cssi/SciSciGPT-SciSciNet huggingface dataset:
The pH-Dependent Trigger in Diphtheria Toxin T Domain Comes with a Safety Latch

Protein-side-chain protonation, coupled to conformational rearrangements, is one way of regulating physiological function caused by changes in protein environment. Specifically, protonation of histidine residues has been implicated in pH-dependent conformational switching in several systems, including the diphtheria toxin translocation (T) domain, which is responsible for the toxin's cellular entry via the endosomal pathway. Our previous studies a) identified protonation of H257 as a major component of the T domain's conformational switch and b) suggested the possibility of a neighboring H223 acting as a modulator, affecting the protonation of H257 and preventing premature conformational changes outside the endosome. To verify this "safety-latch" hypothesis, we report here the pH-dependent folding and membrane interactions of the T domain of the wild-type and that of the H223Q mutant, which lacks the latch. Thermal unfolding of the T domain, measured by circular dichroism, revealed that the reduction in the transition temperature for helical unfolding for an H223Q mutant starts at less acidic conditions (pH <7.5) relative to the wild-type protein (pH <6.5). Hydrogen-deuterium-exchange mass spectrometry demonstrates that the H223Q replacement results in a loss of stability of the amphipathic helices TH1-3 and the hydrophobic core helix TH8 at pH 6.5. That this destabilization occurs in solution correlates well with the pH-range shift for the onset of the membrane permeabilization and translocation activity of the T domain, confirming our initial hypothesis that H223 protonation guards against early refolding. Taken together, these results demonstrate that histidine protonation can fine-tune pH-dependent switching in physiologically relevant systems.
Paul Scherrer und Hans Wysling, Quellenkritische Studien zum Werk Thomas Manns (Thomas-Mann-Studien, I.): Bern und München: Francke, 1967. Pp. 347 + 4 plates.

(1968). Paul Scherrer und Hans Wysling, Quellenkritische Studien zum Werk Thomas Manns (Thomas-Mann-Studien, I.) The Germanic Review: Literature, Culture, Theory: Vol. 43, No. 4, pp. 304-307.
Relative Effect of Limb Alignment Versus Tray Alignment on Risk for Tibial Subsidence After Total Knee Arthroplasty

Introduction Component and limb alignment (especially varus >3°) have been associated with soft-tissue imbalance, increased polyethylene wear, and tibial tray subsidence. However, not all clinical outcome studies have found significant correlation between tibial varus and revision surgery. While the link between limb alignment and failure has been attributed to increased medial compartmental loading and generation of shear stress, quantitative biomechanical evidence to directly support this mechanism is incomplete. In this study, we analyzed the effect of limb alignment and tibial tray alignment on the risk for bone damage and subsequent risk for tray loosening. Methods A finite element model of knee arthroplasty previously validated with in vitro cadaver testing was used. Models of four subjects were constructed with tibial resections simulating a 0°, 3°, 5°, and 7° varus alignment with respect to the mechanical axis of the tibia and the tray implanted at the corresponding angles. Tibial tray orientation was simulated without change in limb alignment (i.e. maintaining the mechanical axis of the knee at 0°) and with limb alignment ranging from 3° valgus to 7° varus (Fig 1). A static load equivalent to three times the bodyweight of the subject was applied in line with the mechanical knee axis. Relative motion between the tibial tray and tibial bone was calculated. Elements with an equivalent von Mises strain >0.4% were selected and assigned an elastic modulus of 5 MPa to reflect damaged bone. Simulation was repeated and after-damage micromotion recorded. Results At neutral limb alignment, average tray micromotion was Discussion We did not find significant increase in micromotion with increased tray varus (of up to 7°) as long as neutral limb mechanical axis was maintained by compensating for tibial varus with femoral valgus. The volume of bone at risk also did not increase significantly with increasing tray varus. Removing the damaged bone did little to affect after-damage micromotion. This suggests that the “damaged” bone was not an important factor and likely did not contribute to the stability of the tray under the loading conditions analyzed in this report. Changes in limb alignment significantly offset the net axial load vector resulting in damage in a greater volume of elements due to overloading. This is due to the shift in Mechanical axis and load vector with subsequent increase in moment applied to the model. The micromotion was also substantially increased after the damage indicating that the damaged bone was providing structural support to the tray. This emphasizes the effects of increasing the static coronal loading in this model. Consequently, it identifies the benefit of neutral limb alignment in this loading scenario. This model is an extremely valuable tool in studying the effect of surgical alignment, loading, and activity on damage to proximal bone.
Axial-Plane Biomechanical Evaluation of 2 Suspensory Cortical Button Fixation Constructs for Acromioclavicular Joint Reconstruction.

