bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surgical, Speech, and Audiologic Outcomes in Patients With Orofacial Cleft and Van der Woude Syndrome
Authors: Kitchin Spencer , Grames Lynn , Naidoo Sybill D. , Skolnick Gary , Schoenborn Alyssa , Snyder-Warwick Alison , Patel Kamlesh 
Published: May 2019

Objective:The purpose of this study was to investigate the surgical, speech, and audiologic outcomes in patients with Van der Woude syndrome (VWS) and compare them to patients with nonsyndromic cleft palate with or without cleft lip (NS-CP ± L) treated at the same institution.Design:Retrospective chart review.Setting:A single children's hospital at a major academic institution.Patients:The records of 18 patients with VWS who had been treated at a single institution from 1989 to 2017 have been retrospectively examined. Thirty-eight patients with NS-CP ± L who were also treated at the same institution during that same time frame were selected to closely match sex and date of birth.Main Outcome Measures:Demographic, clinical, surgical, and speech pathology data were gathered from medical charts.Result:By age 4, 88% of subjects with VWS and 76% of subjects with NS-CP ± L (P = 0.732) had been, or were actively involved in, speech therapy. By age 10, 100% of remaining subjects with VWS and 58% of remaining subjects with NS-CP ± L remained involved in speech therapy (P = 0.027).About 33% of patients with VWS and 16% of patients with NS-CP ± L had a secondary procedure for velopharyngeal dysfunction (VPD) (P = 0.171).Conclusion:The VWS group had more than twice the rate of secondary procedures for VPD repair, and a higher rate of continuing involvement for speech therapy at age 10. No differences were found in the rate of participation in speech therapy at or by age 4.
Admission Leukocyte Count is Associated with Late Cardiogenic Shock Development and All-Cause 30-Day Mortality in Patients with St-Elevation Myocardial Infarction
Authors: Klein Anika , Wiberg Sebastian , Hassager Christian , Winther-Jensen Matilde , Frikke-Schmidt Ruth , Bang Lia Evi , Lindholm Matias Greve , Holmvang Lene , Moeller-Helgestad Ole , Ravn Hanne Berg , Jensen Lisette Okkels , Kjaergaard Jesper , Moeller Jacob Eifer , Frydland Martin 
Published: May 2019

ABSTRACT

Background:
Thirty-day mortality in ST-elevation myocardial infarction (STEMI) patients is primarily driven by cardiogenic shock (CS). High neutrophil counts and high neutrophil/lymphocyte ratios (NLR) have previously been associated with mortality in STEMI patients; however, there is only sparse knowledge regarding their association with CS.

Purpose:
We sought to assess the associations between neutrophil count and NLR with the development of CS as well as 30-day mortality in STEMI patients.

Methods:
Patients admitted with STEMI at two tertiary Heart Centres throughout 1 year were included in the study and stratified into quartiles according to the level of leukocyte count upon admission. The primary endpoint was development of CS both before (early CS) and after leaving the catheterization laboratory (late CS). The secondary endpoint was all-cause 30-day mortality.

Results:
A total of 1,892 STEMI patients were included, whereof 194 (10%) developed CS while 122 (6.4%) died within 30 days. Patients in the highest quartile of neutrophils (OR: 2.54; 95% CI: 1.40–4.60; P = 0.002) and NLR (OR: 3.64; 95% CI: 2.02–6.54; P<0.0001) were at increased risk of developing late CS compared with patients in the lower quartiles, whereas there was no risk difference across quartiles regarding development of early CS. Both biomarkers correlated strongly to an increased 30-day mortality (plogrank<0.0001) and, moreover, a high level of neutrophils was independently associated with 30-day mortality (HR: 1.95; 95% CI: 1.25–3.03; P = 0.003).

Conclusion:
High levels of neutrophils and a high NLR upon admission for STEMI were independently associated with an increased risk of developing late CS and, additionally, both biomarkers showed association to 30-day mortality.
Stressors in Midlife and Risk of Dementia
Authors: Gilsanz Paola , Quesenberry Charles P. , Mayeda Elizabeth Rose , Glymour M. Maria , Farias Sarah T. , Whitmer Rachel A. 
Published: May 2019

Background:
Posttraumatic stress disorder is associated with increased dementia risk but less is known about stress because of everyday problems in diverse populations.

