bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for heterogeneous subsarcolemmal Na+ levels in rat ventricular myocytes
Authors: Skogestad J. , Lines G. T. , Louch W. E. , Sejersted O. M. , Sjaastad I. , Aronsen J. M. 
Published: January 2019

The intracellular Na+ concentration ([Na+]) regulates cardiac contractility. Previous studies have suggested that subsarcolemmal [Na+] is higher than cytosolic [Na+] in cardiac myocytes, but this concept remains controversial. Here, we used electrophysiological experiments and mathematical modeling to test whether there are subsarcolemmal pools with different [Na+] and dynamics compared with the bulk cytosol in rat ventricular myocytes. A Na+ dependency curve for Na+-K+-ATPase (NKA) current was recorded with symmetrical Na+ solutions, i.e., the same [Na+] in the superfusate and internal solution. This curve was used to estimate [Na+] sensed by NKA in other experiments. Three experimental observations suggested that [Na+] is higher near NKA than in the bulk cytosol: 1) when extracellular [Na+] was high, [Na+] sensed by NKA was ~6 mM higher than the internal solution in quiescent cells; 2) long trains of Na+ channel activation almost doubled this gradient; compared with an even intracellular distribution of Na+, the increase of [Na+] sensed by NKA was 10 times higher than expected, suggesting a local Na+ domain; and 3) accumulation of Na+ near NKA after trains of Na+ channel activation dissipated very slowly. Finally, mathematical models assuming heterogeneity of [Na+] between NKA and the Na+ channel better reproduced experimental data than the homogeneous model. In conclusion, our data suggest that NKA-sensed [Na+] is higher than [Na+] in the bulk cytosol and that there are differential Na+ pools in the subsarcolemmal space, which could be important for cardiac contractility and arrhythmogenesis. NEW & NOTEWORTHY Our data suggest that the Na+-K+-ATPase-sensed Na+ concentration is higher than the Na+ concentration in the bulk cytosol and that there are differential Na+ pools in the subsarcolemmal space, which could be important for cardiac contractility and arrhythmogenesis. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/heterogeneous-sodium-in-ventricular-myocytes/ .
Impact of 24 weeks of supervised endurance versus resistance exercise training on left ventricular mechanics in healthy untrained humans
Authors: Oxborough David L. , Spence Angela , George Keith P. , Van Oorschot Frederieke , Thijssen Dick H. T. , Green Daniel J. 
Published: January 2019

In addition to the well-known cardiac structural adaptation to exercise training, little work has examined changes in left ventricle (LV) mechanics. With new regional and global indexes available we sought to determine the effect of 24-wk endurance versus resistance training on LV mechanics. Twenty-three male subjects were randomly allocated to a 24-wk endurance or resistance training program. Pre- and posttraining two-dimensional echocardiographic images were acquired. Global LV mechanics [strain (ε)] were recorded in longitudinal, circumferential, and radial planes. Rotation was assessed at apical and basal levels. In addition, longitudinal ε-volume loops, across the cardiac cycle, were constructed from simultaneous LV ε (longitudinal and transverse strain) and volume measurements across the cardiac cycle as a novel measure of LV mechanics. Marginal differences in ε and rotation data were found between groups. After training, we found no change in global peak ε data. Peak basal rotation significantly increased after training, with changes in the endurance group (−2.2 ± 1.9° to −4.5 ± 3.3°) and the resistance group (−2.9 ± 3.0° to −3.4 ± 2.9°). LV ε-volume loops revealed a modest rightward shift in both groups. Although most global and regional indexes of LV mechanics were not significantly altered, 24 wk of intense supervised exercise training increased basal rotation. Further studies that assess LV mechanics in larger cohorts of subjects and those with cardiovascular disease and risk factors may reveal important training impacts. NEW & NOTEWORTHY This study builds on previous work by our group and presents a comprehensive assessment of cardiac mechanics after dichotomous exercise training programs. We highlight novel findings in addition to the inclusion of strain-volume loops, which shed light on subtle differences in longitudinal and transverse contribution to volume change throughout the cardiac cycle. Our findings suggest that training has an impact on basal rotation and possibly strain-volume loops.
Endoplasmic Reticulum Stress Contributes to Mitochondrial Exhaustion of CD8+ T Cells
Authors: Hurst Katie E. , Lawrence Kiley A. , Essman Matthew T. , Walton Zeke J. , Leddy Lee R. , Thaxton Jessica E. 
Published: January 2019

