cssi/SciSciGPT-SciSciNet huggingface dataset:
Polarization Sensitive Surface Relief Gratings Formed on Amorphous Azopolymer Films

Azobenzene chromophore functionalized polymer films belong to an important class of photoanisotropic materials [1].
SURG-11THE IMPACT OF PRE-OPERATIVE TUMOR FEATURES ON RESECTION AND SURVIVAL OUTCOMES IN GLIOBLASTOMA: A PHASE II FLUORESCENCE-GUIDED SURGERY STUDY

BACKGROUND: The survival benefit provided by "more complete" resection of glioblastoma (GBM) remains under debate. Part of this debate is likely due to the lack of reliable tools for pre- and post-surgical volumetric tumor measurement. In this study, we used a validated, semi-automated tumor segmentation tool to evaluate the relationship between pre-operative tumor morphology metrics, resection outcomes, and survival outcomes in a 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery (FGS) trial. METHODS: Thirty-one patients from a prospective Phase II trial evaluating 5-ALA FGS for newly diagnosed GBM were assessed. Tumors were segmented pre-operatively using a semi-automated method to assess morphological features, such as surface area (SA), SA to volume ratio (SAVR), and percent necrosis (NV%), as well as post-operatively to evaluate extent-of-resection (EOR) and residual tumor volume (RTV). Multivariate analysis was performed using a general linear model to assess the effects of multiple covariates on RTV and to describe resectability in terms of pre-operative tumor features. The impact of morphological, clinical, and resection measures on progression-free survival (PFS) and overall survival (OS) were evaluated using univariate and multivariate Cox proportional hazard regression. RESULTS: Median EOR and RTV were 94.3% and 0.821 cm3, respectively. Pre-operative tumor volume, SA, SAVR, and NV% exhibited statistically-significant associations with RTV. In addition to age and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, preoperative tumor SA, SAVR, NV%, and volume were shown to impact the likelihood of complete resection. Pre-operative SAVR and RTV were significantly associated with OS, even controlling for the known confounders of age, KPS, and MGMT methylation. CONCLUSIONS: This study supports claims that 5-ALA FGS is more effective than conventional microsurgery in decreasing tumor burden in GBM. Moreover, morphological indices describing tumor shape and composition may impact not only resection outcomes, but also patient survival, and should be considered in tumor resection studies.
Filtering method of LIDAR data based on contours

Filtering is an important method to extract digital terrain model(DTM)form Light Detection and Ranging(LIDAR)data and has made some good effects in application,but existing filtering methods are deficiency in certain applications,especially unsuitable for undulated terrain.In this paper,a new filtering method which is based on contours is developed.The method mainly consists of three steps:Firstly,digital surface model(DSM)is generated from raw LIDAR data by surface interpolation methods,such as the nearest neighbor interpolation method,and then contours of DSM are generated.Secondly,these DSM contours are separated into three groups:ground contour,which only consists of points on ground;object contour,which only consists of points off-ground,such as on trees or roofs;and mixing contour,which consists of points on ground or off-ground.According to some properties of contours,including closeness,start-to-end distance,length of curve,denseness,ground contours and ground contour section of mixing contours are extracted and then some ground points are obtained,finally an initial approximation of the DTM is determined by interpolating those ground points.Then a refined DTM is obtained by an iterative method:comparing the approximate DTM with the original DSM and if the difference is below a predefined threshold the original DSM points are selected and made into DTM data points.Otherwise,the location is marked as no data;and then the no data points are interpolated using the selected DSM data.Comparisons between initial and refined DTM obtained by methods proposed previously is done.To calculate the accurate probability,the objects obtained by new filter is compared with standard objects obtained from aerial images manually.All the experimental results show that the proposed method is a simple and practical one needing little calculation,and can be used in undulating terrain area.
Online speaking rate estimation using recurrent neural networks

A reliable online speaking rate estimation tool is useful in many domains, including speech recognition, speech therapy intervention, speaker identification, etc. This paper proposes an online speaking rate estimation model based on recurrent neural networks (RNNs). Speaking rate is a long-term feature of speech, which depends on how many syllables were spoken over an extended time window (seconds). We posit that since RNNs can capture long-term dependencies through the memory of previous hidden states, they are a good match for the speaking rate estimation task. Here we train a long short-term memory (LSTM) RNN on a set of speech features that are known to correlate with speech rhythm. An evaluation on spontaneous speech shows that the method yields a higher correlation between the estimated rate and the ground-truth rate when compared to the state-of-the-art alternatives. The evaluation on longitudinal pathological speech shows that the proposed method can capture long-term and short-term changes in speaking rate.
A renaissance for fluoxetine in the management of depression in the elderly