Methods:
A total of 9605 health care plan members who provided information regarding midlife stressors in 1972 to 1973 (ages, 40 to 55 y) were followed for dementia diagnosis between 1996 and 2017. Cox proportional hazard models evaluated associations between midlife stressors and dementia adjusting for demographics and lifecourse health indicators.

Results:
Reporting at least 1 midlife stressor was associated with 17% greater dementia risk [hazard ratio (HR), 1.17; 95% confidence interval (CI),1.07-1.27] versus 0 midlife stressors and 26% increased risk among those with less than equal to high school education (HR, 1.26; 95% CI,1.09-1.44) adjusting for demographics. Compared with whites without stressors, whites with ≥1 stressor had 13% greater dementia risk (HR, 1.13; 95% CI, 1.02-1.24), blacks without stressors 19% greater risk (HR, 1.19; 95% CI,1.08-1.32), and blacks with ≥1 stressors 47% greater risk (HR, 1.47; 95% CI,1.27-1.69) in fully adjusted models. Resource problems were associated with 20% greater risk (HR, 1.20; 95% CI, 1.01-1.42) than interpersonal problems.

Conclusion:
Reporting ≥1 serious midlife stressor was associated with elevated dementia risk, especially stressors related to resources problems and for those with less than equal to high school education. Everyday stressors can impact brain health over the long term and may contribute to racial inequities in dementia rates, though education can be a mitigating factor.
Myeloid Tribbles 1 induces early atherosclerosis via enhanced foam cell expansion
Authors: Johnston Jessica M , Angyal Adrienn , Bauer Robert C , Hamby Stephen , Suvarna S Kim , Baidžajevas Kajus , Hegedus Zoltan , Dear T Neil , Turner Martin ,   The Cardiogenics Consortium, Wilson Heather L , Goodall Alison H , Rader Daniel J , Shoulders Carol C , Francis Sheila E , Kiss-Toth Endre 
Published: May 2019

AbstractMacrophages drive atherosclerotic plaque progression and rupture, hence attenuating their atherosclerosis-inducing properties holds promise for reducing coronary heart disease (CHD). Recent studies in mouse models have demonstrated that Tribbles 1 (Trib1) regulates macrophage phenotype and shows that Trib1 deficiency increases plasma cholesterol and triglyceride levels, suggesting that reduced TRIB1 expression mediates the strong genetic association between the TRIB1 locus and increased CHD risk in man. However, we report here that myeloid-specific Trib1 (mTrib1) deficiency reduces early atheroma formation and that mTrib1 transgene expression increases atherogenesis. Mechanistically, mTrib1 increased macrophage lipid accumulation and the expression of a critical receptor (OLR1), promoting oxidized low density lipoprotein uptake and the formation of lipid-laden foam cells. As TRIB1 and OLR1 RNA levels were also strongly correlated in human macrophages, we suggest that a conserved, TRIB1-mediated mechanism drives foam cell formation in atherosclerotic plaque and that inhibiting mTRIB1 could be used therapeutically to reduce CHD.
LFPy – multimodal modeling of extracellular neuronal recordings in Python
Authors: Hagen Espen , Næss Solveig , Ness Torbjørn V. , Einevoll Gaute T. 
Published: May 2019

1.AbstractLFPy is an open-source tool for calculating brain signals such as extracellular potentials and magnetic signals from simulated activity in multicompartment neuron models, ranging from single cells to large neuronal networks. The tool is provided as a Python package, and relies on the NEURON simulation environment.
Psychotic symptoms in 16p11.2 copy number variant carriers
Authors: Jutla Amandeep , Turner J. Blake , Snyder LeeAnne Green , Chung Wendy K. , Veenstra-VanderWeele Jeremy 
Published: May 2019

