bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multivariate analysis of biopsychosocial determinants of professional activity among patients after kidney or liver transplantation in Poland
Authors: Wesolowska-Gorniak Katarzyna , Wojtowicz Monika , Gierus Jacek , Wlodarczyk Elzbieta , Federowicz Magdalena , Czarkowska-Paczek Bozena 
Published: July 2019

ObjectiveThe aim of the present study was to assess the employment rate among kidney and liver transplant recipients in Poland and identify the predictors of employment.SettingsThe study was based on a self-prepared questionnaire containing five parts: demographic data and professional, medical, physical and psychological factors. This is a multicentre study involving four hospitals in Poland.ParticipantsThe investigated group consisted of 285 individuals (92 women and 185 men; 8 no sex given) aged between 18 and 45 years who underwent kidney or liver transplantation 1–5 years prior. Because of missing data, 279 questionnaires were considered regarding employment status after transplantation and 277 when sex differences were considered.ResultsA total of 120 patients (43%) worked full-time, 42 (15%) part-time and 117 (42%) remained unemployed, with a higher employment rate post-transplantation among men than women (60% vs 55%, p=0.04). More women performed white collar work (74% vs 41%, p=0.0003) and had to modify their working position than men (22% vs 7%, p=0.0118). Factors determining employment after transplantation included higher level of education (OR=27.08; p=0.0096), employment 1 year prior to transplantation (OR=11.05; p<0.001) and good psychological adaptation (OR=4.23; p<0.001). Men working the year before transplantation had higher education (OR=9.66; p=0.0356). Among men, more kidney recipients worked compared with liver recipients (OR=3.567; p=0.0417). Among women, age determined employment status (OR=0.89; p=0.0234).ConclusionHigher education is the most important predictor of employment after transplantation. Therefore, rehabilitation programmes including vocational activity should be directed to increase the level of education, both pretransplantation and post-transplantation if possible.
Critical design considerations for time-to-event endpoints in amyotrophic lateral sclerosis clinical trials
Authors: van Eijk Ruben P A , Nikolakopoulos Stavros , Roes Kit C B , Middelkoop Bas M , Ferguson Toby A , Shaw Pamela J , Leigh P Nigel , Al-Chalabi Ammar , Eijkemans Marinus J C , van den Berg Leonard H 
Published: July 2019

BackgroundFunding and resources for low prevalent neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) are limited, and optimising their use is vital for efficient drug development. In this study, we review the design assumptions for pivotal ALS clinical trials with time-to-event endpoints and provide optimised settings for future trials.MethodsWe extracted design settings from 13 completed placebo-controlled trials. Optimal assumptions were estimated using parametric survival models in individual participant data (n=4991). Designs were compared in terms of sample size, trial duration, drug use and costs.ResultsPrevious trials overestimated the hazard rate by 18.9% (95% CI 3.4% to 34.5%, p=0.021). The median expected HR was 0.56 (range 0.33–0.66). Additionally, we found evidence for an increasing mean hazard rate over time (Weibull shape parameter of 2.03, 95% CI 1.93 to 2.15, p<0.001), which affects the design and planning of future clinical trials. Incorporating accrual time and assuming an increasing hazard rate at the design stage reduced sample size by 33.2% (95% CI 27.9 to 39.4), trial duration by 17.4% (95% CI 11.6 to 23.3), drug use by 14.3% (95% CI 9.6 to 19.0) and follow-up costs by 21.2% (95% CI 15.6 to 26.8).ConclusionsImplementing distributional knowledge and incorporating accrual at the design stage could achieve large gains in the efficiency of ALS clinical trials with time-to-event endpoints. We provide an open-source platform that helps investigators to make more accurate sample size calculations and optimise the use of their available resources.
5.3.5 Rule for examining the muscles of the upper limb
Authors: Gates Peter 
Published: July 2019

