Gerrit A. , Meijer Chris J.L.M. , Hooijberg Erik 
Published: September 2015

Abstract
Purpose: To determine the prognostic and predictive value of tumor-infiltrating lymphocytes (TIL) in colon cancer in a cohort of patients who previously took part in a trial on adjuvant active specific immunotherapy (ASI).
Experimental Design: We determined the number and location of CD3 and CD8 positive T cells in archival tumor samples of 106 colon cancers. We correlated stromal and epithelial TIL numbers with tumor stage and treatment and determined the effects on disease-specific survival (DSS) and recurrence-free interval (RFI).
Results: On the basis of the data presented, we concluded that (i) high numbers of stromal CD3 T cells have positive prognostic value measured as DSS for patients with stage II microsatellite-stable tumors and (ii) high numbers of epithelial CD8-positive T cells have positive prognostic value measured as RFI for the group of patients with stage II microsatellite-stable tumors as well as for the whole group (so stage II plus stage III together). Furthermore, we concluded that high numbers of pre-existing stromal CD3-positive T cells are of positive predictive value in adjuvant ASI treatment measured as DSS as well as RFI.
Conclusions: ASI therapy may contribute to an improved DSS and RFI in patients with microsatellite-stable colon tumors harboring high numbers of pre-existing stromal CD3+ TIL. Validation in future clinical trials is awaited. Clin Cancer Res; 22(2); 346–56. ©2015 AACR.