cssi/SciSciGPT-SciSciNet huggingface dataset:
The autophagy inhibitor chloroquine targets cancer stem cells in triple negative breast cancer by inducing mitochondrial damage and impairing DNA break repair

Triple negative breast cancer (TNBC), characterized by an abundance of treatment-resistant breast cancer stem cells (CSCs), has a poorer prognosis than other types of breast cancers. Despite its aggressiveness, no effective targeted therapy exists for TNBC. Here, we demonstrate that CQ effectively targets CSCs via autophagy inhibition, mitochondrial structural damage, and impairment of double-stranded DNA break repair. Electron microscopy demonstrates CQ-induced mitochondrial cristae damage, which leads to mitochondrial membrane depolarization with a significant reduction in the activity of cytochrome c oxidase and accumulation of superoxide and double-stranded DNA breaks. CQ effectively diminishes the TNBC cells' ability to metastasize in vitro and in a TNBC xenograft model. When administered in combination with carboplatin, CQ effectively inhibits carboplatin-induced autophagy. This combination treatment significantly diminishes the expression of DNA repair proteins in CSC subpopulations, resulting in tumor growth reduction in carboplatin-resistant BRCA1 wild-type TNBC orthotopic xenografts. As TNBC's high treatment failure rate has been attributed to enrichment of CSCs, CQ, an autophagy inhibitor with anti-CSC effects, may be an effective adjunct to current TNBC chemotherapy regimens with carboplatin.
The Hypothetical Wing of the Hymenopterathe

The hypothetical plan of venation of the Hymenoptera as derived by Comstock and Needham is largely based on analogy with the condition in the more specialized Diptera. It involves the assumption that there has been a good deal of fusion of the apices of veins, and largely ignores the evidence of the tracheation.
USP6 genetic rearrangements in cellular fibroma of tendon sheath

Fibroma of tendon sheath is a benign (myo)fibroblastic neoplasm of the tenosynovial soft tissues, typically affecting the distal extremities. It is classically described as a paucicellular, densely collagenized tumor; however, cellular variants have been described. A subset of cellular fibromas of tendon sheath shares similar histological features with nodular fasciitis. As nodular fasciitis very frequently harbors rearrangement of ubiquitin-specific peptidase 6 (USP6), we hypothesized that cellular fibromas of tendon sheath with nodular fasciitis-like features may also contain USP6 rearrangements. Cases of fibroma of tendon sheath (n=19), including cellular (n=9) and classic (n=10) variants, were evaluated for USP6 rearrangement by fluorescence in situ hybridization studies. A subset of cases was tested for MYH9 rearrangements and MYH9-USP6 and CDH11-USP6 fusion products. Classic fibroma of tendon sheath occurred in 5 males and 5 females (median age 67 years, range 23-77 years) as soft tissue masses of the hand (n=4), finger (n=3), forearm (n=1) and foot (n=2). Cellular fibroma of tendon sheath occurred in 5 males and 4 females in a younger age group (median age 32 years, range 12-46 years) as small soft tissue masses of the finger (n=5), hand (n=3) and wrist (n=1). USP6 rearrangements were detected in 6/9 cellular fibromas of tendon sheath. Among cellular fibromas of tendon sheath with USP6 rearrangements, no MYH9 rearrangements were detected. By RT-PCR, neither the MYH9-USP6 or the CDH11-USP6 fusion products were detected in any case. Neither USP6 nor MYH9 rearrangement were detected in any classic fibroma of tendon sheath. We report for the first time the presence of USP6 rearrangements in a subset of cellular fibroma of tendon sheath. Based on the similar morphological and molecular genetic features, we suspect that a subset of cellular fibromas of tendon sheath are under-recognized examples of tenosynovial nodular fasciitis, driven by alternate USP6 fusion genes. Further investigation will delineate how these lesions should best be classified.
Scaphoid position angles: a clinical study.

This study sought to describe the oblique orientation of the scaphoid relative to the anatomic planes of the wrist in terms of two position angles. Longitudinal axes of the scaphoid are defined on posteroanterior (p.a.) and lateral radiographs. These axes, together with the corresponding longitudinal axes of the distal radius, are used to define the frontal and lateral radioscaphoid angles. These angles are called the scaphoid yaw and pitch, respectively. A database representing the normal variation of the scaphoid position angles is obtained from a set of 100 PA and lateral radiographs of structurally normal wrists in a rigorously defined neutral position. To the nearest whole number, the mean scaphoid yaw is 35 degrees with a standard deviation of 6 degrees, and the mean scaphoid pitch is 50 degrees with a standard deviation of 7 degrees.
Elevated Prevalence of Polycystic Ovary Syndrome and Cardiometabolic Disease in South Asian Infertility Patients

