bluuebunny/crossref_metadata_2025_split huggingface dataset:
A quantitative confidence signal detection model: 2. Confidence analysis
Authors: Yi Yongwoo , Wang Wei , Merfeld Daniel M. 
Published: June 2019

Decision making is a fundamental subfield within neuroscience. While recent findings have yielded major advances in our understanding of decision making, confidence in such decisions remains poorly understood. In this paper, we present a confidence signal detection (CSD) model that combines a standard signal detection model yielding a noisy decision variable with a model of confidence. The CSD model requires quantitative measures of confidence obtained by recording confidence probability judgments. Specifically, we model confidence probability judgments for binary direction recognition (e.g., did I move left or right) decisions. We use our CSD model to study both confidence calibration (i.e., how does confidence compare with performance) and the distributions of confidence probability judgments. We evaluate two variants of our CSD model: a conventional model with two free parameters (CSD2) that assumes that confidence is well calibrated and our new model with three free parameters (CSD3) that includes an additional confidence scaling factor. On average, our CSD2 and CSD3 models explain 73 and 82%, respectively, of the variance found in our empirical data set. Furthermore, for our large data sets consisting of 3,600 trials per subject, correlation and residual analyses suggest that the CSD3 model better explains the predominant aspects of the empirical data than the CSD2 model, especially for subjects whose confidence is not well calibrated. Moreover, simulations show that asymmetric confidence distributions can lead traditional confidence calibration analyses to suggest “underconfidence” even when confidence is perfectly calibrated. These findings show that this CSD model can be used to help improve our understanding of confidence and decision making. NEW & NOTEWORTHY We make life-or-death decisions each day; our actions depend on our “confidence.” Though confidence, accuracy, and response time are the three pillars of decision making, we know little about confidence. In a previous paper, we presented a new model — dependent on a single scaling parameter — that transforms decision variables to confidence. Here we show that this model explains the empirical human confidence distributions obtained during a vestibular direction recognition task better than standard signal detection models.
Successful auditory motor adaptation requires task-relevant auditory errors
Authors: Daliri Ayoub , Dittman Jonathan 
Published: June 2019

When we produce speech movements, we also predict the auditory consequences of the movements. We use discrepancies between our predictions and incoming auditory information to modify our future movements (adapt). Although auditory errors are crucial for speech motor learning, not all perceived auditory errors are consequences of our own actions. Therefore, the brain needs to evaluate the relevance of perceived auditory errors. In this study, we examined error assessment processes involved in auditory motor adaptation by systematically manipulating the correspondence between speech motor outputs and their auditory consequences during speaking. Participants ( n = 30) produced speech while they received perturbed auditory feedback (e.g., produced “head” but heard a word that sounded like “had”). In one condition, auditory errors were related to participants’ productions (task-relevant errors). In another condition, auditory errors were defined by the experimenter and had no correspondence with participants’ speech output (task-irrelevant errors). We found that the extent of adaptation and error sensitivity (derived from a state-space model) were greater in the condition with task-relevant auditory errors compared with those in the condition with task-irrelevant auditory errors. Additionally, participants with smaller perceptual targets (derived from a categorical perception task) adapted more to auditory perturbations, and participants with larger perceptual targets adapted less. Similarly, participants with smaller perceptual targets were more sensitive to errors in the condition with task-relevant auditory errors. Together, our results highlight the intricate mechanisms, involving both perception and production systems, that the brain uses to optimally integrate auditory errors for successful speech motor learning. NEW & NOTEWORTHY Feedback monitoring is essential for accurate speech production. By providing empirical results and a computational framework, we show that 1) the brain evaluates relevance of auditory errors and responds more to relevant errors, and 2) smaller perceptual targets are associated with more sensitivity to errors and more auditory motor adaptation.
A Prospective Study of Toenail Trace Element Levels and Risk of Skin Cancer
Authors: Matthews Natalie H. , Koh Michelle , Li Wen-Qing , Li Tricia , Willett Walter C. , Stampfer Meir J. , Christiani David C. , Morris J. Steven , Qureshi Abrar A. , Cho Eunyoung 
Published: June 2019

Abstract

Background:
Few epidemiologic studies have investigated trace element exposure and skin cancer risk.