OBJECTIVE To review the literature pertaining to the use of the selective serotonin reuptake inhibitor (SSRI) fluoxetine in the management of depression in elders. DATA SOURCES A MEDLINE search was conducted to identify pertinent studies, case reports, letters, and reviews in the English language. All articles published from 1986 to 2002 were reviewed. Additional references were obtained from bibliographies of those articles. STUDY SELECTION All studies evaluating any aspect of the use of fluoxetine in managing geriatric depression. DATA SYNTHESIS Pharmacokinetic studies have demonstrated that the potential for accumulation of fluoxetine and its active metabolite norfluoxetine with chronic dosing in elders is less than or equal to that in young individuals. Renal impairment, a frequent comorbidity of older age, has no significant effect on the pharmacokinetics of fluoxetine/norfluoxetine. In elders, the efficacy of fluoxetine is statistically indistinguishable from that of paroxetine, sertraline, fluvoxamine, and tricyclic antidepressants in controlled trials, as are the adverse event profiles of fluoxetine and other tested SSRIs. The drug interaction potential of fluoxetine is similar to that of fluvoxamine and paroxetine and greater than those of citalopram, escitalopram, and sertraline. CONCLUSION Available data support a reevaluation of the role of fluoxetine in the management of geriatric depression, especially in light of the recent marketing of a generic fluoxetine product that is priced much lower than competitor branded SSRIs. Further studies of fluoxetine use in geriatric depression using adequate numbers of patients are recommended.
Virtual embedded librarianship program: a personal view

This commentary provides an overview of the author's experience as a virtual embedded librarian with the University of South Alabama College of Nursing. My involvement has increased every semester, and most recently, I have been assigned as the solo librarian to classes with 300–500 students. As a virtual embedded librarian, I have never interacted with an enrolled master of science in nursing (MSN)/doctor of nursing practice (DNP) student face to face; however, I have spoken live via telephone with students throughout the United States and abroad, including from Canada, Germany, and Japan. Herein, I present a brief overview of the embedded concept. In addition to summarizing my responsibilities, I discuss the challenges that I have faced and best practices for developing an embedded librarianship program.
What are the Patterns Between Depression, Smoking, Unhealthy Alcohol Use, and Other Substance Use Among Individuals Receiving Medical Care? A Longitudinal Study of 5479 Participants.

To evaluate and characterize the structure of temporal patterns of depression, smoking, unhealthy alcohol use, and other substance use among individuals receiving medical care, and to inform discussion about whether integrated screening and treatment strategies for these conditions are warranted. Using the Veterans Aging Cohort Study (VACS) we measured depression, smoking, unhealthy alcohol use and other substance use (stimulants, marijuana, heroin, opioids) and evaluated which conditions tended to co-occur within individuals, and how this co-occurrence was temporally structured (i.e. concurrently, sequentially, or discordantly). Current depression was associated with current use of every substance examined with the exception of unhealthy alcohol use. Current unhealthy alcohol use and marijuana use were also consistently associated. Current status was strongly predicted by prior status (p < 0.0001; OR = 2.99–22.34) however, there were few other sequential relationships. Associations in the HIV infected and uninfected subgroups were largely the same with the following exceptions. Smoking preceded unhealthy alcohol use and current smoking was associated with current depression in the HIV infected subgroup only (p < 0.001; OR = 1.33–1.41 and p < 0.001; OR = 1.25–1.43). Opioid use and current unhealthy alcohol use were negatively associated only in the HIV negative subgroup (p = 0.01; OR = 0.75). Patterns of depression, smoking, unhealthy alcohol use, and other substance use were temporally concordant, particularly with regard to depression and substance use. These patterns may inform future development of more integrated screening and treatment strategies.
Metal Hypersensitivity Reactions to Orthopedic Implants.

Total hip and knee replacement surgery using metal alloy devices is common. Type IV allergic reactions to these implants occur, though infrequently. While uncommon, peri-implant metal allergic reactions may cause significant morbidity for the affected individual—including aseptic loosening, pseudotumor formation and frank device failure. It is challenging to predict who will have these reactions, even in those with established pre-implant metal allergy. At this time, the scientific literature clearly supports few conclusions. Despite this, we believe several conclusions can be made: routine pre-implant testing in asymptomatic individuals is not indicated; listen to patient’s concerns about metal allergy if the concern arises; patch testing is probably the best pre- and post-implant screening test; post-implantation testing is controversial and even positive LTT or patch test does not definitively diagnose morbidity from a metal allergy; and complete recovery following revision placement of an immunologically inert device is diagnostic. More research is needed to scientifically approach this issue.
Macroscopic liquid-state molecular hydrodynamics

Experimental evidence and theoretical modeling suggest that piles of confined, high-restitution grains, subject to low-amplitude vibration, can serve as experimentally-accessible analogs for studying a range of liquid-state molecular hydrodynamic processes. Experiments expose single-grain and multiple-grain, collective dynamic features that mimic those either observed or predicted in molecular-scale, liquid state systems, including: (i) near-collision-time-scale hydrodynamic organization of single-molecule dynamics, (ii) nonequilibrium, long-time-scale excitation of collective/hydrodynamic modes, and (iii) long-time-scale emergence of continuum, viscous flow. In order to connect directly observable macroscale granular dynamics to inaccessible and/or indirectly measured molecular hydrodynamic processes, we recast traditional microscale equilibrium and nonequilibrium statistical mechanics for dense, interacting microscale systems into self-consistent, macroscale form. The proposed macroscopic models, which appear to be new with respect to granular physics, and which differ significantly from traditional kinetic-theory-based, macroscale statistical mechanics models, are used to rigorously derive the continuum equations governing viscous, liquid-like granular flow. The models allow physically-consistent interpretation and prediction of observed equilibrium and non-equilibrium, single-grain, and collective, multiple-grain dynamics.
Feasibility of upright patient positioning and intubation success rates At two academic EDs.

