Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased pulse wave velocity is associated with low creatinine clearance and proteinuria in a screened cohort.

BACKGROUND Chronic kidney disease (CKD) is a risk factor for future cardiovascular disease. Although pulse wave velocity (PWV), which reflects arterial stiffness, was increased in subjects with CKD, little is known regarding whether renal function is associated with PWV in a low-risk population and whether proteinuria and decreased renal function synergistically affect PWV. METHODS Subjects are 3,387 persons (mean age, 52 years) who attended a health checkup program in Okinawa, Japan. We measured brachial-ankle PWV (baPWV) by using an automatic oscillometric method. Proteinuria was semiquantified by using the dipstick method. Creatinine clearance (CCr) was estimated by using the Cockcroft-Gault formula. RESULTS baPWV was accelerated with increases in age, systolic blood pressure, fasting glucose level, and total cholesterol level; male sex; presence of proteinuria; and decrease in CCr. All these factors independently predicted baPWV in multiple regression analysis. When subjects were divided into 6 groups according to CCr of 90 or greater, 60 to 89, or 30 to 59 mL/min (> or =1.50, 1.00 to 1.48, or 0.50 to 0.98 mL/s) and the absence or presence of proteinuria, baPWV, after adjustment for age, sex, and systolic blood pressure, increased in a stepwise fashion corresponding to decreases in CCr regardless of proteinuria, with the relationship exaggerated in the presence of proteinuria. CONCLUSION Arterial stiffness increases with a decrease in renal function or with proteinuria independently of other risk factors.
Vestibular Impairment in Dementia

Objective: Recent studies suggest an association between vestibular and cognitive function. The goal of the study was to investigate whether vestibular function was impaired in individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared with cognitively normal individuals. Study Design: Cross-sectional study. Setting: Outpatient memory clinic and longitudinal observational study unit. Patients: Older individuals ≥55 years with MCI or AD. Age, sex, and education-matched normal controls were drawn from the Baltimore Longitudinal Study of Aging (BLSA). Intervention: Saccular and utricular function was assessed with cervical and ocular vestibular-evoked myogenic potentials (c- and oVEMPs) respectively, and horizontal semicircular canal function was assessed with video head impulse testing. Main Outcome Measures: Presence or absence of VEMP responses, VEMP amplitude, and vestibular ocular reflex (VOR) gain were measured. Results: Forty-seven individuals with cognitive impairment (MCI N = 15 and AD N = 32) underwent testing and were matched with 94 controls. In adjusted analyses, bilaterally absent cVEMPs were associated with an over three-fold odds of AD (OR 3.42, 95% CI 1.33–8.91, p = 0.011). One microvolt increases in both cVEMP and oVEMP amplitudes were associated with decreased odds of AD (OR 0.28, 95% CI 0.09–0.93, p = 0.038 and OR 0.92, 95% CI 0.85–0.99, p = 0.036, respectively). There was no significant difference in VOR gain between the groups. Conclusions: These findings confirm and extend emerging evidence of an association between vestibular dysfunction and cognitive impairment. Further investigation is needed to determine the causal direction for the link between peripheral vestibular loss and cognitive impairment.
Differential Control of the CCAAT/Enhancer-binding Protein β (C/EBPβ) Products Liver-enriched Transcriptional Activating Protein (LAP) and Liver-enriched Transcriptional Inhibitory Protein (LIP) and the Regulation of Gene Expression during the Response to Endoplasmic Reticulum Stress*

