cssi/SciSciGPT-SciSciNet huggingface dataset:
Automatic validation of object-oriented database structures

The philosophy of explicitly representing simple range classes for properties and explicitly specifying range and/or cardinality restrictions on inherited properties is adopted so that the membership of an object in classes is characterized by the object's property values. The motivation for this approach is twofold: first, it is in keeping with the database philosophy of emphasizing the representation of an application (rather than some intrinsic meaning); and second, it provides a framework for algorithmically verifying the structural aspects of the schema. An automatic classifier for the structural validation of object-oriented schemas based on sound and complete rules of inference is presented. If the classifier discovers structural relationships and/or inconsistencies, the designer can refine the schema to reflect the semantics of the application. Thus the classifier serves as an interactive design tool that can be used at any stage during the design process. >
What Is Benford's Law?

Summary The surprising property of many data sets that their first significant digits follow Benford's Law provides examples that can pique and hold students’ interest. Several ideas for student activities are presented.
An inverse model and mathematical solution for inferring viscoelastic properties and dynamic deformations of heterogeneous structures

Abstract We proposed an adjoint-based inverse method and mathematical solutions using Lagrange multiplier theorem for inferring dynamic viscoelastic properties of heterogeneous structures with displacement observations to improve computation reliability and efficiency. Existing methods such as the one using finite-difference approximated gradient may not be efficient and accurate enough for considering complex situations of the coupled effects of dynamic loading, material deformation memory, and structural heterogeneity. The proposed method derives both gradient and Hessian mathematically to satisfy the first-order necessary and second-order sufficient optimal conditions, which has great advantages compared to other approaches. We also proposed robust numerical algorithms for accurate and fast computations, including a regularization to control reasonable parameter ranges, a Newton’s method with Hessian function to determine search direction for fast convenience, and a modified Armijo rule to find a stable step length. We developed a Galerkin time-domain finite-element method for numerical solutions of resulting partial differential equations, and validated the model for a layered structure under dynamic loading tests. Results indicate that the proposed method has greatly improved computation accuracy and speed as compared to existing approaches. It may be applied to a broad range of heterogeneous materials and structures at different length and time scales.
Interactions between metabolic intermediates and β-galactosidase from Escherichia coli

1. 5-Phosphorylribose 1-pyrophosphate, in the presence of beta-mercaptoethanol, protected beta-galactosidase from heat inactivation. Many other substances, including 3':5'-cyclic-AMP, were without effect. 2. The efficiency of complementation in vitro of beta-galactosidase segments was decreased by 5-phosphorylribose 1-pyrophosphate but not by 3':5'-cyclic-AMP. Neither substance affected the activity of the complete enzyme. 3. Some indications as to the possible identity of the catabolite repression effector are presented.
Breast Cancer Screening: Balancing Evidence With Culture, Politics, Money, and Media

Abstract Culture, politics, money, and media intersect to influence the interpretation of scientific evidence with direct effects on the lives of women. Before venturing into detailed chapters reviewing the scientific evidence on breast cancer screening, we begin this textbook with an overview of the history of the breast, of breast cancer screening, and the perfect storm of politics and science surrounding this topic. We examine the complex forces that determine the lens through which many well-intentioned individuals view the same scientific evidence, yet arrive at different interpretations.
Studies on the mitochondrial electron transport system in Aspergillus.

SummaryMitochondria from two strains of Aspergillus niger were examined for succinate-cytochrome c reductase, NADH cytochrome c reductase, cytochrome c oxidase, succinoxidase, and NADH oxidase activities, and for phosphate-acceptor control. Except for NADH-cytochrome c reductase, each of these activities was considerably higher in the nitroaryl-resistant strain than in the wild type. These data supplied further evidence of augmented mitochondrial function in the resistant strain which aids in explaining metabolic differences between the two. Although intact Aspergillus mitochondria oxidize exogenous NADH, this activity did not appear to be coupled to phosphorylation.
Reversal of a Sudeck's atrophy by the adjunctive use of transcutaneous electrical nerve stimulation. A case report.

The patient, a 43-year-old man, fell from a ladder on January 19, 1981, sustaining fractures of the right distal tibia and fibula plus contusion and strain of the low back. He was treated with closed reduction of the fractures, and the leg was cast-braced. After the cast was removed, the patient was unable to bear weight on the right lower extremity because of pain and required fairly constant medication for analgesic, anti-inflammatory, and sedative effects. A secondary diagnosis of Sudeck's atrophy was made.1 This condition proved very resistant to treatment. On February 28, 1982, 13 months after the injury, the patient was referred to our physical therapy department for transcutaneous electrical nerve stimulation (TENS) treatment as a pain control measure. The treatment goal was to improve weight acceptance of the right leg, thereby leading to an increase in bone stock for the correction of the Sudeck's atrophy.
Social-Emotional Features