Abstract
Tumor antigen–specific T cells rapidly lose energy and effector function in tumors. The cellular mechanisms by which energy loss and inhibition of effector function occur in tumor-infiltrating lymphocytes (TILs) are ill-defined, and methods to identify tumor antigen–specific TILs that experience such stress are unknown. Processes upstream of the mitochondria guide cell-intrinsic energy depletion. We hypothesized that a mechanism of T-cell–intrinsic energy consumption was the process of oxidative protein folding and disulfide bond formation that takes place in the endoplasmic reticulum (ER) guided by protein kinase R-like endoplasmic reticulum kinase (PERK) and downstream PERK axis target ER oxidoreductase 1 (ERO1α). To test this hypothesis, we created TCR transgenic mice with a T-cell–specific PERK gene deletion (OT1+Lckcre+PERKf/f, PERK KO). We found that PERK KO and T cells that were pharmacologically inhibited by PERK or ERO1α maintained reserve energy and exhibited a protein profile consistent with reduced oxidative stress. These T-cell groups displayed superior tumor control compared with T effectors. We identified a biomarker of ER-induced mitochondrial exhaustion in T cells as mitochondrial reactive oxygen species (mtROS), and found that PD-1+ tumor antigen–specific CD8+ TILs express mtROS. In vivo treatment with a PERK inhibitor abrogated mtROS in PD-1+ CD8+ TILs and bolstered CD8+ TIL viability. Combination therapy enabled 100% survival and 71% tumor clearance in a sarcoma mouse model. Our data identify the ER as a regulator of T-cell energetics and indicate that ER elements are effective targets to improve cancer immunotherapy.
Meteorological Impacts on Commercial Aviation Delays and Cancellations in the Continental United States
Authors: Goodman Christopher J. , Small Griswold Jennifer D. 
Published: January 2019

AbstractWeather creates numerous operational and safety hazards within the National Airspace System (NAS). In 2014, extreme weather events attributed 4.3% to the total number of delay minutes recorded by the Bureau of Transportation Statistics. When factoring weather’s impact on the NAS delays and aircraft arriving late delays, weather was responsible for 32.6% of the total number of delay minutes recorded. Hourly surface meteorological aviation routine weather reports (METARs) at major airports can be used to provide valuable insight into the likely causes of weather delays at individual airports. When combined with the Federal Aviation Administration’s (FAA’s) Operations Network (OPSNET) delay data, METARs can be used to identify the major causes of delays and to create delay climatologies for a specific airport. Also, patterns for delays and cancellations for the study period of 2003–15 can be identified for the individual airports included in this study. These patterns can be useful for operators and airport planners to optimize performance in the future.
Formulation of Three-Dimensional Quasi-Residual Mean Flow Balanced with Diabatic Heating Rate and Potential Vorticity Flux
Authors: Kinoshita Takenari , Sato Kaoru , Ishijima Kentaro , Takigawa Masayuki , Yamashita Yousuke 
Published: January 2019

Abstract
Three-dimensional (3D) quasi-residual mean flow is derived to diagnose 3D dynamical material transport associated with stationary planetary waves. The 3D quasi-residual mean vertical flow does not include the vertical flow due to tilting of the potential temperature caused by stationary waves, which is apparent but not seen in the mass-weighted isentropic mean state. Thus, the quasi-residual mean vertical flow is balanced with the term of diabatic heating rate. The 3D quasi-residual mean horizontal flow is balanced with the sum of the forcing due to transient wave activity flux divergence and the forcing associated with fluctuation of the potential vorticity due to stationary waves (defined as the effective Coriolis forcing). The zonal mean of the effective Coriolis forcing corresponds to the divergence of stationary wave activity flux. Thus, the zonal mean of derived 3D quasi-residual mean flow is exactly equal to the traditional residual mean flow. To demonstrate the usefulness of this quasi-residual mean flow, we analyze material transport of atmospheric sulfur hexafluoride (SF6) by using an atmospheric chemistry transport model. Comparison between the derived 3D quasi-residual mean flow and traditional residual mean flow shows that the zonal mean of advection of SF6 associated with the 3D quasi-residual mean flow derived is almost equal to that of the traditional residual mean flow. Next, it is confirmed that the horizontal structure of advection of SF6 associated with the 3D quasi-residual mean flow is balanced with the transport because of the nonlinear, nonconservative effects of disturbances. This relation is similar to the results for traditional residual mean flow in the zonal-mean state.
A Prognostic Nested k-Nearest Approach for Microwave Precipitation Phase Detection over Snow Cover
Authors: Takbiri Zeinab , Ebtehaj Ardeshir , Foufoula-Georgiou Efi , Kirstetter Pierre-Emmanuel , Turk F. Joseph 
Published: January 2019

