cssi/SciSciGPT-SciSciNet huggingface dataset:
Clock Genes Explain a Large Proportion of Phenotypic Variance in Systolic Blood Pressure and This Control Is Not Modified by Environmental Temperature.

Background Diurnal variation in blood pressure (BP) is regulated, in part, by an endogenous circadian clock; however, few human studies have identified associations between clock genes and BP. Accounting for environmental temperature may be necessary to correct for seasonal bias. Methods We examined whether environmental temperature on the day of participants' assessment was associated with BP, using adjusted linear regression models in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) (n = 819) and the Boston Puerto Rican Health Study (BPRHS) (n = 1,248) cohorts. We estimated phenotypic variance in BP by 18 clock genes and examined individual single-nucleotide polymorphism (SNP) associations with BP using an additive genetic model, with further consideration of environmental temperature. Results In GOLDN, each additional 1 °C increase in environmental temperature was associated with 0.18 mm Hg lower systolic BP [SBP; β ± SE = -0.18 ± 0.05 mm Hg; P = 0.0001] and 0.10mm Hg lower diastolic BP [DBP; -0.10 ± 0.03 mm Hg; P = 0.001]. Similar results were seen in the BPRHS for SBP only. Clock genes explained a statistically significant proportion of the variance in SBP [V G/V P ± SE = 0.071 ± 0.03; P = 0.001] in GOLDN, but not in the BPRHS, and we did not observe associations between individual SNPs and BP. Environmental temperature did not influence the identified genetic associations. Conclusions We identified clock genes that explained a statistically significant proportion of the phenotypic variance in SBP, supporting the importance of the circadian pathway underlying cardiac physiology. Although temperature was associated with BP, it did not affect results with genetic markers in either study. Therefore, it does not appear that temperature measures are necessary for interpreting associations between clock genes and BP. Clinical trial registration Trials related to this study were registered at clinicaltrials.gov as NCT00083369 (Genetic and Environmental Determinants of Triglycerides) and NCT01231958 (Boston Puerto Rican Health Study).
Colonel Blotto with Imperfect Targeting

Colonel Blotto games have been widely applied in a variety of contests where the players allocate resources across a number of battlefields and the winner in each battlefield is the one with more resources there. One drawback of this standard model is the assumption that players can perfectly target their efforts toward different battlefields. In many situations, players can only imperfectly target different battlefields, with an allocation affecting more than one battlefield. We develop an extension of Colonel Blotto that incorporates this type of interrelation. The equilibria here generally utilize mixed strategies that tend to be asymmetric across battlefields. That is, at least one player will have zero probability of dividing resources equally across battlefields, even if the characteristics of the battlefields are similar. We use advertising data from the 2002 races for governor and US senate to test the application of the Blotto model to political contests. Although the Colonel Blotto model has been used extensively to model political campaigns, we find that candidates' advertising allocations across markets are far too symmetric to fit the model.
The Packing Structure of Dry Pressed Si3N4 Powder

Si3N4 powders, of which particle sizes were in the order of micron meter, were compacted at high pressure, and the porosity and representative pore size were examined. It was found that particle size distribution affected the porosity of the packed body although the effect of aggromeration was important. On the other hand, the representative pore sizes of the packed body were related to the specific surface area of the powder.
Vitamin E and the risk of childhood asthma

ABSTRACTIntroduction: Asthma, a heterogeneous disease with multiple phenotypes, remains a significant health problem. Present treatments are not curative and prevention should be our ultimate goal. Vitamin E supplementation presents a potential easy and cheap preventive therapy but the results of studies are confusing and sometimes contradictory. Clarification is needed.Areas covered: Animal studies and research in pregnant women suggest enhanced lifetime resistance to asthma with appropriate fetal exposure to vitamin E. Vitamin E’s preventive role is complex and includes functional variations of the different isoforms.Expert commentary: We review the most recent literature on the role of vitamin E isoforms on: lung inflammation, immune development, animal and clinical studies during pregnancy, and the potential influence of vitamin E isoforms on asthma development in offspring. We point out where data are seemingly contradictory, explain why this is so, and comment on where further clarifying research is...
Solid-State Optical Refrigeration