Abstract16p11.2 copy number variation (CNV) is implicated in neurodevelopmental disorders, with the duplication and deletion associated with autism spectrum disorder (ASD) and the duplication associated with schizophrenia (SCZ). The 16p11.2 CNV may therefore provide insight into the relationship between ASD and SCZ, distinct disorders that co-occur at an elevated rate and are difficult to distinguish from each other and from common co-occurring diagnoses such as obsessive compulsive disorder (OCD), itself a potential risk factor for SCZ. As psychotic symptoms are core to SCZ but distinct from ASD, we sought to examine their predictors in a population (n = 546) of 16p11.2 CNV carriers and their noncarrier siblings recruited by the Simons Variation in Individuals Project. We hypothesized that psychotic symptoms would be most common in duplication carriers followed by deletion carriers and noncarriers, that an ASD diagnosis would predict psychotic symptoms among CNV carriers, and that OCD symptoms would predict psychotic symptoms among all participants. Using data collected across multiple measures, we identified 19 participants with psychotic symptoms. Logistic regression models adjusting for biological sex, age, and IQ found that 16p11.2 duplication and ASD diagnosis predicted psychotic symptom presence. Our findings suggest that the association between 16p11.2 duplication and psychotic symptoms is independent of ASD diagnosis and that ASD diagnosis and psychotic symptoms may be associated in 16p11.2 CNV carriers.Lay SummaryEither deletion or duplication at chromosome 16p11.2 raises the risk of autism spectrum disorder, and duplication, but not deletion, has been reported in schizophrenia. In a sample of 16p11.2 deletion and duplication carriers, we found that having the duplication or having an autism diagnosis may increase the risk of psychosis, a key feature of schizophrenia.
Optimizing systemic insecticide use to improve malaria control
Authors: Meredith Hannah R. , Furuya-Kanamori Luis , Yakob Laith 
Published: May 2019

AbstractLong lasting insecticidal nets and indoor residual sprays have significantly reduced the burden of malaria. However, several hurdles remain before elimination can be achieved: mosquito vectors have developed resistance to public health insecticides, including pyrethroids, and have altered their biting behaviour to avoid these indoor control tools. Systemic insecticides, drugs applied directly to blood-hosts to kill mosquitoes that take a blood meal, offer a promising vector control option. To date, most studies focus on repurposing ivermectin, a drug used extensively to treat river blindness. There is concern that over-dependence on a single drug will inevitably repeat past experiences with the rapid spread of pyrethroid resistance in malaria vectors. Diversifying the arsenal of systemic insecticides used for mass drug administration would improve this strategy’s sustainability. Here, a review was conducted to identify systemic insecticide candidates and consolidate their pharmacokinetic/pharmacodynamic properties. The impact of alternative integrated vector control options and different dosing regimens on malaria transmission reduction are illustrated through a mathematical model simulation. The review identified drugs from four classes commonly used in livestock and companion animals: avermectics, milbemycins, isoxazolines, and spinosyns. Simulations predicted that isoxazoline and spinosyn drugs were promising candidates for mass drug administration, as they were predicted to need less frequent application than avermectins and milbemycins to maintain mosquitocidal blood concentrations. These findings will provide a guide for investigating and applying different systemic insecticides to achieve better mosquito control strategies.SignificanceThe widespread use of long lasting insecticidal nets (LLINs) and indoor residual spray has selected for mosquitoes that are resistant to pyrethroids or avoid exposure by feeding outdoors or on livestock. Systemic insecticides, drugs that render a host’s blood toxic to feeding mosquitoes, could be an effective control strategy for mosquitoes with pyrethroid resistance and/or outdoor feeding tendencies. Here, a number of existing systemic insecticide candidates are identified and their pharmacokinetic properties in different drug-host-route scenarios consolidated. These data were used to parameterise a mathematical model that illustrated the projected gains achievable in malaria control programmes already employing LLINs. The findings provide a guide for investigating and applying different systemic insecticides to improve mosquito control strategies and reduce malaria transmission.
Dopamine replacement remediates risk aversion in Parkinson’s disease in a value-independent manner
Authors: Cherkasova Mariya V. , Corrow Jeffrey C. , Taylor Alisdair , Yeung Shanna C. , Stubbs Jacob L. , McKeown Martin J. , Appel-Cresswell Silke , Stoessl A. Jon , Barton Jason J. S. 
Published: May 2019

