bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adverse physiologic effects of Western diet on right ventricular structure and function: role of lipid accumulation and metabolic therapy
Authors: Brittain Evan L. , Talati Megha , Fortune Niki , Agrawal Vineet , Meoli David F. , West James , Hemnes Anna R. 
Published: November 2018

Little is known about the impact of metabolic syndrome (MS) on right ventricular (RV) structure and function. We hypothesized that mice fed a Western diet (WD) would develop RV lipid accumulation and impaired RV function, which would be ameliorated with metformin. Male C57/Bl6 mice were fed a WD or standard rodent diet (SD) for eight weeks. A subset of mice underwent pulmonary artery banding (PAB). Treated mice were given 2.5 g/kg metformin mixed in food. Invasive hemodynamics, histology, Western, and quantitative polymerase chain reaction (qPCR) were performed using standard techniques. Lipid content was detected by Oil Red O staining. Mice fed a WD developed insulin resistance, RV hypertrophy, and higher RV systolic pressure compared with SD controls. Myocardial lipid accumulation was greater in the WD group and disproportionately affected the RV. These structural changes were associated with impaired RV diastolic function in WD mice. PAB‐WD mice had greater RV hypertrophy, increased lipid deposition, and lower RV ejection fraction compared with PAB SD controls. Compared to untreated mice, metformin lowered HOMA‐IR and prevented weight gain in mice fed a WD. Metformin reduced RV systolic pressure, prevented RV hypertrophy, and reduced RV lipid accumulation in both unstressed stressed conditions. RV diastolic function improved in WD mice treated with metformin. WD in mice leads to an elevation in pulmonary pressure, RV diastolic dysfunction, and disproportionate RV steatosis, which are exacerbated by PAB. Metformin prevents the deleterious effects of WD on RV function and myocardial steatosis in this model of the metabolic syndrome.
Wearable strain gauge-based technology measures manual tactile forces during the activities of daily living
Authors: Riddle Michael , MacDermid-Watts Kevin , Holland Sara , MacDermid Joy C , Lalone Emily , Ferreira Louis 
Published: November 2018

Introduction Current methods of determining applied forces in the hand rely on grip dynamometers or force-measurement gloves which are limited in their ability to isolate individual finger forces and interfere with the sense of touch. The objective of this study was to develop an improved force measurement system that could be used during various activities of daily living. Methods Custom-made strain gauge sensors were secured to the fingernail of four fingers and two middle phalanges and calibrated to measure hand forces in eight healthy individuals during five activities of daily living. Results These sensors were capable of measuring forces as small as 0.17 N and did not saturate at high force tasks around 15 N, which is within the envelope of forces experienced during daily life. Preliminary data demonstrate the ability of these tactile sensors to reliably distinguish which fingers/segments were used in various tasks. Conclusions Until now, there has been no method for real-time unobtrusive monitoring of force exposure during the tasks of daily life. The system used in this study provides a new type of low-cost wearable technology to monitor forces in the hands without interfering with the contact surface of the hand.
Prediction of setup times for an advanced upper limb functional electrical stimulation system
Authors: Smith Christine , Kenney Laurence , Howard David , Waring Karen , Sun Minxgu , Luckie Helen , Hardiker Nicholas , Cotterill Sarah 
Published: November 2018

Introduction Rehabilitation devices take time to don, and longer or unpredictable setup time impacts on usage. This paper reports on the development of a model to predict setup time for upper limb functional electrical stimulation. Methods Participants’ level of impairment (Fugl Meyer-Upper Extremity Scale), function (Action Research Arm Test) and mental status (Mini Mental Scale) were measured. Setup times for each stage of the setup process and total setup times were recorded. A predictive model of setup time was devised using upper limb impairment and task complexity. Results Six participants with stroke were recruited, mean age 60 (±17) years and mean time since stroke 9.8 (±9.6) years. Mean Fugl Meyer-Upper Extremity score was 31.1 (±6), Action Research Arm Test 10.4 (±7.9) and Mini Mental Scale 26.1 (±2.7). Linear regression analysis showed that upper limb impairment and task complexity most effectively predicted setup time (51% as compared with 39%) (F(2,21) = 12.782, adjusted R2 = 0.506; p < .05). Conclusions A model to predict setup time based on upper limb impairment and task complexity accounted for 51% of the variation in setup time. Further studies are required to test the model in real-world settings and to identify other contributing factors.
Clinical outcomes and survival rate of cementless modular distal fixation femoral stem for revision hip arthroplasty: A minimum 6-year follow-up
Authors: Kang Joon Soon , Na Yeop , Ko Bong Seong , Jeon Yoon Sang 
Published: November 2018

