Miracle-dz/UniFAR-FTUs huggingface dataset:
The SIMARD Screening Tool to Identify Unfit Drivers

Dobbs and Schopflocher published an article in which they introduced a tool to identify people who are unfit to drive because of cognitive impairment. In our view, their conclusion that this tool has “. a high degree of accuracy that can be used for immediate decisions in the clinical setting”1(p119) is too strongly stated, particularly given that the cut-points they used yield false positive (FP) and false negative (FN) percentages in the 6% to 11% range. We believe the reason for using dual cut-points is to ensure that FP and FN fractions are both controlled very stringently, and that it would be more appropriate to set cut-offs that maintain both of them closer to 1%. Using our own data, we constructed two pairs of dual cut-points—one pair that yielded FP and FN percentages similar to those from the Dobbs and Schopflocher article and another pair that yielded FP and FN percentages no greater than 1%. For the first pair of cut-points, 53% of test results were indeterminate (compared to 50% for Dobbs and Schopflocher). For the second pair of cut-points, 86% of test results were indeterminate. Presumably, the same pattern would be observed in Dobbs and Schopflocher’s data if their current dual cut-points were replaced with cut-points that controlled the FP and FN percentages at more appropriate levels. We also plotted receiver operating characteristic curves, and calculated the area under the curve (AUC) for the Screen for the Identification of Cognitively Impaired Medically At-Risk Drivers, A Modification of the DemTect (SIMARD-MD) and for the combination of the Mini-Mental State Examination and Trail-Making Test A (using our data for the latter). The difference between them was trivial (AUC = 0.75 and 0.72, respectively). Taken together, the results of the two analytic approaches suggest that other tools currently in use by physicians perform at least as well as the SIMARD-MD, and that it does not represent a significant breakthrough.
A Delay-Tolerant Asynchronous Two-Way-Relay System over Doubly-Selective Fading Channels

We consider design of asynchronous orthogonal frequency division multiplexing (OFDM) based diamond two-way-relay (DTWR) systems in a time-varying frequency-selective (doubly-selective) fading channel. In a DTWR system, two users exchange their messages with the help of two relays. Most of the existing works on asynchronous DTWR systems assume only small relative propagation delays between the received signals at each node that do not exceed the length of the cyclic-prefix (CP). However, in certain practical communication systems, significant differences in delays may take place, and hence existing solutions requiring excessively long CPs may be highly inefficient. In this paper, we propose a delay-independent CP insertion mechanism in which the CP length depends only on the number of subcarriers and the maximum delay spread of the corresponding channels. We also propose a symbol detection algorithm that is able to tolerate very long relative delays, that even exceed the length of the OFDM block itself, without a large increase in complexity. The proposed system is shown to significantly outperform other alternatives in the literature through a number of specific examples.
Energy Efficient COGnitive-MAC for Sensor Networks Under WLAN Co-existence

Energy efficiency has been the driving force behind the design of communication protocols for battery-constrained wireless sensor networks (WSNs). The energy efficiency and the performance of the proposed protocol stacks, however, degrade dramatically in case the low-powered WSNS are subject to interference from high-power wireless systems such as WLANs. In this paper we propose COG-MAC, a novel cognitive medium access control scheme (MAC) for IEEE 802.15. 4-compliant WSNS that minimizes the energy cost for multihop communications, by deriving energy-optimal packet lengths and single-hop transmission distances based on the experienced interference from IEEE 802.11 WLANs. We evaluate COG-MAC by deriving a detailed analytic model for its performance and by comparing it with previous access control schemes. Numerical and simulation results show that a significant decrease in packet transmission energy cost, up to 66%, can be achieved in a wide range of scenarios, particularly under severe WLAN interference. COG-MAC is, also, lightweight and shows high robustness against WLAN model estimation errors and is, therefore, an effective, implementable solution to reduce the WSN performance impairment when coexisting with WLANs.
Ieee Transactions on Wireless Communications 1 Massive Mimo with Non-ideal Arbitrary Arrays: Hardware Scaling Laws and Circuit-aware Design