ABSTRACTIntroductionClinical evidence suggests that Parkinson’s Disease (PD) patients are risk averse. Dopaminergic therapy has been reported to increase risk tolerance, but the underlying mechanisms are unclear. Some studies have suggested an amplification of subjective reward value, consistent with the role of dopamine in reward value coding. Others have reported value-independent risk enhancement. We evaluated the value-dependence of the effects of PD and its therapy on risk using tasks designed to sensitively measure risk over a wide range of expected values.Method36 patients with idiopathic PD receiving levodopa monotherapy and 36 healthy matched controls performed two behavioural economic tasks aimed at quantifying 1) risk tolerance/ aversion in the gain frame and 2) valuation of potential gains relative to losses. PD patients performed the tasks on and off their usual dose of levodopa in randomized order; controls performed the same tasks twice.ResultsRelative to the controls, unmedicated PD patients showed significant value-independent risk aversion in the gain frame, which was normalized by levodopa. PD patients did not differ from controls in their valuation of gains relative to losses. However, across both tasks and regardless of medication, choices of the patients were more determined by expected values of the prospects than those of controls.ConclusionDopamine deficiency in PD was associated with risk aversion, and levodopa promoted riskier choice in a value-independent manner. PD patients also showed an increased sensitivity to expected value, which was independent of levodopa and does not appear to result directly from dopamine deficiency.
Sonogenetic modulation of cellular activities using an engineered auditory-sensing protein
Authors: Huang Yao-Shen , Fan Ching-Hsiang , Hsu Ning , Wu Chun-Yao , Chang Chu-Yuan , Hong Shi-Rong , Chang Ya-Chu , Wu Anthony Yan-Tang , Guo Vanessa , Chiang Yueh-Chen , Hsu Wei-Chia , Chiu Nai-Hua , Chen Linyi , Lai Charles Pin-Kuang , Yeh Chih-Kuang , Lin Yu-Chun 
Published: May 2019

AbstractBiomolecules that respond to different external stimuli enable the remote control of genetically modified cells. Chemogenetics and optogenetics, two tools that can control cellular activities via synthetic chemicals or photons, respectively, have been widely used to elucidate underlying physiological processes. These methods are, however, very invasive, have poor penetrability, or low spatiotemporal precision, attributes that hinder their use in therapeutic applications. We report herein a sonogenetic approach that can manipulate target cell activities by focused ultrasound stimulation. This system requires an ultrasound-responsive protein derived from an engineered auditory-sensing protein prestin. Heterogeneous expression of mouse prestin containing two parallel amino acid substitutions, N7T and N308S, that frequently exist in prestins from echolocating species endowed transfected mammalian cells with the ability to sense ultrasound. An ultrasound pulse of low frequency and low pressure efficiently evoked cellular calcium responses after transfecting with prestin(N7T, N308S). Moreover, pulsed ultrasound can also non-invasively stimulate target neurons expressing prestin(N7T, N308S) in deep regions of mice brains. Our study delineates how an engineered auditory-sensing protein can cause mammalian cells to sense ultrasound stimulation. Moreover, owing to the great penetration of low-frequency ultrasound (∼400 mm in depth), our sonogenetic tools will serve as new strategies for non-invasive therapy in deep tissues of large animals like primates.
Associations between EEG functional brain connectivity and a cognitive reserve proxy in healthy older adults
Authors: Moezzi Bahar , Lavrencic Louise M. , Goldsworthy Mitchell R. , Coussens Scott , Keage Hannah A.D. 
Published: May 2019

AbstractCognitive reserve is a concept that explains individual differences in vulnerability to cognitive impairment due to age and dementia-related brain changes. Mechanisms underlying the cognitive reserve effect are poorly understood. We investigated associations between a comprehensive cognitive reserve proxy (Lifetime Experiences Questionnaire/LEQ) and functional connectivity of the prefrontal cortex across the whole scalp, covarying for the level of current cognitive functioning (Addenbrookes Cognitive Examination Revised/ACE-R), using multiblock parallel and orthogonalized partial least squares regression. EEG data were collected from 34 healthy older adults (63 to 83 years) in eyes-open and eyes-closed resting-states, and during 0-back and 1-back tasks. Functional connectivity was estimated using imaginary coherence in the theta and alpha frequency bands, as these bands have been heavily implicated in cognitive ageing, attention and executive function. We found three clusters of electrodes where the absolute values of the regression coefficient were above threshold when covarying for ACE-R: (1) a cluster approximating the right frontocentral region during the eyes-open condition in the theta band with seed electrodes approximating the left prefrontal cortex with positive associations of medium effect size; (2) a cluster approximating the right parietotemporal region during the 0-back task in the theta band with seed electrodes approximating the right prefrontal cortex with negative associations of medium to large effect sizes; and (3) a cluster approximating the occipitoparietal region in the eyes-closed condition in the alpha band with seed electrodes approximating the left prefrontal cortex with negative associations of medium effect size. These relationships between a cognitive reserve proxy and functional connectivity, within key networks and frequency bands associated with attention and executive function, may reflect greater neural capacity and efficiency.
Population structure of Apodemus flavicollis and comparison to Apodemus sylvaticus in northern Poland based on RAD-seq
Authors: Cerezo Maria Luisa Martin , Kucka Marek , Zub Karol , Chan Yingguang Frank , Bryk Jarosław 
Published: May 2019