AbstractThe current technique taught for examining the muscles of the upper limb does not differentiate between the various causes of weakness in the arm, in particular peripheral nerve and nerve root lesions. The 5.3.5 rule describes examining the muscles in a specific order: 5 at the shoulder, 3 at the elbow and 5 at the wrist and hand. The examiner records the number of the weak muscles. They then consult the tables to determine the cause of the weakness. This rule enables the diagnosis of all peripheral nerve and nerve root problems (radiculopathy) that cause weakness in the arm. It does not require detailed knowledge of neuroanatomy. It does require the examiner to learn how to examine each muscle so that they do not miss weakness or ‘detect’ weakness when there is none.
Outcome of two variations of a surgical technique performed for canine unilateral arytenoid lateralisation
Authors: Perez Lopez Pablo , Barnes Darren Christopher , Nelissen Pieter , Demetriou Jackie 
Published: July 2019

BackgroundThe purpose of this study is to compare the rate of aspiration pneumonia and survival time of dogs undergoing two unilateral arytenoid lateralisation (UAL) techniques.MethodsEighty dogs diagnosed with laryngeal paralysis were treated by one of two UAL techniques: (1) a standard technique (ST) and (2) an anatomic preservation technique (APT). Outcome was assessed by in clinic re‐examination and an owner follow‐up questionnaire.ResultsMinor complications were reported for 22 per cent of dogs undergoing ST and 26 per cent for APT. Major complications were 7 per cent for ST versus 23 per cent for APT. Postoperative aspiration pneumonia was reported for 7 per cent of cases in ST and 17 per cent in APT. The median survival time for ST was 636 days and was 1067 days for APT. Cause of death was related to the laryngeal paralysis in 22 per cent, neurological deterioration in 16 per cent and for non‐associated reasons in 59 per cent of cases. There was no statistically significant difference in the rate of aspiration pneumonia or survival time among the treatment groups. Owners reported that their dogs improved after both surgical procedures, with 90 per cent of the owners satisfied with the surgical outcome. Eighteen per cent of the dogs suffered recurrence of clinical signs.ConclusionsIn this study, there was no significant difference in risk of aspiration pneumonia or survival time following arytenoid lateralisation by either an ST or an APT.
Intrinsic temporal tuning of neurons in the optic tectum is shaped by multisensory experience
Authors: Busch Silas E. , Khakhalin Arseny S. 
Published: July 2019

For a biological neural network to be functional, its neurons need to be connected with synapses of appropriate strength, and each neuron needs to appropriately respond to its synaptic inputs. This second aspect of network tuning is maintained by intrinsic plasticity; yet it is often considered secondary to changes in connectivity and mostly limited to adjustments of overall excitability of each neuron. Here we argue that even nonoscillatory neurons can be tuned to inputs of different temporal dynamics and that they can routinely adjust this tuning to match the statistics of their synaptic activation. Using the dynamic clamp technique, we show that, in the tectum of Xenopus tadpole, neurons become selective for faster inputs when animals are exposed to fast visual stimuli but remain responsive to longer inputs in animals exposed to slower, looming, or multisensory stimulation. We also report a homeostatic cotuning between synaptic and intrinsic temporal properties of individual tectal cells. These results expand our understanding of intrinsic plasticity in the brain and suggest that there may exist an additional dimension of network tuning that has been so far overlooked. NEW & NOTEWORTHY We use dynamic clamp to show that individual neurons in the tectum of Xenopus tadpoles are selectively tuned to either shorter (more synchronous) or longer (less synchronous) synaptic inputs. We also demonstrate that this intrinsic temporal tuning is strongly shaped by sensory experiences. This new phenomenon, which is likely to be mediated by changes in sodium channel inactivation, is bound to have important consequences for signal processing and the development of local recurrent connections.
Accurate and affordable assessment of physiological and pathological tremor in rodents using the accelerometer of a smartphone
Authors: Carlsen Eva Maria Meier , Amrutkar Dipak V. , Sandager-Nielsen Karin , Perrier Jean-François 
Published: July 2019