Background Although numerous suture-button fixation techniques for acromioclavicular (AC) joint reconstruction have been validated with biomechanical testing in the superior direction, clinical reports continue to demonstrate high rates of construct slippage and breakage. Purpose To compare the stability of a novel closed-loop double Endobutton construct with a commercially available cortical button system in both the axial and superior directions. Study design Controlled laboratory study. Methods Six matched pairs of fresh-frozen cadaveric upper extremities were anatomically dissected and prepared to simulate a complete AC joint dislocation. One side of each pair was reconstructed with the double Endobutton (DE) construct and other side with the dog bone button (DB) construct. The specimens were then tested using a materials testing machine, determining initial superior and axial displacements with a preload, and then cyclically loaded in the axial direction with 70 N for 5000 cycles. Displacement was again measured with the same preloads at fixed cycle intervals. The specimens were then loaded superiorly to failure. Results At 5000 cycles, the mean axial displacement was 1.7 mm for the DB group and 1.2 mm for the DE group (P = .19), and the mean superior displacement was 1.1 mm for the DB group and 0.7 mm for the DE group (P = .32). Load at failure was similar (558 N for DE, 552 N for DB; P = .96). There was no statistically significant difference in the modes of failure. Conclusion Biomechanical testing of both constructs showed similar fixation stability after cyclical axial loading and similar loads to failure. Clinical relevance The strength of both constructs after cyclical loading in the axial plane and load-to-failure testing in the superior plane validate their continued clinical use for achieving stability in AC joint reconstruction procedures.
Cytokine biomarkers in tear film for primary open-angle glaucoma.

Purpose To determine the utility of tear film cytokines as biomarkers for early primary open-angle glaucoma (POAG). Methods Patients without POAG and eye drop-naive patients with newly diagnosed POAG were recruited from an academic hospital-based glaucoma practice. Tear films of recruited patients were obtained and analyzed using a multiplex, high-sensitivity electrochemiluminescent enzyme-linked immunosorbent assay for proinflammatory cytokines (IFNγ, IL-10, IL-12p70, IL-13, IL-1β, IL-2, IL-4, IL-6, IL-8, and TNFα). Results Mean concentrations of tear film cytokines were lower in the glaucoma group for 8 of 10 cytokines tested. IL-12p70 (3.94±2.19 pg/mL in control vs 2.31±1.156 pg/mL in POAG; P=0.035) was significantly lower in the tear film of patients with newly diagnosed POAG. Conclusion Proinflammatory cytokines were lower in eye drop-naive newly diagnosed glaucoma patients. Tear film cytokine profiles may be used as biomarkers of early POAG.
Predictors of incarcerated women’s postrelease PTSD, depression, and substance-use problems

ABSTRACTThis longitudinal project assessed predictors of women’s mental health postrelease from prison. Women (59) completed mental health and trauma exposure assessments while incarcerated and then postrelease. Women’s mental health did not change postrelease. Lifetime exposure to interpersonal violence and maladaptive coping were significantly associated with increased postrelease PTSD. In addition, adaptive and maladaptive coping were significantly associated with postrelease depression. Ethnicity, prior substance dependence, postrelease PTSD and depression, interpersonal violence since release, and coping were all significantly associated with postrelease substance use and problems. The findings of this study contribute to identification of potential points of intervention for women postrelease.
Effects of the AAA Program Upon Regional Specialization in Agriculture

The task assigned to this paper is that of appraising the effects of the AAA program upon regional shifts and regional specialization in agricultural production. Does it influence, and if so in what way, the ability to maintain an adjustment among regions, which will reasonably approximate the most advantageous adaptation to conditions as they are? Since adjustments resulting from the program come about through decisions by individual farmers, a logical starting point for an examination of these effects would be the individual farm. Through such an approach one might build up a complete analysis of AAA accomplishments in influencing acreages and production, including its regional effects. However, no such comprehensive treatment is possible on the basis of the information to be had at the present time. Neither is it possible within the time allotted to this discussion to give any adequate attention to the considerable volume of pertinent, though scattered and oftentimes fragmentary, material which is available.
Intraspecific differences in morphology correspond to differential spawning habitat use in two riverine catostomid species

Maintaining intraspecific diversity is an important goal for fisheries conservation and recovery actions. While ecomorphological studies have demonstrated intraspecific diversity related to feeding or flow regime, there has been little assessment of such variation in regard to spawning habitat. We evaluated the relationship between individual morphology of Robust Redhorse and Notchlip Redhorse and variables describing the spawning habitat from which they were captured, such as current velocity, depth, and substrate particle size. Robust Redhorse (n = 58) and Notchlip Redhorse (n = 43) were captured from spawning aggregations in the lower Savannah River, South Carolina-Georgia using prepositioned grid electrofishers. They were then measured and photographed before being released. We constructed a truss network using digitized landmarks on each of the photographs. Relationships between the morphological and environmental datasets were assessed using canonical correlation analysis. In both species, these morphological predictors were correlated primarily to depth, though current velocity also contributed to the environmental canonical score for Robust Redhorse. Robust Redhorse captured from the deeper locations with higher current velocities had heads with lower aspect ratio compared to individuals captured from shallower areas. Notchlip Redhorse from shallower areas were deeper-bodied and had shorter trunks than counterparts from deeper areas. These differences suggest that ensuring spawning habitat heterogeneity may be an important component to conserving intraspecific diversity, particularly in systems where such habitat is limiting.
Ubiquitination and its function in defense pathways

Ubiquitination is a posttranslational modification that plays a crucial role in the regulation of both innate and adaptive immunity. In the innate immunity, ubiquitination regulates immune signaling by adjusting the signaling mediators to turn on/off a specific defense response. In this review, we briefly summarize the results from current studies of ubiquitination and compare the functions of ubiquitination between plants and animal.
The Subterranean Economy, Redux

In the past six years there has been a revolutionary development in economics. Six years ago, the subterranean economy — that broad area of productive economic activity which wholly escapes the ministrations of the tax collector and largely that of the statistician — simply did not exist, in the official view, in the perception of the public and among economists.
Fluoroscopy Learning Curve in Hip Arthroscopy-A Single Surgeon's Experience.