Purpose: Revision hip arthroplasty is a very challenging procedure. Use of a modular distal fixation stem is one of the available options for revision arthroplasty in patients with proximal femoral bone deficiency. The purpose of this study was to evaluate mid- to long-term outcomes of cementless modular distal fixation femoral stem implantation in revision hip surgery. Methods: Clinical and radiological findings, complications, and stem survival rate were analyzed for 46 patients (48 hips) who underwent revision hip arthroplasty using a cementless modular distal fixation femoral stem. The mean patient age was 58.8 years (range 31–82 years) and the mean follow-up period was 95 months (72–122 months). The preoperative diagnoses were aseptic loosening (36 hips), infection (4 hips), ceramic fracture (4 hips), and femoral periprosthetic fracture (4 hips). Results: The mean Harris hip score improved from 56.6 preoperatively to 88.2 postoperatively at the last follow-up. All hips showed stable osteointegration and firm fixation. Complications involved four hips (8.3%); there was one case each of periprosthetic fracture, delayed union of osteotomy site, femoral perforation, and infection. One stem re-revision was performed for deep infection of the femoral side. The Kaplan–Meier survival rate was 97.6% at the final follow-up. Conclusion: Revision hip arthroplasty using a cementless modular distal fixation femoral stem showed satisfactory initial firm fixation and mid- to long-term survival rate. Complications can be minimized by careful surgical planning and meticulous procedure.
Is the First-Past-the-Post Necessarily the First?
Authors: Chakrabarty Arijit 
Published: November 2018

In this short note, the probability of the event that in a first-past-the-post voting system, the party winning the maximum number of seats loses in terms of popular votes, is studied under a few simplifying assumptions. It turns out that the said probability is roughly 20 per cent. That is, one-fifth of the times, the said event will happen, on the average. JEL Classifications: D04, D72, D78
Definitive radiotherapy for localized follicular lymphoma staged by 18F-FDG PET-CT: a collaborative study by ILROG
Authors: Brady Jessica L. , Binkley Michael S. , Hajj Carla , Chelius Monica , Chau Karen , Balogh Alex , Levis Mario , Filippi Andrea Riccardo , Jones Michael , Mac Manus Michael , Wirth Andrew , Oguchi Masahiko , Vistisen Anders Krog , Andraos Therese Youssef , Ng Andrea K. , Aleman Berthe M. P. , Choi Seo Hee , Kirova Youlia , Hardy Sara , Reinartz Gabriele , Eich Hans T. , Bratman Scott V. , Constine Louis S. , Suh Chang-Ok , Dabaja Bouthaina , El-Galaly Tarec C. , Hodgson David C. , Ricardi Umberto , Yahalom Joachim , Hoppe Richard T. , Mikhaeel N. George 
Published: November 2018