Abstract The field of optical refrigeration of lanthanide-doped solids emerged in 1994 with the first laser cooling of an Yb 3 + -doped fluoride glass, and it has recently advanced into the cryogenic regime with the demonstration of cooling Yb 3 + -doped fluoride crystals to sub-100 K temperatures. Over the past 20 years, the fundamental understanding, experimental techniques, material science, and device engineering have been developed to a stage where solid-state optical refrigerators can now be integrated into applications such as cooled infrared sensors and gamma-ray detectors, ultrastable optical cavities for metrology, and cryogenic electron microscopy. Cooling of solids by light is achieved by laser-induced anti-Stokes fluorescence that involves the transfer of vibrational energy (heat) from the solid to the radiation field in a cycle that resembles a laser running in reverse. Since optical refrigerators are solid-state devices with no moving parts, they are inherently vibration free and reliable. This chapter gives a comprehensive review of the history of solid-state optical refrigeration, the underlying physical principles and resulting material requirements, the key experimental techniques, the specific material systems in which laser cooling has been observed, and the optical and thermal device engineering aspects.
Turning Boys Into Men: The Incentive-Based System in Urban Meyer’s Plan to Win

This paper examines the incentive-based system of Urban Meyer, head football coach at The Ohio State University. Personal discussions with this coach and members of his football staff took place following a review of his methods as described in biographical and media reports, and were compared with the approaches used by other successful coaches as documented in coaching research. Meyer has created clear guidelines and expectations for behaviors that players must consistently display to be recognized as successful team members and leaders. He also has developed a comprehensive set of processes to promote the development and adherence to those desired behaviors. This examination of Meyer’s approach focuses on the connection between the three levels (Blue, Red and Gold) of his incentive-based system and the three phases of a rite of passage (separation, transformation, and reincorporation) associated with them. The system rewards more grownup behaviors with greater status and privileges befitting the increa...
An Atypical Presentation of Sporadic Jejunal Burkitt’s Lymphoma

Burkitt’s lymphoma is a very aggressive type of B-cell NHL with replication approaching 100%. Primary gastrointestinal lymphoma is rare. In our case, a 24-year-old male initially presented with symptomatic anemia. He was initially evaluated with colonoscopy and EGD, both of which were unremarkable. A capsule endoscopy was then performed to further evaluate his significant anemia which revealed friable inflamed ulcerated mass in the jejunum. A push enteroscopy was then performed to obtain tissue from the jejunal mass. Biopsy results and immunohistochemical stains were consistent with Burkitt’s lymphoma. PET/CT scan revealed only jejunal involvement. Treatment consisted of bowel resection prior to chemotherapy due to concern for perforation with chemotherapy. Patient achieved complete remission after the treatment.
Focal Therapy for Prostate Cancer: A Guide for Patients

In an effort to achieve cancer control and yet minimize damage to these structures, the urological community has been exploring the idea of treating just a specific portion of the prostate where the cancer is located and actively monitoring the untreated portion of the gland. This approach is known as “focal therapy.” We believe that the best outcomes are achieved when an appropriate treatment is matched to a suitable patient based on individual circumstances and needs. We wrote this chapter as a resource to help patients better understand the concept of focal therapy, its benefits, possible side effects, and risks so as to aid them in making an individualized treatment decision for their cancer.
Osteochondral Lesions of the Talus: Osteochondral Allograft Transplantation

Talar osteochondral lesions (OCLs) are common causes of ankle pain. When symptomatic, they may cause significant pain and affect function and quality of life. OCLs may be due to acute trauma or atraumatic, repetitive overuse. Lateral lesions are almost always traumatic, secondary to axial loading of the ankle in inversion and dorsiflexion and relative talar external rotation. Medial lesions are frequently caused by loading the ankle with inversion and plantarflexion. Medial lesions are more common than lateral. The extensive coverage of the talar surface area with articular cartilage limits talar vascular supply and creates multiple watershed areas compromising healing potential. As such, early diagnosis and management of talar OCLs are critical to prevent functional impairment and chronic ankle pain. Asymptomatic or incidentally identified talar lesions may be closely observed. Nonoperative management of symptomatic lesions includes rest, ice, oral nonsteroidal anti-inflammatories, immobilization, and intra-articular injections. In patients who fail nonoperative treatment or have an acute displaced osteochondral fragment, surgery is the treatment of choice. Arthroscopic and open surgical approaches are options. Lesion debridement, loose body removal, marrow stimulation techniques (microfracture, drilling, and abrasion), osteochondral autograft, and autologous chondrocyte implantation may result in excellent outcomes in smaller lesions. For larger defects, osteochondral allograft transplantation is the gold standard surgical treatment.
Analyzing bean extracts using time-dependent SDS trapping to quantify the kinetic stability of phaseolin proteins