South Asians (SA) develop cardiometabolic disease at elevated rates. We investigate whether reproductive-aged SA women are at higher risk for a precursor condition, polycystic ovary syndrome (PCOS), as compared to Caucasian controls. 52 SA and 52 Caucasian infertility patients from a single institution were included in a cross-sectional analysis. Outcomes were compared using Student's t, Mann-Whitney U, Pearson's Chi-squared and Fisher's exact tests. SA women were younger, with six-fold greater odds of PCOS. SA women were not obese, with similar body mass indices to controls. However, when screened, they demonstrated abundant metabolic disease, including insulin resistance, diabetes and dyslipidemia, and endometrial disease, including hyperplasia and polyps. The SA population was younger with more PCOS and high rates of metabolic and endometrial pathology. These findings, in the context of ethnicity-specific elevations in cardiometabolic risk, highlight the need for comprehensive screening and counseling in this patient population.
Audit Committee Influence on Audit Firm Selection and Retention

Accounting researchers and practitioners have expressed the need to better understand the interactions between audit committees and external auditors (CAQ 2013; DeFond and Zhang 2014). We examine these interactions through the lens of management theory. The attraction-selection-attrition (ASA) theory of employer-employee relationships suggests that the initiation and length of these relationships are affected by similarities between employers (i.e., audit committee) and employees (i.e., audit firm). Social integration also suggests that cohesion, or fit, among co-workers improves performance. Consistent with these theories, we find that companies with a former Big 4 partner on their audit committee are more likely to hire the committee member’s former firm and less likely to switch away from the member’s former firm than companies without this affiliation. We also find evidence that former partners have preferences when considering other large audit firms as the external auditor and these preferences manifest themselves in the audit firm hiring decision. Finally, we find evidence that having an affiliated audit committee member increases audit quality, with no evidence that affiliated audit committees give the audit firm inappropriate preferential treatment.
Comparison of polychromatic wave-optics models

Polychromatic laser light can reduce speckle contrast in wavefront-sensing and imaging applications that use direct detection schemes. To help quantify the associated reduction in speckle contrast, this study investigates the accuracy and numerical efficiency of three separate wave-optics models that simulate the active illumination of extended objects with polychromatic laser light. The three separate models use spectral slicing, Monte Carlo averaging, and depth slicing, respectively, to simulate the laser-target interaction. The sampling requirements of all three models are discussed. Comparisons to analytical solutions and experimental data are made when possible. In general, the experiments and theory compare favorably with the models.
Cropping systems modify soil biota effects on wheat (Triticum aestivum) growth and competitive ability

Summary Plants alter soil biota which subsequently modifies plant growth, plant–plant interactions and plant community dynamics. While much research has been conducted on the magnitude and importance of soil biota effects (SBEs) in natural systems, little is known in agro-ecosystems. We investigated whether agricultural management systems could affect SBEs impacts on crop growth and crop–weed competition. Utilising soil collected from eight paired farms, we evaluated the extent to which SBEs differed between conventional and organic farming systems. Soils were conditioned by growing two common annual weeds: Amaranthus retroflexus (redroot pigweed) or Avena fatua (wild oat). Soil biota effects were measured in wheat (Triticum aestivum) growth and crop–weed competition, with SBEs calculated as the natural log of plant biomass in pots inoculated with living soil divided by the plant biomass in pots inoculated with sterilised soil. SBEs were generally more positive when soil inoculum was collected from organic farms compared with conventional farms, suggesting that cropping systems modify the relative abundance of mutualistic and pathogenic organisms responsible for the observed SBEs. Also, as feedbacks became more positive, crop–weed competition decreased and facilitation increased. In annual cropping systems, SBEs can alter plant growth and crop–weed competition. By identifying the management practices that promote positive SBEs, producers can minimise the impacts of crop–weed competition and decrease their reliance on off-farm chemical and mechanical inputs to control weeds, enhancing agroecosystem sustainability.
Addressing Climate Change Through Risk Mitigation: Welfare Implications of Index Insurance in Northeastern Tanzania

While index insurance offers a compelling solution to the problem of covariant risk among smallholder farmers in developing countries, most rainfall-based contracts suffer from poor quality due to a low correlation between the index and farmer losses. Moreover, a lack of historical household-level yield data has made it difficult to quantify the level of basis risk and the impact on farmer welfare. This paper utilizes a unique dataset of plot-level historical rice yields in Northeastern Tanzania to estimate the level of basis risk and the welfare implications of two hypothetical index insurance contracts. One is a standard area-yield contract, while the other uses an index based on publicly available high-resolution satellite data that are mapped to actual yields to minimize basis risk. Our results suggest that the satellite index explains approximately 55 % of the variation in zone-level yields across years. Moreover, despite the presence of large basis risk under both contracts, they are each found to improve the welfare of the average farmer in the sample. Finally, we show that the demand for satellite contracts may be as high as 30 % under reasonable assumptions about loading costs and risk preferences.
An Activity-Related Land Use Mix Construct and its Connection to Pedestrian Travel

Integrating a diverse set of land use types within a neighborhood is a central tenet of smart growth policy. Over a generation of urban planning research has heralded the transportation, land use, ...
Separating IND-CPA and Circular Security for Unbounded Length Key Cycles