Tremor is a common symptom for the most prevalent neurological disorders, including essential tremor, spinal cord injury, multiple sclerosis, or Parkinson’s disease. Despite the devastating effects of tremor on life quality, available treatments are few and unspecific. Because of the need for specific and costly devices, tremor is rarely quantified by laboratories studying motor control without a genuine interest in trembling. We present a simple, reliable, and affordable method aimed at monitoring tremor in rodents, with an accuracy comparable to that of expensive, commercially available equipment. We took advantage of the accelerometer integrated in modern mobile phones working with operating systems capable of running downloaded apps. By fixing a smartphone to a cage suspended by rubber bands, we were able to detect faint vibrations of the cage. With a mouse in the cage, we showed that the acceleration signals on two horizontal axes were sufficient for the detection of physiological tremor and harmaline-induced tremor. We discuss the advantages and limitations of our method. NEW & NOTEWORTHY The majority of patients suffering from neurological disorders suffer from tremor that severely disrupts their life quality. Because of the high cost of specific scientific equipment, tremor is rarely quantified by laboratories working on motor behavior. For this reason, the potential anti-tremor effect of most compounds tested in animals remains unknown. We describe an affordable technique that will allow any laboratory to measure tremor accurately with a smartphone.
Simulating perinodal changes observed in immune-mediated neuropathies: impact on conduction in a model of myelinated motor and sensory axons
Authors: Sleutjes Boudewijn T. H. M. , Kovalchuk Maria O. , Durmus Naric , Buitenweg Jan R. , van Putten Michel J. A. M. , van den Berg Leonard H. , Franssen Hessel 
Published: July 2019

Immune-mediated neuropathies affect myelinated axons, resulting in conduction slowing or block that may affect motor and sensory axons differently. The underlying mechanisms of these neuropathies are not well understood. Using a myelinated axon model, we studied the impact of perinodal changes on conduction. We extended a longitudinal axon model (41 nodes of Ranvier) with biophysical properties unique to human myelinated motor and sensory axons. We simulated effects of temperature and axonal diameter on conduction and strength-duration properties. We then studied effects of impaired nodal sodium channel conductance and paranodal myelin detachment by reducing periaxonal resistance, as well as their interaction, on conduction in the 9 middle nodes and enclosed paranodes. Finally, we assessed the impact of reducing the affected region (5 nodes) and adding nodal widening. Physiological motor and sensory conduction velocities and changes to axonal diameter and temperature were observed. The sensory axon had a longer strength-duration time constant. Reducing sodium channel conductance and paranodal periaxonal resistance induced progressive conduction slowing. In motor axons, conduction block occurred with a 4-fold drop in sodium channel conductance or a 7.7-fold drop in periaxonal resistance. In sensory axons, block arose with a 4.8-fold drop in sodium channel conductance or a 9-fold drop in periaxonal resistance. This indicated that motor axons are more vulnerable to developing block. A boundary of block emerged when the two mechanisms interacted. This boundary shifted in opposite directions for a smaller affected region and nodal widening. These differences may contribute to the predominance of motor deficits observed in some immune-mediated neuropathies. NEW & NOTEWORTHY Immune-mediated neuropathies may affect myelinated motor and sensory axons differently. By the development of a computational model, we quantitatively studied the impact of perinodal changes on conduction in motor and sensory axons. Simulations of increasing nodal sodium channel dysfunction and paranodal myelin detachment induced progressive conduction slowing. Sensory axons were more resistant to block than motor axons. This could explain the greater predisposition of motor axons to functional deficits observed in some immune-mediated neuropathies.
Oncogenic MYC Induces the Impaired Ribosome Biogenesis Checkpoint and Stabilizes p53 Independent of Increased Ribosome Content
Authors: Morcelle Carmen , Menoyo Sandra , Morón-Duran Francisco D. , Tauler Albert , Kozma Sara C. , Thomas George , Gentilella Antonio 
Published: July 2019

Abstract

The role of MYC in regulating p53 stability as a function of increased ribosome biogenesis is controversial. On the one hand, it was suggested that MYC drives the overexpression of ribosomal proteins (RP)L5 and RPL11, which bind and inhibit HDM2, stabilizing p53. On the other, it has been proposed that increased ribosome biogenesis leads the consumption of RPL5/RPL11 into nascent ribosomes, reducing p53 levels and enhancing tumorigenesis. Here, we show that the components that make up the recently described impaired ribosome biogenesis checkpoint (IRBC) complex, RPL5, RPL11, and 5S rRNA, are reduced following MYC silencing. This leads to a rapid reduction in p53 protein half-life in an HDM2-dependent manner. In contrast, MYC induction leads to increased ribosome biogenesis and p53 protein stabilization. Unexpectedly, there is no change in free RPL5/RPL11 levels, but there is a striking increase in IRBC complex bound to HDM2. Our data support a cell-intrinsic tumor-suppressor response to MYC expression, which is presently being exploited to treat cancer.

