cssi/SciSciGPT-SciSciNet huggingface dataset:
Risk of Second Primary Malignancies in Patients with AL Amyloidosis Treated with Lenalidomide

Abstract 1873 An increase in second primary malignancies (SPM) has been reported in patients with myeloma treated with lenalidomide, particularly in association with melphalan. To determine the rate of second primary malignancies in AL amyloidosis patients treated with lenalidomide, we reviewed data on 82 patients treated on clinical trials at Boston Medical Center from 2004–2011. Data from lenalidomide and dexamethasone treatment in AL amyloidosis (ClinicalTrials.gov: NCT00091260) were analyzed in a post-hoc fashion for the incidence rate for SPM. The median age of these 82 patients was 62 years (range, 40–82); and 52 (63%) were male. There were 62 patients (76%) with lambda clonal plasma cell dyscrasia, and 43 (52%) had cardiac involvement by the consensus criteria from the X th International Amyloidosis Symposium. Median duration for lenalidomide treatment was 9 cycles (range, 1–69); and 16 (20%) received lenalidomide for > 24 months. Of the 82 patients, 78 (95%) patients had prior therapies and 77 (94%) had prior alkylating agents based treatment. The median follow-up of the 82 patients was 28 months (range, 3–92). One patient, a smoker, treated with lenalidomide for 24 months, developed metastatic lung cancer. Additionally, there were 5 non-melanoma skin cancers. There was no case of hematologic malignancy or B-cell lymphoproliferative disorder in this group. This corresponds to an incidence rate of 0.44 per 100 patient-years for invasive cancer. The annual incidence of invasive cancers is 2.1 per 100 patient-years for the general population in the US. In conclusion, lenalidomide based treatment in AL amyloidosis did not appear to increase the incidence rate of SPM compared to incidence rate for the invasive cancers in general population. Longer prospective follow-up may be needed in a larger patient population to better define the risk. Disclosures: Sanchorawala: Celgene Corporation: Research Funding. Off Label Use: Use of lenalidomide in the treatment of AL amyloidosis. Seldin: Celgene Corporation: Research Funding.
General Physics Principles in Brachytherapy

Brachytherapy (or Curietherapy) delivers radiation dose to the target by placing a radiation source directly in or near the target. Brachytherapy techniques are classified with implant type, implant duration, source loading type, and dose rate. For brachytherapy radioisotopes, high energy photon sources, low energy photon sources, beta sources, and neutron sources are used. Prior to the development of computerized treatment planning techniques, several classic implant systems were developed to deliver a specified dose to the tumor. Nowadays, anatomy-based inverse planning dose optimization methods have been used to increase target dose coverage and reduce dose to organs at risk. For dose calculations methods, the American Association of Physicists in Medicine (AAPM) Task Group 43 (TG-43) dosimetry protocol in use today and TG-186 protocol (model-based dose calculation techniques in the heterogeneous media) are presented in this chapter.
Volumetric Image Registration From Invariant Keypoints

We present a method for image registration based on 3D scale- and rotation-invariant keypoints. The method extends the scale invariant feature transform (SIFT) to arbitrary dimensions by making key modifications to orientation assignment and gradient histograms. Rotation invariance is proven mathematically. Additional modifications are made to extrema detection and keypoint matching based on the demands of image registration. Our experiments suggest that the choice of neighborhood in discrete extrema detection has a strong impact on image registration accuracy. In head MR images, the brain is registered to a labeled atlas with an average Dice coefficient of 92%, outperforming registration from mutual information as well as an existing 3D SIFT implementation. In abdominal CT images, the spine is registered with an average error of 4.82 mm. Furthermore, keypoints are matched with high precision in simulated head MR images exhibiting lesions from multiple sclerosis. These results were achieved using only affine transforms, and with no change in parameters across a wide variety of medical images. This paper is freely available as a cross-platform software library.
A generalization to set-theoretic model reference adaptive control architecture for enforcing user-defined time-varying performance bounds

It is a challenge to achieve user-defined performance guarantees while utilizing model reference adaptive control laws in the feedback loop. To this end, we recently introduced a set-theoretic model reference adaptive control framework. The key feature of this approach allows the distance between the state of an uncertain dynamical system and the state of a reference model (i.e., the system error) to be less than a user-defined constant performance bound. In this paper, the set-theoretic model reference adaptive control framework is generalized to enforce user-defined time-varying performance bounds on the system error, which gives user the flexibility to control the closed-loop system performance as desired on different time intervals (e.g., transient time interval and steady-state time interval). For this purpose, an architecture is proposed for adaptive command following, where two numerical examples are provided to illustrate the efficacy of the proposed contribution.
Cancer Immunotherapy with Chimeric Antigen Receptor (CAR) T Cells

Chimeric antigen receptor T cell (CAR T) therapy recently won its first U.S. Food and Drug Administration approval for use in the treatment of patients aged 3-25 with relapsed or refractory acute l...
“That They May Hear”: Biblical Foundations for the Oral Reading of Scripture in Worship:

The Western evangelical church has lost both the passion for and the art of reading Scripture orally in worship. This exploration of the biblical roots of reading Scripture orally examines both the...
RANKL-mediated osteoclastogenic differentiation of macrophages in the abdominal aorta of angiotensin II-infused apolipoprotein E knockout mice.