AbstractBackgroundMice of the genus Apodemus are one the most common mammals in the Palaearctic region. Despite their broad range and long history of ecological observations, there are no whole-genome data available for Apodemus, hindering our ability to further exploit the genus in evolutionary and ecological genomics context.ResultsHere we present results from the double-digest restriction site-associated DNA sequencing (ddRAD-seq) on 72 individuals of A. flavicollis and 10 A. sylvaticus from four populations, sampled across 500 km distance in northern Poland. Our data present clear genetic divergence of the two species, with average p-distance, based on 21377 common loci, of 1.51% and a mutation rate of 0.0011 - 0.0019 substitutions per site per million years. We provide a catalogue of 117 highly divergent loci that enable genetic differentiation of the two species in Poland and to a large degree of 20 unrelated samples from several European countries and Tunisia. We also show evidence of admixture between the three A. flavicollis populations but demonstrate that they have negligible average population structure, with largest pairwise FST < 0.086.ConclusionOur study demonstrates the feasibility of ddRAD-seq in Apodemus and provides the first insights into the population genomics of the species.
Bioinformatic Methods and Bridging of Assay Results for Reliable Tumor Mutational Burden Assessment in Non-Small Cell Lung Cancer
Authors: Chang Han , Sasson Ariella , Srinivasan Sujaya , Golhar Ryan , Greenawalt Danielle M. , Geese William J. , Green George , Zerba Kim , Kirov Stefan , Szustakowski Joseph 
Published: May 2019

AbstractIntroductionTumor mutational burden (TMB) has emerged as a clinically relevant biomarker that may be associated with immune checkpoint inhibitor efficacy. Standardization of TMB measurement is essential for implementing diagnostic tools to guide treatment.ObjectiveHere we describe the in-depth evaluation of bioinformatic TMB analysis by whole exome sequencing (WES) in formalin-fixed, paraffin-embedded samples from a phase 3 clinical trial.MethodsIn the CheckMate 026 clinical trial, TMB was retrospectively assessed in 312 patients with non-small cell lung cancer (58% of the intent-to-treat population) who received first-line nivolumab treatment or standard-of-care chemotherapy. We examined the sensitivity of TMB assessment to bioinformatic filtering methods and assessed concordance between TMB data derived by WES and the FoundationOne®CDx assay.ResultsTMB scores comprising synonymous, indel, frameshift, and nonsense mutations (all mutations) were 3.1-fold higher than data including missense mutations only, but values were highly correlated (Spearman’s r = 0.99). Scores from CheckMate 026 samples including missense mutations only were similar to those generated from data in The Cancer Genome Atlas, but those including all mutations were generally higher. Using databases for germline subtraction (instead of matched controls) showed a trend for race-dependent increases in TMB scores. WES and FoundationOne CDx outputs were highly correlated (Spearman’s r = 0.90).ConclusionsParameter variation can impact TMB calculations, highlighting the need for standardization. Encouragingly, differences between assays could be accounted for by empirical calibration, suggesting that reliable TMB assessment across assays, platforms, and centers is achievable.Key PointsTumor mutational burden (TMB) is a clinically relevant biomarker for efficacy of immunotherapy in patients with cancerVariations in TMB assessment parameters can shift the final TMB value. Harmonization and standardization are important to the successful clinical implementation of TMB testingTMB values assessed by different methods are highly correlated. Harmonization of TMB testing in patients with cancer is therefore achievable