Clearly, much has been learned about the neurocognitive, neurolinguistic, and academic characteristics of learning disabilities over the past two decades. For instance, the term learning disability is a generic one, and truly productive research must focus on clearly defined subtypes of the disorder. A body of knowledge has now accumulated that has progressed from a preoccupation with single-factor models for heterogeneous samples of learning disabled individuals to a more fruitful approach focusing on neurocognitive, neurolinguistic, and academic features of relatively homogeneous samples.
The Impact of Grain and Agricultural Comprehensive Subsidies on Farmers Input of Production Factors—Empirical Research based on Farmers' Behavior of Employing Agricultural Machinery in Inner Mongolia

To verify whether grain and agricultural comprehensive subsidies can change farmers' input of production factors and affect agricultural production,120 households engaged in planting production in Inner Mongolia were investigated,and the impact of grain and agricultural comprehensive subsidies on farmers employing agricultural machinery were analyzed. The results showed that,there was a funds shortage problem during farmers buying production factors,grain and agricultural comprehensive subsidy had a positive impact on purchase of production factors. Accordingly,some suggests,such as increasing the stability of existing subsidy and granting subsidy to real land managers,especially inclining to large grain farmers and grain cooperatives,were provided.
Acknowledging and Thanking our Peer Reviewers.

The peer review process greatly improves the articles we publish in American Family Physician. On behalf of the entire editorial team at AFP, many thanks to all of our wonderful reviewers!
Transpubic Suspension of the Bladder Neck for Urinary Incontinence

AbstractWe present a modification of the classic Marshall-Marchetti-Krantz procedure in which only 1 pair of sutures is used. Each suture snugs the periurethral tissue of the anterior vaginal wall on each side to the posterior surface of the symphysis pubis and ipsilateral pubic bone by passing the suture through a hole drilled in each respective pubic bone. Complications have been temporary difficulty in voiding after the catheter has been removed and an occasional incisional hernia. Osteitis pubis has not been a problem possibly because of the use of wide-spectrum antibiotics.
Anomalous small-angle X-ray scattering studies of phase separation in bulk amorphous Zr52.5Ti5Cu17.9Ni14.6Al10*

We have performed differential anomalous small-angle X-ray scattering (ASAXS) experiments on samples of hulk amorphous Zr 52.5 Ti 5 Cu 17.9 Ni 14.6 Al 10 annealed in the supercooled liquid region. We observe the development of strong small-angle scattering, associated with phase separation on the nanometer scale in the supercooled liquid. Analysis of the Zr-edge ASAXS data reveals that this phase separation is largely due to a redistribution of Zr. Continued annealing results in the nucleation and growth of Zr-rich crystalline intennetallic phases.
Improved energy efficient secure multipath AODV routing protocol for MANET

In mobile ad hoc network (MANET), energy consumption is one among the foremost vital restrictions that deteriorate the performance of the whole network. Multi-path routing is better than the single path routing in ad hoc networks, because multi path routing allows the establishment of multiple path between a single source and single destination node. This paper presents a new approach of energy efficient secure multipath AODV (EESM-AODV) routing protocol for MANET based on AODV protocol is modified and converted to work on multiple path. Differing types of routing protocols planned over the years with minimal management overhead and network resources. AODV is well-liked routing protocol among others. It is a loop free, no centralized authority, single path, On-demand routing protocol and its performance is superior than different routing protocols in MANET. However, single path plan is that the most vital drawbacks of AODV. Also, it is a heap of routing overhead at the time of route repair and route discovery method. The mobile nodes in MANET also have restricted resources like battery power, restricted information measure that solely single path protocols cannot handle efficiently. so routing is also a really vital issue inside the look of a MANET. Multipath routing permits the multiple methods between one source and single destination node and during this paper conjointly offer security by filtering route discovery process in AODV routing protocol. The proposed approach contains an adaptive technique in which the our proposed scheme is more energy efficient. The filtering forwarding scheme slows down the spread of excessive RREQs originated by a node per unit time and with success prevents Denial of service attacks. This paper planned multipath extensions of AODV routing protocol and a security improvement against We compared results of AODV routing protocols in attacked condition and after applied our algorithm and enhance the results exploitation multipath scheme for AODV. We used ns-2 to simulate. Simulation results show that the energy consumption of network is less after applying our proposed algorithm and our Network gets more stable and that proposed technique has better packet delivery ratio and improved throughput.
Posterior Tibialis Tendon Rupture in a Closed Bimalleolar-Equivalent Ankle Fracture: Case Report

Ankle fractures with an associated posterior tibialis tendon (PTT) rupture are rare injuries and have only been described in a number of case reports. These prior reports include patients that had ...
The Social Determinants of Conspiratorial Ideation

Scholars have recently become increasingly interested in understanding the prevalence and persistence of conspiratorial beliefs among the public as recent research has shown such beliefs to be both...
Smad Ubiquitination Regulatory Factor-2 and Phosphorylated Smad2/3 Immunoreactivity in Pick's Disease (P04.153)