Abstract
Monitoring changes of precipitation phase from space is important for understanding the mass balance of Earth’s cryosphere in a changing climate. This paper examines a Bayesian nearest neighbor approach for prognostic detection of precipitation and its phase using passive microwave observations from the Global Precipitation Measurement (GPM) satellite. The method uses the weighted Euclidean distance metric to search through an a priori database populated with coincident GPM radiometer and radar observations as well as ancillary snow-cover data. The algorithm performance is evaluated using data from GPM official precipitation products, ground-based radars, and high-fidelity simulations from the Weather Research and Forecasting Model. Using the presented approach, we demonstrate that the hit probability of terrestrial precipitation detection can reach to 0.80, while the probability of false alarm remains below 0.11. The algorithm demonstrates higher skill in detecting snowfall than rainfall, on average by 10%. In particular, the probability of precipitation detection and its solid phase increases by 11% and 8%, over dry snow cover, when compared to other surface types. The main reason is found to be related to the ability of the algorithm in capturing the signal of increased liquid water content in snowy clouds over radiometrically cold snow-covered surfaces.
VHF Radar Observations of Sea Surface in the Northern Taiwan Strait
Authors: Chen Jenn-Shyong , Lai Jian-Wu , Chien Hwa , Wang Chien-Ya , Su Ching-Lun , Lin Kun-I , Chen Meng-Yuan , Chu Yen-Hsyang 
Published: January 2019

Abstract
A VHF pulsed radar system was set up on the Taoyuan County seashore (24°57′58″N, 121°00′30″E; Taiwan) to observe the sea surface in the northern Taiwan Strait for the first time. The radar used a four-element, vertically polarized Yagi antenna to transmit the 52-MHz radar wave. The receiving linear array consists of four vertical dipole antennas that were located 3 m apart and attached with four independent and identical receivers. With the multichannel echoes, the direction of arrival (DOA) of the radar echoes were determined by using an optimization beamforming approach—the Capon method. Echo intensity was observed to vary principally in semidiurnal oscillation, which matched well the time series of tide gauge measurements and sea level simulations. In addition, the oscillatory characteristics of Doppler/radial velocity of the VHF radar were generally consistent with that of the HF coastal ocean dynamics applications radar (CODAR) nearby. Nevertheless, the contributions of various tidal modes to the parameters of DOA, echo intensity, radial velocity, and spectral width, varied with the range and time period (e.g., neap or spring tides). For example, the semidiurnal tides governed the variation in the echo center only in the range interval between ~15 and ~25 km from the seashore but dominated other parameters throughout the detectable range. Correlations and phase relationships between these parameters were diverse; they varied with time and had dramatic changes at around the distances of 3 and 10 km. Possible causes of these features were discussed, including sea surface wind, nearshore current, sea level height, and bathymetric effect.
Diminishing Cognitive Capacities in an Ever Hotter World: Evidence From an Applicable Power-Law Description
Authors: López-Sánchez José Ignacio , Hancock P. A. 
Published: January 2019