—Massive multiple-input multiple-output (MIMO) systems are cellular networks where the base stations (BSs) are equipped with unconventionally many antennas, deployed on co-located or distributed arrays. Huge spatial degrees-of-freedom are achieved by coherent processing over these massive arrays, which provide strong signal gains, resilience to imperfect channel knowledge, and low interference. This comes at the price of more infrastructure; the hardware cost and circuit power consumption scale linearly/affinely with the number of BS antennas N. Hence, the key to cost-efficient deployment of large arrays is low-cost antenna branches with low circuit power, in contrast to today's conventional expensive and power-hungry BS antenna branches. Such low-cost transceivers are prone to hardware imperfections, but it has been conjectured that the huge degrees-of-freedom would bring robustness to such imperfections. We prove this claim for a generalized uplink system with multiplicative phase-drifts, additive distortion noise, and noise amplification. Specifically , we derive closed-form expressions for the user rates and a scaling law that shows how fast the hardware imperfections can increase with N while maintaining high rates. The connection between this scaling law and the power consumption of different transceiver circuits is rigorously exemplified. This reveals that one can make the circuit power increase as √ N , instead of linearly, by careful circuit-aware system design.
Predictors of Success of a Lifestyle Intervention in Relation to Weight Loss and Improvement in Glucose Tolerance Among Individuals at High Risk for Type 2 Diabetes

Aim: The authors assessed the predictors of success of a lifestyle intervention (weight loss ≥ 5% and improved glucose tolerance) in individuals at high risk for type 2 diabetes in a 1-year follow-up in a primary health care setting. Methods: High-risk individuals for type 2 diabetes were identified by opportunistic screening in the implementation of the Finnish National Diabetes Prevention Program (FIN-D2D). All together, 3880 individuals participated in the 1-year follow-up. Sociodemographic characteristics, health status and behavior, family history of diabetes, clinical factors, and health care provider were considered possible predictors of lifestyle intervention success. Results: In sum, 19.3% of individuals lost at least 5% of weight, and 32.6% with abnormal glucose tolerance at baseline showed improvement in glucose tolerance. Abnormal glucose tolerance was the strongest predictor of weight loss and improvement in glucose tolerance. High attendance at lifestyle intervention visits, being outside of labor force, and high body mass index at baseline were also related to weight loss, and high education was related to improvement in glucose tolerance. Conclusions: In “real-life settings,” glucose tolerance status, number of intervention visits, employment status, education, and body mass index explained the success of lifestyle intervention. These factors may help in targeting interventions, although they may not be generalized to other cultural settings.
Use of potentially inappropriate medications in the care of frail older people

Achieving safe prescribing in frail older people is difficult owing to age-related physiological changes, multiple comorbidities, multiple medication use and a higher risk of adverse drug events (ADEs). Among people aged 65 years and over, 7–25% are frail. While frailty is recognized as a major public health problem, there is a lack of consensus on the definition of frailty and validated tools that can be used to assess the effects of frailty on pharmacological response in old age. Frail individuals are at higher risk of adverse clinical outcomes, such as hospitalization, falls, disability and mortality. There is also a lack of consensus on the definition of inappropriate medications. Inappropriate medication use is a major contributor to the risk of ADEs in frail older people. Therefore, development and implementation of tools to optimize appropriate use of medications is necessary for the medical care of frail older people.
Amenorrhoea in Anorexia Nervosa: Assessment and Treatment with Clomiphene Citrate

Seven patients with anorexia nervosa were studied, three during the acute stages of the illness, and four in whom weight gain had been achieved, but who suffered from persistent amenorrhoea of 18 to 79 months9 duration. In the acute stage all patients had low serum luteinizing hormone (LH) levels which were unresponsive to clomiphene citrate. In those who had regained weight the mean basal LH levels were normal, and they responded to clomiphene with an initial doubling of serum LH during administration of the drug, followed by a second peak of serum LH four to seven days after the drug was stopped. Menstruation occurred in these patients 13 to 19 days after the clomiphene was discontinued, and in two patients regular spontaneous menstruation was initiated. The low LH levels unresponsive to clomiphene in the acute stage provide evidence for a hypothalamic abnormality in anorexia nervosa. After regain of body weight the drug seems to be effective in treating the amenorrhoea which may be persistent.
Aquaporin-3 Controls Breast Cancer Cell Migration by Regulating Hydrogen Peroxide Transport and Its Downstream Cell Signaling