OBJECTIVE: To investigate the distribution of the immunoreactivity of Smad ubiquitination regulatory factor-2 (Smurf2) and phosphorylated Smad2/3 (pSmad2/3) in Pick9s disease. BACKGROUND: Smurf2 is an E3 ligase that belongs to the HECT domain ubiquitin ligase family. Smurf2 can interact with TGF-β type I receptor as well as Smad proteins, and promote their ubiquitin-dependent degradation, thereby controlling the cellular levels of these signaling mediators. We recently reported that phosphorylated tau inclusions of progressive supranuclear palsy are immunopositive not only for pSmad2/3 but also for Smurf2. The aberrant accumulation of pSmad2/3 was previously identified within phosphorylated tau inclusions in Pick9s disease. These findings prompt us to speculate that Smurf2 might be involved in 3-repeat tauopathy as well as in 4-repeat tauopathy. DESIGN/METHODS: Sections of frontal and temporal cortex from 14 Pick9s disease and 6 control patients without neurological disease were analyzed with immunohistochemical methods usinig Smurf2, pSmad2/3, CP13 and ubiquitin antibodies. RESULTS: Pick bodies and glial phosphorylated tau inclusions were immunopositive for both pSmad2/3 and Smurf2. However, Pick bodies of a single case without cortical atrophy were minimally immunoreactivity for Smurf2. The Pick cells showed patchy cytoplasmic Smurf2 and pSmad2/3 immunopositivity. Granulovacuolar degeneration was immunonegative for Smurf2. Triple immunofluorescence staining for Smurf2, pSmad2/3, and phosphorylated tau revealed co-localization of these proteins within Pick bodies and glial phophorylated tau inclusions. CONCLUSIONS: Our data indicates that possible disruption of TGF-β signaling pathway by the sequestration of Smurf2 and pSmad2/3 within phosphorylated tau inclusions could be an important event in the pathogenesis of Pick9s disease. Disclosure: Dr. Nakamura has nothing to disclose. Dr. Murray has nothing to disclose. Dr. Castanedes-Casey has nothing to disclose. Dr. Dickson has received personal compensation for activities with Neotope, Inc. as a consultant.
Discussing edaravone with the ALS patient: an ethical framework from a U.S. perspective

AbstractThe recent approval of edaravone by the United States Food and Drug Administration has generated a mix of hope tempered by reality. The costs of the drug, both monetarily and with regard to intensity of treatment, are high. The benefits, while modest, will be viewed through a very different lens by individuals depending on their goals of care. By virtue of our training and experience, physicians are ideally suited to understand and explain new treatments to our patients. As healthcare providers with a fiduciary responsibility to our patients, we must make sure they are fully informed about both the costs and benefits of non-curative therapies such as edaravone, and be prepared to discuss these in the context of their goals of care and potential impact on quality of life. Respect for our patients’ autonomy is critical when discussing these issues, but we should always be guided by the ethical principles of beneficence and non-maleficence.
High-Frequency Oscillating Ventilator Use in a Patient with Severe Pulmonary Contusions

Approximately 25% of trauma deaths can be attributed to thoracic injuries. Severe pulmonary contusions commonly result from blunt trauma to the thorax. The resulting alveolar hemorrhage and edema c...
Degradable Polymeric Carriers for Parenteral Controlled Drug Delivery

Drug loaded carriers from degradable polymers, namely, injectable microparticles, injectable in situ forming implants, and preformed implants, are established in the clinic for parenteral controlled drug delivery. This chapter provides an overview on several factors influencing release behavior such as drug properties, effects of environmental conditions, osmotically mediated mechanisms, and the selection of the carrier type. Moreover, degradation and erosion of the polymeric matrices are discussed in detail in view of their impact on drug release for different relevant polymer classes and groups of bioactive molecules. Additionally, carrier type-specific issues are included based on the knowledge gained to date from available parenteral controlled release products, as obtained from a comprehensive review of the scientific and patent literature. In particular, preparation techniques and related mechanisms, and both advantages and challenges associated with degradable polymer based delivery systems are described. Strategies to establish a continuous drug release are examined based on rational evaluation of specific polymer classes and carrier types.
Appendix B: Isis2 API

Abstract Readers of this text will have learned a great deal about Cornell’s Isis2 platform, available for download from Cornell (under freeBSD licensing) from the web site http://www.cs.cornell.edu/ken/isis2.
Lizards perceived abiotic and biotic stressors independently when competing for shade in terrestrial mesocosms.

Abstract Hormones such as glucocorticoids and androgens enable animals to respond adaptively to environmental stressors. For this reason, circulating glucocorticoids became a popular biomarker for estimating the quality of an environment, and circulating androgens are frequently used to indicate social dominance. Here, we show that access to thermal resources influence the hormones and behavior of male lizards (Sceloporus jarrovi). We exposed isolated and paired males to different thermal landscapes, ranging from one large patch of shade to sixteen smaller patches. Both the presence of a competitor and the patchiness of the thermal environment influenced hormone concentrations and movement patterns. When shade was concentrated in space, paired lizards competed more aggressively and circulated more corticosterone. Even without competitors, lizards circulated more corticosterone in landscapes with fewer patches of shade. Conversely, shifts in circulating testosterone depended only on the relative body size of a lizard; when paired, large males and small males circulated more and less testosterone, respectively. Furthermore, isolated males moved the farthest and covered the most area when shade was concentrated in a single patch, but paired males did the opposite. Because the total area of shade in each landscape was the same, these hormonal and behavioral responses of lizards reflect the ability to access shade. Thus, circulating glucocorticoids should reflect the thermal quality of an environment when researchers have controlled for other factors. Moreover, a theory of stress during thermoregulation would help ecologists anticipate physiological and behavioral responses to changing climates.
Importance of the heart vector origin point definition for an ECG analysis: The Atherosclerosis Risk in Communities (ARIC) study.