Objective: Modeling and evaluating a series of power law descriptions for boundary conditions of undiminished cognitive capacities under thermal stress. Background: Thermal stress degrades cognition, but precisely which components are affected, and to what degree, has yet to be fully determined. With increasing global temperatures, this need is becoming urgent. Power-law distributions have proven their utility in describing differing natural mechanisms, including certain orders of human performance, but never as a rationalization of stress-altered states of attention. Method: From a survey of extant empirical data, absolute thresholds for thermal tolerance for varying forms of cognition were identified. These thresholds were then modeled using a rational power-law description. The implications of the veracity of that description were then identified and analyzed. Results: Cognitive performance thresholds under thermal stress are advanced as power-law relationships, t = f(T) = c[(T – Tref)/Tref]-α. Coherent scaling parameters for diverse cognitive functionalities are specified that are consistent with increases in deep (core) body temperature. Therefore, scale invariance provides a “universal constant,” viz, 20% detriment in mental performance per 10% increase in T deviation, from a comfortable reference temperature Tref. Conclusion: We know the thermal range within which humans can survive is quite narrow. The presented power-law descriptions imply that if making correct decisions is critical for our future existence, then our functional thermal limits could be much more restricted than previously thought. Application: We provide our present findings, such that others can both assess and mitigate the effects of adverse thermal loads on cognition, in whatever human scenario they occur.
The Concise Health Risk Tracking-Self Report: Psychometrics within a placebo-controlled antidepressant trial among depressed outpatients
Authors: Trombello Joseph M , Killian Michael O , Grannemann Bruce D , Rush Augustus John , Mayes Taryn L , Parsey Ramin V , McInnis Melvin , Jha Manish K , Ali Aasia , McGrath Patrick J , Adams Phil , Oquendo Maria A , Weissman Myrna M , Carmody Thomas J , Trivedi Madhukar H 
Published: January 2019

Background/aims: While substantial prior research has evaluated the psychometric properties of the 12-item Concise Health Risk Tracking-Self Report (CHRT-SR12), a measure of suicide propensity and suicidal thoughts, no prior research has investigated its factor structure, sensitivity to change over time, and other psychometric properties in a placebo-controlled trial of antidepressant medication, nor determined whether symptoms change throughout treatment. Methods: Participants in the multi-site Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study ( n=278) provided data to evaluate the factor structure and sensitivity to change over time of the CHRT-SR12 through eight weeks of a clinical trial in which participants received either placebo or antidepressant medication (sertraline). Results/Outcomes: Factor analysis confirmed two factors: propensity (comprised of first-order factors including pessimism, helplessness, social support, and despair) and suicidal thoughts. Internal consistency (α’s ranged from 0.69–0.92) and external validity were both acceptable, with the total score and propensity factor scores significantly correlated with total scores and single-item suicidal-thoughts scores on the self-report Quick Inventory of Depressive Symptoms and the clinician-rated 17-item Hamilton Rating Scale for Depression. Through analyzing CHRT-SR12 changes over eight treatment weeks, the total score and both the factors decreased regardless of baseline suicidal thoughts. Change in clinician-rated suicidal thoughts was reflected by change in both the total score and propensity factor score. Conclusions/interpretation: These results confirm the reliability, validity, and applicability of the CHRT-SR12 to a placebo-controlled clinical trial of depressed outpatients receiving antidepressant medication.
Osteointegration of a Novel Silk Fiber–Based ACL Scaffold by Formation of a Ligament-Bone Interface
Authors: Teuschl Andreas Herbert , Tangl Stefan , Heimel Patrick , Schwarze Uwe Yacine , Monforte Xavier , Redl Heinz , Nau Thomas 
Published: January 2019