Methods:
Toenail levels of mercury, selenium, chromium, iron, and zinc were measured from 6,708 women in the Nurses' Health Study (1984–2012) and 3,730 men in the Health Professionals Follow-up Study (1986–2012) with data from prior nested case–control studies. Participants were free of skin cancer at toenail collection and followed for incident basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. Cox proportional hazards models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) of skin cancer associated with the elements in each study. We calculated pooled multivariable HRs using a fixed-effects model. During 26 to 28 years of follow-up, 2,433 BCC, 334 SCC, and 130 melanoma cases were documented.

Results:
Higher toenail mercury levels were associated with risk of BCC [pooled HR for top vs. bottom quintiles = 1.34 (95% CI, 1.18–1.52), Ptrend &lt; 0.0001]. Similar direct associations were found with risks of SCC [pooled HR for top vs. bottom quartiles = 1.41 (95% CI, 1.03–1.94), Ptrend = 0.04] and melanoma [pooled HR for top vs. bottom quartiles = 1.88 (95% CI, 1.12–3.16), Ptrend = 0.02]. Chromium was positively associated with BCC in women only. No associations were found between other metals and skin cancer risk.

Conclusions:
Our prospective data found that increased toenail mercury concentrations were associated with increased skin cancer risk.

Impact:
If our novel findings are confirmed, mercury may play a role in skin carcinogenesis.
Activation of JAK/STAT Signaling in Megakaryocytes Sustains Myeloproliferation In Vivo
Authors: Woods Brittany , Chen Wei , Chiu Sophia , Marinaccio Christian , Fu Chunling , Gu Lilly , Bulic Marinka , Yang Qiong , Zouak Anouar , Jia Shengxian , Suraneni Praveen Kumar , Xu Kailin , Levine Ross L. , Crispino John D. , Wen Qiang Jeremy 
Published: June 2019

Abstract

Purpose:
The myeloproliferative neoplasms (MPN), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are characterized by the expansion of the erythroid, megakaryocytic, and granulocytic lineages. A common feature of these disorders is the presence of abnormal megakaryocytes, which have been implicated as causative agents in the development of bone marrow fibrosis. However, the specific contributions of megakaryocytes to MPN pathogenesis remain unclear.

Experimental Design:
We used Pf4-Cre transgenic mice to drive expression of JAK2V617F in megakaryocyte lineage–committed hematopoietic cells. We also assessed the critical role of mutant megakaryocytes in MPN maintenance through cell ablation studies in JAK2V617F and MPLW515L BMT models of MPN.

Results:
JAK2V617F-mutant presence in megakaryocytes was sufficient to induce enhanced erythropoiesis and promote fibrosis, which leads to a myeloproliferative state with expansion of mutant and nonmutant hematopoietic cells. The increased erythropoiesis was associated with elevated IL6 level, which was also required for aberrant erythropoiesis in vivo. Furthermore, depletion of megakaryocytes in the JAK2V617F and MPLW515L BMT models ameliorated polycythemia and leukocytosis in addition to expected effects on megakaryopoiesis.

Conclusions:
Our observations reveal that JAK/STAT pathway activation in megakaryocytes induces myeloproliferation and is necessary for MPN maintenance in vivo. These observations indicate that MPN clone can influence the behavior of the wild-type hematopoietic milieu, at least, in part, via altered production of proinflammatory cytokines and chemokines. Our findings resonate with patients who present with a clinical MPN and a low JAK2V617F allele burden, and support the development of MPN therapies aimed at targeting megakaryocytes.
An EGFR-InducedDrosophilaLung Tumor Model Identifies Alternative Combination Treatments
Authors: Bossen Judith , Uliczka Karin , Steen Line , Pfefferkorn Roxana , Mai Mandy Mong-Quyen , Burkhardt Lia , Spohn Michael , Bruchhaus Iris , Fink Christine , Heine Holger , Roeder Thomas 
Published: June 2019