The accumulation of unfolded proteins in the endoplasmic reticulum (ER) triggers a stress response program that protects cells early in the response and can lead to apoptosis during prolonged stress. The basic leucine zipper transcription factor, CCAAT/enhancer-binding protein β (C/EBPβ), is one of the genes with increased expression during ER stress. Translation of the C/EBPβ mRNA from different initiation codons leads to the synthesis of two transcriptional activators (LAP-1 and -2) and a transcriptional repressor (LIP). The LIP/LAP ratio is a critical factor in C/EBPβ-mediated gene transcription. It is shown here that the LIP/LAP ratio decreased by 5-fold during the early phase of ER stress and increased by 20-fold during the late phase, mostly because of changes in LIP levels. The early decrease in LIP required degradation via the proteasome pathway and phosphorylation of the translation initiation factor, eIF2α. The increased LIP levels during the late phase were due to increased synthesis and increased stability of the protein. It is proposed that regulation of synthesis and degradation rates during ER stress controls the LIP/LAP ratio. The importance of C/EBPβ in the ER-stress response program was demonstrated using C/EBPβ-deficient mouse embryonic fibroblasts. It is shown that C/EBPβ attenuates expression of pro-survival ATF4 target genes in late ER stress and enhances expression of cell death-associated genes downstream of CHOP. The inhibitory effect of LIP on ATF4-induced transcription was demonstrated for the cat-1 amino acid transporter gene. We conclude that regulation of LIP/LAP ratios during ER stress is a novel mechanism for modulating the cellular stress response.
Spatiotemporal distribution of SUMOylation components during mouse brain development

Posttranslational modification of proteins might play an important role in brain cellular dynamics via the rapid turnover or functional change of critical proteins controlling neuronal differentiation or synaptic transmission. Small ubiquitin‐like modifier protein (SUMO) is a family of ubiquitin‐like small proteins that are covalently attached to target proteins to modify their function posttranslationally. Many cellular processes, such as transcription and protein trafficking, are regulated by SUMOylation, but its functional significance in the brain remains unclear. Although developmental regulation of SUMOylation levels in rat brain was recently demonstrated, no comparative immunohistochemical analysis of the cellular distribution profiles of SUMOylation components, including SUMO1, SUMO2/3, and Ubc9, has been undertaken so far. The present study used immunohistochemical and immunoblot analysis with the different developmental stages of mice and demonstrated the developmentally regulated distribution of SUMO1, SUMO2/3, and Ubc9 in the brain. During embryonic development, SUMOylation by SUMO1 and SUMO2/3 occurred in the nucleoplasm of nestin‐positive neural stem cells. Although the total amount of SUMO‐modified proteins decreased during postnatal brain development, intense and persistent accumulation of SUMO2/3 was detected throughout life in neural progenitor populations in neurogenic regions, including the subventricular zone and the hippocampal subgranular zone. In contrast, many neurons in the adult brain accumulated SUMO1 rather than SUMO2/3. Heavy immunoreactivity of SUMO1 was found in large projection neurons in the brainstem, whereas SUMO2/3 was almost absent from these areas. This heterogeneous distribution implies that both proteins play a specific and unique role in the brain. J. Comp. Neurol. 522:3020–3036, 2014. © 2014 Wiley Periodicals, Inc.
Pulmonary Embolism: Specific Risk Factor After Pancreas Resection?

Objective Pulmonary embolism (PE) after major abdominal surgery is a serious and potentially lethal complication. The purpose of the present study was to identify risk factors for postoperative PE after pancreas resection. Methods Our prospective database for pancreatic surgery was retrospectively analyzed for patients treated between January 2006 and August 2012 in a tertiary care Swiss hospital. Risk factors for PE were identified in univariate and multivariate analyses that included preoperative, intraoperative, and postoperative variables. Results Among 251 patients, 187 underwent pancreato-duodenectomy (PD), 62 underwent distal pancreatectomy, and 2 underwent other types of pancreas resections. PE was diagnosed in 13 patients (7.0%) after PD and none after other procedures. Compared with the non-PE group, the PE group had higher body mass indices (≥25 kg/m2, P = 0.04), longer median operation times (P = 0.009), higher rates of severe abdominal complications (P < 0.001), longer median intensive care unit stays (P = 0.003), and longer hospital stays (P = 0.01). Multivariate analyses identified the following independent predictors for PE: a history of thromboembolic events (odds ratio [OR], 22.3), prolonged operation time (OR, 5.76), and major abdominal complications (OR, 10.8). Conclusions Prolonged operation times and major postoperative abdominal complications were strong risk factors for PE after PD, in both univariate and multivariate analyses.
Two distinct pathways responsible for the loading of CENP-A to centromeres in the fission yeast cell cycle