Abstract In common beans and lima bean, the storage protein phaseolin is difficult to degrade and SDS-resistant, a sign of kinetic stability. Kinetically stable proteins (KSPs) are characterized by having a high-energy barrier between the native and denatured states that results in very slow unfolding. Such proteins are resistant to proteolytic degradation and detergents, such as SDS. Here the method SDS-Trapping of Proteins (S-TraP) is applied directly on bean extracts to quantify the kinetic stability of phaseolin in lima bean and several common beans, including black bean, navy bean, and small red bean. The bean extracts were incubated in SDS at various temperatures (60–75 °C) for different time periods, followed by SDS-PAGE analysis at room temperature, and subsequent band quantification to determine the kinetics of phaseolin unfolding. Eyring plot analysis showed that the phaseolin from each bean has high kinetic stability, with an SDS-trapping (i.e. unfolding) half-life ranging from about 20–100 years at 24 °C and 2–7 years at 37 °C. The remarkably high kinetic stability of these phaseolin proteins is consistent with the low digestibility of common beans and lima bean, as well as their relatively high germination temperatures. From a practical perspective, this work exemplifies that S-TraP is a useful and cost-effective method for quantifying the kinetic stability of proteins in biological extracts or lysates. Depending on the protein to be studied and its abundance, S-TraP may be performed directly on the extract without need for protein purification.
The Basis for Active Transport at the Blood-Brain Barrier

Certain low molecular weight compounds have been shown to enter the brain by specific carrier-mediated transport systems in the endothelial cell membranes (1–4). At least eight such carriers capable of moving solutes from blood into brain have been described (4). Most of the blood-brain barrier (BBB) transport systems that have been described are not able to move solutes against concentration gradients, but instead, facilitate the equilibration of brain and blood concentrations for their particular substrates. Although the BBB acts as an impermeable wall for some solutes and a passive sieve for others, it is generally agreed that an important function is active regulation of the internal milieu of the central nervous system (CNS) (3,5,6). Several reports have suggested that the BBB can mediate solute efflux from the brain against a concentration gradient (7–13), but these studies utilized intact animals and, consequently, their interpretation is made difficult by the presence of neurons, glia and choroid plexus.
Phospholipase A2 Activity Exhibited by a Bacterial Virulence Protein That Enters and Operates Within a Variety of Host Cells

Phospholipase A2 (PLA2) is a pivotal enzyme in human health and disease. With approximately 30 isoforms exhibiting PLA2 activity expressed within or secreted by a variety of cell and tissue types, the functional significance of this enzyme is multifaceted. Mammalian PLA2s are known contributors during host–pathogen interactions during infectious disease processes. Interestingly, several bacterial pathogens themselves express PLA2 enzymes that exhibit a patatin domain and have sequence similarity to cytosolic and calcium-independent PLA2s. The most prominent example termed ExoU is expressed by Pseudomonas aeruginosa and operates exclusively in eukaryotic host cells. ExoU serves as a potent cytotoxin expressed by P. aeruginosa clinical isolates most associated with severe acute pneumonia and microbial keratitis. The PLA2 activity of ExoU is responsible for this potent toxicity and is also capable of mediating host production of eicosanoids and stimulating cytokine and chemokine production in a variety of cell types. Efforts are underway to better understand and potentially neutralize these potent microbial PLA2 virulence factors.
An evolutionary approach to complex hierarchical societies.