AbstractLung cancer is the leading cause of cancer-associated mortality. Mutations in the EGFR gene are among the most important inducers of lung tumor development, but success of personalized therapies is still limited because of toxicity or developing resistances. We expressed constitutively active EGFR (EGFRCA) exclusively in the airway system of Drosophila melanogaster and performed comprehensive phenotyping. Ectopic expression of EGFRCA induced massive hyper- and metaplasia, leading to early death. We used the lethal phenotype as a readout and screened a library of FDA-approved compounds and found that among the 1,000 compounds, only the tyrosine kinase inhibitors (TKI) afatinib, gefitinib, and ibrutinib rescued lethality in a whole-animal screening approach. Furthermore, we screened the library in the presence of a subtherapeutic afatinib dose and identified bazedoxifene as a synergistically acting compound that rescues EGFR-induced lethality. Our findings highlight the potential of Drosophila-based whole-animal screening approaches not only to identify specific EGFR inhibitors but also to discover compounds that act synergistically with known TKIs. Moreover, we showed that targeting the EGFR together with STAT-signaling is a promising strategy for lung tumor treatment.
ФОРМИ І МЕТОДИ ЯКІСНОГО НАВЧАННЯ НА ЗАНЯТТЯХ З ФАРМАКОЛОГІЇ
Authors: Kazaniuk T. V. 
Published: June 2019

у статті наведено досвід викладання фармакології для студентів, які навчаються за спеціальністю 223 «Медсестринство». Розглянуто методики проведення аудиторної та позааудиторної роботи студентів, використання яких сприятиме підвищенню ефективності підготовки майбутніх медичних сестер до професійної діяльності.
Statin Use and Risk of Vascular Events Among Cancer Patients After Radiotherapy to the Thorax, Head, and Neck
Authors: Boulet Jacinthe , Peña Jessica , Hulten Edward A. , Neilan Tomas G. , Dragomir Alice , Freeman Carolyn , Lambert Christine , Hijal Tarek , Nadeau Lyne , Brophy James M. , Mousavi Negareh 
Published: June 2019

Background
This study aimed to explore whether statins reduce radiation‐induced vascular complications in cancer patients postradiotherapy to the thorax, head, and neck.

Methods and Results

We conducted a retrospective cohort study within a provincial linked database of 5718 cardiac patients with thorax and head or neck cancer having undergone radiotherapy between 2000 and 2011. One thousand five hundred fifty‐two patients were identified as nonstatin users and 4166 as statin users. The primary outcome of interest was the composite of cerebrovascular (transient ischemic attack, and fatal or nonfatal stroke) or cardiovascular events (fatal or nonfatal myocardial infarction). Time‐dependent Cox proportional hazard analyses were performed. The crude event rate was 10.31% for nonusers and 9.03% for statin users (hazard ratio of 0.92 [95%
CI
0.76–1.10,
P
=0.3451]), over a mean time to event/censoring of 534±687 days for nonusers and 594±706 days for the statin users. After adjusting for age, sex, prior history of stroke/transient ischemic attack or myocardial infarction, diabetes mellitus, dyslipidemia, atrial fibrillation, chronic kidney disease, heart failure, and hypertension, statin use postradiotherapy was associated with a nonsignificant 15% relative risk reduction, but a strong trend toward reducing the primary outcome (hazard ratio=0.85 95%
CI
0.69–1.04,
P
=0.0811). The use of statins was associated with a significant reduction of 32% for the outcome of stroke alone (hazard ratio=0.68, 95%
CI
0.48–0.98,
P
=0.0368).

Conclusions
Statin use post radiation therapy was associated with a significant reduction in stroke, with a trend toward significantly reducing cardiovascular and cerebrovascular events.
Burden of Cardiovascular Risk Factors Over Time and Arterial Stiffness in Youth With Type 1 Diabetes Mellitus: The SEARCH for Diabetes in Youth Study
Authors: Urbina Elaine M. , Isom Scott , Bell Ronny A. , Bowlby Deborah A. , D'Agostino Ralph , Daniels Stephen R. , Dolan Lawrence M. , Imperatore Giuseppina , Marcovina Santica M. , Merchant Anwar T. , Reynolds Kristi , Shah Amy S. , Wadwa R. Paul , Dabelea Dana ,   for the SEARCH for Diabetes in Youth Study Group
Published: June 2019

Background
The incidence of type 1 diabetes mellitus (T1DM) in children is increasing, resulting in higher burden of cardiovascular diseases due to diabetes mellitus–related vascular dysfunction.