Abstract Objectives Endotracheal intubation is most commonly taught and performed in the supine position. Recent literature suggests that elevating the patient's head to a more upright position may decrease peri-intubation complications. However, there is little data on the feasibility of upright intubation in the emergency department. The goal of this study was to measure the success rate of emergency medicine residents performing intubation in supine and non-supine, including upright positions. Methods This was a prospective observational study. Residents performing intubation recorded the angle of the head of the bed. The number of attempts required for successful intubation was recorded by faculty and espiratory therapists. The primary outcome of first past success was calculated with respect to three groups: 0–10° (supine), 11–44° (inclined), and ≥ 45° (upright); first past success was also analyzed in 5 degree angle increments. Results A total of 231 intubations performed by 58 residents were analyzed. First pass success was 65.8% for the supine group, 77.9% for the inclined group, and 85.6% for the upright group (p = 0.024). For every 5 degree increase in angle, there was increased likelihood of first pass success (AOR = 1.11; 95% CI = 1.01–1.22, p = 0.043). Conclusions In our study emergency medicine residents had a high rate of success intubating in the upright position. While this does not demonstrate causation, it correlates with recent literature challenging the traditional supine approach to intubation and indicates that further investigation into optimal positioning during emergency department intubations is warranted.
An Optical-Fiber-Based Airborne Particle Sensor

A new optical-fiber-based airborne particle counter is reported. Unlike traditional light-scatter-based techniques, the particle is detected through the drop in optical fiber coupling efficiency as the particle disrupts the electromagnetic mode of the optical beam. The system is simple, substantially smaller than traditional systems, and does not require high power laser input. This makes it attractive for wearable air quality monitors where size is a premium. There is close agreement between theoretical model and experimental results for solid and liquid particles in the 1 to 10 µm range.
Advanced water splitting for green hydrogen gas production through complete oxidation of starch by in vitro metabolic engineering

Starch is a natural energy storage compound and is hypothesized to be a high-energy density chemical compound or solar fuel. In contrast to industrial hydrolysis of starch to glucose, an alternative ATP-free phosphorylation of starch was designed to generate cost-effective glucose 6-phosphate by using five thermophilic enzymes (i.e., isoamylase, alpha-glucan phosphorylase, 4-α-glucanotransferase, phosphoglucomutase, and polyphosphate glucokinase). This enzymatic phosphorolysis is energetically advantageous because the energy of α-1,4-glycosidic bonds among anhydroglucose units is conserved in the form of phosphorylated glucose. Furthermore, we demonstrated an in vitro 17-thermophilic enzyme pathway that can convert all glucose units of starch, regardless of branched and linear contents, with water to hydrogen at a theoretic yield (i.e., 12 H2 per glucose), three times of the theoretical yield from dark microbial fermentation. The use of a biomimetic electron transport chain enabled to achieve a maximum volumetric productivity of 90.2mmol of H2/L/h at 20g/L starch. The complete oxidation of starch to hydrogen by this in vitro synthetic (enzymatic) biosystem suggests that starch as a natural solar fuel becomes a high-density hydrogen storage compound with a gravimetric density of more than 14% H2-based mass and an electricity density of more than 3000Wh/kg of starch.
Eps8 expression is significantly lower in p16+ head and neck squamous cell carcinomas (HNSCCs) compared with p16− HNSCCs

Summary In vitro head and neck cancer studies have demonstrated that epidermal growth factor receptor kinase substrate 8 (Eps8) overexpression contributes to squamous carcinogenesis. Oral squamous cell carcinoma studies have correlated Eps8 expression with metastatic disease and poor prognosis. Head and neck squamous cell carcinoma (HNSCC) studies comparing its expression by anatomic site or in in vivo regional metastases have not been performed. In this study, we compared Eps8 expression in HNSCCs arising in the oral cavity (OCSCC) and oropharynx (OPSCC) along with their corresponding regional lymph node (LN) metastases. We then correlated our findings with clinicopathologic data including tumor-node-metastasis stage, p16 status, age, sex, and smoking and alcohol history. Eps8 immunohistochemistry was performed on 69 archived OCSCCs and OPSCCs, and 24 paired and 4 unpaired LNs. Expression was scored from 0 to 3. Eps8 expression was detected in 49% of combined OCSCC and OPSCC cases. We found that expression correlated with advanced tumor stage ( P = .022) and p16 status ( P = .032) but not with anatomic site. Notably, p16 + HNSCCs had significantly lower Eps8 expression than p16 − HNSCCs. No significant difference was observed between primary HNSCCs and their corresponding metastatic LNs. Neither p16 status nor anatomic site influenced Eps8 expression in regional LN metastases. In conclusion, our data offer in vivo support that, in HNSCCs, Eps8 is involved in tumor invasion but not necessarily the development of regional LN metastasis. The association between low Eps8 expression and p16 + HNSCCs suggests that alternative signaling pathways may be used for their tumorigenesis.
The role of ACTH in the episodic release of aldosterone in patients with idiopathic adrenal hyperplasia, hypertension, and hyperaldosteronism.