Abstract Aim Our goal was to investigate the effect of a global XYZ median beat construction and the heart vector origin point definition on predictive accuracy of ECG biomarkers of sudden cardiac death (SCD). Methods Atherosclerosis Risk In Community study participants with analyzable digital ECGs were included (n = 15,768; 55% female, 73% white, mean age 54.2 ± 5.8 y). We developed an algorithm to automatically detect the heart vector origin point on a median beat. Three different approaches to construct a global XYZ beat and two methods to locate origin point were compared. Global electrical heterogeneity was measured by sum absolute QRST integral (SAI QRST), spatial QRS-T angle, and spatial ventricular gradient (SVG) magnitude, azimuth, and elevation. Adjudicated SCD served as the primary outcome. Results There was high intra-observer (kappa 0.972) and inter-observer (kappa 0.984) agreement in a heart vector origin definition between an automated algorithm and a human. QRS was wider in a median beat that was constructed using R-peak alignment than in time-coherent beat (88.1 ± 16.7 vs. 83.7 ± 15.9 ms; P Conclusion Time-coherent global XYZ median beat with physiologically meaningful definition of the heart vector's origin point improved predictive accuracy of SCD biomarkers.
Long-term outcomes of cardiac resynchronization therapy by left ventricular ejection fraction.

Aims Despite our prior report suggesting heart failure (HF) risk reduction from cardiac resynchronization therapy with defibrillator (CRT-D) in mild HF patients with higher left ventricular ejection fraction (LVEF > 30%), data on mortality benefit in this cohort are lacking. We aimed to assess long-term mortality benefit from CRT-D in mild HF patients by LVEF > 30%. Methods and results Among 1274 patients with mild HF and left bundle branch block enrolled in MADIT-CRT, we analysed long-term effects of CRT-D vs. implantable cardioverter defibrillator (ICD) therapy only, and reverse remodelling to CRT-D (left ventricular end-systolic volume percent change ≥ median at 1 year), on all-cause mortality and HF for the LVEF ≤ 30% and LVEF > 30 subgroups using Kaplan-Meier and Cox analyses. During long-term follow-up, CRT-D vs. ICD was associated with reduction in all-cause mortality in both patients with LVEF > 30% and LVEF ≤ 30% [hazard ratio (HR) 0.47, 95% confidence interval (CI) 0.25-0.85, P = 0.036 vs. HR 0.69, 95% CI 0.49-0.98, P = 0.013, interaction P = 0.261]. The efficacy of CRT-D vs. ICD only to reduce HF was similar in those with LVEF above and below 30% (HR 0.36, 95% CI 0.35-0.61, P 30% or LVEF ≤ 30% (HR 0.17 and 0.39), but no mortality benefit was seen in patients with less reverse remodelling. HF events, however, were reduced in both CRT-D-induced high and low reverse remodelling vs. ICD only, in both LVEF subgroups. Conclusions In MADIT-CRT, left bundle branch block patients with higher LVEF (> 30%) derive long-term mortality benefit from CRT-D when exhibiting significant reverse remodelling. Clinical trial registration ClinicalTrials.gov ID NCT00180271, NCT01294449, and NCT02060110.
The Tribological Properties of Ion-implanted JIS SUS304 Stainless Steel

Experiments using unimplanted JIS SUS304 as well as N + -, B + -, N + +B + - and Ar + -implanted JIS SUS304 were performed with a self-manufactured tribology testing apparatus. From the experimental results, the coefficient of friction was significantly dependent on the kind of the opposite component in the tribological tests. It has also be observed that the magnitude of the wear damage on JIS SUS304 is dependent upon the kind of the ions implanted.
Ste5 Membrane Localization Allows MAPK Pathway Signaling in trans Between Kinases on Separate Scaffold Molecules [preprint]

The MAP kinase cascade is a ubiquitous eukaryotic signaling module that can be controlled by a diverse group of scaffold proteins. In budding yeast, activation of the mating MAP kinase cascade involves regulated membrane recruitment of the archetypal scaffold protein Ste5. This event promotes activation of the first kinase, but it also enhances subsequent signal propagation through the remainder of the cascade. By studying this latter effect, we find that membrane recruitment promotes signaling in trans between kinases on separate Ste5 molecules. First, trans signaling requires all Ste5 domains that mediate membrane recruitment, including both protein-binding and membrane-binding domains. Second, artificial membrane tethering of Ste5 can drive trans signaling, bypassing the need for native localization domains. Third, trans signaling can occur even if the first kinase does not bind the scaffold but instead is localized independently to the plasma membrane. Moreover, the trans signaling reaction allowed us to separate Ste5 into distinct functional domains, and then achieve normal regulation of signal output by tethering one domain to the membrane and stimulating membrane recruitment of the other. Overall, the results support a heterogeneous "ensemble" model of signaling in which scaffolds need not organize multiprotein complexes but instead can serve as binding sinks that co-concentrate enzymes and substrates at specific subcellular locales. These properties relax assembly constraints for scaffold proteins, increase regulatory flexibility, and can facilitate both natural evolution and artificial design of new signaling proteins and pathways.
Cardiac Surgery in the Elderly

