bluuebunny/crossref_metadata_2025_split huggingface dataset:
A composite peripheral blood gene expression measure as a potential diagnostic biomarker in bipolar disorder
Authors: Munkholm K , Peijs L , Vinberg M , Kessing L V 
Published: August 2015

AbstractGene expression in peripheral blood has the potential to inform on pathophysiological mechanisms and has emerged as a viable avenue for the identification of biomarkers. Here, we aimed to identify gene expression candidate genes and to explore the potential for a composite gene expression measure as a diagnostic and state biomarker in bipolar disorder. First, messenger RNA levels of 19 candidate genes were assessed in peripheral blood mononuclear cells of 37 rapid cycling bipolar disorder patients in different affective states (depression, mania and euthymia) during a 6–12-month period and in 40 age- and gender-matched healthy control subjects. Second, a composite gene expression measure was constructed in the first half study sample and independently validated in the second half of the sample. We found downregulation of POLG and OGG1 expression in bipolar disorder patients compared with healthy control subjects. In patients with bipolar disorder, upregulation of NDUFV2 was observed in a depressed state compared with a euthymic state. The composite gene expression measure for discrimination between patients and healthy control subjects on the basis of 19 genes generated an area under the receiver-operating characteristic curve of 0.81 (P<0.0001) in sample 1, which was replicated with a value of 0.73 (P<0.0001) in sample 2, corresponding with a moderately accurate test. The present findings of altered POLG, OGG1 and NDUFV2 expression point to disturbances within mitochondrial function and DNA repair mechanisms in bipolar disorder. Further, a composite gene expression measure could hold promise as a potential diagnostic biomarker.
Countering antivaccination attitudes
Authors: Horne Zachary , Powell Derek , Hummel John E. , Holyoak Keith J. 
Published: August 2015

Significance
Myths about the safety of vaccinations have led to a decline in vaccination rates and the reemergence of measles in the United States, calling for effective provaccine messages to curb this dangerous trend. Prior research on vaccine attitude change suggests that it is difficult to persuade vaccination skeptics and that direct attempts to do so can even backfire. Here, we successfully countered people’s antivaccination attitudes by making them appreciate the consequences of failing to vaccinate their children (using information provided by the Centers for Disease Control and Prevention). This intervention outperformed another that aimed to undermine widespread vaccination myths.
Identification of a functional hotspot on ubiquitin required for stimulation of methyltransferase activity on chromatin
Authors: Holt Matthew T. , David Yael , Pollock Sam , Tang Zhanyun , Jeon Jongcheol , Kim Jaehoon , Roeder Robert G. , Muir Tom W. 
Published: August 2015

Significance
This article applies a range of protein ligation methods at the level of chromatin to understand the cross-talk mechanism between the well-established biomedical target the human Dot1 (hDot1L) methyltransferase and the ubiquitylation of H2B at lysine 120. Through a systematic structure–activity relationship study of the ubiquitin surface in regard to hDot1L-mediated H3K79 methylation and further investigation with precisely engineered chromatin substrates, a functional hotspot within ubiquitin was identified that is essential to the stimulation of hDot1L activity. More broadly, this work shows how chemical synthesis approaches can be used to precisely tailor protein posttranslational modifications to afford mechanistic insights that would be impossible by other methods.
Telogen elongation in the hair cycle ofob/obmice
Authors: Tasaki Natsumi , Minematsu Takeo , Mugita Yuko , Ikeda Shin-ichi , Nakagami Gojiro , Sanada Hiromi 
Published: August 2015

AbstractAlopecia impairs the physical and mental health of patients. We have previously shown that 8-week-old ob/ob mice have no reactivity to depilation, which is a stimulus that induces anagen transition in normal mice, while no hair cycle abnormalities have been reported in other studies until mice reach 7 weeks of age. Therefore, we hypothesized that ob/ob mice have abnormalities in hair cycle progression beyond 7 weeks of age. We examined 6- to 24-week-old ob/ob and 6- to 10-week-old normal mice. After acclimation, the dorsal skin was harvested and the hair cycle phase was identified histologically and immunohistochemically. Normal mice showed catagen–telogen and telogen–anagen transitions at 6 and 8–9 weeks old, respectively. In contrast, the anagen–catagen transition was observed in 7-week-old mice and the telogen phase was maintained from 10 to 24 weeks in most ob/ob mice. These results suggests that ob/ob mice are a possible model animal for telogen effluvium.
Pulmonary Hypertension is a Manifestation of Congestive Heart Failure and Left Ventricular Diastolic Dysfunction in Octogenarians with Severe Aortic Stenosis
Authors: Raina Amresh , Gertz Zachary M. , O'Donnell William T. , Herrmann Howard C. , Forfia Paul R. 
Published: August 2015