Methods and Results

We examined cardiovascular risk factors (
CVRF
s) and arterial parameters in 1809 youth with T1DM. Demographics, anthropometrics, blood pressure, and laboratory data were collected at T1DM onset and 5 years later. Pulse wave velocity and augmentation index were collected with tonometry.
ANOVA
or chi‐square tests were used to test for differences in measures of arterial parameters by
CVRF
. Area under the curve of
CVRF
s was entered in general linear models to explore determinants of accelerate vascular aging. Participants at the time of arterial measurement were 17.6±4.5 years old, 50% female, 76% non‐Hispanic white, and duration of T1DM was 7.8±1.9 years. Glycemic control was poor (glycated hemoglobin, 9.1±1.8%). All arterial parameters were higher in participants with glycated hemoglobin ≥9% and pulse wave velocity was higher with lower insulin sensitivity or longer duration of diabetes mellitus. Differences in arterial parameters were found by sex, age, and presence of obesity, hypertension, or dyslipidemia. In multivariable models, higher glycated hemoglobin, lower insulin sensitivity, body mass index, blood pressure, and lipid areas under the curve were associated with accelerated vascular aging.

Conclusions

In young people with T1DM, persistent poor glycemic control and higher levels of traditional
CVRF
s are independently associated with arterial aging. Improving glycemic control and interventions to lower
CVRF
s may prevent future cardiovascular events in young individuals with T1DM.
Downregulation of Orexin Receptor in Hypothalamic Paraventricular Nucleus Decreases Blood Pressure in Obese Zucker Rats
Authors: Zhou Jing‐Jing , Ma Hui‐Jie , Shao Jianying , Wei Yan , Zhang Xiangjian , Zhang Yi , Li De‐Pei 
Published: June 2019

Background

Orexin and its receptors are critical regulating sympathetic vasomotor tone under physiological and pathophysiological conditions. Orexin receptor 1 (
OXR
1) is upregulated in the paraventricular nucleus (
PVN
) in the hypothalamus and contributes to increased sympathetic outflow in obese Zucker rats (
OZR
s). We hypothesized that silencing
OXR
1 expression in the
PVN
decreases heightened blood pressure and elevated sympathetic outflow in
OZR
s.

Methods and Results

An adeno‐associated virus (
AAV
) vector containing a short hairpin
RNA
(sh
RNA
) targeting rat
OXR
1 was designed to silence
OXR
1 expression in the
PVN
. The
AAV
‐
OXR
1‐sh
RNA
or scrambled sh
RNA
was injected into the
PVN
in
OZR
s. The arterial blood pressure in free‐moving
OZR
s was continuously monitored by using a telemetry approach. The firing activity of spinally projecting
PVN
neurons in rat brain slices was recorded 3 to 4 weeks after injection of viral vectors. The free‐moving
OZR
s treated with
AAV
‐
OXR
1‐sh
RNA
had markedly lower
OXR
1 expression and lower mean arterial blood pressure, heart rate, and ratio of low‐ to high‐frequency components of heart rate variability compared with
OZR
s treated with scrambled sh
RNA
. Furthermore,
AAV
‐
OXR
1‐sh
RNA
treatment markedly reduced renal sympathetic nerve activity and attenuated sympathoexcitatory response induced by microinjection of orexin A into the
PVN
. In addition, treatment with
AAV
‐
OXR
1‐sh
RNA
substantially decreased the basal firing activity of spinally projecting
PVN
neurons in
OZR
s and attenuated the excitatory effect of orexin A on the firing activity of these neurons.

Conclusions

These data suggest that chronic downregulation of
OXR
1 expression in the
PVN
reduces sympathetic vasomotor tone in obesity‐related hypertension.
Efficacy of Long‐Term Remote Ischemic Conditioning on Vascular and Neuronal Function in Type 2 Diabetes Patients With Peripheral Arterial Disease
Authors: Hansen Christian S. , Jørgensen Marit E. , Fleischer Jesper , Bøtker Hans Erik , Rossing Peter 
Published: June 2019

Background

Peripheral artery disease is a major socioeconomic challenge in the diabetes mellitus community and non‐surgical treatment options are limited. As remote ischemic conditioning (
RIC
) improves vascular function and attenuates ischemia‐induced tissue damage, we investigated the efficacy of
RIC
on vascular and neuronal function in type 2 diabetes mellitus patients with peripheral artery disease.