A public key encryption scheme is said to be n-circular secure if no PPT adversary can distinguish between encryptions of an n length key cycle and n encryptions of zero.
A Firefly Luciferase Dual Color Bioluminescence Reporter Assay Using Two Substrates To Simultaneously Monitor Two Gene Expression Events

Effective methods for monitoring eukaryotic gene expression and regulation based on bioluminescence - the emission of light by living organisms - are well established. Typically, the expression of a gene of interest is reported on with high sensitivity and over a wide dynamic range by the emission of light from a variety of engineered luciferase genes from beetles and marine organisms. The luciferase reporter genes are expressed downstream of the target gene or promoter and detected after exogenous addition of luciferin substrates. We describe a novel bioluminescence reporter method for the simultaneous monitoring of two genes expressing engineered firefly luciferase variants that emit readily distinguishable green and red light signals. The key feature is the selectivity of the enzymes for two luciferin substrates that determine each emission color. To validate our method, we performed a complex promoter transactivation experiment side-by-side with the Dual-Luciferase Reporter protocol and obtained essentially identical results. Additional comparative experiments demonstrated that our assay system provided improvements in background, cell normalization, and detectability compared to representative available methods. With access to a luminometer equipped with two optical filters, this method is an excellent choice for genetic reporter assays that can be performed with a single reagent solution.
Dynamic Pelvic Magnetic Resonance Imaging Evaluation of Pelvic Organ Prolapse Compared to Physical Examination Findings.

Abstract Objective To compare dynamic magnetic resonance imaging (dMRI) defecography phase findings with physical examination (PE) grading in the evaluation of pelvic organ prolapse (POP). Methods We retrospectively reviewed 274 consecutive patients who underwent dMRI with defecography. Baden-Walker grading of POP, absolute dMRI values, and grading by dMRI were collected for anterior, apical, and posterior compartments. Anatomically significant POP on PE was defined as Baden-Walker Grade ≥3 and on dMRI by dMRI Grade ≥2. A Spearman's Rank correlation was performed between absolute dMRI values and respective POP grades. Results A total of 178 female patients were included. Anatomically insignificant and significant cystoceles had a 26.4% (19/72) and 84.6% (66/78) agreement respectively. Anatomically insignificant and significant apical prolapse had a 2.0% (2/100) and 62.9% (17/27) agreement respectively. Anatomically insignificant and significant posterior prolapse had a 49.5% (51/103) and 78.7% (59/75) agreement respectively. PE detected only 30% (9/30) of total dMRI detected enteroceles and misdiagnosed 10% (3/30) of these patients with a rectocele. Conclusion The dMRI defecography phase correlated well for anatomically significant prolapse in anterior and posterior compartments. dMRI was superior to PE for enterocele detection and was better able to distinguish an enterocele from a rectocele. Thus, dMRI may have the greatest diagnostic value in cases where the presence of an enterocele is unclear in apical and/or posterior compartments.
Large Molecular Species of Human Chorionic Gonadotropin

Human chorionic gonadotropin (hCG) is a glycoprotein composed of two non-identical glycosylated subunits, designated as α and β. The α-subunit of hCG is virtually identical to pituitary glycoprotein hormones -- luteinizing hormone (LH), follicle stimulating hormone (FSH), and thyroid stimulating hormone (TSH); the β-subunit is structurally distinct and confers biologic and immunologic specificity to each of the glycoprotein hormones.
Lefamulin: a promising new pleuromutilin antibiotic in the pipeline

Introduction: Community-acquired bacterial pneumonia (CABP) represents a significant clinical and financial burden within infectious disease. In the advent of increasing resistance from bacteria su...
Marijuana Decriminalization, Medical Marijuana Laws, and Fatal Traffic Crashes in US Cities, 2010-2017.

Objectives. To determine the impact of city-level cannabis decriminalization and medical marijuana laws (MMLs) on fatal traffic crashes in US cities.Methods. Using a census of fatal traffic crashes...
The Cycle of Action and Reaction: Developments and Trends in Intellectual Property and Health

The wheel of the global medicines supply market is broken, but proposals for fixing it are at very early stages. The patent is an instrument designed to aggregate production capital, and for some product sectors the patent may be the best means for promoting the introduction of new products. But patents are not a stand-alone mechanism for addressing the world’s medicines supply needs. The patent-market system distributes output on the basis of capacity to pay, and allocates R&D toward financial demand, irrespective of public health priorities. The next chapter in the public health debate should consider the regulatory mechanisms most likely to serve the medicines interests of the wider world community, whether that involves new regulation of the existing patent system, or changing the patent spoke on the broken supply wheel.
Improving Locality-Aware Scheduling with Acyclic Directed Graph Partitioning.

We investigate efficient execution of computations, modeled as Directed Acyclic Graphs (DAGs), on a single processor with a two-level memory hierarchy, where there is a limited fast memory and a larger slower memory. Our goal is to minimize execution time by minimizing redundant data movement between fast and slow memory. We utilize a DAG partitioner that finds localized, acyclic parts of the whole computation that can fit into fast memory, and minimizes the edge cut among the parts. We propose a new scheduler that executes each part one-by-one, obeying the dependency among parts, aiming at reducing redundant data movement needed by cut-edges. Extensive experimental evaluation shows that the proposed DAG-based scheduler significantly reduces redundant data movement.
A study of intra-speaker and inter-speaker affective variability using electroglottograph and inverse filtered glottal waveforms.