Previous studies have suggested that pulmonary hypertension (PH) in severe aortic stenosis (AS) is a risk factor for operative mortality with aortic valve replacement (AVR). Conversely, others have shown that patients with AS and PH extract a large symptomatic and survival benefit from AVR compared with those patients not treated surgically. We sought to evaluate the prevalence, severity, and mechanism of PH in an elderly patient cohort with severe AS. We prospectively evaluated 41 patients aged ≥80 years with severe AS. All patients underwent cardiac catheterization and transthoracic echocardiography within 24 hours. We found that PH was common in this cohort: 32 patients (78%) had PH; however, the predominant mechanism of PH was left heart congestion. Patients with PH had nearly double the pulmonary artery wedge pressure of patients without PH (23 vs. 13 mmHg; P ≤ 0.001). In patients with PH compared with those without, pulmonary vascular resistance was higher yet still under 3 Wood units (WU; 2.9 vs. 1.5 WU; P = 0.001), and the transpulmonary gradient (11 vs. 7 mmHg; P = 0.01) and diastolic pulmonary gradient (DPG; 3.0 vs. 2.7 mmHg; P = 0.74) were in normal range. Left ventricular diastolic abnormalities were more common in patients with severe AS and PH. Right ventricular (RV) dysfunction was common (13/41 patients, 32%), but the PH and non‐PH groups had similar tricuspid annular plane systolic excursion (2.0 vs. 2.3 cm; P = 0.15). Only 2 subjects had both RV dysfunction and an elevated DPG. In conclusion, PH is common in elderly patients with severe AS. This occurs largely due to left heart congestion, with a relative absence of pulmonary vascular disease and RV dysfunction, and as such, PH may serve as a heart failure equivalent in these patients.
Differential Effect of Initiating Moderate Red Wine Consumption on 24-h Blood Pressure by Alcohol Dehydrogenase Genotypes: Randomized Trial in Type 2 Diabetes
Authors: Gepner Yftach , Henkin Yaakov , Schwarzfuchs Dan , Golan Rachel , Durst Ronen , Shelef Ilan , Harman-Boehm Ilana , Spitzen Shosana , Witkow Shula , Novack Lena , Friger Michael , Tangi-Rosental Osnat , Sefarty Dana , Bril Nitzan , Rein Michal , Cohen Noa , Chassidim Yoash , Sarusi Benny , Wolak Talia , Stampfer Meir J. , Rudich Assaf , Shai Iris 
Published: August 2015

Abstract

AIMS
Observational studies report inconsistent associations between moderate alcohol intake and blood pressure (BP). In a sub-study of a larger randomized controlled trial, we assessed the effect of initiating moderate red wine consumption on 24-h BP recordings and the effect of a common genetic variant of alcohol dehydrogenases (ADH) among patients with type 2 diabetes.

METHODS
Fifty-four type 2 diabetes, alcohol abstainers were randomized to consume 150ml/dinner dry red wine or mineral water. Both groups were guided to adhere to a Mediterranean diet, without caloric restriction. We measured 24-h ambulatory BP monitoring (ABPM) at baseline and after 6 months.

RESULTS
Participants (age = 57 years; 85% men; mean 24-h BP = 129/77mm Hg) had 92% 6-month retention. After 6 months of intervention, the average 24-h BP did not differ between the wine and water groups. A transient decrease in BP was observed in the red wine group at midnight (3–4 hours after wine intake: systolic BP: red wine = −10.6mm Hg vs. mineral water = +2.3mm Hg; P = 0.031) and the following morning at 7–9 am (red wine: −6.2mm Hg vs. mineral water: +5.6mm Hg; P = 0.014). In a second post hoc sub-analysis among the red wine consumers, individuals who were homozygous for the gene encoding ADH1B*2 variant (Arg48His; rs1229984, TT, fast ethanol metabolizers), exhibited a reduction in mean 24-h systolic BP (−8.0mm Hg vs. +3.7mm Hg; P = 0.002) and pulse pressure (−3.8mm Hg vs. +1.2mm Hg; P = 0.032) compared to heterozygotes and those homozygous for the ADH1B*1 variant (CC, slow metabolizers).