CENP-A is a centromere-specific histone H3 variant that is- essential for faithful chromosome segregation in all eukaryotes thus far investigated. We genetically identified two factors, Ams2 and Mis6, each of which is required for the correct centromere localization of SpCENP-A (Cnp1), the fission yeast homologue of CENP-A. Ams2 is a cell-cycle-regulated GATA factor that localizes on the nuclear chromatin, including on centromeres, during the S phase. Ams2 may be responsible for the replication-coupled loading of SpCENP-A by facilitating nucleosomal formation during the S phase. Consistently, overproduction of histone H4, but not that of H3, suppressed the defect of SpCENP-A localization in Ams2-deficient cells. We demonstrated the existence of at least two distinct phases for SpCENP-A loading during the cell cycle: the S phase and the late-G2 phase. Ectopically induced SpCENP-A was efficiently loaded onto the centromeres in G2-arrested cells, indicating that SpCENP-A probably undergoes replication-uncoupled loading after the completion of S phase. This G2 loading pathway of SpCENP-A may require Mis6, a constitutive centromere-binding protein that is also implicated in the Mad2-dependent spindle attachment checkpoint response. Here, we discuss the functional relationship between the flexible loading mechanism of CENP-A and the plasticity of centromere chromatin formation in fission yeast.
A Novel Transgenic Mouse Model of Hyperfibrinogenemia

Summary Hyperfibrinogenemia is a risk predictor in several diseases, including cardiovascular disease. Nevertheless, it remains unknown whether elevated fibrinogen has an etiologic role in or is a reflection of disease pathogenesis, or both. To examine this question, we generated a mouse model of hyperfibrinogenemia. We isolated the mouse fibrinogen locus, containing the three fibrinogen genes, in a single P1 clone. This ~ 100 kb clone was injected into C57Bl/6J zygotes. Three transgenic lines were identified, two with elevated fibrinogen, 1.4- and 1.7-fold relative to normal. We characterized the line with the higher level. Northern blots of total RNA showed transgene expression was liver specific, and the message levels were 2- to 3-fold enhanced. Fibrinogen in transgenic mice was normal in both immunologic and clotting assays. Our data indicate that over-expression of all three fibrinogen genes is necessary to achieve hyperfibrinogenemia. We saw no increase in mortality or morbidity, no gross abnormalities in the organs, and no histologic differences in lung, liver, spleen or kidney, in transgenic mice relative to normal littermates. We conclude that elevated fibrinogen did not cause disease in mice. We anticipate that breeding these mice to other mouse models of disease will demonstrate whether hyper-fibrinogenemia has a role in the initiation or progression of symptomatic disease.
Migration, social mobility and common mental disorders: critical review of the literature and meta-analysis

Objective. Changes in socio-economic position in people who migrate may have adverse associations with mental health. The main objective of this review was to assess the association of social mobility with common mental disorders in migrant and second-generation groups, to inform future research. Design. Systematic review and meta-analysis of English-language studies assessing the association of social mobility in migrant or second-generation groups with common mental disorders. Approaches to operationalise ‘social mobility’ were reviewed. Results. Twelve studies (n=18,548) met criteria for retrieval. Very few included second-generation groups, and most studies were cross-sectional in design. Approaches to operationalise ‘social mobility’ varied between studies. Downward intragenerational social mobility was associated with migration in the majority of studies. Random effects meta-analysis (n=5179) suggested that migrants to higher income countries who experienced downward mobility or underemployment were more likely to screen positive for common mental disorders, relative to migrants who were upwardly mobile or experienced no changes to socio-economic position. Conclusions on second-generation groups were limited by the lack of research highlighted for these groups. Downward intragenerational mobility associated with migration may be associated with vulnerability to common mental disorders in some migrant groups. Conclusion. Given the increasing scale of global migration, further research is needed to clarify how changes to socio-economic position associated with international migration may impact on the mental health of migrants, and in their children.
Correlation between expression of CD44 splice variant v8-v9 and invasiveness of fibroblast-like synoviocytes in an in vitro system.