Abstract Evolutionary anthropologists have been remarkably successful in developing ‘dual inheritance’ theories of gene/culture coevolution that analyze the interaction of each of these factors without reducing either one to the other’s terms. However, efforts to extend this type of analysis to encompass complex, class-divided hierarchical societies, grounded in formal laws, political institutions, and trajectories of sustained economic development have scarcely begun. This article proposes a provisional framework for advancing such a multi-level co-evolutionary analysis that can encompass multiple forms of social organization from simple hunting/foraging groups to agrarian states and empires, up through the global capitalist system of our own day. The article formulates tools to conceptualize some of the ways in which ‘selection’ and ‘adaptation’ operate at every level to bring genes, cultures, states, and market exchange into provisional alignment with one another. It considers some of the ways in which modes of production’, ‘modes of coercion’ and ‘modes of persuasion’ interact complexly, at different societal levels.
Geometrization in Representation Theory

The common theme of the articles “γ-function of Representations and Lifting” and “Geometric and Unipotent Crystals” is the geometrization of familiar objects. In the first article we interpret some special functions appearing in the theory of representations as materializations of geometric objects which we call algebraic-geometric distributions in the second one we interpret elements of the crystalline basis which parametrize the special basis of finite-dimensional representations of reductive groups as materializations of geometric crystals. Moreover these two topics are very much interwoven since the theory of geometric crystals is necessary for the construction of our algebraic-geometric distributions.
A Wearable Fiberless Optical Sensor for Continuous Monitoring of Cerebral Blood Flow in Mice

Continuous and longitudinal monitoring of cerebral blood flow (CBF) in animal models provides information for studying the mechanisms and interventions of various cerebral diseases. Since anesthesia may affect brain hemodynamics, researchers have been seeking wearable devices for use in conscious animals. We present a wearable diffuse speckle contrast flowmeter (DSCF) probe for monitoring CBF variations in mice. The DSCF probe consists of a small low-power near-infrared laser diode as a point source and an ultrasmall low-power CMOS camera as a two-dimensional detector array, which can be affixed on a mouse head. The movement of red blood cells in brain cortex (i.e., CBF) produces spatial fluctuations of laser speckles, which are captured by the camera. The DSCF system was calibrated using tissue phantoms and validated in a human forearm and mouse brains for continuous monitoring of blood flow increases and decreases against the established technologies. Significant correlations were observed among these measurements ( $\text{R}^{2}\geq \,{\text{0.80}}$ , $\text{p} ). This small fiberless probe has the potential to be worn by a freely moving conscious mouse. Moreover, the flexible source–detector configuration allows for varied probing depths up to ${\sim\text{8 mm}}$ , which is sufficient for transcranially detecting CBF in the cortices of rodents and newborn infants.
Bioelectrical Impedance Analysis: A Review of Principles and Applications

Whole-body bioelectrical impedance analysis (BIA) is widely used by researchers and clinicians as a noninvasive and safe method to estimate body composition and body water volume in children and adults. Development of new approaches, such as segmental and multifrequency analyzers, should greatly expand the utility of this electrical technique. This article reviews the principles, underlying assumptions, clinical applications and future directions of the BIA method.
A combined hiPSC-derived endothelial cell and in vitro microfluidic platform for assessing biomaterial-based angiogenesis.

Abstract Human induced pluripotent stem cell (hiPSC) derived angiogenesis models present a unique opportunity for patient-specific platforms to study the complex process of angiogenesis and the endothelial cell response to biomaterial and biophysical changes in a defined microenvironment . We present a refined method for differentiating hiPSCs into a CD31 + endothelial cell population (hiPSC-ECs) using a single basal medium from pluripotency to the final stage of differentiation. This protocol produces endothelial cells that are functionally competent in assays following purification . Subsequently, an in vitro angiogenesis model was developed by encapsulating the hiPSC-ECs into a tunable, growth factor sequestering hyaluronic acid (HyA) matrix where they formed stable, capillary-like networks that responded to environmental stimuli. Perfusion of the networks was demonstrated using fluorescent beads in a microfluidic device designed to study angiogenesis. The combination of hiPSC-ECs, bioinspired hydrogel, and the microfluidic platform creates a unique testbed for rapidly assessing the performance of angiogenic biomaterials.
Abstract P3-14-10: Intralesional steroid injection: A novel method to treat the symptoms of idiopathic granulomatous mastitis