Methods and Results

We enrolled 36 type 2 diabetes mellitus patients with moderately reduced toe pressure (40–70 mm Hg) in a randomized sham‐controlled double‐masked trial. Patients were allocated to 12 weeks once daily upper arm cuff‐based treatment of either
RIC
treatment (4 cycles of 5‐minute ischemia followed by 5‐minute reperfusion) or similar sham‐device treatment. Primary outcome was transcutaneous tissue oxygen tension of the instep of the feet. Secondary outcomes were aortic pulse wave velocity, toe pressure and toe‐brachial index. Tertiary outcomes were markers of peripheral and autonomic nerve function. We enrolled 36 patients (83% men). Patients had a mean (
SD
) age of 70.7 years (6.8), diabetes mellitus duration of 18.4 years (8.3), HbA1c (gycated hemoglobin) of 59.7 mmol/mol (11.2). Eighty percent had peripheral symmetrical neuropathy. The mean difference in change of transcutaneous tissue oxygen tension from baseline between the
RIC
and sham‐treated groups was −0.03 mm Hg ([95%
CI
−0.1; 0.04],
P
=0.438).
RIC
did not elicit any change in additional outcomes. Three patients experienced transient skin petechiae in the treated arm.

Conclusions
Long‐term repeated remote ischemic conditioning treatment have no effect on tissue oxygenation, vascular or neuronal function in patients with type 2 diabetes mellitus and moderate peripheral artery disease.

Clinical Trial Registration

URL
:
http://www.ClinicalTrials.gov
. Unique identifier:
NCT
02749942.
Early Versus Delayed Stroke After Cardiac Surgery: A Systematic Review and Meta‐Analysis
Authors: Gaudino Mario , Rahouma Mohammed , Di Mauro Michele , Yanagawa Bobby , Abouarab Ahmed , Demetres Michelle , Di Franco Antonino , Arisha Mohammed J. , Ibrahim Dina A. , Baudo Massimo , Girardi Leonard N. , Fremes Stephen 
Published: June 2019

Background
Although it is traditionally regarded as a single entity, perioperative stroke comprises 2 separate phenomena (early/intraoperative and delayed/postoperative stroke). We aimed to systematically evaluate incidence, risk factors, and clinical outcome of early and delayed stroke after cardiac surgery.

Methods and Results

A systematic review (
MEDLINE
,
EMBASE
, Cochrane Library) was performed to identify all articles reporting early (on awakening from anesthesia) and delayed (after normal awakening from anesthesia) stroke after cardiac surgery. End points were pooled event rates of stroke and operative mortality and incident rate of late mortality. Thirty‐six articles were included (174 969 patients). The pooled event rate for early stroke was 0.98% (95%
CI
0.79% to 1.23%) and was 0.93% for delayed stoke (95%
CI
0.77% to 1.11%;
P
=0.68). The pooled event rate of operative mortality was 28.8% (95%
CI
17.6% to 43.4%) for early and 17.9% (95%
CI
14.0% to 22.7%) for delayed stroke, compared with 2.4% (95%
CI
1.9% to 3.1%) for patients without stroke (
P
<0.001 for early versus delayed, and for perioperative stroke, early stroke, and delayed stroke versus no stroke). At a mean follow‐up of 8.25 years, the incident rate of late mortality was 11.7% (95%
CI
7.5% to 18.3%) for early and 9.4% (95%
CI
5.9% to 14.9%) for delayed stroke, compared with 3.4% (95%
CI
2.4% to 4.8%) in patients with no stroke. Meta‐regression demonstrated that off‐pump was inversely associated with early stroke (β=−0.009,
P
=0.01), whereas previous stroke (β=0.02,
P
<0.001) was associated with delayed stroke.

Conclusions
Early and delayed stroke after cardiac surgery have different risk factors and impacts on operative mortality as well as on long‐term survival.
Estimation of Atlantic Tropical Cyclone Rainfall Frequency in the United States
Authors: Feldmann Monika , Emanuel Kerry , Zhu Laiyin , Lohmann Ulrike 
Published: June 2019

AbstractTropical cyclones pose a significant flood risk to vast land regions in their path because of extreme precipitation. Thus it is imperative to quantitatively assess this risk. This study compares exceedance frequencies of tropical cyclone precipitation derived from two independent observational datasets with those estimated using a tropical cyclone rainfall algorithm applied to large sets of synthetic tropical cyclones. The modeled rainfall compares reasonably well to observed rainfall across much of the southern United States but does less well in the mid-Atlantic states. Possible causes of this disparity are discussed.