Abstract Objective Osteoclastogenic activation of macrophages (OCG) occurs in human abdominal aortic aneurysms (AAAs) and in calcium chloride-induced degenerative AAAs in mice, which have increased matrix metalloproteinase activity. As the activity of OCG in dissecting aneurysms is not clear, we tested the hypothesis that OCG contributes to angiotensin II (Ang II)-induced dissecting aneurysm (Ang II-induced AAA) in apolipoprotein E knockout mice. Methods AAAs were produced in apolipoprotein E knockout mice via the administration of Ang II. Additionally, receptor activator of nuclear factor kB ligand (RANKL)-neutralizing antibody (5 mg/kg) was administered to one group of mice 7 days prior to Ang II infusion. Aneurysmal sections were probed for presence of RANKL and tartrate-resistant acid phosphatase via immunohistochemistry and immunofluorescence staining. Mouse aortas were also examined for RANKL and matrix metalloproteinase 9 expression via Western blot. In vitro murine vascular smooth muscle cells (MOVAS) and murine macrophages (RAW 264.7) were analyzed for the expression of osteogenic factors via Western blot, qPCR, and flow cytometry in response to Ang II or RANKL stimulation. The signaling pathway that mediates Ang II-induced RANKL expression in MOVAS cells was also investigated via application of TG101348, a Janus kinase 2 (JAK2) inhibitor, and Western blot analysis. Results Immunohistochemical staining of Ang II-induced AAA sections revealed OCG as evidenced by increased RANKL and tartrate-resistant acid phosphatase expression compared with control mice. Immunofluorescence staining of AAA sections revealed co-localization of vascular smooth muscle cells and RANKL, revealing vascular smooth muscle cells as one potential source of RANKL. Systemic administration of RANKL-neutralizing antibody suppressed Ang II-induced AAA, with significant reduction of the maximum diameter of the abdominal aorta compared with vehicle controls (1.5 ± 0.4 mm vs 2.2 ± 0.2 mm). Ang II (1 μM) treatment induced a significant increase in RANKL messenger RNA expression levels in MOVAS cells compared with the vehicle control (1.0 ± 0.2 vs 2.8 ± 0.2). The activities of JAK2 and signal transducer and activator of transcription 5 (STAT5) were also significantly increased by Ang II treatment. Inhibition of JAK2/STAT5 suppressed Ang II-induced RANKL expression, suggesting the involvement of the JAK2/STAT5 signaling pathway. Conclusions OCG with increased RANKL expression was present in Ang II-induced AAA, and neutralization of RANKL suppressed AAA formation. As neutralization of RANKL has been used clinically to treat osteoporosis and other osteoclast-related diseases, additional study of the effectiveness of RANKL neutralization in AAA is warranted.
THE ROLE OF ICEBERG UTILIZATION IN SOLVING THE SAUDI ARABIAN WATER PROBLEMS

The demand pattern of water in Saudi Arabia is analyzed for the next decade. Plans to augment present water supplies are discussed to provide a framework for the investigation of the potential of icebergs as a water resource. It is shown that the present and future demands of water in the domestic and industrial sectors cannot be met satisfactorily by conventional desalination units. The development of Saudi Arabia especially in industrial and agricultural activities cannot be easily achieved without comprehensive programs to explore novel options; such as utilization of icebergs for fresh water.
Increased leptin supply to hypothalamus by gene therapy confers life-long benefits on energy homeostasis, disease cluster of metabolic syndrome- diabetes type 1 and 2, dyslipidemia and cardiovascular ailments- and bone remodeling

Leptin insufficiency in the hypothalamus is causally linked to increased fat accrual, diseases of the metabolic syndrome, skeletal abnormalities and shortened life-span. We show that leptin sufficiency attained with hypothalamic leptin gene therapy (i) suppressed food intake, the agerelated and energy enriched diet-induced fat accrual, and dyslipidemia, (ii) attenuated episodic insulin secretion and enhanced insulin sensitivity, (iii) enhanced glucose tolerance and maintained euglycemia by concurrently stimulating glucose metabolism and non-shivering thermogenesis, even in the absence of circulating insulin, and (iv) augmented ghrelin secretion. Aside from these metabolic benefits, similar optimal leptin sufficiency in the hypothalamus (i) decreased risks for cardiovascular diseases as indicated by suppression of circulating levels of the systemic proinflammatory markers, C-reactive protein and interleukin-6, and hypergly-cemia-induced risk factors for cardiomyopathy, (ii) improved bone health by promoting growth of long bones and reduction of cancellous bone volume in association with increased release of osteoblast-specific osteocalcin, and (iii) reduced early mortality and doubled the life-span of obese ob/ob mice. On the basis of these global long-lasting health benefits, we advocate clinical testing of central leptin gene therapy or of long acting leptin mimetics to prevent life-threatening pathophysiologic sequalae attending the worldwide epidemic of obesity and the metabolic syndrome.
Languages Associated with Crystallographic Symmetry