It is well-known that different speakers utilize their vocal instruments in diverse ways to express linguistic intention with some paralinguistic coloring such as emotional quality. The study of voice source features, which describe the action of the vocal folds, is important for a deeper understanding of emotion encoding in speech. In this study we investigate inter and intra-speaker differences in voicing activities as a function of emotion using electroglottography (EGG) and an inverse filtering technique. Results demonstrate that while voice quality features are good indicators of affective state, voice source descriptors vary in affective information across speakers. Glottal ratio measurements taken directly from the EGG signal are more reliable than measurements from the inverse-filtered glottal airflow signal, but the spectral harmonic amplitude differences of EGG are less useful than from inverse filtering. Index Terms: emotion, speech production, voice source, EGG, inverse filtering
Development of tubes filled with aluminium foams for lightweight vehicle manufacturing

Abstract This paper aims to investigate different filling methods of ex situ aluminium foam-filled thin-walled Al alloy tubes to determine the best option for possible applications in automotive industry. The main applied filling methods were joining with heat dilatation, mechanical compression and adhesive bonding. Foam specimens were prepared by shaping and machining operations from an original foam block. The density of the filler foams was 250 kg/m3, 500 kg/m3 and 750 kg/m3 respectively. The foam rods were inserted into empty thin-walled tubes and subjected to quasi-static bending and compression loading conditions. The connection methods between the aluminium foam and the thin-walled tube were examined by microscopy technique. The quality of the assemble was highly influenced by the filling method itself and the surface defects caused by machining operations. The foam-filled tubes, empty tubes and foams were compared in terms of the maximum load carry capacity, specific load capacity, crash energy absorption and specific energy absorption. The obtained results showed that adhesive bonding has the best specific load carrying ability under quasi-static bending loading. Also, it had the lowest average total weight of the specimens. The maximum flexure displacement achieved by the heat dilatation filling method and the minimum was reached by mechanical compression method. Adhesive bonding and mechanical compression showed good energy absorption capabilities against bending loading. The maximum specific energy absorption was produced by density of 750 kg/m3 but the failure of the specimens came earlier than in case of fillers with lower densities. The foams with density of 250 kg/m3 had the lowest specific values but they had the highest displacement values. The machinability is directly proportional with the growing of density. Foams with a density of 500 kg/m3 are very good fillers because they can be machined well, have the best specific load-bearing capacity and less cell displacement under load. The 500 kg/m3 was the best density for ex situ filling with all this in mind. In the case of compression tests, the stress-strain curve of the adhesive bonding filling method exceeded the sum of the stress-strain curve of individual components. The specific energy absorption curve of the adhesive bonding method overtakes the curve of the empty tube at a certain strain. The novelty of this article is the application, investigation and comparison of different filling methods for the production of ex situ foam-filled thin-walled tubes. The experiments were made with very small wall thickness which is even harder to fill with metal foams. The machinability of aluminium foams was also tested in this article. Overall, the goal was to produce foam-filled structures with tools that are widely used in the automotive industry.
Standardization of an Ambulatory Hand Hygiene Observation Program

Background Hand hygiene (HH) is the single most important infection prevention practice to prevent the transmission of organisms to patients and employees in a healthcare setting. Hand hygiene compliance monitoring in our diverse pediatric ambulatory network has occurred since 2011 via staff observation or family feedback forms. A review of HH data collected in 2018 for 97 ambulatory locations raised concerns about data integrity and reliability. Methods In partnership with ambulatory network leaders, sixteen (16) locations were selected for targeted observations of the data collection process due to data integrity concerns including: data saturation due to over submission of observation data, consistent high compliance of sites, consistent low compliance of sites, failure to submit data, and incorrect submission of HH moments. Our HH program manager visited each site to interview and observe staff responsible for onsite HH monitoring. Results Each of the 16 locations had variable data collection processes. Targeted observations identified errors in the data submission process, an incomplete understanding of the number of observations to be performed, and inconsistencies in defining HH breaches. Qualitative interviews with staff elicited lack of formal training on how to observe, collect, and enter data. Staff also expressed discomfort providing feedback when HH breaches/misses are observed. A standard operating procedure (SOP) was developed to address inconsistency in knowledge and practice. Issues with submission and compliance inconsistencies were addressed through mistake proofing the database where collected HH data are submitted. Conclusions Comprehensive rounding of HH data collection across a diverse pediatric ambulatory network revealed need for standardized education and data collection methods and tools for ambulatory hand hygiene observers. Consistent communication and continued interfacing with staff and leadership has increased the capability of the collection of reliable HH data across a variety of ambulatory practice settings.
Carbon Nanotube/Reduced Graphene Oxide/Aramid Nanofiber Structural Supercapacitors