The relationship of plasma aldosterone concentration to its identified stimuli was examined in three patients with hypertension, hyperaldosteronism, and idiopathic adrenal hyperplasia. Four patients with hyperaldosteronism due to adrenal adenomas served as controls. Plasma aldosterone, cortisol, sodium, and potassium concentrations and renin activity were measured in blood samples taken at 20 minute intervals from 2 A.M. to 8 A.M. during recumbency and sleep. The tests were performed on all patients following a regular sodium diet both before and after short-term treatment with dexamethasone. Two of the three subjects with adrenal hyperplasia were re-examined after 2 weeks of dexamethasone therapy. All four control patients with adenomas had episodic increases of plasma aldosterone which were significantly correlated with those of plasma cortisol (r = +0.48 to +0.90). This confirms the previously reported relationship between aldosterone and ACTH in such patients. Two patients with idiopathic adrenal hyperplasia had a similar secretion pattern and a highly significant correlation of the two hormones (r = +0.76 and +0.77); one did not (r = 0.13). Short-term dexamethasone pretreatment attenuated the episodic release pattern and partially suppressed the mean plasma concentrations of aldosterone in the four patients with an adenoma and in the two patients with idiopathic hyperplasia whose plasma aldosterone and cortisol concentrations were positively correlated. There was no such effect in the third patient. The first two patients with idiopathic hyperplasia were subsequently retested following 2 weeks of dexamethasone treatment to determine if the episodic secretion pattern of plasma aldosterone would correlated with other stimuli following this period of ACTH suppression. One showed little change from the pattern observed after short-term glucocorticoid treatment. The second had a similarly blunted aldosterone response until ACTH secretion led to a resumption of episodic changes in plasma aldosteerone concentrations. These data indicate that ACTH frequently is the dominant stimulus of the episodic secretion of aldosterone in patients with either adrenal adenomas or hyperplasia. When ACTH is suppressed, the hypersecretion of aldosterone is presumably sustained by an intrinsic adrenal abnormality or by an as yet unidentified stimulus.
Direct Reprogramming of Amniotic Cells into Endothelial Cells

Organ regeneration promises unlimited access to replacement tissues. The current paradigm of organ regeneration requires transplantation of adult tissue-restricted stem and progenitor cells to repair the damaged organ. However, healing injured organs often leads to fibrosis with little recovery of function. An alternative approach is to harness the regenerative activity of microvascular endothelial cells (ECs) to support endogenous organ repair. Recent work demonstrates that organ regeneration can be directed by paracrine mediators, called “Angiocrine Factors,” elaborated by tissue-specific ECs to support stem and progenitor cells to directly induce organ regeneration without maladaptive fibrosis. Yet, the regenerative function and the repertoire of angiocrine factors elaborated by ECs depend upon the organ from which they originate.
OCEAN SURFACE CURRENT DETECTION BY SYNTHETIC APERTURE RADAR

Synthetic aperture radar Doppler histories have been used to obtain estimates of ocean surface currents. For currents in excess of 1 meter/second, airborne radar measurements agree with surface observations to within 25 percent. Satellite measurements, however, yield current speeds far in excess of surface estimates. The technique developed to obtain the Doppler information is described, and possible sources of error are discussed.
Effects of clotrimazole troches on tacrolimus dosing in heart transplant recipients.

Background Tacrolimus is a cornerstone of immunosuppression after transplantation but is highly susceptible to changes from interacting variables and has a narrow therapeutic index. Clotrimazole troches are commonly used as a non-systemic antifungal to prevent oral candidiasis. Studies suggest that clotrimazole troches, though minimally absorbed systemically, may affect tacrolimus concentrations by inhibition of metabolic enzyme activity in the intestines. However, the magnitude of the impact of clotrimazole on tacrolimus dosing requirements to maintain goal levels is not well described. Methods To assess this, tacrolimus dose adjustments and trough concentrations were retrospectively examined in 95 heart transplant recipients before and after the discontinuation of clotrimazole. Results The median percent tacrolimus dose change was an increase of 66.7% (IQR 28.6%, 100%) after clotrimazole discontinuation, and the median trough concentration percent change from baseline to the first trough after clotrimazole discontinuation (in the absence of a dose change) was -42.5% (IQR -52.3%, -30.9%). Five cases of allograft rejection were observed. Conclusion In conclusion, clotrimazole troches exert a meaningful interaction with tacrolimus that requires close monitoring and dose adjustment. The data from this single-center study provide novel information that could guide providers on the degree of tacrolimus dose adjustment needed when discontinuing clotrimazole prophylaxis after heart transplantation.
Capital Gains Taxes and Liquidity