We establish a relationship between periodic graphs representing crystallographic structures and an infinite hierarchy of intersection languages \(\mathcal{DCL}_d\), d = 0,1,2,…, within the intersection classes of deterministic context-free languages. We introduce a class of counter machines that accept these languages, where the machines with d counters recognize the class \(\mathcal{DCL}_d\). Each language in \(\mathcal{DCL}_d\) is an intersection of d languages in \(\mathcal{DCL}_1\). We prove that there is a one-to-one correspondence between sets of walks starting and ending in the same unit of a d-dimensional periodic (di)graph and the class of languages in \(\mathcal{DCL}_d\).
A Step Out from the Middle

I will make two types of comments. First, I will summarize my thoughts as they relate to the four individual papers. Then, I want to focus on some ideas that these papers stimulated about middle range theory and organizational behavior more generally.
Pathways to Abortion at a Tertiary Care Hospital: Examining Obesity and Delays.

Context Advancing gestational age can increase the cost of an abortion and is a significant risk factor for complications. While obesity is not associated with increased risks, anecdotal evidence suggests that obese women seeking services at freestanding abortion clinics are often referred for hospital-based care, which can lead to delays. Methods In 2016, a cross-sectional survey collected data on the experiences of 201 women who had obtained abortions at a hospital-based clinic in Philadelphia; rates of medical complications were determined from hospital records. Multivariable logistic regression analysis was used to assess if obesity was associated with whether patients had been referred from freestanding abortion clinics or reported other paths to care. Differences in wait time and up-front out-of-pocket costs were examined by women's referral status. Results No difference in rates of abortion complications was found between patient groups. Women who were severely obese (body mass index of at least 40 kg/m2 ) were more likely than normal-weight individuals to have been referred from a freestanding abortion clinic (odds ratio, 7.5). The median wait time to get an abortion was 28 days for referred patients and 12 days for others. Multivariable analysis confirmed that referred patients waited twice as long as other patients (rate ratio, 2.0) and paid 66% more in up-front costs. Conclusions Future research is needed to determine whether obese women seeking abortions are being referred despite evidence that they do not require hospital-based care. If obese women are suffering delays because of referral, strategies to help overcome delay should also be explored.
Automotive Intrusion Detection Based on Constant CAN Message Frequencies Across Vehicle Driving Modes

The modern automobile relies on numerous electronic control units communicating over the de facto standard of the controller area network (CAN) bus. This communication network was not developed with cybersecurity in mind. Many methods based on constant time intervals between messages have been proposed to address this lack of security issue with the CAN bus. However, these existing methods may struggle to handle variable time intervals between messages during transitions of vehicle driving modes. This paper proposes a simple and cost-effective method to ensure the security of the CAN bus that is based on constant message frequencies across vehicle driving modes. This proposed method does not require any modifications on the existing CAN bus and it is designed with the intent for efficient execution in platforms with very limited computational resources. Test results with the proposed method against two different vehicles and a frequency domain analysis are also presented in the paper.
Arsenic and old FLT3

FLT3-internal tandem duplication (FLT3-ITD) mutations are common in acute promyelocytic leukemia (APL) and render the disease more difficult to manage or cure. In this issue of Blood, Esnault et al begin to unravel how the mutation-activated FLT3 receptor impedes the effects of all-trans retinoic acid (ATRA) and how arsenic counters this.1
Social robots with a theory of mind (ToM): Are we threatened when they can read our emotions?

How would human users react to social robots that possess a theory of mind (ToM)? Would robots that can infer their users’ cognitions and emotions threaten their sense of uniqueness and evoke other negative reactions because ToM is a uniquely human trait? If so, can we alleviate these negative user reactions by framing robots as members of our ingroup? We addressed these questions with a 3 (robot’s affective ToM: correct vs. incorrect vs. control) × 2 (robot’s group membership: ingroup vs. outgroup) × 2 (user gender: female vs. male) between-subjects online experiment. Participants were asked to complete an online task with a robot named Pepper that was identified as an ingroup member or outgroup member. They first read a passage describing a past user’s interaction with Pepper, in which the user expressed sarcasm and Pepper correctly or incorrectly identified the user’s sarcasm or made a neutral comment. Males reacted more negatively to Pepper that correctly identified sarcasm and reported lower expected enjoyment with Pepper than females. Ingroup Pepper made participants feel closer to the robot but also threatened their sense of uniqueness than the outgroup Pepper. Design implications for fostering better human-robot interaction (HRI) are discussed.
Room-temperature heterodyne terahertz detection with quantum-level sensitivity