Reduced graphene oxide/aramid nanofiber (rGO/ANF) supercapacitor electrodes have a good combination of energy storage and mechanical properties, but ion transport remains an issue toward achieving ...
Detecting Diabetes-Induced Abnormal Chirality in Urine via Accumulation-Assisted Plasmonic Chiral Sensing

We demonstrate the label-free chiral detection of metabolic molecules in urine via accumulation-assisted plasmonic chiral sensing, which will benefit the development of point-of-care devices for first-line noninvasive screening of diabetes.
The Constitution Abroad: A Structural Analysis

Building on the work of Charles Black, the article argues that the structure of the Constitution mitigates in favor of finding that the rights and limits protected should extend beyond the water’s edge to anywhere the United States government acts. After defining structuralism, providing examples, and addressing potential critiques and counterarguments to the reliance on constitutional structure, the article makes an important original contribution by applying this framework to the extraterritorial reach of the document. It provides a brief history of the Court’s treatment of the question of extraterritoriality before providing a comprehensive theory for determining when courts should extend its protections abroad.
Ticks and Tax: The Effects of Price Discreteness and Taxation on Ex-Dividend Day Returns

We investigate changes in the relation between dividend yield and exdividend day stock returns across four regimes, defined by two reductions in share price discreteness and two changes in differen...
The discovery and reporting of internal control deficiencies prior to SOX-mandated audits

Abstract We use internal control deficiency (ICD) disclosures prior to mandated internal control audits to investigate economic factors that expose firms to control failures and managements’ incentives to discover and report control problems. We find that, relative to non-disclosers, firms disclosing ICDs have more complex operations, recent organizational changes, greater accounting risk, more auditor resignations and have fewer resources available for internal control. Regarding incentives to discover and report internal control problems, ICD firms have more prior SEC enforcement actions and financial restatements, are more likely to use a dominant audit firm, and have more concentrated institutional ownership.
A Positive Rights Interpretation of the Establishment Clause

In this article, I use two Establishment Clause cases – the Ninth Circuit’s decision in Newdow v. U.S. Congress and the Supreme Court’s decision in Zelman v. Simmons-Harris – as vehicles for critiquing the Supreme Court’s Establishment Clause jurisprudence. My primary thesis is that the justices, liberal and conservative alike, set unduly modest goals for the Establishment Clause. I contend that the justices require only that governmental actions affecting church/state relations not be harmful – in other words, that the actions do not lead to religious strife, make members of society feel excluded, or corrupt either state or church institutions. I argue that the Court should go beyond asking whether governmental actions are harmful and ask more affirmatively whether they “do good.” I suggest that, even if a governmental action is not demonstrably harmful to church/state interests, it can still be unconstitutional if it does not help further the Establishment Clause’s larger goal of creating an inclusive society that welcomes all members, regardless of their religious affiliation or lack thereof.
Hospital-acquired Legionella pneumonia outbreak at an academic medical center: Lessons learned.

Abstract Background An outbreak of Legionella pneumonia occurred at a university hospital using copper-silver ionization for potable water disinfection. We present the epidemiological and laboratory investigation of the outbreak, and associated case-control study. Methods Cases were defined by syndrome compatible with Legionella pneumonia with laboratory-confirmed Legionella infection. The water circuit and disinfection system were assessed, and water samples collected for Legionella culture. Whole genome multi-locus sequence typing (wgMLST) was used to compare the genetic similarity of patient and environmental isolates. A case-control study was conducted to identify risk factors for Legionella pneumonia. Results We identified 13 cases of hospital-acquired Legionella. wgMLST revealed >99.9% shared allele content among strains isolated from clinical and water samples. Smoking (P= .008), steroid use (P= .007), and documented shower during hospitalization (P= .03) were risk factors for Legionella pneumonia on multivariable analysis. Environmental assessment identified modifications to the hospital water system had occurred in the month preceding the outbreak. Multiple mitigation efforts and application of point of use water filters stopped the outbreak. Conclusions Potable water system Legionella colonization occurs despite existing copper-silver ionization systems, particularly after structural disruptions. Multidisciplinary collaboration and direct monitoring for Legionella are important for outbreak prevention. Showering is a modifiable risk factor for nosocomial Legionella pneumonia. Shower restriction and point-of-use filters merit consideration during an outbreak.
Identifying Biological Signatures of N-Acetylcysteine for Non-Suicidal Self-Injury in Adolescents and Young Adults †