CONCLUSIONS
Initiating moderate red wine consumption at dinner among type 2 diabetes patients does not have a discernable effect on mean 24-h BP. Yet, a modest temporal BP reduction could be documented, and a more pronounced BP-lowering effect is suggested among fast ethanol metabolizers.

CLINICAL TRIALS REGISTRATION
ClinicalTrials.gov Identifier: NCT00784433.
Pretreatment HIV Drug Resistance Increases Regimen Switches in Sub-Saharan Africa
Authors: Boender T. Sonia , Hoenderboom Bernice M. , Sigaloff Kim C. E. , Hamers Raph L. , Wellington Maureen , Shamu Tinei , Siwale Margaret , Labib Maksimos Eman E. F. , Nankya Immaculate , Kityo Cissy M. , Adeyemo Titilope A. , Akanmu Alani Sulaimon , Mandaliya Kishor , Botes Mariette E. , Ondoa Pascale , Rinke de Wit Tobias F. 
Published: August 2015

Abstract
Background.  After the scale-up of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection in Africa, increasing numbers of patients have pretreatment drug resistance.
Methods.  In a large multicountry cohort of patients starting standard first-line ART in six African countries, pol genotyping was retrospectively performed if viral load (VL) ≥1000 cps/mL. Pretreatment drug resistance was defined as a decreased susceptibility to ≥1 prescribed drug. We assessed the effect of pretreatment drug resistance on all-cause mortality, new AIDS events and switch to second-line ART due to presumed treatment failure, using Cox models.
Results.  Among 2579 participants for whom a pretreatment genotype was available, 5.5% had pretreatment drug resistance. Pretreatment drug resistance was associated with an increased risk of regimen switch (adjusted hazard ratio [aHR] 3.80; 95% confidence interval [CI], 1.49–9.68; P = .005) but was not associated with mortality (aHR 0.75, 95% CI, .24–2.35; P = .617) or new AIDS events (aHR 1.06, 95% CI, .68–1.64; P = .807). During three years of follow up, 106 (4.1%) participants switched to second-line, of whom 18 (17.0%) switched with VL &lt; 1000 cps/mL, 7 (6.6%) with VL ≥ 1000 cps/mL and no drug resistance mutations (DRMs), 46 (43.4%) with VL ≥ 1000 cps/mL and ≥1 DRMs; no HIV RNA data was available for 32 (30.2%) participants.
Conclusions.  Given rising pretreatment HIV drug resistance levels in sub-Saharan Africa, these findings underscore the need for expanded access to second-line ART. VL monitoring can improve the accuracy of failure detection and efficiency of switching practices.
The confidence effects of fiscal consolidations
Authors: Beetsma Roel , Cimadomo Jacopo , Furtuna Oana , Giuliodori Massimo 
Published: August 2015

AbstractWe explore how fiscal consolidations affect private sector confidence, a possible channel for the transmission of fiscal policy that has received particular attention recently as a result of governments embarking on austerity trajectories in the aftermath of the crisis. Panel regressions based on the annual action-based datasets of Devries et al. (2011) and Alesina et al. (2014a) show that consolidations, and in particular their unanticipated components, affect confidence negatively. To obtain a more accurate picture of how consolidations affect confidence, we construct a monthly dataset of consolidation announcements, so that we can investigate the confidence effects in real time using an event study. The results suggest that consumer confidence falls around announcements of consolidation measures, an effect likely driven by revenue-based measures. Moreover, these effects are highly relevant for European countries with weak institutional arrangements, as measured by the tightness of fiscal rules or budgetary transparency. The effects on producer confidence are generally similar, but weaker than for consumer confidence. Long-term interest rates, as a measure of confidence in the sovereign, tend to fall around spending-based consolidation announcements. We have no evidence that the confidence effects of consolidation announcements are worse in slumps than in booms. Generally, strengthening institutional arrangements may help in mitigating adverse confidence effects of consolidations.
Efficacy and safety of treatment simplification to atazanavir/ritonavir + lamivudine in HIV-infected patients with virological suppression: 144 week follow-up of the AtLaS pilot study
Authors: Mondi A. , Fabbiani M. , Ciccarelli N. , Colafigli M. , D'Avino A. , Borghetti A. , Gagliardini R. , Cauda R. , De Luca A. , Di Giambenedetto S. 
Published: August 2015