Background: Given the unsatisfactory results and reported drawbacks of anterior cruciate ligament (ACL) reconstruction, such as donor site morbidity and the limited choice of grafts in revision surgery, new regenerative approaches based on tissue-engineering strategies are currently under investigation. Purposes: To determine (1) if a novel silk fiber–based ACL scaffold is able to initiate osteointegration in the femoral and tibial bone tunnels under in vivo conditions and (2) if the osteointegration process will be improved by intraoperatively seeding the scaffolds with the autologous stromal vascular fraction, an adipose-derived, stem cell–rich isolate from knee fat pads. Study Design: Controlled laboratory study. Methods: A total of 33 sheep underwent ACL resection and were then randomly assigned to 2 experimental groups: ACL reconstruction with a scaffold alone and ACL reconstruction with a cell-seeded scaffold. Half of the sheep in each group were randomly chosen and euthanized 6 months after surgery and the other half at 12 months. To analyze the integration of the silk-based scaffold in the femoral and tibial bone tunnels, hard tissue histology and micro–computed tomography measurements were performed. Results: Hard tissue histological workup showed that in all treatment groups, with or without the application of the autologous stromal vascular fraction, an interzone of collagen fibers had formed between bone and silk-based graft. This collagen-fiber continuity partly consisted of Sharpey fibers, comparable with tendon-bone healing known for autografts and allografts. Insertion sites were more broad based at 6 months and more concentrated on the slightly protruding, bony knoblike structures at 12 months. Histologically, no differences between the treatment groups were detectable. Analysis of micro–computed tomography measurements revealed a significantly higher tissue density for the cell-seeded scaffold group as compared with the scaffold-alone group in the tibial but not femoral bone tunnel after 12 months of implantation. Conclusion: The novel silk fiber–based scaffold for ACL regeneration demonstrated integration into the bone tunnels via the formation of a fibrous interzone similar to allografts and autografts. Histologically, additional cell seeding did not enhance osteointegration. No significant differences between 6 and 12 months could be detected. After 12 months, there was still a considerable amount of silk present, and a longer observation period is necessary to see if a true ligament-bone enthesis will be formed. Clinical Relevance: ACL regeneration with a silk fiber–based scaffold with and without additional cell seeding may provide an alternative treatment option to current techniques of surgical reconstruction.
Prolactinoma: A rare, important and treatable cause of male infertility
Authors: Ralph Oliver , Shroff Nikita 
Published: January 2019

Infertility as a result of hyperprolactinemia from a functional prolactinoma is a rare yet treatable cause of morbidity. As in this case, if infertility is the presenting symptom, then urology is only the first specialty needed along the road of effective treatment, highlighting the role of the multidisciplinary team. What made this case so interesting was the almost immediate return to fertility on tumour resection (as shown by the resulting pregnancy) and the emphasis the patient placed on his fertility, above all other concerns. It shows that in complex cases such as these, medical and surgical specialities have to work together to achieve the outcome that is in the best interests of the patient. We present the case of a 33-year-old man who presented with anejaculation and a loss of fertility that lead to significant patient distress. After surgery and hormone replacement, the patient showed an increase in sperm count, normal morphology and density. This report will highlight the journey that the patient underwent from diagnosis through investigations and surgery in order to re-establish fertility. The aim of this case report is to highlight the need to consider hyperprolactinemia as a cause of reversible male infertility and to show the potentially short-term positive impact of effective treatment. The report provides fertility data to quantify this improvement after both endocrinology and then neurosurgical intervention. This case is a wonderful example of the success a multidisciplinary approach can have in the treatment of a complex, rare condition. Level of evidence: Case report – level 5
Defining “High-risk Sexual Behavior” in the Context of Substance Use
Authors: Chawla Nishtha , Sarkar Siddharth 
Published: January 2019

Introduction: Sexual behavior is a behavior exhibited by individuals to gratify one of their basic needs, that is the sexual need. Often the way in which sexual behavior is practiced may lead to negative consequences. However, the definition of a sexual behavior as risky varies with regards to culture, gender, age, and the threshold. Objectives: This review aims to study different definitions of high-risk sexual behavior available in literature, the differences in the prevalence of various risks associated with risky sex in substance-using population as compared to general population, and eventually formulating a tentative definition of “high-risk sexual behavior” in the context of substance use. Current evidence and results of literature search as we have entered into the epidemic of human immunodeficiency virus globally, it is important clinically as well as from the public health perspective to define high-risk sexual behavior discretely helping the researchers quantify the burden and the clinicians focus on the population at risk. High-risk sexual behavior has often been discussed and studied in various studies till date. However, literature lacks a discrete definition of high-risk sexual behavior. Risky sex (or high-risk sexual behavior) has been variably defined in different studies. Majority of the definitions in the studies focus on sexually transmitted infection, especially human immunodeficiency virus. A few studies talk about unintended pregnancies or abortions. Conclusion: The association between high-risk sexual behavior and substance use has been well established. Further research is warranted to obtain a definition which has greater precision and clinical utility, and which can be integrated in preventive and promotive pursuits.