Our Universe is most radiant at terahertz frequencies (0.1–10.0 THz) (ref. 1), providing critical information on the formation of the planets, stars and galaxies, as well as the atmospheric constituents of the planets, their moons, comets and asteroids2–9. The detection of faint fluxes of photons at terahertz frequencies is crucial for many planetary, cosmological and astrophysical studies10–14. For example, understanding the physics and molecular chemistry of the life cycle of stars and their relationship with the interstellar medium in galaxies requires heterodyne detectors with noise temperatures close to the quantum limit15. Near-quantum-limited heterodyne terahertz detection has so far been possible only through the use of cryogenically cooled superconducting mixers as frequency downconverters15–18. Here we introduce a heterodyne terahertz detection scheme that uses plasmonic photomixing for frequency downconversion to offer quantum-level sensitivities at room temperature. Frequency downconversion is achieved by mixing terahertz radiation and a heterodyning optical beam with a terahertz beat frequency in a plasmonics-enhanced semiconductor active region. We demonstrate terahertz detection sensitivities down to three times the quantum limit at room temperature. With a versatile design capable of broadband operation over a 0.1–5.0 THz bandwidth, this plasmonic photomixer has broad applicability to astronomy, cosmology, atmospheric studies, gas sensing and quantum optics. The measurement of faint fluxes of photons from across the Universe requires sensitive terahertz detectors, cooled to minimize noise. By using a photomixer with plasmonics-based semiconductors to downconvert the high frequencies, terahertz detection can be accomplished at room temperature.
Embryonic Exposure to 2,2',3,5',6-pentachlorobiphenyl (PCB-95) Causes Developmental Malformations in Zebrafish.

2,2',3,5',6-Pentachlorobiphenyl (PCB-95) is an environmental neurotoxicant. There is accumulated evidence that some neurotoxic effects of PCB-95 are caused by increased spontaneous Ca2+ oscillations in neurons resulting from modifying ryanodine receptors (RyR) in calcium-releasing channels. However, there are large gaps in explaining brain and other developmental malformations on embryonic PCB-95 exposure. In the present study, we address those deficiencies by studying the toxic effects of PCB-95 using zebrafish as an ontogenetic model. To characterize these effects, zebrafish embryos with intact chorions were exposed to 4 different concentrations of PCB-95 (0.25, 0.5, 0.75, and 1 ppm) for 3 consecutive days. The controls were maintained in 0.5 × E2 medium or egg water and in 0.1% (v/v) dimethyl sulfoxide (DMSO)/0.5 × E2 medium or egg water. PCB-95-treated groups showed dose-dependent decreases in survival and hatching rates, with increased rates of developmental malformations when compared to controls. These include morphological malformations, brain cell necrosis, and smaller eye sizes at 5 d post fertilization. These data suggest potential mechanisms underlying the abnormal behavior observed in a visual stimulus assay. The present study provides insight into PCB-95-induced developmental toxicity and supports the use of the zebrafish model in understanding the effects of PCB-95 exposure. Environ Toxicol Chem 2019;39:162-170. © 2019 SETAC.
A call for better depression treatment in people with Parkinson disease

Although long established as a quintessential movement disorder, Parkinson disease (PD) is increasingly recognized as a complex neuropsychiatric condition. In fact, more people with PD (PWP) have at least one neuropsychiatric symptom, such as anxiety, apathy, cognitive impairment, depression, or psychosis, than have rest tremor. Depression alone affects half of all PWP and is one of the most important factors affecting quality of life over the course of the disease.1 Depression also compounds disability in PWP, leading to more rapid mental and physical decline and greater impairment in activities of daily living, resulting in greater burden on caregivers, health care services, and the economy.2,3 Treating depression using an interdisciplinary approach is therefore an essential part of the overall management of PD.
A System-of-Systems Model to Simulate the Complex Emergent Behavior of Vehicle Traffic on an Urban Transportation Infrastructure Network

Abstract Transportation agencies face escalating challenges in forecasting the traffic demand. Traditional prediction methods focused on individual transportation sectors and failed to study the inter-dependencies between the different transportation systems. Hence, there is a need for more advanced and holistic modeling techniques. To this end, this paper models and analyses an urban transportation system-of-systems incorporating seven various systems: population and GDP, CO2 emission, gasoline price and total vehicle trips, traffic demand, public and private transportation, transportation investment, and traffic congestion. Accordingly, this research simulates transportation networks as a collection of task-oriented systems that combine their resources to form a complex system with increased functionality. The goal of this paper is to understand the traffic complex behavior of urban transportation networks and to study the interdependencies between the different variables. The proposed framework could be implemented to any urban city, county, state, or country. The developed model incorporates a hybrid modeling approach that includes: logistic model, system dynamics, stochastic cellular automata, chaos theory, and Lotka-Volterra model. The final model is demonstrated using a case study. The contribution of this paper lies in modeling the transportation network as a dynamic system of systems rather than as static model as provided in previous studies.
Has Your Physician Heard of Williams-Beuren Syndrome?

As a child, my family would come together during the holidays, and the grandchildren would play in my grandmother’s basement. However, every time we asked our cousin Cynthia (her name has been changed to protect her privacy) to join us, she would have difficulty participating. As she aged, she
An Adaptive Error Inhibiting Block One-Step Method for Ordinary Differential Equations

An explicit error inhibiting block one-step method was developed by Ditkowski and Gottlieb in 2017. It is motivated by a class of one-step methods described in Shampine and Watts (Math Comp 23:731–740, 1969), which takes initial s step values to generate the next s step values at each step. The error inhibiting method shares the form of the diagonally implicit multistage integration method of type 3 introduced in Butcher (Appl Numer Math 11:347–363, 1993). With the explicit error inhibiting scheme, the convergence of the global error is one order higher than that of the local truncation error, while in general the global error decays with the same order as the local truncation error. In this work, we improve the explicit error inhibiting block one-step method in order to further enhance the convergence and accuracy of the method. The main idea is to adopt the radial basis functions as a reconstruction basis replacing the polynomial basis. The numerical results confirm that the proposed method is efficient in providing enhanced order of accuracy.
From Bayt to Stanza: Arabic Khayāl and the Advent of Italian Vernacular Poetry