Reports in 1948 and 1949 of series of young patients undergoing closed transatrial mitral commissurotomy (Harken et al. 1948, Bailey 1949), later modified to a transventricular approach (Logan and Turner 1959), were in time followed by documentation of successful open-heart procedures on older patients (Spencer et al. 1964, Bowles et al. 1966, Ahmad and Starr 1969). The intervening 20 years saw the development of cardiopulmonary bypass in 1954 (Gibbon 1954), the replacement of diseased aortic and mitral valves by ball-valve prostheses in 1960 (Harken et al. 1960, Starr and Edwards 1961), the use of homografts in 1962 (Ross 1962), and the beginnings of direct surgical treatment for coronary artery disease in 1964 (Effler et al. 1964). The latter has now been extended to include surgical treatment for the complications of myocardial infarction.
CRL4 regulates recombination and synaptonemal complex aggregation in the Caenorhabditis elegans germline

To maintain the integrity of the genome, meiotic DNA double strand breaks (DSBs) need to form by the meiosis-specific nuclease Spo11 and be repaired by homologous recombination. One class of products formed by recombination are crossovers, which are required for proper chromosome segregation in the first meiotic division. The synaptonemal complex (SC) is a protein structure that connects homologous chromosomes during meiotic prophase I. The proper assembly of the SC is important for recombination, crossover formation, and the subsequent chromosome segregation. Here we identify the components of Cullin RING E3 ubiquitin ligase 4 (CRL4) that play a role in SC assembly in Caenorhabditis elegans. Mutants of the CRL4 complex (cul-4, ddb-1, and gad-1) show defects in SC assembly manifested in the formation of polycomplexes (PCs), impaired progression of meiotic recombination, and reduction in crossover numbers. PCs that are formed in cul-4 mutants lack the mobile properties of wild type SC, but are likely not a direct target of ubiquitination. In C. elegans, SC assembly does not require recombination and there is no evidence that PC formation is regulated by recombination as well. However, in one cul-4 mutant PC formation is dependent upon early meiotic recombination, indicating that proper assembly of the SC can be diminished by recombination in some scenarios. Lastly, our studies suggest that CUL-4 deregulation leads to transposition of the Tc3 transposable element, and defects in formation of SPO-11-mediated DSBs. Our studies highlight previously unknown functions of CRL4 in C. elegans meiosis and show that CUL-4 likely plays multiple roles in meiosis that are essential for maintaining genome integrity.
Conducting spoken word recognition research online: Validation and a new timing method

Models of spoken word recognition typically make predictions that are then tested in the laboratory against the word recognition scores of human subjects (e.g., Luce & Pisoni Ear and Hearing, 19, 1-36, 1998). Unfortunately, laboratory collection of large sets of word recognition data can be costly and time-consuming. Due to the numerous advantages of online research in speed, cost, and participant diversity, some labs have begun to explore the use of online platforms such as Amazon's Mechanical Turk (AMT) to source participation and collect data (Buhrmester, Kwang, & Gosling Perspectives on Psychological Science, 6, 3-5, 2011). Many classic findings in cognitive psychology have been successfully replicated online, including the Stroop effect, task-switching costs, and Simon and flanker interference (Crump, McDonnell, & Gureckis PLoS ONE, 8, e57410, 2013). However, tasks requiring auditory stimulus delivery have not typically made use of AMT. In the present study, we evaluated the use of AMT for collecting spoken word identification and auditory lexical decision data. Although online users were faster and less accurate than participants in the lab, the results revealed strong correlations between the online and laboratory measures for both word identification accuracy and lexical decision speed. In addition, the scores obtained in the lab and online were equivalently correlated with factors that have been well established to predict word recognition, including word frequency and phonological neighborhood density. We also present and analyze a method for precise auditory reaction timing that is novel to behavioral research. Taken together, these findings suggest that AMT can be a viable alternative to the traditional laboratory setting as a source of participation for some spoken word recognition research.
Fragmentation pathways of α-pyrrolidinophenone synthetic cathinones and their application to the identification of emerging synthetic cathinone derivatives