OBJECTIVES Rheumatoid arthritis is characterized by inflammation, hyperplasia of the synovial membrane, pannus formation and degradation of cartilage and bone. Fibroblast-like synoviocytes are thought to be involved in the invasion and subsequent degradation of cartilage. Two processes play a role in cellular invasion: cellular migration and degradation of the extracellular matrix. The adhesion molecule CD44 and chemokine receptors are instrumental in migration and invasion. Both components have been reported to play a role in tumour metastasis but also appear to be implicated in the destruction of synovial joints in rheumatoid arthritis. CD44, an ubiquitously expressed receptor for the glycosaminoglycan hyaluronan, contains 9 exons that are alternatively spliced and this gives rise to the expression of multiple splice variants, each exhibiting different functional capacities. METHODS In this report we describe an analysis of the expression of chemokine receptors and CD44 splice variants in diseased synovial tissues using the Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). We have correlated our findings with the clinical diagnosis of rheumatoid or osteoarthritis, with invasion into the extracellular matrix in vitro, and with the rate of proliferation of fibroblast-like synoviocytes. RESULTS AND CONCLUSIONS We conclude that fibroblast-like synoviocytes from both osteo- and rheumatoid arthritis express a number of different chemokine receptors and CD44-splice variants, but none of these correlate with a particular diagnosis. However, elevated expression of CD44v8-9 was found to correlate negatively with the invasive capacity of fibroblast-like synoviocytes.
Consequences of a green image of drone food delivery services: The moderating role of gender and age

Drone food delivery services play a significant role in protecting the environment, because the services are operated by batteries that can be charged with electricity. Therefore, this study tried to examine a green image in the context of drone food delivery services. More specifically, this study proposed that a green image of drone food delivery services plays an important role in the formation of attitude toward using the services. In addition, it was hypothesized that the attitude has a positive influence on behavioral intentions including intentions to use, word‐of‐mouth intentions, and willingness to pay more. Lastly, the moderating role of gender and age was proposed during the theory‐building process. A theoretical model, which included 12 hypotheses, was developed and tested using a total of 427 samples collected in Korea. The data analysis results showed that a green image of drone food delivery services has a positive influence on attitude toward using the services, which in turn positively affects three subdimensions of behavioral intentions. Furthermore, gender and age played partly as a moderator. The current paper was the first to study the green image of drone food delivery services, so the findings of this study mean a lot to the theoretical aspect.
Nomenclatural realignment of Neotyphodium species with genus Epichloë

Nomenclatural rule changes in the International Code of Nomenclature for algae, fungi and plants, adopted at the 18th International Botanical Congress in Melbourne, Australia, in 2011, provide for a single name to be used for each fungal species. The anamorphs of Epichloë species have been classified in genus Neotyphodium, the form genus that also includes most asexual Epichloë descendants. A nomenclatural realignment of this monophyletic group into one genus would enhance a broader understanding of the relationships and common features of these grass endophytes. Based on the principle of priority of publication we propose to classify all members of this clade in the genus Epichloë. We have reexamined classification of several described Epichloë and Neotyphodium species and varieties and propose new combinations and states. In this treatment we have accepted 43 unique taxa in Epichloë, including distinct species, subspecies, and varieties. We exclude from Epichloë the two taxa Neotyphodium starrii, as nomen dubium, and Neotyphodium chilense, as an unrelated taxon.
Craniocervical instability in the setting of os odontoideum: assessment of cause, presentation, and surgical outcomes in a series of 279 cases.