Abstract
Radiotherapy (RT) can be curative in patients with localized follicular lymphoma (FL), with historical series showing a 10-year disease-free survival of 40 to 50%. As 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography with computerized tomography (PET-CT) upstages 10 to 60% of patients compared to CT, we sought to evaluate outcomes in patients staged by PET-CT, to determine if more accurate staging leads to better patient selection and results. We conducted a multicenter retrospective study under the direction of the International Lymphoma Radiation Oncology Group (ILROG). Inclusion criteria were: RT alone for untreated stage I to II FL (grade 1-3A) with dose equivalent ≥24 Gy, staged by PET-CT, age ≥18 years, and follow-up ≥3 months. End points were freedom from progression (FFP), local control, and overall survival (OS). A total of 512 patients treated between 2000 and 2017 at 16 centers were eligible for analysis; median age was 58 years (range, 20-90); 410 patients (80.1%) had stage I disease; median RT dose was 30 Gy (24-52); and median follow-up was 52 months (3.2-174.6). Five-year FFP and OS were 68.9% and 96%. For stage I, FFP was 74.1% vs 49.1% for stage II (P &lt; .0001). Eight patients relapsed in-field (1.6%). Four had marginal recurrences (0.8%) resulting in local control rate of 97.6%. On multivariable analysis, stage II (hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.44-3.10) and BCL2 expression (HR, 1.62; 95% CI, 1.07-2.47) were significantly associated with less favorable FFP. Outcome after RT in PET-CT staged patients appears to be better than in earlier series, particularly in stage I disease, suggesting that the curative potential of RT for truly localized FL has been underestimated.
IDH2 inhibition enhances proteasome inhibitor responsiveness in hematological malignancies
Authors: Bergaggio Elisa , Riganti Chiara , Garaffo Giulia , Vitale Nicoletta , Mereu Elisabetta , Bandini Cecilia , Pellegrino Elisa , Pullano Verdiana , Omedè Paola , Todoerti Katia , Cascione Luciano , Audrito Valentina , Riccio Anna , Rossi Antonio , Bertoni Francesco , Deaglio Silvia , Neri Antonino , Palumbo Antonio , Piva Roberto 
Published: November 2018

Abstract
Proteasome inhibitors (PI) are extensively used for the therapy of multiple myeloma (MM) and mantle cell lymphoma. However, patients continuously relapse or are intrinsically resistant to this class of drugs. Here, to identify targets that synergize with PI, we carried out a functional screening in MM cell lines using a short hairpin RNA library against cancer driver genes. Isocitrate dehydrogenase 2 (IDH2) was identified as a top candidate, showing a synthetic lethal activity with the PI carfilzomib (CFZ). Combinations of US Food and Drug Administration–approved PI with a pharmacological IDH2 inhibitor (AGI-6780) triggered synergistic cytotoxicity in MM, mantle cell lymphoma, and Burkitt lymphoma cell lines. CFZ/AGI-6780 treatment increased death of primary CD138+ cells from MM patients and exhibited a favorable cytotoxicity profile toward peripheral blood mononuclear cells and bone marrow–derived stromal cells. Mechanistically, the CFZ/AGI-6780 combination significantly decreased tricarboxylic acid cycle activity and adenosine triphosphate levels as a consequence of enhanced IDH2 enzymatic inhibition. Specifically, CFZ treatment reduced the expression of nicotinamide phosphoribosyltransferase (NAMPT), thus limiting IDH2 activation through the NAD+-dependent deacetylase SIRT3. Consistently, combination of CFZ with either NAMPT or SIRT3 inhibitors impaired IDH2 activity and increased MM cell death. Finally, inducible IDH2 knockdown enhanced the therapeutic efficacy of CFZ in a subcutaneous xenograft model of MM, resulting in inhibition of tumor progression and extended survival. Taken together, these findings indicate that NAMPT/SIRT3/IDH2 pathway inhibition enhances the therapeutic efficacy of PI, thus providing compelling evidence for treatments with lower and less toxic doses and broadening the application of PI to other malignancies.
Obsessive–compulsive disorder and child safeguarding
Authors: Gupta Sumeet , Kiran Shashi 
Published: November 2018

SUMMARYObsessive–compulsive disorder (OCD) is a common psychiatric condition and many patients have childcare responsibilities. A small proportion have aggressive and sexual thoughts about their children. There is little risk that they will act on these thoughts, but primary healthcare and social care professionals are often unaware of this and instigate unnecessary and potentially harmful child safeguarding processes. Psychiatrists have an essential role in educating and liaising with other professionals to prevent these inappropriate interventions.DECLARATION OF INTERESTNone.
Phase II Trial of Trastuzumab and Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2–Positive Salivary Duct Carcinoma
Authors: Takahashi Hideaki , Tada Yuichiro , Saotome Takashi , Akazawa Kohei , Ojiri Hiroya , Fushimi Chihiro , Masubuchi Tatsuo , Matsuki Takashi , Tani Kaori , Osamura Robert Y. , Hirai Hideaki , Yamada Shuhei , Kawakita Daisuke , Miura Kouki , Kamata Shin-etsu , Nagao Toshitaka 
Published: November 2018