Purpose To determine if (1) absorbed radiation dose and (2) fluoroscopy time decreased with experience over the first 100 cases of a single surgeon's hip arthroscopy practice. Methods Subjects who underwent hip arthroscopy for symptomatic femoroacetabular impingement and labral injury were eligible for analysis. Inclusion criteria included the first 100 subjects who underwent hip arthroscopy by a single surgeon (December 2013 to December 2014). Subject demographics, procedure details, fluoroscopy absorbed dose (milligray [mGy]), and time were recorded. Subjects were categorized by date of surgery to one of 4 possible groups (25 per group). One-way analysis of variance was used to determine if a significant difference in dose (mGy) or time was present between groups. Simple linear regression analysis was performed to determine the relation between case number and both radiation dose and fluoroscopy time. Results Subjects underwent labral repair (n = 93), cam osteoplasty (n = 90), and pincer acetabuloplasty (n = 65). There was a significant ( P P = .003). Comparing individual groups, group 4 was found to have a significantly lower amount of radiation than group 1 ( P = .002), though it was not significantly lower than that of group 2 ( P = .09) or group 3 ( P = .08). A significant difference in fluoroscopy time was observed between groups, group 1 the highest and group 4 the lowest times ( P = .05). Comparing individual groups, group 4 was found to have a significantly lower fluoroscopy time than group 1 ( P = .039). Correction for weight, height, and body mass index all revealed the same findings: significant ( P Conclusions The absorbed dose of radiation and fluoroscopy time decreased significantly over the first 100 cases of a single surgeon's hip arthroscopy practice learning curve. Level of Evidence Level IV, therapeutic, retrospective, noncomparative case series.
Vanillin derived from lignin liquefaction: a sustainability evaluation

Hydrothermal liquefaction of lignin has been demonstrated as a successful process for the synthesis of value-added phenolic chemical compounds such as vanillin. Vanillin has commercial value as a flavor and fragrance ingredient. This study performs a comparative process simulation and life cycle assessment (LCA) of synthesis of vanillin from depolymerization of lignin, one of the most abundant natural polymers on Earth. Laboratory-scale scenarios for alkali lignin treatment were analyzed using LCA (TRACI 2.1) and green design metrics (process and energy efficiency, waste prevention, renewability, and hazard/pollution avoidance); scenarios included temperature, residence time, lignin loading, gas presence, and catalyst variants. Results show that models which adhere better to green design metrics also result in environmental impact reductions, demonstrating a positive correlation between both sustainability metrics. Vanillin yield increased ~ 7% when reaction time increased from 10 to 20 min; however, the energy used for maintaining operational conditions during process increased between 10 and 50%. Catalyst selection was found to be a deterministic factor affecting results. A catalytic system comprised of a heterogeneous catalyst (nickel oxide) and acidic homogeneous catalyst (supercritical carbon dioxide) was identified as the best option; the catalyst reduced carcinogenic and ecotoxicity impacts by ~ 80 and 90%, respectively when compared to molybdenum oxide. Use of energy and dichloromethane were found to be significant overall environmental impact contributors. Laboratory results can be used and evaluated via LCA to identify sustainable pathways for commercial chemical processing development.
Symposium review: Possibilities in an age of genomics: The future of selection indices.

ABSTRACT Selective breeding has been practiced since domestication, but early breeders commonly selected on appearance (e.g., coat color) rather than performance traits (e.g., milk yield). A breeding index converts information about several traits into a single number used for selection and to predict an animal's own performance. Calculation of selection indices is straightforward when phenotype and pedigree data are available. Prediction of economic values 3 to 10 yr in the future, when the offspring of matings planned using the index will be lactating, is more challenging. The first USDA selection index included only milk and fat yield, whereas the latest version of the lifetime net merit index includes 13 traits and composites (weighted averages of other additional traits). Selection indices are revised to reflect improved knowledge of biology, new sources of data, and changing economic conditions. Single-trait selection often suffers from antagonistic correlations with traits not in the selection objective. Multiple-trait selection avoids those problems at the cost of less-than-maximal progress for individual traits. How many and which traits to include is not simple to determine because traits are not independent. Many countries use indices that reflect the needs of different producers in different environments. Although the emphasis placed on trait groups differs, most indices include yield, fertility, health, and type traits. Addition of milk composition, feed intake, and other traits is possible, but they are more costly to collect and many are not yet directly rewarded in the marketplace, such as with incentives from milk processing plants. As the number of traits grows, custom selection indices can more closely match genotypes to the environments in which they will perform. Traditional selection required recording lots of cows across many farms, but genomic selection favors collecting more detailed information from cooperating farms. A similar strategy may be useful in less developed countries. Recording important new traits on a fraction of cows can quickly benefit the whole population through genomics.
Microbiota-Brain-Gut Axis and Neurodegenerative Diseases