I predict that tax-sensitive investors’ reluctance to realize capital gains in a particular stock reduces noise trading in the stock and thus decreases the stock’s liquidity. After controlling for information asymmetry, I find that over the period 1988-2008, a one standard deviation increase in the unrealized gains of institutional investors who are unambiguously tax-sensitive results in a 0.44 percent increase in Ahimud’s measure of illiquidity, a 1.8 percent increase in the quoted bid-ask spread, and a 1.2 percent increase in the effective bid-ask spread for the mean firm each quarter. I find that a hedge portfolio that goes long in firms with a relatively large difference between the unrealized gains of tax-sensitive investors and those of institutional investors that are unambiguously tax-insensitive and short in firms with a relatively small difference earns on average a positive and significant risk-adjusted return equal to 0.016 percent per quarter and 0.049 percent per year.
How does hard-to-reach status affect antiretroviral therapy adherence in the HIV-infected population? Results from a meta-analysis of observational studies.

Socially disadvantaged groups, such as drug users, sex workers and homeless individuals, are labelled as “hard-to-reach” (HTR) in public health and medical research. HIV disproportionately impacts these populations, but data on how the HTR status could affect antiretroviral therapy (ART) adherence among HIV-positive people are limited and have not been previously synthesized in a systematic manner. We performed a meta-analysis to explore the association between HTR status and optimal antiretroviral therapy adherence in the HIV-infected population to provide evidence and recommendations regarding ART adherence improvement and HIV infection control and prevention among HTR people. The PubMed, EMBASE, and Cochrance Library databases and the bibliographies of relevant studies were systematically searched up to December 2018. Full-text studies published in English were included, and no geographic or race restrictions were applied. Studies that quantitatively assessed the association between HTR status and optimal ART adherence among HIV-infected populations with a status of homelessness, sex work, or drug use were eligible for inclusion. We estimated the pooled odds ratios (ORs) of HTR characteristics related to ART adherence from each eligible study using a random effects model. The sensitivity, heterogeneity and publication bias were assessed. Our search identified 593 articles, of which 29 studies were eligible and included in this meta-analysis. The studies were carried out between 1993 and 2017 and reported between 1999 and 2018. The results showed that HTR status resulted in a 45% reduction in the odds of achieving optimal ART adherence compared to odds in the general population (OR = 0.55, 95% confidential intervals (CIs) 0.49–0.62), and this significant inverse association was consistently found regardless of study design, exposure measurement, adherence cut-off points, etc. Subgroup analyses revealed that the HTRs tend to be suboptimal adhering during a longer observational period. HIV treatment adherence is extremely negatively affected by HTR status. It is crucial to develop appropriate interventions to improve ART adherence and health outcomes among HTR people who are HIV-infected.
Soil surface disturbance alters cyanobacterial biocrusts and soil properties in dry grassland and shrubland ecosystems

Biological soil crusts (biocrusts) dominate soil surfaces in drylands, providing services that include soil stabilization and carbon uptake. In this study, we investigated the direct and biocrust-mediated effects of anthropogenic disturbances in two dryland ecosystems. We applied low intensity soil surface disturbance (twice-yearly footfalls) in grassland and shrubland ecosystems in northern Chihuahuan Desert, USA. After five years of disturbance, biocrust photosynthetic capacity (chlorophyll a) declined by 44%. Declines were largest in interspaces between grassland plants. Levels of scytonemin, a biocrust sunscreen pigment, were 38% greater in shrubland than grassland and 44% greater under grass canopy than in interspaces, but decreased only 5% with disturbance. Disturbance reduced soil surface stability 2 times more in the grassland than shrubland. Disturbance effects on other hydrologic and physical properties were indirectly mediated by the photosynthetic capacity of biocrusts. Disturbance indirectly increased infiltration depth and shallow (2–3 cm) soil moisture in the grassland but reduced surface moisture (<1 cm) in the shrubland. Biocrusts were more sensitive to low intensity soil disturbance in a grassland than shrubland ecosystem. While biocrusts mediated the effects of soil disturbance on dryland soil hydrological and physical properties, the nature of their influence differed between ecosystem types.
Secondary Voltage Control Via Demand-Side Energy Storage with Temporal Logic Specifications

This paper proposes a secondary voltage control method that can handle temporal logic specifications (TLSs). The control objective is to schedule a control signal for an energy storage system (ESS) such that the voltage variation of a defined critical bus satisfies TLSs. The TLS allows definitions of set and timing constraints at the same time, such as a finite-time restoration. A simplified analytical model is derived to describe the voltage variation of critical buses. Based on this model, a numerical optimal control problem is formulated as a mixed integer linear program to generate the proper control input for the ESS. The proposed control is verified on a lumped distribution system model. With this control diagram, supportive controllers can easily be designed to make voltage behaviors comply with grid codes and avoid unnecessary relay actions.
Methylation of the IGFBP-3 gene and prognosis of epithelial ovarian cancer