ABSTRACT Most breast cancer mortality is due to clinical relapse associated with metastasis. CXCL12/CXCR4-dependent cell migration is a critical process in breast cancer progression; however, its underlying mechanism remains to be elucidated. Here, we show that the water/glycerol channel protein aquaporin-3 (AQP3) is required for CXCL12/CXCR4-dependent breast cancer cell migration through a mechanism involving its hydrogen peroxide (H2O2) transport function. Extracellular H2O2, produced by CXCL12-activated membrane NADPH oxidase 2 (Nox2), was transported into breast cancer cells via AQP3. Transient H2O2 accumulation was observed around the membrane during CXCL12-induced migration, which may be facilitated by the association of AQP3 with Nox2. Intracellular H2O2 then oxidized PTEN and protein tyrosine phosphatase 1B (PTP1B) followed by activation of the Akt pathway. This contributed to directional cell migration. The expression level of AQP3 in breast cancer cells was related to their migration ability both in vitro and in vivo through CXCL12/CXCR4- or H2O2-dependent pathways. Coincidentally, spontaneous metastasis of orthotopic xenografts to the lung was reduced upon AQP3 knockdown. These findings underscore the importance of AQP3-transported H2O2 in CXCL12/CXCR4-dependent signaling and migration in breast cancer cells and suggest that AQP3 has potential as a therapeutic target for breast cancer.
OBSERVATIONS ON THE HEARTS OF MEN ENGAGED IN ATHLETICS

It is not an unusual occurrence at athletic contests to see a collapse during or at the end of a hard race. When he collapses the clinical picture is that of utter exhaustion, the patient gasping for air and yet being unable to take a full breath. He complains of abdominal pain and is more comfortable lying on his side doubled up, with both hands pressed tightly against the abdomen. The pulse is rapid and not of good quality. Although the patient is perspiring freely, his body feels cold. There is often considerable nausea and not uncommonly vomiting, and in extreme cases there may be unconsciousness. Various reasons have been given in explanation of the cause of this collapse. Rarely it has been brought about by rupture of a heart valve. Some medical observers have attributed it to an acute cardiac dilatation. The latter condition does not seem to fit
Insulin-Like Growth Factor (IGF) Binding Protein 2 Functions Coordinately with Receptor Protein Tyrosine Phosphatase β and the IGF-I Receptor To Regulate IGF-I-Stimulated Signaling

ABSTRACT Insulin-like growth factor I (IGF-I) is a mitogen for vascular smooth muscle cells (VSMC) and has been implicated in the development and progression of atherosclerosis. IGF binding proteins (IGFBPs) modify IGF-I actions independently of IGF binding, but a receptor-based mechanism by which they function has not been elucidated. We investigated the role of IGFBP-2 and receptor protein tyrosine phosphatase β (RPTPβ) in regulating IGF-I signaling and cellular proliferation. IGFBP-2 bound RPTPβ, which led to its dimerization and inactivation. This enhanced PTEN tyrosine phosphorylation and inhibited PTEN activity. Utilization of substrate trapping and phosphatase-dead mutants showed that RPTPβ bound specifically to PTEN and dephosphorylated it. IGFBP-2 knockdown led to decreased PTEN tyrosine phosphorylation and decreased AKT Ser473 activation. IGFBP-2 enhanced IGF-I-stimulated VSMC migration and proliferation. Analysis of aortas obtained from IGFBP-2−/− mice showed that RPTPβ was activated, and this was associated with inhibition of IGF-I stimulated AKT Ser473 phosphorylation and VSMC proliferation. These changes were rescued following administration of IGFBP-2. These findings present a novel mechanism for coordinate regulation of IGFBP-2 and IGF-I signaling functions that lead to stimulation of VSMC proliferation. The results have important implications for understanding how IGFBPs modulate the cellular response to IGF-I.
Patient and Provider Factors Associated With American Indian and Alaska Native Adolescent Tobacco Use Screening