AbstractObjectivesAtLaS was a single-arm pilot study that demonstrated promising efficacy and safety of treatment simplification to a dual regimen with atazanavir/ritonavir + lamivudine in virologically suppressed HIV-positive patients. Here, we report data from the 144 week follow-up.MethodsAt baseline, patients treated with a three-drug atazanavir/ritonavir-based regimen were switched to 300/100 mg of atazanavir/ritonavir plus 300 mg of lamivudine once daily. Major clinical events, laboratory parameters, neurocognitive performance, bone composition and body fat distribution were monitored. Treatment failure was defined as a discontinuation/switch of the regimen or virological failure (HIV-RNA &gt;50 copies/mL in two consecutive determinations or a single level above 1000 copies/mL).ResultsAfter 144 weeks, 9/40 (22.5%) treatment failures occurred, including two virological failures (Weeks 48 and 53, without resistance). A significant increase in the CD4 count was observed at Week 96 (+124 cells/mm3; P = 0.002) and Week 144 (+94 cells/mm3; P = 0.008). After 144 weeks, a significant increase in total cholesterol (+25 mg/dL; P = 0.001), HDL cholesterol (+6 mg/dL; P = 0.024) and LDL cholesterol (+12 mg/dL; P = 0.008) was observed, without any change in triglyceride levels, total cholesterol/HDL ratio or LDL/HDL ratio. A significant increase in the estimated glomerular filtration rate (+25 mL/min/1.73 m2; P &lt; 0.001) and lumbar spine T-score and Z-score (+0.2, P = 0.011; and +0.35, P = 0.001, respectively) and a decrease in trunk fat (−1.898 g; P = 0.005) were also observed. Neurocognitive function did not decline over time. Concerning safety, 10 moderate to severe adverse events were recorded in eight patients; overall seven cases of renal colic (possibly treatment related) were observed, leading to a discontinuation of treatment in two patients.ConclusionsData from the 144 week follow-up suggested good long-term efficacy of the simplification strategy that was investigated, with rare virological failure and a potential for improvement of the CD4 count, renal function and bone mineral density. This strategy warrants further investigation in a randomized trial.
Neuropathies associated with lymphoma†
Authors: Grisold Wolfgang , Grisold Anna , Marosi Christine , Meng Stefan , Briani Chiara 
Published: August 2015

AbstractNeuropathy occurs with various manifestations as a consequence of lymphoma, and an understanding of the etiology is necessary for proper treatment. Advances in medical imaging have improved the detection of peripheral nerve involvement in lymphoma, yet tissue diagnosis is often equally important. The neoplastic involvement of the peripheral nervous system (PNS) in lymphoma can occur within the cerebrospinal fluid (CSF), inside the dura, or outside of the CSF space, affecting nerve root plexuses and peripheral nerves. The infiltration of either cranial or peripheral nerves in lymphoma is termed neurolymphomatosis (NL). These infiltrations can occur as mononeuropathy, multifocal neuropathy, symmetric neuropathies, or plexopathies. In rare cases, intravascular lymphoma (IL) can affect the PNS and an even rarer condition is the combination of NL and IL. Immune-mediated and paraneoplastic neuropathies are important considerations when treating patients with lymphoma. Demyelinating neuropathies, such as Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy, occur more frequently in non-Hodgkin's lymphoma than in Hodgkin's disease. Paraproteinemic neuropathies can be associated with lymphoma and paraneoplastic neuropathies are rare. While the treatment of lymphomas has improved, a knowledge of neurotoxic, radiotherapy, neoplastic, immune-mediated and paraneoplastic effects are important for patient care.
Limited Open Quadriceps Release for Treatment of Congenital Dislocation of the Knee
Authors: Youssef Ahmed Omar 
Published: August 2015

Background:
Congenital dislocation of the knee (CDK) is a rare condition for which the treatment is difficult and remains controversial. The aim of this case series is to evaluate the results of limited open quadriceps release for treatment of CDK.

Methods:
Sixteen patients with CDK were managed at our institute from May 2006 to May 2014, and included 10 boys and 6 girls, with a mean age at presentation of 5 weeks (range, 1 to16 wk). Three patients who had an underlying neuromuscular syndrome were excluded. The remaining 13 patients had no identifiable syndrome. There were 9 bilateral cases and 4 unilateral, with a total of 22 dislocated knees. Treatment began with gentle manipulation and serial weekly long-leg plaster casting in the outpatient clinic. Limited open quadriceps release was performed after failure of conservative treatment or in cases that presented late (>12 wk). The mean follow-up was 26.8 months (range, 12 to 48 mo).