1059 Insulin-like growth factor binding protein-3 (IGFBP-3) is a member of the IGF binding protein family (IGFBP) which regulates the mitogenic and anti-apoptotic effects of insulin-like growth factors (IGFs). IGFBP-3 is the most abundant IGFBP in the circulation and hypermethylation of the IGFBP-3 promoter has been found to suppress its expression. To evaluate the role of IGFBP-3 in ovarian cancer progression, we examined the survival of ovarian cancer patients in relation to IGFBP-3 promoter methylation and IGFBP-3 protein levels in ovarian tumor tissue. Two hundred forty-nine consecutive epithelial ovarian cancer patients were selected for the study from the Department of Gynecology and Obstetric at University of Turin and were followed for a median of 31 months after surgery. Genomic DNA was extracted from fresh frozen tumor tissue and treated with sodium bisulfite. IGFBP-3 promoter methylation was analyzed using methylation-specific PCR (MSP). Tissue cytosol was prepared with the use of a protein extraction kit and IGFBP-3 protein levels in the cytosol were determined using a commercial ELISA. Cox regression survival analysis was performed to examine the association of IGFBP-3 methylation with disease-free and overall survivals. The majority of patients in the study had advanced disease (69%, Stage III and IV) and aggressive tumors (66%, Grade 3). Promoter methylation of the IGFBP-3 gene was detected in 43% (107/248) of the patients. IGFBP-3 promoter methylation was not associated with disease progression (p=0.3972) or death (p=0.2983) in univariate analyssis, but the associations became statistically significant when clinical and pathological variables, including age at diagnosis, disease stage, histologic grade, debulking results, residual tumor size, and IGFBP-3 levels in tumor tissue, were adjusted in the analysis. The relative risk was 1.62 (95% CI: 1.06-2.47) for disease progression and 1.59 (95% CI: 1.04-2.43) for death. Tissue levels of IGFBP-3 protein were not significantly different by methylation status (p=0.30), and were not associated with disease progression (p=0.33) or death (p=0.18). In conclusion, the study did not find strong evidence to support the notion that IGFBP-3 promoter methylation suppresses IGFBP-3 expression in ovarian cancer and can be used as a molecular marker for ovarian cancer prognosis.
Effect of neonatal therapy on the motor, cognitive, and behavioral development of infants born preterm: a systematic review.

Aim To synthesize the existing literature and determine the efficacy of neonatal therapy, starting in the neonatal intensive care unit (NICU), on the motor, cognitive, and behavioral outcomes of infants born preterm. Method Databases were searched for randomized controlled trials or quasi-randomized controlled trials of direct therapy early intervention for infants with a gestational age of less than 37 weeks, initiated in the NICU and delivered by a therapist or parent with therapist support. Quality was evaluated using the Cochrane standardized risk of bias assessment tool. Recommendations were made using the Grading of Recommendations, Assessment, Development and Evaluations approach. Results Fifteen studies met the inclusion criteria. Studies were categorized into four intervention categories: (1) parent-delivered motor intervention (PDMI); (2) therapist-delivered postural control intervention (TDPCI); (3) developmental care; and (4) oromotor intervention. Risk of bias varied from low (10 studies) to high (three studies) or was unclear (two studies). Interpretation Preliminary support indicates that daily PDMI improves motor and cognitive outcomes in the short-term and possibly long-term. TDPCI is effective in promoting short-term gains in motor development. Developmental care programs designed by a neonatal therapist appear to be effective in improving short-term behavior but are inconclusive for motor and cognitive outcomes or long-term behavioral outcomes. Regarding oromotor interventions, there is insufficient research to be confident in their efficacy on improving developmental outcomes. What this paper adds Parent-delivered motor interventions (PDMIs) are more effective in improving motor and cognitive outcomes than other interventions. Preliminary support indicates that daily PDMI improves motor and cognitive outcomes in the short- and possibly long-term. Therapist-delivered postural control interventions are effective in promoting short-term gains in motor development. Developmental care programs designed by a neonatal therapist are effective in improving the short-term behavior of infants born preterm. Oral motor interventions were found to have no effect on improving developmental outcomes.
RSS-Based Detection of Drones in the Presence of RF Interferers

Drones will have extensive use cases across various commercial, government, and military sectors, ranging from delivery of consumer goods to search and rescue operations. To maintain safety and security of people and infrastructure, it becomes critically important to quickly and accurately detect non-cooperating drones. In this paper we formulate a received signal strength (RSS) based detector, leveraging the existing wireless infrastructures that might already be serving other devices. Thus the detector should be able to detect the presence of a drone signal buried in radio frequency (RF) interference and thermal noise, in a mixed line-of-sight (LOS) and non-LOS (NLOS) environment. We develop analytical expressions for the probability of false alarm and the probability of detection of a drone, which quantify the impact of aggregate interference and air-to-ground (A2G) propagation characteristics on the detection performance of individual sensors. We also provide analytical expressions for the average network probability of detection, which captures the impact of sensor density on a network's detection coverage. Finally, we find the critical sensor density that maximizes the average network probability of detection for a given requirement of probability of false alarm.
Endurance exercise training in pulmonary hypertension increases skeletal muscle electron transport chain supercomplex assembly