The purposes of this review were as follows: first, to provide an overview of the gut microbiota and its interactions with the gut and the central nervous system (the microbiota-gut-brain axis) in health, second, to review the relevance of this axis to the pathogenesis of neurodegenerative diseases, such as Parkinson’s disease, and, finally, to assess the potential for microbiota-targeted therapies. Work on animal models has established the microbiota-gut-brain axis as a real phenomenon; to date, the evidence for its operation in man has been limited and has been confronted by considerable logistical challenges. Animal and translational models have incriminated a disturbed gut microbiota in a number of CNS disorders, including Parkinson’s disease; data from human studies is scanty. While a theoretical basis can be developed for the use of microbiota-directed therapies in neurodegenerative disorders, support is yet to come from high-quality clinical trials. In theory, a role for the microbiota-gut-brain axis is highly plausible; clinical confirmation is awaited.
Studies of x-ray localization and thickness dependence in atomic-scale elemental mapping by STEM energy-dispersive x-ray spectroscopy using single-frame scanning method.

Abstract The delocalization of x-ray signals limits the spatial resolution in atomic-scale elemental mapping by scanning transmission electron microscopy (STEM) using energy-dispersive x-ray spectroscopy (EDS). In this study, using a SrTiO3 [001] single crystal, we show that the x-ray localization to atomic columns is strongly dependent on crystal thickness, and a thin crystal is critical for improving the spatial resolution in atomic-scale EDS mapping. A single-frame scanning technique is used in this study instead of the multiple-frame technique to avoid peak broadening due to tracking error. The strong thickness dependence is realized by measuring the full width at half maxima (FWHM) as well as the peak-to-valley (P/V) ratio of the EDS profiles for Ti K and Sr K + L, obtained at several crystal thicknesses. A FWHM of about 0.16 nm and a P/V ratio of greater than 7.0 are obtained for Ti K for a crystal thickness of less than 20 nm. With increasing crystal thickness, the FWHM and P/V ratio increases and decreases, respectively, indicating the advantage of using a thin crystal for high-resolution EDS mapping.
Seed Viability and Viability Testing

Although the concept of seed viability is well blown, there may sometimes be disagreement and confusion as to its precise meaning. To most seed technologists and most people in the seed industry, viability means that a seed is capable of germinating and producing a “normal” seedling. Therefore, it is used synonymously with germination capacity. In this sense, a given seed is either viable or nonviable, depending on its ability to germinate and produce a normal seedling; thus, only seed lots representing populations of seeds may exhibit levels of viability.
Sleep Issues in Myopathic Disorders and Muscular Dystrophies

Myopathies and muscular dystrophies are disease inherent to muscles and have the common feature of muscle weakness. Multiple sleep disorders are associated with them. Sleep disordered breathing disorder (SRBD) is the most common sleep disorder in both myopathies and muscular dystrophies. Various different factors contributed to the development of SRBD that include diaphragmatic involvement, coexisting cardiac abnormalities, reduction in lung volumes and capacities, and airway obstruction. Other sleep disorders in these conditions include insomnia, restless legs syndrome, hypersomnolence, and parasomnias.
Metabolic Changes in Burned Patients

The systemic metabolic and circulatory alterations following thermal injury are directed to support the healing wound. The open wound is an immediate priority of the body; structural and functional components of uninjured tissue undergo breakdown to provide energy, substrate, and micronutrients for the healing wound. Glucose is synthesized by the liver and utilized by granulation tissue. Wound blood flow is elevated and the injured surface is heated to enhance repair. These changes in systemic metabolism and directed by alterations in neurohumoral control; the exact mechanisms ultilized by the wound to initiate these changes are presently not known.
General Safety Considerations

Fast reactors exhibit some unique characteristics related to safety in comparison to thermal reactors. At first glance, it might appear that achieving exceptional safety in a fast reactor might be more challenging than in a thermal reactor, considering that sodium-cooled fast reactors (SFR) have a higher core power density, the neutron lifetime is shorter, the effective delayed neutron fraction is less, the core is not arranged in its most reactive configuration, the sodium void effect is usually positive, and sodium interacts rather violently with air or water. On the other hand, the boiling point of sodium is sufficiently high that the reactor can be operated near atmospheric conditions (eliminating the massive pressures required for water-cooled systems), sodium has a very high heat capacity and thermal conductivity, the neuron mean free path is sufficiently long that spatial power shifts are negligible, and xenon poisoning is a non-issue. Furthermore, it has been demonstrated that passive safety features can be more easily incorporated than in the thermal reactor systems.
Chapter V-1 – Fungi: Identification