Abstract The expanding use of emerging synthetic drugs is creating a growing problem for both seized drug analysts and toxicologists because the clandestine suppliers continually tweak the chemical structures to keep one step ahead of the law. Synthetic cathinones, commonly referred to as bath salts, are a specific class of emerging synthetic drugs. These substances are derivatives of cathinone, which is the psychoactive component of the Catha edulis plant, commonly referred to as khat. Of the synthetic cathinone class of compounds, the α-pyrrolidinophenone synthetic cathinone derivatives stand out as one of the most abused designer drugs. The fragmentation behavior of a series of α-pyrrolidinophenone synthetic cathinones was studied with three different ionization and fragmentation techniques to enhance the current understanding of α-pyrrolidinophenone synthetic cathinones in mass spectrometers. Gas chromatography-electron ionization-mass spectrometry (GC-EI-MS) fragmentation is commonly used by seized drug analysts, whereas liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) is more commonly used in toxicological analyses. Direct analysis in real time mass spectrometry (DART-MS) is becoming more popular as a screening technique, especially in national laboratories. Each ionization and activation method encourage particular pathways of fragmentation, and whereas some pathways are conserved across all platforms, other pathways are unique to a particular instrument. This study combines isotope-labeling, multi-stage mass spectrometry (MSn) and accurate mass measurements with high-resolution mass spectrometry (HRMS) to enhance the current understanding about α-pyrrolidinophenone synthetic cathinones. This manuscript provides characteristic protonated tandem mass spectrometry fragmentation pathways and the mechanistic origins of the EI-MS fragmentation observed for this class of synthetic cathinones and provides examples of how this knowledge can be applied to the identification of novel synthetic cathinones.
Long-term outcome in outpatients with depression treated with acute and maintenance intravenous ketamine: A retrospective chart review

Abstract Background Little is known about the long-term outcomes of repeated ketamine infusions for depression. We conducted a retrospective chart review to investigate outcomes of maintenance intravenous ketamine treatment at Massachusetts General Hospital. Methods Eighty-five patients with treatment-resistant depression (TRD) who started intravenous ketamine from October 2018 to November 2019 were examined. Symptom severity was evaluated with the 16-item Quick Inventory of Depressive Symptomatology-Self Report scale (QIDS-SR16) at every visit prior to administration. The initial ketamine dose was usually 0.5 mg/kg infused over 40 min. Intravenous ketamine was administered twice-weekly for three weeks in an induction phase, followed by maintenance with a variable administration schedule and dose. Response was defined as a ≥50% reduction in total QIDS-SR16 score from baseline. Results Forty (47.1%) of the 85 patients who started treatment discontinued during or right after the induction phase; 3 (3.5%) were still on induction at the time of this report, and 42 (49.4%) transitioned to maintenance after completing induction. Among these patients, 14 (16.5%) discontinued during maintenance and 28 (32.9%) continued on maintenance. The mean ketamine dosage during maintenance was 0.91±0.28 mg/kg. Fifteen out of 82 patients (18.3%) responded to induction treatment and 6 (7.3%) remained in responder status at the time of data analysis during maintenance. Three patients discontinued ketamine due to side-effects. Conclusions Despite the apparently low response rate in QIDS-SR16 scores and considerable out-of-pocket costs, almost half of real-world outpatients with TRD decided to continue with maintenance ketamine treatment due to perceived significant improvement.
Chromatin State Dynamics Confers Specific Therapeutic Strategies in Enhancer Subtypes of Colorectal Cancer

The extent and function of chromatin state aberrations during colorectal cancer (CRC) progression is not completely understood. Here, by comprehensive epigenomic characterization of 56 tumors, adenomas, and their matched normal tissues, we define the dynamics of chromatin states during the progression of colorectal cancer. H3K27ac-marked active enhancer state could distinguish between different stages of CRC progression. By epigenomic editing, we present evidence that gains of tumor-specific enhancers for crucial oncogenes, such as ASCL2 and FZD10, was crucial for excessive proliferation. Consistently, combination of MEK plus bromodomain (BET) inhibition was found to have synergistic effects in CRC patient-derived xenograft (PDX) models. Probing inter-tumor heterogeneity, we identified four distinct enhancer subtypes (EpiC), three of which correlate well with previously defined transcriptomic subtypes (CMSs). Importantly, CMS2 can be divided into two EpiC subgroups with significant survival differences. Leveraging such correlation, we devised a combinatorial therapeutic strategy of enhancer-blocking bromodomain inhibitors with pathway-specific inhibitors (PARPi, EGFRi, and TGFBi) for three EPIC groups. Our data suggest that the dynamics of active enhancer underlies colorectal cancer progression and the patient-specific active enhancer patterns govern their unique gene expression patterns which can be leveraged for precision combination therapy.
Statistical Analysis of Decoding Performances of Diverse Populations of Neurons.

A central theme in computational neuroscience is determining the neural correlates of efficient and accurate coding of sensory signals. Diversity, or heterogeneity, of intrinsic neural attributes i...
Single atom catalysis poised to transition from an academic curiosity to an industrially relevant technology.

During the past decade, initial skepticism rapidly changed into widespread recognition of the role of single atoms in heterogeneous catalysts. The next decade could usher in the era of industrial applications as manufacturing of durable single atom catalysts is perfected.
Eczematous reactions to psoriasis biologics treated with dupilumab: A case series.