At the twilight of Arabic literary culture in thirteenth-century Sicily, poets writing in the vernacular Italian use the term “stanza,” meaning a “dwelling,” to refer to a lyric strophe. Since ther...
Effects of salinity, dietary level of protein and 17α-methyltestosterone on growth hormone (GH) and prolactin (tPRL177 and tPRL188) levels in the tilapia, Oreochromis mossambicus

In the present study, we examined the long-term effects of environmental salinity, diet (35% and 25% crude protein) and 17α-methyltestosterone (MT) on corresponding levels of pituitary and serum growth hormone (GH) and prolactins (tPRL177 and tPRL188) in the tilapia (Oreochromis mossambicus). We observed no discernible patterns in serum GH that would suggest an effect of salinity, diet or MT. However, serum GH levels in all treatments declined at 1 and 3h after first feeding. Serum tPRL177 and tPRL188 were significantly higher in freshwater (FW) than in seawater (SW) and levels were significantly affected by dietary protein. tPRL177 levels were higher in all groups fed a 35% protein diet, but tPRL188 levels were higher only in the groups fed the MT-treated 35% protein diet; only serum tPRL188 levels were affected by MT. Moreover, serum tPRL177 and tPRL188 increased throughout the sampling time-course. Subsequent work using fasted tilapia suggests that first feeding is likely to initiate the post-prandial suppression of serum GH levels. In contrast with the picture observed in blood, pituitary glands of SW animals showed higher levels of GH than FW fish. Pituitary GH was elevated by MT in both FW and SW. We also observed that pituitary tPRL177 and tPRL188 levels were higher in FW fish than in SW fish; tPRL177 and tPRL188 levels were elevated by MT only in FW animals. To assess the somatomedin activity of plasma from FW- and SW-reared tilapia, we measured [35S]-sulfate incorporation into ceratobranchial cartilage explants in vitro. Plasma from SW-adapted tilapia showed greater activity in this assay than plasma from FW-reared tilapia, suggesting that the GH-dependent IGF bioactivity of plasma is higher in SW-reared tilapia. Collectively, these studies suggest that the growth-promoting actions of SW rearing and of MT administration in tilapia may be linked to elevations in GH and/or prolactin (tPRL177 and tPRL188)levels.
Smartphone-Based Assessment of Preoperative Decision Conflict and Postoperative Physical Activity Among Patients Undergoing Cancer Surgery: A Prospective Cohort Study.

Objective To determine the prevalence of clinically significant decision conflict (CSDC) among patients undergoing cancer surgery and associations with postoperative physical activity, as measured through smartphone accelerometer data. Background Patients with cancer face challenging treatment decisions, which may lead to CSDC. CSDC negatively affects patient-provider relationships, psychosocial functioning, and health-related quality of life; however, physical manifestations of CSDC remain poorly characterized. Methods Adult smartphone-owners undergoing surgery for breast, skin-soft-tissue, head-and-neck, or abdominal cancer (July 2017-2019) were approached. Patients downloaded the Beiwe application that delivered the Decision Conflict Scale (DCS) preoperatively and collected smartphone accelerometer data continuously from enrollment through 6 months postoperatively. Restricted-cubic-spline regression, adjusting for a priori potential confounders (age, type of surgery, support status, and postoperative complications) was used to determine trends in postoperative daily physical activity among patients with and without CSDC (DCS score≥25/100). Results Among 99 patients who downloaded the application, 85 completed the DCS (86% participation rate). Twenty-three (27%) reported CSDC. These patients were younger (mean age 48.3 [standard deviation 14.2]-vs.-55.0 [13.3],p = 0.047) and more frequently lived alone (22%-vs.-6%,p = 0.042). There were no differences in preoperative physical activity (115.4 minutes [95%CI 90.9,139.9]-vs.-110.8 [95% 95.7,126.0],p = 0.753). Adjusted postoperative physical activity was lower among patients reporting CSDC at 30 days (difference 33.1 minutes [95%CI 5.93,60.2],p = 0.017), 60 days (35.5[95%CI 8.50,62.5],p = 0.010) and 90 days (31.8[95%CI 5.44,58.1],p = 0.018) postoperatively. Conclusions CSDC was prevalent among patients who underwent cancer surgery and associated with lower postoperatively daily physical activity. These data highlight the importance of addressing modifiable decisional needs of patients through enhanced shared decision-making.
Engineered spin-orbit interactions in LaAlO3/SrTiO3-based 1D serpentine electron waveguides