Publisher Summary This chapter presents the basic skills and information needed to allow nonmycologists to identify the major genera and the most common species of fungal entomopathogens to the generic. Major species of fungal entomopathogens have basic diagnostic characters making them quickly identifiable. The identification of most entomopathogenic fungi necessarily depends on the observation of microscopic characters. Vegetative states of most fungi have little taxonomic value and are not characterized in the key. It is suggested that if no spores are seen in a collection, specimens should be incubated for a further time in room conditions of temperature, humidity and light. Outside the Entomophthorales, the only other significant associations with arthropods are found in the Trichomycetes, a diverse group of fungi that are mainly endocommensal in the guts of insects or crustaceans. Watermolds produce uni- or biflagellate zoospores that are both dispersive and infective units. Flagellate zoospores may be released from two possible sorts of sporangia, those with either thin or thick walls. It would be unusual to detect hosts infected by these fungi during their vegetative states, as these fungi are usually only detected when sporangia have been formed or are releasing zoospores.
Alpha 2-macroglobulin levels in normal human and keratoconus corneas.

Purpose. To compare the levels of a2-macroglobulin, one of the major proteinase inhibitors,in corneas with keratoconu to thos iesn normal human cornea and corneas s with otherdiseases.Methods. An immunoperoxidase technique was used to visualize the presence of a2-macroglob-ulin in the corneas. Western blot analysis was performed and, the level s of this inhibito irnextracts of keratoconus and normal human corneas were subsequently analyze a dod bt y blo tassay.Results. a2-Macroglobulin wa demonstrates d immunohistochemicall in th epitheliume y,stroma, and endotheliu omf al corneal l sections. Compared with normal human controlspecimens, the staining intensit in thy epitheliue omf keratoconus cornea was markedls yreduced. The majorit oy f scarred and other diseased corneas exhibited normal staining inten-sity for a2-macroglobulin Do. blot t assays showed th thae a2-macroglobulit n level in thseepithelial and stromal extract osf keratoconus corneas were lower than those found in normalhuman control counterparts.Conclusion. Keratoconus corneas containe a reduced d leve olf a2-macroglobulin. This resultlends further support t thoe hypothesis that degradation processes may be aberrant in kerato-conus. Invest Ophthalmol Vis 1994 Sci. 35:4008-4014; .l\eratoconus is a progressive disease characterize bdythinning and scarrin ogf th centrae l portio ofn thecornea.
Host Plant Characteristics of Common Bean Lines Selected Using Indirect Measures of N2 Fixation

The genetic variability in common bean (Phaseolus vulgaris L.) germplasm for the amount of atmospheric N fixed by the bean - Rhizobium phaseoli symbiosis has been estimated using direct methods such as growth on N-free medium (Rennie and Kemp, 1981) and 15N isotope dilution (Rennie and Kemp, 1983; Westermann et al., 1981), and indirect methods to analyze plant traits that affect fixation potential. Although the correlations between amounts of N2 fixed and indirect measures such as plant mass, nodule mass and acetylene reduction activity (ARA) vary depending on a great many factors that affect symbiotic expression, indirect methods have been used to select plants with enhanced fixation potential (McFerson, 1983). Although the indirect methods offer relative simplicity, low cost and utility for large numbers of samples, the effectiveness of selection when they are used as selection criteria must be determined by measuring the superiority of selected progenies relative to their parents and other standard genotypes.
PHOTOREACTIVATION OF Escherichia coli IRRADIATED WITH IONIZING RADIATION

ABSTRACT By comparing the results for a uvrA recA and a uvrA uvrB recA phr strain, we conclude that the photoreactivation after ionizing irradiation involves the same enzyme that is responsible for the photoreactivation of UV-induced cyclobutadipyrimidines. A comparison of the photoreactivable sectors in a uvrA recA strain after UV and 137Cs-y-irradiation indicates that 10 krads of γ-radiation produces about 0.07 Jm−2-equivalents of 254 nm-induced photoreactivable damage. After 400 krads, an acid hydrolysate of the isolated DNA revealed the presence of thymine-containing cyclobutadipyrimidines, as evidenced by their chromatographic properties and their photochemical reversibility. Thus, the photoreactivation observed after ionizing radiation in strains that are blocked in excision repair and in postreplication repair is due to the production of trace amounts of cyclobutadipyrimidines.
Approach to cardiopulmonary resuscitation induced consciousness, an emergency medicine perspective.