The prevalence of non-suicidal self-injury (NSSI) is high in adolescents and young adults. However, there is a paucity of evidence-based treatments to address this clinical problem. An open-label, pilot study in the target population showed that treatment with oral N-acetylcysteine (NAC), a widely available dietary supplement, was associated with reduction in NSSI frequency. In preparation for a biologically informed design of an efficacy trial, a critical preliminary step is to clarify NAC’s biological signatures, or measures of the mechanisms underlying its clinical effects. Toward that end, we propose a 2-stage project to investigate NAC’s biological signatures (changes in glutathione (GSH) and/or glutamate (Glu)) in women with NSSI. The first stage; a double-blind randomized placebo-controlled study will focus on identifying the optimal dose to achieve meaningful change in GSH and Glu during short-term (4 weeks) NAC treatment in 36 women aged 16–24 years with NSSI. Go/No-go criteria to determine if the study will progress to the second stage include pre-specified changes in brain and blood measures of GSH. Changes in the brain GSH are measured through magnetic resonance spectroscopy (MRS). The dose for the stage 2 will be selected based on the biological changes and the tolerability observed in the stage 1. The stage 2 will seek to replicate the biological signature findings in an 8-week trial in a new patient cohort, and examine the relationships among biological signatures, NAC pharmacokinetics and clinical response. This 2-stage project is unique as it unifies clinical psychiatric measurements, quantitative MRS and pharmacological approaches in the first placebo-controlled clinical trial of NAC in young women with NSSI. Trial registration: The stage 1 trial protocol has been registered on https://clinicaltrials.gov/ with ClinicalTrials.gov ID “NCT04005053” (Registered on 02 July 2019. Available from: https://clinicaltrials.gov/ct2/show/NCT04005053).
Low Grade Papillary Sinonasal (Schneiderian) Carcinoma: A Series of Five Cases of a Unique Malignant Neoplasm with Comparison to Inverted Papilloma and Conventional Nonkeratinizing Squamous Cell Carcinoma.

There have been a few case reports and one small series of low grade papillary sinonasal (Schneiderian) carcinomas (LGPSC) which mimic papillomas but have overtly invasive growth and which occasionally metastasize. We describe the morphologic, clinical, immunohistochemical, and molecular features of five patients with LGPSC compared with eight cases each of inverted papilloma (IP) and conventional nonkeratinizing squamous cell carcinoma (SCC) with papillary growth. All LGPSC were nested with predominantly pushing invasion, no stromal reaction, and frequent surface papillary growth. All consisted of one cell type only, with polygonal cells with round nuclei, no (or limited) cytologic atypia, low mitotic activity, and prominent neutrophilic infiltrate. One patient had slightly more infiltrative bone invasion, another lymphovascular, perineural, and skeletal muscle invasion, and a third nodal metastasis after 17 years. By comparison, IPs had bland cytology, neutrophilic microabscesses, mixed immature squamous, goblet cell, and respiratory epithelium, and extremely low mitotic activity. Nonkeratinizing SCCs had basaloid-appearing cells with nuclear pleomorphism, brisk mitotic activity, and apoptosis. All LGPSC were p63 positive. Mitotic activity and Ki67 indices were significantly higher for LGPSCs than IPs and significantly lower than NKSCCs, while p53 immunohistochemistry in LGPSC was identical to nonkeratinizing SCC and higher than for IP. Sequencing showed all five tumors to harbor a MUC6 mutation, one tumor to harbor CDKN2A and PIK3R1 mutations, and one tumor to harbor a NOTCH1 mutation. All LGPSC lacked EGFR and KRAS mutations and lacked copy number variations of any main cancer genes. At a median follow up of 12 months, two LGPSC recurred locally, and one patient died after massive local recurrences and nodal metastases. LGPSC is a distinct, de novo sinonasal carcinoma that can be differentiated from papillomas by morphology and selected immunohistochemistry.
Innovative Therapies for Mood Disorders: A Case Report

Background: Mood disorders, including depression and anxiety, are complex and multifactorial, impacting the quality of life for those suffering and making them difficult to manage for their providing health care providers. Diet, stress, medication, genetics, and the microbiome have been attributed to playing a role. Currently, prescription drugs are the first course of treatment despite the World Health Organization calling for a need to develop lifestyle interventions to manage these disorders. The use of single amino acids to impact selected neurotransmitters has demonstrated positive outcomes in the literature, however, the use of multiple amino acids, alongside personalized nutritional therapies is not well documented for mood disorders. This case report demonstrates the effective use of amino acids as an innovative therapy for the management of mood disorders. Case Description: A 26-year-old Caucasian female presented with anxiety, depression, sleep disturbances, carbohydrate cravings, and low energy. She had been diagnosed with Post Traumatic Stress Disorder (PTSD), bipolar depression II and generalized anxiety. The patient was under the care of a counselor and physician and was prescribed Lamictal (200 mg/day). With moderate success with other therapies, the patient sought nutritional counseling. A personalized nutrition intervention was created to include targeted amino acid therapy (tryptophan, glycine, L-glutamine, D-phenylalanine, L-theanine, and L-tyrosine), select nutrients (multivitamin/mineral, zinc, vitamin C, GLA, and magnesium) and a low-glycemic diet to be followed for 12 weeks. Conclusion: This case report demonstrated the use of targeted micronutrient and amino acid therapy, along with a low glycemic diet, resulted in a marked improvement in all mood disorder symptoms this patient experienced. It also highlights that a comprehensive integrative approach may be a beneficial option for individuals with mood disorders.
Multifaceted mentorship community: resisting historical mentoring to create mentee-initiated and sustained mentorship for women doctoral students

In the absence of an institutionally sponsored doctoral mentoring program, a small group of women doctoral students developed a new model of mentoring by initiating and sustaining a multifaceted me...
Topical Review: Developmental Framework of Moderators of Family Conflict for Type 1 Diabetes Outcomes.