Psoriasis is characterized by a T helper (Th)1 and Th17 immune response and a unique cytokine profile, including elevated interleukin (IL)-17 and IL-23.1 Biologic therapy for psoriasis targets the imbalance of cytokines characteristic of the disease and has revolutionized disease management. However, recent reports have described eczematous eruptions that occur as adverse reactions to biologic therapy for psoriasis and often require discontinuation of the biologic.2 Here, we report of 3 patients, who developed eczematous reactions while on a biologic targeting Th1 or Th17 cytokines. We successfully treated the reactions with the addition of dupilumab to the existing biologic regimen with no adverse events.
Facial emotion recognition in major depressive disorder: A meta-analytic review

Abstract Background Major depressive disorder (MDD) has been associated with difficulties in social and interpersonal functioning. Deficits in emotion processing may contribute to the development and maintenance of interpersonal difficulties in MDD. Although some studies have found that MDD is associated with deficits in recognition of emotion in faces, other studies have failed to find any impairment. Methods: The present meta-analysis of 23 studies, with 516 dysthymic/depressed participants and 614 euthymic control participants, examined facial emotion recognition accuracy in MDD. Several potential moderators were investigated, including type of emotion, symptom severity, patient status, method of diagnosis, type of stimulus, and stimulus duration. Results Results showed that participants with MDD in inpatient settings (Hedges’ g = -0.35) and with severe levels of symptom severity (g = -0.42) were less accurate in recognizing happy facial expressions of emotion (g = -0.25) compared to participants in outpatient settings (g = -0.24) and with mild symptoms of depression (g = -0.17). Studies that presented stimuli for longer durations (g = -0.26) tended to find lower accuracy levels in dysthymic/depressed, relative to euthymic, participants. Limitations Limitations include a lack of studies which examined gender identity, as well as other potential moderators. Conclusions Results of the current study support the existence of a broad facial emotion recognition deficit in individuals suffering from unipolar depression. Clinicians should be mindful of this and other research which suggests broad-based deficits in various forms of information processing, including attention, perception, and memory in depression.
Temporal Feature Warping for Video Shadow Detection.

While single image shadow detection has been improving rapidly in recent years, video shadow detection remains a challenging task due to data scarcity and the difficulty in modelling temporal consistency. The current video shadow detection method achieves this goal via co-attention, which mostly exploits information that is temporally coherent but is not robust in detecting moving shadows and small shadow regions. In this paper, we propose a simple but powerful method to better aggregate information temporally. We use an optical flow based warping module to align and then combine features between frames. We apply this warping module across multiple deep-network layers to retrieve information from neighboring frames including both local details and high-level semantic information. We train and test our framework on the ViSha dataset. Experimental results show that our model outperforms the state-of-the-art video shadow detection method by 28%, reducing BER from 16.7 to 12.0.
Inborn errors of immunity: Recent progress.

Recent advances in the field of inborn errors of immunity (IEIs) have been wide in scope, including progress in mechanisms of disease, diagnosis, and management. New gene defects affecting the immune response continue to be reported, as many as 26 in the year 2020. It was noted that the presentation of IEIs might not include recurrent infections in 9% of cases, and that current diagnostic methods can identify molecular causes in 92% of patients with severe combined immunodeficiency. Progress in immunopathogenesis explained mechanisms leading to symptoms of autosomal-recessive hyper-IgE syndrome. There was an emphasis on research in primary antibody deficiencies. The benefit of antibiotic prophylaxis to reduce the frequency of infections was demonstrated in these patients. The regimen of rituximab and azathioprine or mycophenolate was proven effective for chronic granulocytic interstitial pneumonia. The efficacy and adverse events of hematopoietic stem cell transplant in different IEI conditions were reported, as well as different strategies to improve outcomes, supporting its use in immunodeficiency and immunodysregulatory syndromes. The recent pandemic of coronavirus disease 2019 affected patients with IEIs, in particular those with deficiency in the interferon-mediated activation of the immune response. Initial data suggest that coronavirus disease 2019 vaccines might elicit anti–coronavirus disease 2019–neutralizing antibody responses in some patients with IEI conditions.
Static Fracture Response of Materials

Attention to the fracture of aerospace materials is critical to the safety and performance of aerospace structural systems. Basic concepts of linear elastic fracture mechanics, including crack tip stress and displacement fields, stress intensity factor, energy release rate and fracture initiation, and growth criteria are reviewed. Analytical, computational, and experimental methods for calculating and measuring crack tip stress intensity factors are discussed. Several experimental methods for the measurement of fracture initiation toughness and crack propagation resistance are described as well. Keywords: fracture mechanics; stress intensity factor; energy release rate; -curve; experimental methods; photoelasticity; strain gauges; digital image correlation; fracture toughness
Thermoelectricity in Semiconductor Nanostructures