Abstract Background Cardiopulmonary resuscitation (CPR) remains the key intervention following cardiac arrest because of its ability to continue circulation. Recent focus on high quality compressions during CPR has coincided with more frequent encounters of CPR Induced Consciousness (CPRIC). CPRIC represents a poorly understood patient experience during CPR and defined as signs of consciousness and pain perception during CPR. Methods Articles were selected using PubMed, MEDLINE, CINAHL and Scopus search for the keywords “cardiopulmonary resuscitation”, “consciousness”, “awareness”, “resuscitation”, “cardio-cerebral resuscitation”, “agitation” and “patient experience” yielding 336 articles. Results and their references were assessed for relevance. Articles were filtered by English language and the keyword. Case reports and case series were included. All remaining articles were reviewed and findings were discussed. Results A total of ten articles were selected, which included data on 123 cases. Sample size varied per study from 1 to 112. Studies included cases of out-of-hospital cardiac arrest and in hospital cardiac arrest. Compressions were manually provided in most cases. Patient total recall was reported in 40% of cases. Use of sedation was reported in 40% of cases. Conclusions There is need for continued research to better describe, explain and manage the phenomena of CPRIC. From the articles reviewed here, it is clear that further investigation has the potential to properly elucidate the patient experience including lasting psychological effects of CPRIC. Importantly, there is need for more than recognition of CPRIC from national authorities. Future research efforts should focus on establishing guidelines for the use of sedation and physical restraints, as well as the potential impact of treating CPRIC on survival.
Contrast-enhanced ultrasound to ultrasound fusion during microwave ablation: feasibility study in a perfused porcine liver model

To obtain a complete response with thermal ablation, the margin and entire tumor volume must be treated. Real-time ultrasound visualization is limited during ablation due to gas production. This study assesses the feasibility of fusing volumetric contrast-enhanced ultrasound (CEUS), obtained immediately prior to microwave ablation, with real-time CEUS during and following ablation in a machine-perfused porcine liver. Ten, 3–4 cm microwave ablations were performed in five explanted perfused livers. Prior to ablation, microbubbles were injected into the vasculature while an ultrasound sweep across the liver captured a volumetric image during maximum enhancement. This volumetric image was then fused to overlay the real-time ultrasound imaging. Since the perfused livers did not have tumors, a spherical marker circumscribing a target volume was placed on the images. Approximatively, 75% of the total intended circumscribed spherical volume was ablated. Following ablation, a second bolus injection of ultrasound contrast was administered demonstrating continued enhancement of the intentionally non-ablated 25%. A second volumetric image of the post-ablation CEUS was then fused to overlay the real-time ultrasound images for guidance during ablation of the remaining enhancing volume. Technical success was achieved in 100% of the cases. The pre- and then the post-ablation CEUS volume was fused with real-time imaging during antenna placement for initial and subsequent ablation. CEUS–CEUS fusion during thermal ablation is feasible and greatly improves the workflow. The approach may augment the use of dynamic CEUS for guidance, improving antenna placement, and aiding in the identification and ablation of initial and residual enhancing tissue.
The T99K variant of glycosylasparaginase shows a new structural mechanism of the genetic disease aspartylglucosaminuria.

Aspartylglucosaminuria (AGU) is an inherited disease caused by mutations in a lysosomal amidase called aspartylglucosaminidase (AGA) or glycosylasparaginase (GA). This disorder results in an accumulation of glycoasparagines in the lysosomes of virtually all cell types, with severe clinical symptoms affecting the central nervous system, skeletal abnormalities, and connective tissue lesions. GA is synthesized as a single-chain precursor that requires an intramolecular autoprocessing to form a mature amidase. Previously, we showed that a Canadian AGU mutation disrupts this obligatory intramolecular autoprocessing with the enzyme trapped as an inactive precursor. Here, we report biochemical and structural characterization of a model enzyme corresponding to a new American AGU allele, the T99K variant. Unlike other variants with known 3D structures, this T99K model enzyme still has autoprocessing capacity to generate a mature form. However, its amidase activity to digest glycoasparagines remains low, consistent with its association with AGU. We have determined a 1.5-A-resolution structure of this new AGU model enzyme and built an enzyme-substrate complex to provide a structural basis to analyze the negative effects of the T99K point mutation on KM and kcat of the amidase. It appears that a "molecular clamp" capable of fixing local disorders at the dimer interface might be able to rescue the deficiency of this new AGU variant.
Decomposition of complete graphs into connected unicyclic graphs with eight edges and pentagon

A G -decomposition of the complete graph K n is a family of pairwise edge disjoint subgraphs of K n , all isomorphic to G , such that every edge of K n belongs to exactly one copy of G . Using standard decomposition techniques based on ρ -labelings, introduced by Rosa in 1967, and their modifications we show that each of the ten non-isomorphic connected unicyclic graphs with eight edges containing the pentagon decomposes the complete graph K n whenever the necessary conditions are satisfied.
Anesthesia for Thoracic Surgery in Children

Thoracic surgery is performed in children for different reasons to adults—congenital malformations and cysts are more common than tumors. The physiology of one-lung ventilation in children is similar to adults, and children tolerate one lung ventilation well because they do not usually have lung disease other than the condition needing surgery. Although surgical retraction is tolerated well by a child’s lung compared to an adult lung, surgical exposure is better with single-lung ventilation. There are technical challenges to isolating a child’s lung.
Brief Relaxation Training for the Prevention of Stress-Related Difficulties: A Pilot Study:

The present study piloted a brief, single-session behavioral intervention to prevent stress-related illnesses in college students. Participants were recruited at a large public university (N = 213)...
Time-Encoded Gamma-Ray Imaging Using a 3-D Position-Sensitive CdZnTe Detector Array