Objective To present a developmental framework of family conflict in youth with type 1 diabetes (T1D) that aims to guide future research. Methods Developmental and pediatric literature are reviewed to highlight family factors that may modify the degree to which diabetes-related family conflict is related to adolescent health outcomes. Results Developmental literature suggests that family conflict is not inherently bad; rather, conflict that arises under optimal conditions (moderate frequency, warm and accepting relationships) can be adaptive for adolescents. However, family conflict is consistently associated with poor disease outcomes in youth with T1D, with few researchers examining specific moderators of these associations. In this topical review, we highlight moderators of family conflict and developmental outcomes identified in adolescents without chronic illness (e.g., cultural factors, parent-child relationship quality, conflict characteristics) and how these moderators may operate for a pediatric chronic illness such as T1D. Conclusions Incorporating conceptualizations of family conflict from mainstream developmental research has important implications for future research and intervention adaptations on family conflict in pediatric populations.
Addressing energy storage needs at lower cost via on-site thermal energy storage in buildings

Cost-effective energy storage is a critical enabler for the large-scale deployment of renewable electricity. Significant resources have been directed toward developing cost-effective energy storage, with research and development efforts dominated by work on lithium ion (Li-ion) battery technology. Though Li-ion batteries have many attractive qualities, it is not clear whether they can provide an affordable levelized cost of storage (LCOS) for certain applications, such as buildings. Buildings consume most of the world's electricity, and as much as 50% of their consumption goes toward meeting thermal loads. Thermal energy storage (TES) can provide a cost-effective alternative to Li-ion batteries for buildings; however, two questions remain to be answered. First, how much of total building energy storage requirements can be met via thermal storage for building loads? Second, can the LCOS for TES be favorable compared with Li-ion batteries? In this perspective, using the United States as a case study, we show that the total requirement for TES in buildings is in the range of ∼1200–4500 electrical GW h, depending on the fraction of solar versus wind in the generation mix. Furthermore, we show that with at least 25% wind generation, all of the storage needed by buildings to support the grid can be met by TES. We also introduce a framework to calculate LCOS for on-site TES in buildings to enable a direct comparison with electrical storage technologies such as Li-ion batteries. This is not trivial, because the input energy type for TES (electricity) differs from the output energy type (thermal energy), and the efficiency can depend on ambient conditions. Our LCOS analysis shows that in many situations, TES can be more cost-effective for buildings than Li-ion batteries. We conclude our perspective by discussing future research and development opportunities that can significantly advance the deployment of TES for buildings to help enable a renewable electricity-dependent grid.
Earthly Encounters and Temporal Sedimentation in Patrick Modiano’s Paris

The portrayal of modern Paris that Modiano delineates in his novels continuously preserves the filthy residues of History, in an imagined urban geography saturated with figurative modalities of the...
Toward A Genetic Analysis of Unusually Successful Neural Aging

The genetic analysis of neural function during aging has been dominated by an interest in susceptibility to late life-disease, particularly to dementias of the Alzheimer type. The phenotypes of interest are amenable to quantitative trait analysis. This assumes that the genetic basis for the quantitative variation of the specific phenotype of interest is not attributable to small effects of allelic variation at many dozens or hundreds of loci. The phenotype of interest should be a highly discrete aspect of neural function. The more discrete the function, the more likely one might be able to discover a few major genes controlling differential rates of decline in aging populations. It is suggested that phenotypes should have been standardized with a large population of subjects, should exhibit high-order sensitivity, and should reflect a wide range of function, such that differential performance at both the high end and low end of the functional potential in nondiseased populations may be assayed. It is found that for the peripheral nervous system, a candidate phenotype would be the velocity and amplitude of peripheral nerve conduction.
Computers in Social Work and Social Welfare Issues and Perspective

This paper provides a general overview of the areas in which technology has had significant impact. These are specifically important for social workers, since technology poses many challenges for both society and the social work profession. Most important about modern technology is that It can either improve the human condition or destroy society. With this In mind, social workers must learn about technology, so that Its benefits are understood and problems avoided. This will not occur, however, if technology is ignored or treated as something which is inherently bad because it disrupts the status gun.
Isolation of flagellar paraxonemal rod proteins.