Pulmonary hypertension is associated with pronounced exercise intolerance (decreased V ċ O2 max) that can significantly impact quality of life. The cause of exercise intolerance in pulmonary hypert...
Chapter 28 – Selected Zoonoses

Human risks of acquiring a zoonotic disease from animals used in biomedical research have declined over the last decade because higher quality research animals have defined microbiologic profiles. Even with diminished risks, the potential for exposure to infectious agents still exists, especially from larger species such as nonhuman primates, which may be obtained from the wild, and from livestock, dogs, ferrets, and cats, which are generally not raised in barrier facilities and are not subject to the intensive health monitoring performed routinely on laboratory rodents and rabbits. Additionally, when laboratory animals are used as models for infectious disease studies, exposure to microbial pathogens presents a threat to human health. Also, with the recognition of emerging diseases, some of which are zoonotic, constant vigilance and surveillance of laboratory animals for zoonotic diseases are still required.
A strategy for large-scale comparison of evolutionary- and reaction-based classifications of enzyme function

Determining the molecular function of enzymes discovered by genome sequencing represents a primary foundation for understanding many aspects of biology. Historically, classification of enzyme reactions has used the enzyme nomenclature system developed to describe the overall reactions performed by biochemically characterized enzymes, irrespective of their associated sequences. In contrast, functional classification and assignment for the millions of protein sequences of unknown function now available is largely done in two computational steps, first by similarity-based assignment of newly obtained sequences to homologous groups, followed by transferring to them the known functions of similar biochemically characterized homologs. Due to the fundamental differences in their etiologies and practice, `how' these chemistry- and evolution-centric functional classification systems relate to each other has been difficult to explore on a large scale. To investigate this issue in a new way, we integrated two published ontologies that had previously described each of these classification systems independently. The resulting infrastructure was then used to compare the functional assignments obtained from each classification system for the well-studied and functionally diverse enolase superfamily. Mapping these function assignments to protein structure and reaction similarity networks shows a profound and complex disconnect between the homology- and chemistry-based classification systems. This conclusion mirrors previous observations suggesting that except for closely related sequences, facile annotation transfer from small numbers of characterized enzymes to the huge number uncharacterized homologs to which they are related is problematic. Our extension of these comparisons to large enzyme superfamilies in a computationally intelligent manner provides a foundation for new directions in protein function prediction for the huge proportion of sequences of unknown function represented in major databases. Interactive sequence, reaction, substrate and product similarity networks computed for this work for the enolase and two other superfamilies are freely available for download from the Structure Function Linkage Database Archive (http://sfld.rbvi.ucsf.edu).
Opioid Prescriptions and the Educational Performance of Children

This study examines the relationship between local-area opioid prescription rates and student performance on end-of-year mathematics exams in the state of South Carolina between 2006-2017. We link individual test score data for 3rd-8th grade students to county-level changes in opioid prescriptions per 100 people. Findings show that an increase in the opioid prescription rate in a county statistically reduced white student test scores, but no such decline was found among non-white students. Among white students the effects are strongest on rural students in households that are not receiving SNAP or TANF benefits. These results are robust to controls for changing county-level economic conditions and controls for student-level poverty.
Dissipativity-Based Verification for Autonomous Systems in Adversarial Environments

In this chapter, we investigate the problem of verifying desired properties of large-scale cyber-physical systems that operate in uncertain, adversarial environments. We focus on properties relating to dissipativity and we propose approaches to achieve verification with minimum knowledge of the system dynamics. In order to achieve compositionality in large-scale models, we distribute the verification process among individual subsystems, which utilize limited information received locally from their immediate neighbors. The need for knowledge of the subsystem parameters is avoided via a novel reinforcement learning-inspired approach that enables decentralized evaluation of appropriate storage functions that can be used to verify dissipativity. Our method allows the addition of learning-enabled subsystems to the cyber-physical network while dissipativity is ensured. We show how different learning rules can be used to guarantee different properties, such as \(L_2\)-gain stability or losslessness. Finally, the need for verification of complex properties is addressed and we propose new directions for this problem.
Observable Evidence and Partnership Possibilities for Governing Board Involvement in Diversity, Equity, and Inclusion: A Content Analysis

Researchers conducted a qualitative content analysis to investigate the observable involvement of 22 Governing Boards with Diversity, Equity, and Inclusion (DEI) efforts at colleges and universities. Using a merged theoretical framework of Rall et al.’s (Journal of Education Human Resources 38:139–164, 2020) Culturally Sustaining Governance and LePeau’s (The Review of Higher Education 39:97–122, 2015) Cycle of Making Continuous Commitments to Diversity and Inclusion, the findings revealed that Boards act in similar ways to an electrical socket between internal and external stakeholders associated with DEI efforts. Boards receive information from stakeholders at points in time and episodically ‘plug in’ to DEI efforts such as endorsing policies or diversity plans. The study highlights the nature and potential of governance partnerships to advance DEI work. Implications encourage Boards to enhance their capacity to partner and support organizational change.
Sleep and longitudinal cognitive performance in preclinical and early symptomatic Alzheimer’s disease