Background: Idiopathic granulomatous mastitis (IGM) is a chronic, inflammatory breast condition of benign nature that can clinically mimic breast cancer. Patients frequently present with a large, painful breast mass with associated inflammatory changes of the skin, and possible ulceration or fistula of the breast. Attempted methods for symptomatic relief include surgical excision and medical therapies including oral corticosteroids. Due to the success of treating dermatologic conditions with intralesional steroid injections, it was hypothesized that injecting the subdermal lesions of IGM may benefit patients with this disease. The use of intralesional steroid injections for the treatment of IGM has not been previously described in the literature. Methods: Retrospective chart review was performed on a series of four patients with IGM who received intralesional steroid injections between August 2017 and April 2018. Patients were selected for treatment with injections based on their subjective report of painful breast lesions, lesion characteristics including size and depth, and the patient9s desire to stop oral steroid therapy due to side effects despite active or residual disease. Data were collected on demographics, initial physical examination findings, prior and current treatments, characteristics of disease, details of injections performed, objective and subjective response to treatment, and recurrence. Results: All patients presented with breast pain and either a mass, swelling, or hardness of the breast. Each patient received between one and three injection treatments, with one to four lesions treated in each session. Patients demonstrated improvement in subjective and objective symptoms after 87.5% of injection sessions (7 out of 8) by the subsequent follow-up visit (21-34 days). During the study period, three patients experienced resolution of at least one breast lesion within about 2 months (31-139 days, mean 68 days) without recurrence. One patient had four breast lesions that completely resolved (35-217 days, mean 88 days), but three of them recurred (63-217 days, mean 149 days). Conclusion: In a small group of patients with idiopathic granulomatous mastitis, intralesional steroid injections were associated with an improvement in both subjective symptomatic relief and objective breast lesion characteristics in most cases. This treatment was associated with a good rate of lesion resolution and a low short-term recurrence rate. Citation Format: Manst DJ, Ganschow PS, Marcus EA, Holden C, Datta S. Intralesional steroid injection: A novel method to treat the symptoms of idiopathic granulomatous mastitis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-14-10.
Late Pleistocene range expansion of North American topminnows accompanied by admixture and introgression

AIM: We used genome‐scale sampling to assess the phylogeography of a group of topminnows in the Fundulus notatus species complex. Two of the species have undergone extensive range expansions resulting in broadly overlapping distributions, and sympatry within drainages has provided opportunities for hybridization and introgression. We assessed the timing and pattern of range expansion in the context of late Pleistocene–Holocene drainage events and evaluated the evidence for introgressive hybridization between species. LOCATION: Central and southern United States including drainages of the Gulf of Mexico Coastal Plain and portions of the Mississippi River drainage in and around the Central Highlands. TAXON: Topminnows, Genus Fundulus, subgenus Zygonectes—Fundulus notatus, Fundulus olivaceus, Fundulus euryzonus. METHODS: We sampled members of the F. notatus species complex throughout their respective ranges, including numerous drainage systems where species co‐occur. We collected genome‐wide single nucleotide polymorphisms (SNPs) using the genotype‐by‐sequencing (GBS) method and subjected data to population genetic analyses to infer the population histories of both species, including explicit tests for admixture and introgression. The methods employed included STRUCTURE, principal coordinates analysis, TreeMix and approximate Bayesian computation. RESULTS: Genetic data are presented for 749 individuals sampled from 14 F. notatus, 20 F. olivaceus and 2 F. euryzonus populations. Members of the species complex differed in phylogeographic structure, with F. notatus exhibiting geographic clusters corresponding to Pleistocene coastal drainages and F. olivaceus comparatively lacking in phylogeographic structure. Evidence for interspecific introgression varied by drainage. MAIN CONCLUSIONS: Populations of F. notatus and F. olivaceus exhibited contrasting patterns of lineage diversity among coastal drainages, indicating interspecific differences in their Pleistocene southern refugia. Phylogeographic patterns in both species indicated that range expansions into the northern limits of contemporary distributions coincided with and continued subsequent to the Last Glacial Maximum. There was evidence of introgression between species in some, but not all drainages where the species co‐occur, in a pattern that is correlated with previous estimates of hybridization rates.
Rebuilding Legitimacy: Hwang Chun Pi and His Landscape Paintings in Postwar Taiwan

Born in Guangzhou in 1898, Hwang Chun Pi (Huang Junbi, 1898–1991) was best known for his landscape paintings. Although Hwang was considered a traditionalist, he encouraged the modernization of Chin...
Aldosterone and glucocorticoid receptor-specific agonists regulate ion transport in rat proximal colon.