Purpose Clinical evidence demonstrating the effectiveness of systemic therapy for advanced salivary duct carcinoma (SDC) is lacking because of the disease’s rarity. We assessed the efficacy and toxicity of trastuzumab plus docetaxel in patients with locally advanced and/or recurrent or metastatic human epidermal growth factor receptor 2–positive SDC. Patients and Methods This was a single-center, single-arm, open-label, phase II study in Japan. The patients received trastuzumab at a loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks. Docetaxel 70 mg/m2 was administrated every 3 weeks. The primary end point was the overall response rate; the secondary end points included the clinical benefit rate, progression-free survival, overall survival, and toxicity. This study is registered with the University Hospital Medical Information Network Clinical Trials Registry (Identification No. UMIN000009437). Results Fifty-seven eligible patients with SDC were enrolled. The overall response rate was 70.2% (95% CI, 56.6% to 81.6%), and the clinical benefit rate was 84.2% (95% CI, 72.1% to 92.5%). Median progression-free and overall survival times were 8.9 months (95% CI, 7.8 to 9.9 months) and 39.7 months (95% CI, not reached), respectively. The most frequent adverse event was anemia (52 patients [91%]), followed by a decreased WBC count (51 patients [89%]) and neutropenia (50 patients [88%]). The most frequently observed grade 4 adverse event was a decreased neutrophil count (34 patients [60%]). Grade 3 febrile neutropenia was reported in eight patients (14%). No grade 2 or greater adverse events of heart failure or left ventricular ejection fraction decline to less than 50% occurred. Conclusion Our data show encouraging efficacy of trastuzumab plus docetaxel therapy in patients with human epidermal growth factor receptor 2–positive SDC, with a manageable toxicity profile.
Influence of Outdoor Temperature and Relative Humidity on Incidence and Etiology of Hyponatremia
Authors: Sailer Clara O , Winzeler Bettina , Nigro Nicole , Bernasconi Luca , Mueller Beat , Christ-Crain Mirjam 
Published: November 2018

Abstract

Context
Hyponatremia is the most common electrolyte disturbance in hospitalized patients. Known risk factors are heart or renal failure, excessive drinking, or the use of diuretics. The incidence of hyponatremia may also be influenced by climate.

Objective
Analyzing the influence of outdoor temperature and relative humidity on the incidence and etiology of hyponatremia.

Design
Cohort A: cross-sectional study from January 2011 to December 2016. Cohort B: prospective observational study from June 2011 to August 2013.

Setting
Emergency departments of two tertiary centers.

Patients
Cohort A: patients with plasma sodium ≤145 mmol/L (n = 222,217). Cohort B: consecutive patients (n = 294) with profound hyponatremia (plasma sodium ≤125 mmol/L).

Main Outcome Measure
The effects of outdoor temperature and relative humidity on the incidence of mild (sodium 126 to 134 mmol/L) and profound hyponatremia (sodium ≤125 mmol/L) were investigated via logistic regression models. The effects of outdoor temperature and relative humidity on hyponatremia etiology were evaluated.

Results
In cohort A, 9.9% had mild and 1.08% had profound hyponatremia. Outdoor temperature was significantly associated with the incidence of profound but not mild hyponatremia (P &lt; 0.01, P = 0.3). Relative humidity was not associated with the incidence of hyponatremia. In cohort B, diuretic-induced hyponatremia occurred more frequently with higher outdoor temperatures, whereas other etiologies showed no clear variation with outdoor temperature or relative humidity.