Results:
Manipulation and serial casting were successful in 6 knees. The mean postmanipulation passive arc of range of motion of the affected knees was 118 degrees (range: 100 to 140 degrees). At final follow-up, the knee outcome was excellent in 2 knees and good in 4 knees. Sixteen knees were managed by limited open quadriceps release. The age of the patients at the time of surgery ranged between 8 and 16 weeks with a mean of 10 weeks. The mean postoperative passive arc of range of motion of the affected knees was 110 degrees (range: 95 to 145 degrees). Minor degrees of flexion deformity at the knee were encountered frequently (mean 8.5 degrees). Slight instability was observed in 6 cases. At final follow-up, the knee outcome was excellent in 6 knees and good in 10 knees.

Conclusions:
Management of CDK preferably should be started early with gentle manipulation and serial casting. Failure of conservative treatment or delayed presentation will need surgical intervention. Limited open quadriceps release has satisfactory results.

Level of Evidence:
Level IV–case series.
The Anterolateral Ligament of the Knee: An Inconsistent Finding in Pediatric Cadaveric Specimens
Authors: Shea Kevin G. , Polousky John D. , Jacobs John C. , Yen Yi-Meng , Ganley Theodore J. 
Published: August 2015

Background:
The anterolateral ligament (ALL) of the knee has been identified as a structure that limits internal rotation, and thus, affects the pivot shift mechanism. It has previously been reported in a high percentage of adult subjects. The purpose of the current study was to evaluate whether the ALL could be identified on pediatric cadaveric knee specimens and compare these findings to previously published reports.

Methods:
Eight skeletally immature cadaver knee specimens were examined through gross dissection: ages 3 months, 4 months, 1 year, 2 years, 3 years, 3 years, 8 years, and 10 years. There were 3 male and 5 female (7 right, 1 left) specimens. The presence or absence of the ALL was documented in each specimen, through dissection, intermittent internal and external rotation of the tibia, and anterior translation of the tibia, to produce tension of the lateral collateral tissues and joint capsule. These dissections were performed by a group of fellowship-trained orthopaedic surgeons.

Results:
The iliotibial band, entire lateral joint capsule, lateral collateral ligament, and popliteus were readily identified in each specimen. In 7 specimens, a distinct ALL structure was not identified during dissection. The ALL was identified in 1 of 8 specimens (1-year-old female, right knee). The ALL was further delineated under applied internal rotational stress.

Conclusions:
Previous research has suggested that this ligament is present in the majority of adult specimens. This finding was not reproduced in the current study of pediatric cadaveric specimens, where only one of 8 specimens had an identifiable ALL. This suggests that this ligament may develop later in life, after physiological loads are applied to the joint capsule. Further research in both adult and pediatric knees needs to be conducted to further elucidate the development of this ligament, and the role of this structure in knee stability.

Clinical Relevance:
The ALL is a knee ligament that has been described in adults. However, it is unclear whether this structure is present or fully developed in younger populations. The current study sought to identify the ALL in pediatric cadaver knee specimens, identifying this structure in only one of 8 specimens. The findings of this study suggest that the ALL may be an inconsistent structure in the pediatric population.
Biomimetic and Non-biomimetic Extraction of Motor Control Signals Through Matched Filtering of Neural Population Dynamics
Authors: Badreldin Islam S. , Oweiss Karim G. 
Published: August 2015

ABSTRACTBrain-machine interfaces rely on extracting motor control signals from brain activity in real time to actuate external devices such as robotic limbs. Whereas biomimetic approaches to neural decoding use motor imagery/observation signals, non-biomimetic approaches assign an arbirary transformation that maps neural activity to motor control signals. In this work, we present a unified framework for the design of both biomimetic and non-biomimetic decoders based on kernel-based system identification. This framework seamlessly incorporates the neural population dynamics in the decoder design, is particularly robust even with short training data records, and results in decoders with small filter delays. The theory and results presented here provide a new formulation of optimal linear decoding, a formal method for designing non-biomimetic decoders, and a set of proposed metrics for assessing decoding performance from an online control perspective. The theoretical framework is also applicable to the design of closed-loop neural control schemes.