Publisher Summary The paraxonemal rod (PR) is a well-ordered lattice of cytoskeletal filaments with properties distinct from those of microtubules, microfilaments, and intermediate filaments. It is a major component of some lower eukaryotic flagella. Paracrystalline PR of Trypanosoma is composed of two major helix-like proteins, which are present in approximately equal molar ratios and are resistant to extraction by nonionic detergent and low salt; in contrast, the major proteins of the coiled-sheet PR found in the Euglena emergent flagellum exhibit a greater degree of heterogeneity. PR is directly coupled to both the tip-assembled axonemal doublets and to the base-assembled surface mastigonemes. 6–12 isoelectric isoforms migrating in the range 64–75 kDa are recognized by an anti-PR monoclonal antibody, and biochemical complexity is further suggested from the heterogeneous population of cDNA clones. In addition, Euglena PR proteins are readily solubilized with detergents, salts, or chaotropes and are extremely sensitive to trypsin and Pronase digestion. Limited protease digestion of Trypanosoma PR proteins, on the other hand, consistently produces a 65-kDa protease-resistant core. The more stable PR proteins from Trypanosoma cruzi have been successfully urea-extracted and purified by column chromatography. For Euglena , thermal fractionation protocols have been developed that can produce PR-enriched flagellar fractions for in vitro flagellar reassembly studies and PR protein binding assays. Procedures for the thermal enrichment of Euglena PR proteins and purification of Trypanosoma PR proteins are summarized in this chapter. The thermal fractionation of Euglena paraxonemal rod proteins—enrichment of paraxonemal rod proteins, fractionation of PR1 and PR2, and purification of Trypanosoma paraxonemal rod proteins—are also discussed.
Systems Approaches as Phytosanitary Measures: Techniques and Case Studies

The development of export strategies for horticultural products considered to be hosts of quarantine pests follows a logical series of steps. The foundation for the process is the completion of a commodity plant pest risk assessment that satisfies the needs of the national plant protection organization of the importing country. After identifying the significant pests, a set of proposed mitigation measures is designed. Regulatory officials are increasingly using systems approaches to supplement or substitute for direct postharvest treatments in developing export strategies. The components of systems approaches can be divided into a series of five categories of measures: field and production measures, preharvest measures, postharvest measures, inspection and certification measures, and shipping and distribution measures. The United States Department of Agriculture (USDA), working with the national plant protection organizations of other countries, has used the systems approach concept to develop quarantine strategies for both the domestic movement and the importation of fruit fly host commodities. The Mexican fruit fly Anastrepha ludens (Loew) programme in the Texas citrus production area of the lower Rio Grande River Valley is an example of a domestic systems approach. USDA allows the importation of papayas from Central America when produced in accordance with a systems approach that primarily targets the Mediterranean fruit fly Ceratitis capitata (Wiedemann). Systems approaches are groups of integrated pest risk management measures designed to provide importing countries with adequate phytosanitary security while facilitating trade in situations where direct postharvest commodity treatment is undesirable, not feasible or non-existent, or imported products are marginal hosts of the quarantine pest produced in a low-pest prevalence area.
Epidemiology of AIDS-Defining Malignancies

AIDS-defining malignancies are a subset of HIV-associated malignancies that include Kaposi sarcoma, some forms of non-Hodgkin lymphoma (NHL), and invasive cervical cancer (see also Chap. 3). Kaposi sarcoma along with Pneumocystis carinii pneumonia was among the first diseases that comprised the original surveillance definition of AIDS in the USA. Subsequently NHL (1985) and invasive cervical cancer were added (CDC 1992). Compared to non-AIDS-defining malignancies, Kaposi sarcoma and NHL demonstrated the highest incidence in the early AIDS epidemic. As shown in the first figure of this chapter, with the introduction of highly active antiretroviral therapy (HAART) in 1996, the incidence patterns of these cancers with the exception of cervical cancer dropped significantly. It is hypothesized that HAART restores immune function and delays progression to AIDS. However, even with improved clinical outcomes, HAART has not eliminated the risk of AIDS-defining malignancies. HIV-positive persons still remain at a substantially increased risk of developing these cancers as compared to the general population and AIDS-related and non-AIDS-related cancers combined are the most frequent underlying causes of death in AIDS in the USA.
Texture discrimination by Gabor functions

A 2D Gabor filter can be realized as a sinusoidal plane wave of some frequency and orientation within a two dimensional Gaussian envelope. Its spatial extent, frequency and orientation preferences as well as bandwidths are easily controlled by the parameters used in generating the filters. However, there is an "uncertainty relation" associated with linear filters which limits the resolution simultaneously attainable in space and frequency. Daugman (1985) has determined that 2D Gabor filters are members of a class of functions achieving optimal joint resolution in the 2D space and 2D frequency domains. They have also been found to be a good model for two dimensional receptive fields of simple cells in the striate cortex (Jones 1985; Jones et al. 1985). The characteristic of optimal joint resolution in both space and frequency suggests that these filters are appropriate operators for tasks requiring simultaneous measurement in these domains. Texture discrimination is such a task. Computer application of a set of Gabor filters to a variety of textures found to be preattentively discriminable produces results in which differently textured regions are distinguished by first-order differences in the values measured by the filters. This ability to reduce the statistical complexity distinguishing differently textured region as well as the sensitivity of these filters to certain types of local features suggest that Gabor functions can act as detectors of certain "texton" types. The performance of the computer models suggests that cortical neurons with Gabor like receptive fields may be involved in preattentive texture discrimination.