BACKGROUND Our clinical understanding of os odontoideum (OO) remains incomplete. Congenital and traumatic causes have been proposed and advocated. Clinical presentations range from asymptomatic to axial pain to myelopathy or vertebral-basilar ischemia. A consensus for surgical management exists for those found to have an unstable atlantoaxial complex or symptomatic cranial-vertebral junction compression. OBJECTIVE To evaluate the clinical presentation and surgical outcomes of patients with OO and an unstable atlantoaxial complex or symptomatic cranial-vertebral junction compression. METHODS Patients with a diagnosis of OO who underwent surgical management were included. Patients were excluded on the basis of previous C2 fracture, Fielding diagnostic criteria, and inadequate follow-up. History of trauma and presenting symptoms were assessed. Clinical and neurological improvements were measured with the use of patient satisfaction scores and the Japanese Orthopaedic Association scores. Fusion status was documented with the use of radiographs and computed tomographic imaging. RESULTS Of 279 patients, 112 reported a history of cranial-vertebral junction trauma, whereas 28 were diagnosed with congenital malformations. Clinically, 84.9% of patients presented with myelopathy, with pain presented in 42.6%. Atlantoaxial fixation was performed in 240 patients, occiput-to-C2 fixation in 35 patients, and extended occipito-cervical fixation in 4 patients. Mean follow-up was 40.3 months. Complications were reported in 2.4% of patients. Japanese Orthopaedic Association scores improved from a preoperative mean of 12.4 to 14.8. Two hundred thirty-five patients (77.7%) improved, with 30 patients experiencing no change in symptoms and 14 patients deteriorating. Fusion was achieved in 96.8% of patients. CONCLUSION Our data reveal that surgical treatment for OO using the indications and techniques delineated is associated with high satisfaction rates, improved functional scores, and high fusion rates with low complication rates.
Use of serum procalcitonin to detect bacterial infection in patients with autoimmune diseases: a systematic review and meta-analysis.

OBJECTIVE To systematically review evidence of the accuracy of the procalcitonin test for diagnosis of bacterial infection in patients with autoimmune disease. METHODS The major databases Medline, EMBase, and the Cochrane Library were searched for studies published between January 1966 and October 2011 that evaluated procalcitonin, alone or in comparison with other laboratory markers such as C-reactive protein (CRP), as a diagnostic marker for bacterial infection in patients with autoimmune disease and provided sufficient data to permit construction of 2 × 2 tables. RESULTS Nine studies were included in the final meta-analysis. The area under the summary receiver operating characteristic curve values were 0.91 (95% confidence interval [95% CI] 0.88-0.93) for procalcitonin and 0.81 (95% CI 0.78-0.84) for CRP. In general, testing for procalcitonin was highly specific for identifying infectious complications, although it was not as sensitive as testing for CRP. Pooled sensitivity was 0.75 (95% CI 0.63-0.84) for procalcitonin tests and 0.77 (95% CI 0.67-0.85) for CRP tests. Pooled specificity was 0.90 (95% CI 0.85-0.93) for procalcitonin tests and 0.56 (95% CI 0.25-0.83) for CRP tests. The positive likelihood ratio for procalcitonin (7.28 [95% CI 5.10-10.38]) was sufficiently high to qualify procalcitonin testing as a rule-in diagnostic tool, while the negative likelihood ratio (0.28 [95% CI 0.18-0.40]) was not sufficiently low to qualify procalcitonin testing as a reliable rule-out diagnostic tool. CONCLUSION Procalcitonin has higher diagnostic value than CRP for the detection of bacterial sepsis in patients with autoimmune disease, and the test for procalcitonin is more specific than sensitive. A procalcitonin test is not recommended to be used in isolation as a rule-out tool.
Molecular and Cellular Mechanisms of Axonal Regeneration After Spinal Cord Injury*

Following axotomy, a complex temporal and spatial coordination of molecular events enables regeneration of the peripheral nerve. In contrast, multiple intrinsic and extrinsic factors contribute to the general failure of axonal regeneration in the central nervous system. In this review, we examine the current understanding of differences in protein expression and post-translational modifications, activation of signaling networks, and environmental cues that may underlie the divergent regenerative capacity of central and peripheral axons. We also highlight key experimental strategies to enhance axonal regeneration via modulation of intraneuronal signaling networks and the extracellular milieu. Finally, we explore potential applications of proteomics to fill gaps in the current understanding of molecular mechanisms underlying regeneration, and to provide insight into the development of more effective approaches to promote axonal regeneration following injury to the nervous system.