Introduction: Tobacco use is the leading behavioral cause of death among adults 25 years or older. American Indian (AI) and Alaska Native (AN) communities confront some of the highest rates of tobacco use and of its sequelae. Primary care–based screening of adolescents is an integral step in the reduction of tobacco use, yet remains virtually unstudied. We examined whether delivery of tobacco screening in primary care visits is associated with patient and provider characteristics among AI/AN adolescents. Methods: We used a cross-sectional analysis to examine tobacco screening among 4757 adolescent AI/AN patients served by 56 primary care providers at a large tribally managed health system between October 1, 2011 and May 31, 2014. Screening prevalence was examined in association with categorical patient characteristics (gender, age, clinic visited, insurance coverage) and provider characteristics (gender, age, tenure) using multilevel logistic regressions with individual provider identity as the nesting variable. Results: Thirty-seven percent of eligible patients were screened. Gender of both providers and patients was associated with screening. Male providers delivered screening more often than female providers (odds ratio [OR] 1.6, 95% confidence interval [CI] 0.7-3.9). Male patients had 20% lower odds of screening receipt (OR 0.8, 95% CI 0.7-0.9) than female patients, independent of patient age and provider characteristics. Individual provider identity significantly contributed to variability in the mixed-effects model (variance component 2.2; 95% CI 1.4-3.4), suggesting individual provider effect. Conclusions: Low tobacco screening delivery by female providers and the low receipt of screening among younger, male patients may identify targets for screening interventions.
Distinct Amino Acid Compositional Requirements for Formation and Maintenance of the [PSI+] Prion in Yeast

ABSTRACT Multiple yeast prions have been identified that result from the structural conversion of proteins into a self-propagating amyloid form. Amyloid-based prion activity in yeast requires a series of discrete steps. First, the prion protein must form an amyloid nucleus that can recruit and structurally convert additional soluble proteins. Subsequently, maintenance of the prion during cell division requires fragmentation of these aggregates to create new heritable propagons. For the Saccharomyces cerevisiae prion protein Sup35, these different activities are encoded by different regions of the Sup35 prion domain. An N-terminal glutamine/asparagine-rich nucleation domain is required for nucleation and fiber growth, while an adjacent oligopeptide repeat domain is largely dispensable for prion nucleation and fiber growth but is required for chaperone-dependent prion maintenance. Although prion activity of glutamine/asparagine-rich proteins is predominantly determined by amino acid composition, the nucleation and oligopeptide repeat domains of Sup35 have distinct compositional requirements. Here, we quantitatively define these compositional requirements in vivo. We show that aromatic residues strongly promote both prion formation and chaperone-dependent prion maintenance. In contrast, nonaromatic hydrophobic residues strongly promote prion formation but inhibit prion propagation. These results provide insight into why some aggregation-prone proteins are unable to propagate as prions.
Knowledge and Acceptability of Long-Acting Reversible Contraception Among Adolescent Women Receiving School-Based Primary Care Services

Background: A key strategy to reduce unintended adolescent pregnancies is to expand access to long-acting reversible contraceptive (LARC) methods, including intrauterine devices and subdermal contraceptive implants. LARC services can be provided to adolescents in school-based health and other primary care settings, yet limited knowledge and negative attitudes about LARC methods may influence adolescents’ utilization of these methods. This study aimed to evaluate correlates of knowledge and acceptability of LARC methods among adolescent women at a school-based health center (SBHC). Methods: In this cross-sectional study, female patients receiving care at 2 SBHCs in Seattle, Washington completed an electronic survey about sexual and reproductive health. Primary outcomes were (1) LARC knowledge as measured by percentage correct of 10 true-false questions and (2) LARC acceptability as measured by participants reporting either liking the idea of having an intrauterine device (IUD)/subdermal implant or currently using one. Results: A total of 102 students diverse in race/ethnicity and socioeconomic backgrounds completed the survey (mean age 16.2 years, range 14.4-19.1 years). Approximately half reported a lifetime history of vaginal sex. Greater LARC knowledge was associated with white race (regression coefficient [coef] = 26.8; 95% CI 13.3-40.4; P < .001), history of vaginal intercourse (coef = 29.9; 95% CI 17.1-42.7; P < .001), and current/prior LARC use (coef = 22.8; 95% CI 6.5-40.0; P = .007). Older age was associated with lower IUD acceptability (odds ratio = 0.53, 95% CI 0.30-0.94; P = .029) while history of intercourse was associated with greater implant acceptability (odds ratio 5.66, 95% CI 1.46-22.0; P = .012). Discussion: Adolescent women in this SBHC setting had variable knowledge and acceptability of LARC. A history of vaginal intercourse was the strongest predictor of LARC acceptability. Our findings suggest a need for LARC counseling and education strategies, particularly for young women from diverse cultural backgrounds and those with less sexual experience.
Maximal STAT5-Induced Proliferation and Self-Renewal at Intermediate STAT5 Activity Levels