The quest to understand, design, and synthesize new forms of quantum matter guides much of contemporary research in condensed matter physics. One-dimensional (1D) electronic systems form the basis for some of the most interesting and exotic phases of quantum matter. Here, we describe a family of quasi-1D nanostructures, based on LaAlO3/SrTiO3 electron waveguides, in which a sinusoidal transverse spatial modulation is imposed. These devices display unique dispersive features in the subband spectra, namely, a sizeable shift (∼7 T) in the spin-dependent subband minima, and fractional conductance plateaus. The first property can be understood as an engineered spin-orbit interaction associated with the periodic acceleration of electrons as they undulate through the nanowire (ballistically), while the second property signifies the presence of enhanced electron-electron scattering in this system. The ability to engineer these interactions in quantum wires contributes to the tool set of a 1D solid-state quantum simulation platform.
Developing a Social Media Intervention to Connect Alaska Native People Who Smoke with Resources and Support to Quit Smoking: The Connecting Alaska Native Quit Study

Background Face-to-face tobacco cessation has had limited reach and efficacy in Alaska Native (AN) communities. We describe our two-phased approach to develop content for Connecting Alaska Native People to Quit Smoking, a Facebook group intervention to reduce barriers to evidence-based smoking cessation treatment for AN people in Alaska. Methods Phase 1 included semi-structured telephone interviews with 30 AN people who smoke and ten stakeholders. They provided feedback on existing content from the Centers for Disease Control and Prevention Tips campaign and AN digital stories. Phase 2 included an online survey with a new group of 40 AN smokers who provided feedback on existing content via a measure of perceived effectiveness and cultural relevance. Results Phase I results revealed participants evaluated content based upon story strength, relevance to AN culture, emotional appeal, relatability to AN people, and favorite video. No single posting was rated highly across all themes. All perceived effectiveness (PE) and cultural relevance median scores fell between 3.5 and 4.4 (range 1-5). PE scores varied across participant demographic groups. Conclusions Content embodying characteristics perceived to be most appealing, effective, and culturally relevant were selected for the private Facebook group content library with refinements made to incorporate images of AN people engaged in AN activities. PE scores indicate a need for a wide variety of content that moderators could pull from when conducting the intervention. Implications Social media content targeting specific population sectors, such as American Indian/AN people for tobacco cessation needs to be culturally tailored. Our approach provides a model others can follow to determine what is appealing, relevant, and effective messaging. Clinical trial registration NCT03645941.
A cross‐cultural examination of pleasant events and depressive symptoms

OBJECTIVES To examine the associations between pleasant or reinforcing activities (as they relate to the behavioral theory of depression) and depressive symptoms across cultures. METHODS We tested for differences in the strength of association between pleasant events and depressive symptoms in probability samples of adults from the United States (N = 619) and Japan (N = 232). RESULTS Results indicate that frequency, enjoyment, and obtained pleasure from pleasant events were significantly and negatively associated with depressive symptoms for both American and Japanese adults, and these associations were significantly greater in magnitude for American adults relative to Japanese adults. CONCLUSIONS Findings suggest that there is a cross-sectional association between pleasant events and depressive symptoms in both the United States and Japan, and that this association is stronger in the United States.
A 44 To 64 GHz Broadband 90° Hybrid Doherty PA With Quasi Non-Foster Tuner in 0.13 μm SiGe

This letter presents a simultaneous broadband and back-off efficient mm-wave linear Doherty PA utilizing quadrature hybrid and a Doherty bandwidth enhancement technique exploiting quasi non-Foster impedance synthesis at the quadrature isolation port. We show analytically the design methodology of the non-Foster synthesis with ON-chip impedance tuner that allows broadband back-off efficiency, without suffering from nonlinearity due to the low-leakage power of the isolated port. Across 44–64 GHz, the proposed SiGe PA achieves collector efficiency of 26%–34.7% at peak power and 14%–23.2% at 6 dB back-off with 18.5–21.5 dBm Psat and peak gain of 18.5 dB. It supports 6 Gbps 64 QAM signal with −26.5 dB/−28.3 dBc EVM/ACLR at average Pout/PAE of 14.6 dBm/14.6% at 54 GHz. To the best of the authors’ knowledge, this work achieves highest bandwidth among silicon-based mm-wave power amplifiers (PAs) where higher than class-B back-off efficiency is achieved.
Development of PEGylated chitosan/CRISPR-Cas9 dry powders for pulmonary delivery via thin-film freeze-drying.

Abstract Gene therapy and more recently, gene editing is attractive via pulmonary delivery for enhanced regional targeting. However, processing of sensitive therapeutics into dry powders for inhalation can be problematic due to relatively stressful spraying or milling steps. Thin-film freeze-drying (TFFD) has attracted attention with its promising application in the production of DPI formulations possessing respirable particle size range (1–5 µm) particularly for thermally or shear sensitive therapeutics. In this study, gene editing dry powder formulations containing PEGylated chitosan/CRISPR-Cas9 nanocomplexes were prepared by TFFD. To evaluate stability during processing, nanocomplex size, zeta potential and transfection efficiency of reconstituted formulations were evaluated, and six potential DPI formulations were identified and characterized in terms of geometric particle size, powder surface morphology, and crystallinity. It was found that two formulations containing 3% mannitol with or without leucine were identified as suitable for inhalation with a desired aerodynamic performance. The flow rate dependency and inhaler dependency of these two formulations were also evaluated at different flow rates (60 L/min and 45 L/min) and different inhaler devices (RS01 DPI and HandiHaler) using NGI testing. This study demonstrated that TFFD processing of CRISPR-Cas9 polymer nanocomplexes resulted in a suitable dry powder for inhalation.
Alzheimer's Disease Progressively Reduces Visual Functional Network Connectivity.