Sleep monitoring may provide markers for future Alzheimer's disease; however, the relationship between sleep and cognitive function in preclinical and early symptomatic Alzheimer's disease is not well understood. Multiple studies have associated short and long sleep times with future cognitive impairment. Since sleep and the risk of Alzheimer's disease change with age, a greater understanding of how the relationship between sleep and cognition changes over time is needed. In this study, we hypothesized that longitudinal changes in cognitive function will have a non-linear relationship with total sleep time, time spent in non-REM and REM sleep, sleep efficiency and non-REM slow wave activity. To test this hypothesis, we monitored sleep-wake activity over 4-6 nights in 100 participants who underwent standardized cognitive testing longitudinally, APOE genotyping, and measurement of Alzheimer's disease biomarkers, total tau and amyloid-β42 in the CSF. To assess cognitive function, individuals completed a neuropsychological testing battery at each clinical visit that included the Free and Cued Selective Reminding test, the Logical Memory Delayed Recall assessment, the Digit Symbol Substitution test and the Mini-Mental State Examination. Performance on each of these four tests was Z-scored within the cohort and averaged to calculate a preclinical Alzheimer cognitive composite score. We estimated the effect of cross-sectional sleep parameters on longitudinal cognitive performance using generalized additive mixed effects models. Generalized additive models allow for non-parametric and non-linear model fitting and are simply generalized linear mixed effects models; however, the linear predictors are not constant values but rather a sum of spline fits. We found that longitudinal changes in cognitive function measured by the cognitive composite decreased at low and high values of total sleep time (P < 0.001), time in non-REM (P < 0.001) and REM sleep (P < 0.001), sleep efficiency (P < 0.01) and <1 Hz and 1-4.5 Hz non-REM slow wave activity (P < 0.001) even after adjusting for age, CSF total tau/amyloid-β42 ratio, APOE e4 carrier status, years of education and sex. Cognitive function was stable over time within a middle range of total sleep time, time in non-REM and REM sleep and <1 Hz slow wave activity, suggesting that certain levels of sleep are important for maintaining cognitive function. Although longitudinal and interventional studies are needed, diagnosing and treating sleep disturbances to optimize sleep time and slow wave activity may have a stabilizing effect on cognition in preclinical or early symptomatic Alzheimer's disease.
Inhaled corticosteroids in children with asthma: pharmacologic determinants of safety and efficacy and other clinical considerations.

The role of inhaled corticosteroids (ICS) in the treatment of childhood asthma has been well established. An ideal corticosteroid should demonstrate high pulmonary deposition and residency time, in addition to a low systemic bioavailability and rapid systemic clearance. The lung depositions of the ICS have been compared, with beclomethasone (beclometasone)-hydrofluoroalkane (HFA) and ciclesonide showing the highest lung deposition. Lung deposition is influenced by not only the inhalation device and type of propellant (HFA or chlorofluorocarbon), but also by whether the aerosol is a solution or suspension, and the particle size of the respirable fraction. Pulmonary residency time increases when budesonide and des-ciclesonide undergo reversible fatty acid esterification. The bioavailability of the drug depends on the oral bioavailable fraction and the amount absorbed directly from the pulmonary vasculature. The clearance rate of des-ciclesonide is very high (228 L/h), increasing its safety profile by utilizing extra-hepatic clearance mechanisms. Both des-ciclesonide and mometasone have a high protein binding fraction (98–99%). The volume of distribution (Vd) is proportional to the lipophilicity of the drug, with the Vd of fluticasone being 332L compared with 183L for budesonide. Increasing the Vd will also increase the elimination half-life of a drug. The pharmacodynamics of ICS depend on both the receptor binding affinity and the dose-response curve. Among the ICS, fluticasone and mometasone have the highest receptor binding affinity (1800 and 2200, respectively), followed by budesonide at 935 (relative to dexamethasone = 100). Compared with other nonsteroid asthma medications (long-acting β-agonists, theophylline, and montelukast) ICS have proven superiority in improving lung function, symptom-free days, and inflammatory markers. One study suggests that early intervention with ICS reduces the loss in lung function (forced expiratory volume in 1 second) over 3 years. Whether airway remodeling is reduced or prevented in the long term is unknown. Potential adverse drug effects of ICS include adrenal and growth suppression. While in low-to-medium doses ICS have shown little suppression of the adrenal pituitary axis, in high doses the potential for significant adrenal suppression and adrenal crisis exists. Several longitudinal studies evaluating the effect of ICS on growth have shown a small decrement in growth velocity (≈1–2cm) during the first year of treatment. However, when investigators followed children treated with budesonide for up to 10 years, no change in target adult height was noted. In conclusion, the development of optimal delivery devices for young children, as well as optimizing favorable pharmacokinetic properties of ICS should be priorities for future childhood asthma management.