The gamma-ray response of thick pixelated CdZnTe detectors varies spatially but is relatively constant as a function of time. Detector irregularities arise from flaws in the material, electrode fabrication, and gaps between the detectors in an array. These nonuniformities generate artifacts in coded aperture images that can obscure a source of interest. This article presents the theory, design, and demonstration of a 3-D CdZnTe-based time-encoded imager. Experimental results show the gamma-ray images of point-like and extended 57Co and HEU-metal sources formed using a spatially nonuniform 3-D CdZnTe detector array and moving coded aperture mask. Image signal-to-noise ratio (SNR) for a point source was within 10% of its statistical limit at 250k counts.
Response Inhibition, Peer Preference and Victimization, and Self-Harm: Longitudinal Associations in Young Adult Women with and without ADHD

Self-harm (suicidal ideation and attempts; non-suicidal self-injuries behavior) peaks in adolescence and early-adulthood, with rates higher for women than men. Young women with childhood psychiatric diagnoses appear to be at particular risk, yet more remains to be learned about the key predictors or mediators of self-harm outcomes. Our aims were to examine, with respect to self-harm-related outcomes in early adulthood, the predictive validity of childhood response inhibition, a cardinal trait of attention-deficit hyperactivity disorder (ADHD), as well as the potential mediating effects of social preference and peer victimization, ascertained in early adolescence. Participants were an ethnically and socioeconomically diverse sample of 228 girls with and without ADHD, an enriched sample for deficits in response inhibition. Childhood response inhibition (RI) predicted young-adult suicide ideation (SI), suicide attempts (SA), and non-suicidal self-injury (NSSI), over and above full-scale IQ, mother's education, household income, and age. Importantly, teacher-rated social preference in adolescence was a partial mediator of the RI-SI/SA linkages; self-reported peer victimization in adolescence emerged as a significant partial mediator of the RI-NSSI linkage. We discuss implications for conceptual models of self-harm and for needed clinical services designed to detect and reduce self-harm.
12.17 – Intrauterine Infection

Infections during pregnancy, if left untreated, can ultimately lead to the death of the mother, fetus, or neonate and other serious sequelae such as meningitis. It is estimated that 50% of preterm births are a consequence of infection. We review some common outcomes of infections during pregnancy, such as meningitis, hydrocephaly, low birth weight, developmental delays, and sepsis, along with the known mechanisms by which these occur. Following these outcomes, we discuss three examples of pathogens that adversely affect pregnancy – Listeria monocytogenes, Plasmodium, and cytomegalovirus – and the known mechanisms for their pathogenicity to the fetus. The response of the maternal and/or neonatal immune system will help determine the severity of infection. Inflammatory responses to a pathogen can increase the expression of cytokines, other molecules, and their receptors and initiate cascades of events, leading to cytotoxicity or preterm labor. Some pathogens can evade the immune system with specialized mechanisms, leading to systemic infection and/or adverse effects on the maternal and neonatal central nervous systems. These infections can be bacterial, viral, parasitic, or fungal. Many of these infections have common outcomes, but it is yet to be determined whether these share common mechanisms of action. While there is a wealth of knowledge about some of these infections, there is still much to be learned. A better understanding of the mechanisms by which these pathogens cause infections and lead to adverse outcomes is needed to develop preventions, treatments, and/or therapies to reduce the incidence of fetal morbidity and mortality.
Homologous Recombination Repair Defect May Predict Treatment Response to Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumors

Lutetium-177-dotatate (177 Lu-dotatate), a form of peptide receptor radionuclide therapy, was approved by the U.S. Food and Drug Administration for the treatment of advanced somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (NETs) in 2018 based on the promising results of the NETTER-1 trial for grade 1-2 midgut NETs. Here, we present a patient with a grade 3 pancreatic neuroendocrine tumor and BRCA1 germline mutation who had a significant response to 177 Lu-dotatate.
Route of 41BB/41BBL Costimulation Determines Effector Function of B7-H3-CAR.CD28ζ T Cells.

B7-H3 is actively being explored as an immunotherapy target for pediatric patients with solid tumors using monoclonal antibodies or T cells expressing chimeric antigen receptors (CARs). B7-H3-CARs containing a 41BB costimulatory domain are currently favored by several groups based on preclinical studies. In this study, we initially performed a detailed analysis of T cells expressing B7-H3-CARs with different hinge/transmembrane (CD8α versus CD28) and CD28 or 41BB costimulatory domains (CD8α/CD28, CD8α/41BB, CD28/CD28, CD28/41BB). Only subtle differences in effector function were observed between CAR T cell populations in vitro. However, CD8α/CD28-CAR T cells consistently outperformed other CAR T cell populations in three animal models, resulting in a significant survival advantage. We next explored whether adding 41BB signaling to CD8α/CD28-CAR T cells would further enhance effector function. Surprisingly, incorporating 41BB signaling into the CAR endodomain had detrimental effects, while expressing 41BBL on the surface of CD8α/CD28-CAR T cells enhanced their ability to kill tumor cells in repeat stimulation assays. Furthermore, 41BBL expression enhanced CD8α/CD28-CAR T cell expansion in vivo and improved antitumor activity in one of four evaluated models. Thus, our study highlights the intricate interplay between CAR hinge/transmembrane and costimulatory domains. Based on our study, we selected CD8α/CD28-CAR T cells expressing 41BBL for early phase clinical testing.
Pseudophakic glaucoma and angle closure in a patient with an anterior chamber intraocular lens.