Background Postmortem studies of brains with Alzheimer's disease (AD) not only find amyloid-beta (Aβ) and neurofibrillary tangles (NFT) in the visual cortex, but also reveal temporally sequential changes in AD pathology from higher-order association areas to lower-order areas and then primary visual area (V1) with disease progression. Objective This study investigated the effect of AD severity on visual functional network. Methods Eight severe AD (SAD) patients, 11 mild/moderate AD (MAD), and 26 healthy senior (HS) controls undertook a resting-state fMRI (rs-fMRI) and a task fMRI of viewing face photos. A resting-state visual functional connectivity (FC) network and a face-evoked visual-processing network were identified for each group. Results For the HS, the identified group-mean face-evoked visual-processing network in the ventral pathway started from V1 and ended within the fusiform gyrus. In contrast, the resting-state visual FC network was mainly confined within the visual cortex. AD disrupted these two functional networks in a similar severity dependent manner: the more severe the cognitive impairment, the greater reduction in network connectivity. For the face-evoked visual-processing network, MAD disrupted and reduced activation mainly in the higher-order visual association areas, with SAD further disrupting and reducing activation in the lower-order areas. Conclusion These findings provide a functional corollary to the canonical view of the temporally sequential advancement of AD pathology through visual cortical areas. The association of the disruption of functional networks, especially the face-evoked visual-processing network, with AD severity suggests a potential predictor or biomarker of AD progression.
Single-nucleus chromatin accessibility and transcriptomic characterization of Alzheimer's disease.

The gene-regulatory landscape of the brain is highly dynamic in health and disease, coordinating a menagerie of biological processes across distinct cell types. Here, we present a multi-omic single-nucleus study of 191,890 nuclei in late-stage Alzheimer’s disease (AD), accessible through our web portal, profiling chromatin accessibility and gene expression in the same biological samples and uncovering vast cellular heterogeneity. We identified cell-type-specific, disease-associated candidate cis-regulatory elements and their candidate target genes, including an oligodendrocyte-associated regulatory module containing links to APOE and CLU. We describe cis-regulatory relationships in specific cell types at a subset of AD risk loci defined by genome-wide association studies, demonstrating the utility of this multi-omic single-nucleus approach. Trajectory analysis of glial populations identified disease-relevant transcription factors, such as SREBF1, and their regulatory targets. Finally, we introduce single-nucleus consensus weighted gene coexpression analysis, a coexpression network analysis strategy robust to sparse single-cell data, and perform a systems-level analysis of the AD transcriptome. An integrative analysis of single-nucleus assay for transposase-accessible chromatin with sequencing and RNA sequencing in normal and Alzheimer’s disease brain tissue identifies cell-type-specific cis-regulatory elements and candidate target genes at disease-associated loci.
Social Robots for Older Adults with Dementia: A Narrative Review on Challenges & Future Directions.

Worldwide, approximately 50 million people live with Alzheimer’s disease or other dementias and there are nearly 10 million new cases every year. Social robots have been a promising approach to supplement human caregivers in dementia care. In this narrative review, we reviewed 62 articles to gain insight into the attitudes and perceptions among people with dementia and other stakeholders worldwide towards using social robots to assist dementia care. Then, we discussed some critical factors and challenges found in these studies influencing people’s perceptions as well as future directions in this field. The primary influencing challenges include cultural factors, users’ limited experiences with technologies, methodological challenges underlying qualitative studies as well as technological malfunctions in current robot system. We further suggested several aspects to be taken into more consideration in future research, including collaborations with other stakeholders, design of individual or group use for dementia care, an adaptive level of autonomy in a social robot and long-term human-robot interaction.
Using observations to recognize the behavior of interacting multi-agent systems

Behavioral research involves the study of the behaviors of one or more agents (often animals) in order to better understand the agents’ thoughts and actions. Identifying subject movements and behaviors based upon those movements is a critical, time-consuming step in behavioral research. To successfully perform behavior analysis, three goals must be met. First, the agents of interest are observed, and their movements recorded. Second, each individual must be uniquely identified. Finally, behaviors must be identified and recognized. I explore a system that can uniquely identify and track agents, then use these tracks to automatically build behavioral models and recognize similar behaviors in the future. I address the tracking and identification problems using a combination of laser range finders, active RFID sensors, and probabilistic models for real-time tracking. The laser range component adds environmental flexibility over vision based systems, while the RFID tags help disambiguate individual agents. The probabilistic models are important to target identification during the complex interactions with other agents of similar appearance. In addition to tracking, I present work on automatic methods for generating behavioral models based on supervised learning techniques using the agents’ tracked data. These models can be used to classify new tracked data and identify the behavior exhibited by the agent, which can then be used to help automate behavior analysis.
Neural Tube Defects: Genetics