Conclusions
Higher outdoor temperature, but not relative humidity, seems to be associated with the incidence of profound hyponatremia. Our data suggest that diuretics should be used with caution during hot weather.
Characterization of spatial and temporal development of Type I and Type II hair cells in the mouse utricle using new cell-type-specific markers
Authors: McInturff Stephen , Burns Joseph C. , Kelley Matthew W. 
Published: November 2018

ABSTRACTThe utricle of the inner ear, a vestibular sensory structure that mediates perception of linear acceleration, is comprised of two morphologically and physiologically distinct types of mechanosensory hair cells, referred to as Type Is and Type IIs. While these cell types are easily discriminated in an adult utricle, understanding their development has been hampered by a lack of molecular markers that can be used to identify each cell type prior to maturity. Therefore, we collected single hair cells at three different ages and used single cell RNAseq to characterize the transcriptomes of those cells. Analysis of differential gene expression identified Spp1 as a specific marker for Type I hair cells and Mapt and Anxa4 as specific markers for Type II hair cells. Antibody labeling confirmed the specificity of these markers which were then used to examine the temporal and spatial development of utricular hair cells. While Type I hair cells develop in a gradient that extends across the utricle from posterior-medial to anterior-lateral, Type II hair cells initially develop in the central striolar region and then extend uniformly towards the periphery. Finally, by combining these markers with genetic fate mapping, we demonstrate that over 98% of all Type I hair cells develop prior to birth while over 98% of Type II hair cells develop post-natally. These results are consistent with previous findings suggesting that Type I hair cells develop first and refute the hypothesis that Type II hair cells represent a transitional form between immature and Type I hair cells.
Gliding for a free lunch: biomechanics of foraging flight in common swifts (Apus apus)
Authors: Hedrick Tyson L. , Pichot Cécile , de Margerie Emmanuel 
Published: November 2018

ABSTRACT
Although the biomechanics of animal flight have been well studied in laboratory apparatus such as wind tunnels for many years, the applicability of these data to natural flight behaviour has been examined in few instances and mostly in the context of long-distance migration. Here, we used rotational stereo-videography to record the free-flight trajectories of foraging common swifts. We found that, despite their exquisite manoeuvring capabilities, the swifts only rarely performed high-acceleration turns. More surprisingly, we also found that despite feeding on tiny insects probably moving with ambient flow, the birds adjust their air speed to optimize cost of transport over distance. Finally, swifts spent only 25% of their time flapping; the majority of their time (71%) was spent in extended wing gliding, during which the average power expended for changes in speed or elevation was 0.84 W kg−1 and not significantly different from 0. Thus, gliding swifts extracted sufficient environmental energy to pay the cost of flight during foraging.
The Mixed-Lineage Kinase Inhibitor URMC-099 Protects Hippocampal Synapses in Experimental Autoimmune Encephalomyelitis
Authors: Bellizzi Matthew J. , Hammond Jennetta W. , Li Herman , Gantz Marker Mary A. , Marker Daniel F. , Freeman Robert S. , Gelbard Harris A. 
Published: November 2018

AbstractTreatments to stop gray matter degeneration are needed to prevent progressive disability in multiple sclerosis (MS). We tested whether inhibiting mixed-lineage kinases (MLKs), which can drive inflammatory microglial activation and neuronal degeneration, could protect hippocampal synapses in C57BL/6 mice with experimental autoimmune encephalomyelitis (EAE), a disease model that recapitulates the excitatory synaptic injury that occurs widely within the gray matter in MS. URMC-099, a broad spectrum MLK inhibitor with additional activity against leucine-rich repeat kinase 2 (LRRK2) and other kinases, prevented loss of PSD95-positive postsynaptic structures, shifted activated microglia toward a less inflammatory phenotype, and reversed deficits in hippocampal-dependent contextual fear conditioning in EAE mice when administered after the onset of motor symptoms. A narrow spectrum inhibitor designed to be highly selective for MLK3 failed to protect synapses in EAE hippocampi, and could not rescue cultured neurons from trophic deprivation in anin vitromodel of MLK-driven neuronal degeneration. These results suggest that URMC-099 may have potential as a neuroprotective treatment in MS and demonstrate that a broad spectrum of inhibition against a combination of MLK and other kinases is more effective in neuroinflammatory disease than selectively targeting a single kinase.