Abstract Purpose To report use of ultrasound biomicroscopy (UBM) and anterior segment ocular coherence tomography (AS-OCT) in a case of pseudophakic glaucoma in a patient with an anterior chamber intraocular lens. Observations UBM and AS-OCT were critical in determining a non-drug related etiology of angle closure. Images indicated anterior obstruction of the pupil secondary to anterior chamber intraocular lens, but also posterior obstruction of the pupil secondary to the anterior hyaloid face. Conclusions When evaluating a patient with suspected angle closure, it is important to perform a full ophthalmologic examination, including gonioscopy, as well as a thorough review of past medical history and medications so as not to miss systemic-related etiologies. Imaging with B-scan, UBM, and, more recently in the last decade, AS-OCT is a key component of evaluation of a patient in angle closure, especially one with a complex medical and ocular history.
Measuring Family Resilience: Evaluating the Walsh Family Resilience Questionnaire:

With a continued focus by practitioners, such as marriage and family counselors, behavioral/social scientists, and policy makers, on promoting resilience among families, it is important to ensure t...
Every-other-day clutch-initiation synchrony as an adaptive response to egg cannibalism in Glaucous-winged Gulls (Larus glaucescens)

Sea surface temperatures (SST) in the Pacific Northwest of North America rose 1 °C during the last half of the twentieth century. Cannibalism, a behavior observed in diverse taxa, is often associated with low food supplies, which for marine animals can be precipitated by high SSTs. In an 8 year study, we found that in years of higher sea surface temperatures, Glaucous-winged Gulls (Larus glaucescens) breeding in a colony in Washington State, Salish Sea, USA, tended to exhibit higher rates of egg cannibalism by males, higher levels of every-other-day clutch-initiation synchrony by females, and longer egg-laying seasons than in years of lower SST. Clutch-initiation synchrony increased the odds that an egg survived cannibalism and may serve as an adaptive response to egg cannibalism. Short-term climate and resource fluctuations associated with El Nino Southern Oscillation (ENSO) events may select for behavioral plasticity in marine organisms, allowing long-lived individuals such as marine birds to switch between alternative life history tactics. The implications for long-term SST warming, however, remain unknown.
Mineralocorticoid and Estrogen Receptors in Endothelial Cells Coordinately Regulate Microvascular Function in Obese Female Mice.

Obesity impairs endothelial-mediated vasodilation, the earliest step in vascular disease and a contributor to hypertension. We previously demonstrated that endothelial cell MR (mineralocorticoid receptor) deletion prevents obesity-induced microvascular dysfunction in females by increasing nitric oxide (NO)-mediated vasodilation. ERα (Estrogen receptor α) can oppose MR function, therefore, we hypothesized that ERα mediates the benefits of endothelial MR deficiency. Females lacking endothelial MR or wild-type littermates were fed control or high-fat diet for 20 weeks to cause obesity. MR deletion improved mesenteric artery endothelial-dependent vasodilation in obese females, and ex vivo ERα inhibition negated this protective effect. Endothelial MR deletion resulted in significantly more ERα mRNA and protein. In vitro, estrogen increased endothelial NO synthase phosphorylation, and this was inhibited by aldosterone and dependent on MR. Both proteins coimmunoprecipitated with striatin and a mimetic peptide that disrupts ERα-striatin binding also decreased MR-striatin interaction. Finally, removing endothelial MR in obese females restored endothelial function by increasing the NO component of vasodilation. Combined deletion of endothelial ERα negated the benefit of endothelial MR deletion. These results indicate that endothelial ERα prevents the detrimental effects of MR in obesity by increasing NO to rescue vasodilation in females. MR and ERα may compete for striatin binding within endothelial cells to regulate NO. These data identify a novel mechanism that promotes MR antagonism to prevent obesity-induced microvascular dysfunction in females.
An Overview of Perinatal Mood and Anxiety Disorders: Epidemiology and Etiology

This chapter provides a way of thinking about perinatal mood and anxiety disorders (PMADs) broadly: their definition and expression, as well as their similarities to and differences from depression and anxiety disorders outside of the perinatal period. We review the epidemiology and then describe our current understanding of the underlying pathogenesis of PMADs. Perinatal depression (PND), in particular, comprises a group of affective disorders that may include co-morbid anxiety symptoms. PND is currently defined with variable onset in relation to time of childbirth and is the most robustly studied PMAD to date. Proximity to pregnancy/delivery suggests a possible pathogenic role of reproductive steroids, especially for onset of symptoms that are triggered by childbirth. The identification of the biological mechanisms (i.e., network dysregulation and genetic contributions) underlying the triggering and susceptibility to depression in women with PND will, ideally, enable efforts directed toward prevention and early treatment of these devastating disorders.