ABSTRACT The level of transcription factor activity critically regulates cell fate decisions, such as hematopoietic stem cell (HSC) self-renewal and differentiation. We introduced STAT5A transcriptional activity into human HSCs/progenitor cells in a dose-dependent manner by overexpression of a tamoxifen-inducible STAT5A(1*6)-estrogen receptor fusion protein. Induction of STAT5A activity in CD34+ cells resulted in impaired myelopoiesis and induction of erythropoiesis, which was most pronounced at the highest STAT5A transactivation levels. In contrast, intermediate STAT5A activity levels resulted in the most pronounced proliferative advantage of CD34+ cells. This coincided with increased cobblestone area-forming cell and long-term-culture-initiating cell frequencies, which were predominantly elevated at intermediate STAT5A activity levels but not at high STAT5A levels. Self-renewal of progenitors was addressed by serial replating of CFU, and only progenitors containing intermediate STAT5A activity levels contained self-renewal capacity. By extensive gene expression profiling we could identify gene expression patterns of STAT5 target genes that predominantly associated with a self-renewal and long-term expansion phenotype versus those that identified a predominant differentiation phenotype.
On the Power Allocation for MIMO-NOMA Systems With Layered Transmissions

In this paper, we study optimal power allocation for multiple-input multiple-output (MIMO) nonorthogonal multiple access (NOMA) systems when a layered transmission scheme is employed. An approach to maximize the sum rate of MIMO-NOMA with layered transmissions is proposed once we show that the sum rate is concave in allocated powers to multiple layers of users. We also derive a closed-form expression for the average sum rate when statistical channel state information (CSI) is available at a transmitter, which allows us to allocate powers to multiple layers for the maximization of the average sum rate. We find lower- and upper-bounds on the average sum rate, from which it is shown that the scaling property of MIMO-NOMA with layered transmissions also holds as conventional MIMO does (i.e., the average sum rate grows linearly with the number of antennas).
Defective Autophagy and mTORC1 Signaling in Myotubularin Null Mice

ABSTRACT Autophagy is a vesicular trafficking pathway that regulates the degradation of aggregated proteins and damaged organelles. Initiation of autophagy requires several multiprotein signaling complexes, such as the ULK1 kinase complex and the Vps34 lipid kinase complex, which generates phosphatidylinositol 3-phosphate [PtdIns(3)P] on the forming autophagosomal membrane. Alterations in autophagy have been reported for various diseases, including myopathies. Here we show that skeletal muscle autophagy is compromised in mice deficient in the X-linked myotubular myopathy (XLMTM)-associated PtdIns(3)P phosphatase myotubularin (MTM1). Mtm1-deficient muscle displays several cellular abnormalities, including a profound increase in ubiquitin aggregates and abnormal mitochondria. Further, we show that Mtm1 deficiency is accompanied by activation of mTORC1 signaling, which persists even following starvation. In vivo pharmacological inhibition of mTOR is sufficient to normalize aberrant autophagy and improve muscle phenotypes in Mtm1 null mice. These results suggest that aberrant mTORC1 signaling and impaired autophagy are consequences of the loss of Mtm1 and may play a primary role in disease pathogenesis.