Significance:
Oncogenic MYC induces the impaired ribosome biogenesis checkpoint, which could be potentially targeted for cancer treatment.
DNA–SWCNT Biosensors Allow Real-Time Monitoring of Therapeutic Responses in Pancreatic Ductal Adenocarcinoma
Authors: Bhattacharya Santanu , Gong Xun , Wang Enfeng , Dutta Shamit K. , Caplette Joseph R. , Son Manki , Nguyen Freddy T. , Strano Michael S. , Mukhopadhyay Debabrata 
Published: July 2019

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly desmoplastic cancer with limited treatment options. There is an urgent need for tools that monitor therapeutic responses in real time. Drugs such as gemcitabine and irinotecan elicit their therapeutic effect in cancer cells by producing hydrogen peroxide (H2O2). In this study, specific DNA-wrapped single-walled carbon nanotubes (SWCNT), which precisely monitor H2O2, were used to determine the therapeutic response of PDAC cells in vitro and tumors in vivo. Drug therapeutic efficacy was evaluated in vitro by monitoring H2O2 differences in situ using reversible alteration of Raman G-bands from the nanotubes. Implantation of the DNA–SWCNT probe inside the PDAC tumor resulted in approximately 50% reduction of Raman G-band intensity when treated with gemcitabine versus the pretreated tumor; the Raman G-band intensity reversed to its pretreatment level upon treatment withdrawal. In summary, using highly specific and sensitive DNA-SWCNT nanosensors, which can determine dynamic alteration of hydrogen peroxide in tumor, can evaluate the effectiveness of chemotherapeutics.

Significance:
A novel biosensor is used to detect intratumoral hydrogen peroxide, allowing real-time monitoring of responses to chemotherapeutic drugs.
Molecular Profiling Establishes Genetic Features Predictive of the Efficacy of the p110β Inhibitor KIN-193
Authors: Sethi Isha , Cai Zhenying , Roberts Thomas M. , Yuan Guo-Cheng 
Published: July 2019

Abstract

Aberrant activation of the PI3K pathway is a common alteration in human cancers. Therapeutic intervention targeting the PI3K pathway has achieved limited success due to the intricate balance of its different components and isoforms. Here, we systematically investigated the genomic and transcriptomic signatures associated with response to KIN-193, a compound specifically targeting the p110β isoform. By integrating genomic, transcriptomic, and drug response profiles from the Genomics of Drug Sensitivity in Cancer database, we identified mutational and transcriptomic signatures associated with KIN-193 and further created statistical models to predict the treatment effect of KIN-193 in cell lines, which may eventually be clinically valuable. These predictions were validated by analysis of the external Cancer Cell Line Encyclopedia dataset. These results may assist precise therapeutic intervention targeting the PI3K pathway.

Significance:
These findings provide new insights into molecular signatures associated with sensitivity of the p110β inhibitor KIN-193, which may provide a useful guide for developing precise treatment methods for cancer.
BORIS Expression in Ovarian Cancer Precursor Cells Alters the CTCF Cistrome and Enhances Invasiveness through GALNT14
Authors: Hillman Joanna C. , Pugacheva Elena M. , Barger Carter J. , Sribenja Sirinapa , Rosario Spencer , Albahrani Mustafa , Truskinovsky Alexander M. , Stablewski Aimee , Liu Song , Loukinov Dmitri I. , Zentner Gabriel E. , Lobanenkov Victor V. , Karpf Adam R. , Higgins Michael J. 
Published: July 2019