Thermoelectrics are devices that convert heat to electricity directly, or vice versa. To be technologically useful, thermoelectric materials with high efficiency must be found, along with better tools to understand them. In his Perspective, Majumdar discusses the reports by Hsu et al . and Lyeo et al . that tackle these issues. Hsu et al . have found a new bulk material that exhibits a so-called figure of merit with a value around 2, which is an encouraging step on the road to materials that could compete with conventional thermodynamic devices such as power generators and refrigerators. Lyeo et al . report on a new technique for measuring thermoelectric properties over nanometer scales. The interdisciplinary combination of thermoelectric research with microelectronics and nanotechnology, Majumdar argues, will have a positive impact on both fields.
Comparison of efficacy of differing partner-assisted skin examination interventions for melanoma patients: A randomized clinical trial

Importance Early detection of melanoma may improve survival. The present study continued research establishing that in-person training on skin self-examinations (SSEs) was significantly enhanced when delivered to patients with their partners present instead of to patients alone. Objective To examine 3 alternative SSE training approaches that included partners compared with a treatment-as-usual control condition. Design, setting, and participants A randomized clinical trial with 4- and 12-month follow-up visits was conducted at the clinical offices in the ambulatory care area of a hospital. The evaluable population included 494 patients with stage 0 to IIB melanoma and their skin check partners drawn from an electronic medical record melanoma registry and advertisements in large regional newspapers. The study was conducted from June 6, 2011, to April 14, 2014, and analysis was performed between December 4 and December 11, 2014. Interventions Pairs of patients and their partners were randomly assigned to (1) in-person intervention, (2) take-home booklet intervention, and (3) treatment-as-usual controls. An additional subgroup of patients received an electronic interactive tablet personal computer intervention. The MoleScore content was comparable across formats and consisted of demonstrations of the ABCDE (assess border, color, diameter, and evolution of pigmented lesions) rule and skills training. Main outcomes and measures Outcomes were self-reported SSE of the total body as well as easy-to-see and difficult-to-see regions at baseline, 4 months, and 12 months. Results No significant differences in SSEs were observed between the 3 intervention conditions on all of the body areas; results for all 3 intervention conditions were significantly higher than for controls at 4- and 12-month follow-ups (all P Conclusions and relevance The findings of the research support the sustainability and efficacy at 12 months of partner-assisted SSE interventions for early detection targeting individuals with a history of melanoma. Trial registration clinicaltrials.gov Identifier: NCT01432860.
Medical Education in Saudi Arabia

University curricula in Saudi Arabia can be approximately dichotomized into subjects taught in English-the natural sciences; and those taught in Arabic-the cultural areas. Medical education is conducted in English. Many medical students are poorly prepared in English; in consequence, there is high stress in the classroom and examination hall. Saudi educators are hesitant about reliance upon a foreign language in the curriculum. The psychocultural meanings of the English/Arabic dichotomy within the social structure of the medical education are explored as a device leading toward a general understanding of the process of modernization.
Probabilistic evaluating of bias for learning systems

Abstract A method for using probabilistic background knowledge to select features for representing learned concepts is described. The method uses a model of the tradeoff between accuracy (predictiveness) and simplicity (size) of hypothesis spaces. Preliminary results of using various biases for a learning task in a randomized test domain are discussed.
A Real-Time Fast-Flow Tube Study of VOC and Particulate Emissions from Electronic, Potentially Reduced-Harm, Conventional, and Reference Cigarettes.

Tobacco-free electronic cigarettes (e-cigarettes), which are currently not regulated by the FDA, have become widespread as a “safe” form of smoking. One approach to evaluate the potential toxicity of e-cigarettes and other types of potentially “reduced-harm” cigarettes is to compare their emissions of volatile organic compounds (VOCs), including reactive organic electrophilic compounds such as acrolein, and particulate matter to those of conventional and reference cigarettes. Our newly designed fast-flow tube system enabled us to analyze VOC composition and particle number concentration in real-time by promptly diluting puffs of mainstream smoke obtained from different brands of combustion cigarettes and e-cigarettes. A proton transfer reaction time-of-flight mass spectrometer (PTRMS) was used to analyze real-time cigarette VOC emissions with a 1-s time resolution. Particles were detected with a condensation particle counter (CPC). This technique offers real-time analysis of VOCs and particles in each puf...
X-chromosome-counting mechanisms that determine nematode sex.

Sex is determined in Caenorhabditis elegans by an X-chromosome-counting mechanism that reliably distinguishes the twofold difference in X-chromosome dose between males (1X) and hermaphrodites (2X)1,2. This small quantitative difference is translated into the ‘;on/off’ response of the target gene, xol-1, a switch that specifies the male fate when active and the hermaphrodite fate when inactive3. Specific regions of X contain counted signal elements whose combined dose sets the activity of xol-1 (ref. 4). Here we ascribe the dose effects of one region to a discrete, protein-encoding gene, fox-1. We demonstrate that the dose-sensitive signal elements on chromosome X control xol-1 through two different molecular mechanisms. One involves the transcriptional repression of xol-1 in XX animals. The other uses the putative RNA-binding protein encoded by fox-1 to reduce the level of xol-1 protein. These two mechanisms of repression act together to ensure the fidelity of the X-chromosome counting process.