Neural tube defects (NTDs) are malformations of the brain and the spinal cord, resulting from lack of closure of the developing neural tube during embryological development. NTDs are complex birth disorders with a worldwide prevalence from 0.5 to 2.0 per 1000 births. The two most common types of NTD are anencephaly and spina bifida, which involve failure of neural tube closure in the cranial and in the back regions respectively. NTDs are hypothesised to be a result of genetic abnormalities and environmental factors; yet, the aetiology remains undetermined. Research studies over the past decade have indicated that maternal folate deficiency is an extremely important risk factor for an NTD birth, with maternal folate supplementation decreasing risk. However, the role that folate plays in NTD risk is not well defined. Key Concepts: Neural tube defects (NTDs) are congenital malformations of the brain and spinal cord. The prevalence rates of NTDs vary worldwide. NTDs are complex birth defects composed of both genetic and environmental components. The underlying mechanism remains undetermined. NTDs are classified by whether they are open or closed and by the location of the lesion. Folic acid supplementation ameliorates NTD risk. The majority of NTDs are sporadic and nonsyndromic. To date, association studies in relatively small patient cohorts have been used in an attempt to find causative genes. Future additional approaches will include Genome-Wide Association Study (GWAS) and high-throughput sequencing. Keywords: genetics; neural tube defects; complex disorder; folic acid; candidate genes
Phrase detection and the associative memory neural network

This paper describes the use of a novel associative memory neural network architecture to perform unsupervised phrase detection in a large, unstructured, English text corpus. To significantly increase the difficulty associated with processing the text corpus, the network is exposed to over 270 thousand Web pages from the .edu domain with no textual substitution or alteration (for spelling, grammar, etc.). The corpus, consisting of 150M words, is represented as a string of sparse tokens and phrase detection is performed through the use of the unique information theoretic quantity of mutual significance.
A pilot study of parent training in young children with autism spectrum disorders and disruptive behavior.

Guidance on effective interventions for disruptive behavior in young children with autism spectrum disorders (ASDs) is limited. We present feasibility and initial efficacy data on a structured parent training program for 16 children (ages 3–6) with ASD and disruptive behavior. The 6-month intervention included 11 Core and up to 2 Optional sessions. The program was acceptable to parents as evidenced by an attendance rate of 84 % for Core sessions. Fourteen of 16 families completed the treatment. An independent clinician rated 14 of 16 subjects as much improved or very much improved at Week 24. Using last observation carried forward, the parent-rated Aberrant Behavior Checklist-Irritability subscale decreased 54 % from 16.00 (SD = 9.21) to 7.38 (SD = 6.15).
The cardiovascular interaction between caffeine and nicotine in humans

In a placebo-controlled, double-blind randomized design, we investigated the cardiovascular interaction between caffeine (250 mg intravenously) and nicotine (4 mg chewing gum) in 10 healthy volunteers, both under baseline conditions and during physical and mental stress (standing up and mental arithmetic). Caffeine alone induced a significant increase in blood pressure associated with a decrease in heart rate, whereas nicotine alone increased both blood pressure and heart rate. The combination of caffeine and nicotine increased systolic and diastolic blood pressure by 10.8 +/- 2.0 and 12.4 +/- 1.9 mm Hg, respectively. This pressor response did not differ significantly from the calculated additive effects of caffeine and nicotine on blood pressure, measuring 12.9 +/- 2.0 and 14.2 +/- 2.1 mm Hg, respectively. Heart rate and forearm blood flow also showed a similar response when the combination of caffeine and nicotine was compared with the calculated sum. During physical stress (standing up), blood pressure, heart rate, and plasma catecholamines increased in the placebo test. The pressor response to standing up was less pronounced after the combination of caffeine and nicotine compared with the sum of the separate effects (combination versus sum: delta diastolic blood pressure, 24.7 +/- 1.9 versus 35.2 +/- 2.6 mm Hg [p < 0.01]; delta mean arterial pressure, 22.1 +/- 2.0 mm Hg versus 28.6 +/- 1.6 mm Hg [p < 0.05]). The plasma catecholamine response did not differ between the combination and the sum of both drugs. During mental arithmetic, blood pressure, heart rate, and forearm blood flow increased in the placebo test. The forearm vasodilator response to mental stress was attenuated by the combination of caffeine and nicotine compared with the sum of both drugs (combination versus sum: delta forearm blood flow, -0.1 +/- 0.3 versus 1.4 +/- 0.5 ml/100 ml/min [p < 0.05]). We conclude that the combined administration of caffeine and nicotine shows additive effects on cardiovascular parameters during baseline conditions but less than additive effects during sympathoadrenal stimulation.
Sympathy and phonological opacity

A central idea in rule-based phonology is the serial derivation (Chomsky & Halle 1968). In a serial derivation, an underlying form passes through a number of intermediate representations on its way to the surface:[Scheme here]Implementational details can differ: the order of rules might be stipulated or it might be derived from universal principles; the steps might be called ‘rules’, ‘cycles’ or ‘levels’; the steps might involve applying rules or enforcing constraints. But, details aside, the defining characteristic of a serial derivation, in the sense I will employ here, is the pre-eminence of the chronological metaphor: the underlying form is transformed into a succession of distinct, accessible intermediate representations on its way to the surface. I will call any theory with this property ‘serialism’.