Abstract

High-grade serous carcinoma (HGSC) is the most aggressive and predominant form of epithelial ovarian cancer and the leading cause of gynecologic cancer–related death. We have previously shown that CTCFL (also known as BORIS, Brother of the Regulator of Imprinted Sites) is expressed in most ovarian cancers, and is associated with global and promoter-specific DNA hypomethylation, advanced tumor stage, and poor prognosis. To explore its role in HGSC, we expressed BORIS in human fallopian tube secretory epithelial cells (FTSEC), the presumptive cells of origin for HGSC. BORIS-expressing cells exhibited increased motility and invasion, and BORIS expression was associated with alterations in several cancer-associated gene expression networks, including fatty acid metabolism, TNF signaling, cell migration, and ECM–receptor interactions. Importantly, GALNT14, a glycosyltransferase gene implicated in cancer cell migration and invasion, was highly induced by BORIS, and GALNT14 knockdown significantly abrogated BORIS-induced cell motility and invasion. In addition, in silico analyses provided evidence for BORIS and GALNT14 coexpression in several cancers. Finally, ChIP-seq demonstrated that expression of BORIS was associated with de novo and enhanced binding of CTCF at hundreds of loci, many of which correlated with activation of transcription at target genes, including GALNT14. Taken together, our data indicate that BORIS may promote cell motility and invasion in HGSC via upregulation of GALNT14, and suggests BORIS as a potential therapeutic target in this malignancy.

Implications:
These studies provide evidence that aberrant expression of BORIS may play a role in the progression to HGSC by enhancing the migratory and invasive properties of FTSEC.
Antropofagia Literária e Literal na sua relação com os Estudos da Tradução
Authors: Vieira Filho Edgar Rosa 
Published: July 2019

O presente ensaio tem como objetivo realizar uma apreciação crítica das reflexões que deslocam a metáfora/conceito antropofágico oswaldiano e, mais recentemente, o ritual antropófago via estudos sobre perspectivismo ameríndio em Viveiros de Castro, para o campo dos Estudos da Tradução. A fim de se compreender a relação e os desdobramentos suscitados pela associação entre Antropofagia e prática tradutória, buscou-se distinguir, pautando-se na proposição terminológica do antropólogo brasileiro Carlos Fausto, as diferentes bases/fontes que orientam tais reflexões aproximativas.
Palavras-chave: Antropofagia modernista; Perspectivismo ameríndio; Estudos da Tradução; Xamanismo; Alteridade.
Impact of Diabetes Mellitus in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents
Authors: Baber Usman , Stefanini Giulio G. , Giustino Gennaro , Stone Gregg W. , Leon Martin B. , Sartori Samantha , Aquino Melissa , Steg P. Gabriel , Windecker Stephan , Wijns William , Serruys Patrick W. , Valgimigli Marco , Morice Marie–Claude , Camenzind Edoardo , Weisz Giora , Smits Pieter C. , Kandzari David E. , von Birgelen Clemens , Dangas George D. , Galatius Soren , Jeger Raban V. , Kimura Takeshi , Mikhail Ghada W. , Itchhaporia Dipti , Mehta Laxmi , Ortega Rebecca , Kim Hyo-Soo , Kastrati Adnan , Chieffo Alaide , Mehran Roxana 
Published: July 2019

Background:
Data examining the impact of diabetes mellitus (DM) on ischemic risk after percutaneous coronary intervention in women are limited as most clinical trial participants are male. We evaluated (1) the impact of DM on ischemic outcomes in women undergoing drug-eluting stent (DES) implantation and (2) whether the outcomes of new- versus early-generation DES vary by DM status.

Methods and Results:

We pooled patient-level data of 10 448 women undergoing percutaneous coronary intervention with DES from 26 randomized trials. Baseline characteristics and 3-year clinical outcomes were stratified according to DM status (noninsulin-dependent and insulin-dependent) and DES generation. The primary end point was the composite of all-cause death or myocardial infarction. Secondary end points were definite or probable stent thrombosis and target lesion revascularization. Compared with women without DM (n=7154, 68.5%), adjusted risks (adjusted hazard ratios [95% CI]) for death or myocardial infarction among women with noninsulin-dependent DM (n=2241, 21.4%) and insulin-dependent DM (n=1053, 10.1%) were 1.30 (1.11–1.53) and 1.71 (1.41–2.07), respectively (
P
trend
<0.001). Similar trends were observed for def/prob stent thrombosis and target lesion revascularization. Compared with early-generation DES, use of newer-generation DES was associated with significant reductions in death or myocardial infarction in the absence of DM whereas differences were nonsignificant in the presence of DM, with similar findings for def/prob stent thrombosis and target lesion revascularization.

Conclusions:
The presence of DM is associated with substantial, graded, and durable risks for ischemic events among women undergoing percutaneous coronary intervention with DES. The safety and efficacy profile of newer-generation DES is preserved among women without DM, while benefits are nonsignificant among women with DM.