Dietary sodium depletion increases electroneutral Na-Cl absorption and potassium secretion in the proximal colon of the rat. Although sodium depletion results in secondary hyperaldosteronism, the s...
Hepatocyte gene expression and DNA methylation as ancestry-dependent mechanisms in African Americans.

African Americans (AAs) are an admixed population with widely varying proportion of West African ancestry (WAA). Here we report the correlation of WAA to gene expression and DNA methylation in AA-derived hepatocytes, a cell type important in disease and drug response. We perform mediation analysis to test whether methylation is a mediator of the effect of ancestry on expression. GTEx samples and a second cohort are used as validation. One hundred and thirty-one genes are associated with WAA (FDR < 0.10), 28 of which replicate and represent 220 GWAS phenotypes. Among PharmGKB pharmacogenes, VDR, PTGIS, ALDH1A1, CYP2C19, and P2RY1 nominally associate with WAA (p < 0.05). We find 1037 WAA-associated, differentially methylated regions (FDR < 0.05), with hypomethylated genes enriched in drug-response pathways. In conclusion, WAA contributes to variability in hepatocyte expression and DNA methylation with identified genes previously implicated for diseases disproportionately affecting AAs, including cardiovascular (PTGIS, PLAT) and renal (APOL1) disease, and drug response (CYP2C19).
The tipping point: could increasing the subminimum wage reduce poverty-related antenatal stressors in U.S. women?

Abstract Purpose Tipped workers, primarily women of reproductive-age, can be paid a “subminimum wage” 71% lower than the federal minimum wage, contributing to economic hardship. Poverty-related antenatal stress has deleterious health effects for women and their children. The purpose of this study was to investigate the effects of increasing the state-level subminimum wage (currently $2.13 per hour) on poverty-related antenatal stress for women in the United States. Methods Utilizing a difference-in-differences approach comparing state wage policies over time, we estimated the impact of increases in the subminimum wage on poverty-related antenatal stress using data from 35 states participating in the Pregnancy Risk Assessment Monitoring System between 2004 and 2014, linked to state-level wage laws, census, and antipoverty policy data. Results The effect of increasing the subminimum wage on poverty-related stress differed by year and sociodemographics. Wage increases in 2014 were associated with the largest decreases in stress for unmarried women of color with less than a college degree, a population that we estimated would have experienced a 19.7% reduction in stress from 2004 to 2014 if subminimum wage was equivalent to the federal minimum wage. Conclusions Increasing the subminimum wage can reduce poverty-related stress and may be a potential intervention for reducing poor health outcomes.
Characterization of a novel S-RNase allele and genotyping of new apple cultivars

Abstract Apples (Malus × domestica Borkh.) are an economically important crop in many temperate growing regions around the world. Apple being characterized by gametophytic self-incompatibility (GSI) requires cross-pollination with compatible apple pollen during bloom to achieve sufficient fruit set for commercial production. For this reason, in commercial orchards it is common practice to plant pollinizer trees, which can be either crabapples or different apple cultivars, at a density of 5–10%. Crabapple trees, in addition to their ornamental traits, are valued as a source of genetic diversity for pollinating apple orchards. The genetics underlying cross-compatible responses among crabapples and domesticated apples, especially recently released cultivars, have been largely understudied. In this study, we characterized one novel S-RNase allele from the crabapple Malus ‘Doubloons’, named S59, and report an allele-specific PCR method for detection of this allele from genomic DNA. Further, we characterized the self-incompatibility genotypes (S-genotypes) of over twenty previously unreported Malus accessions, including some recent releases from the breeding programs of the University of Minnesota and Washington State University. The results of this work aim to provide new information about cross-compatibility of cultivars and pollinizers and may be used to aid parent selection in apple breeding programs, as well as pollinizer selection for the commercial orchard.
Reducing Theft of Petrified Wood at Petrified Forest National Park

The theft of petrified wood from Petrified Forest National Park is the park's primary resource-protection problem. Several interventions to control theft currently exist in the park, yet an estimat...
Sex-related Differences in Stress Reactivity and Cingulum White Matter.

Abstract The prefrontal cortex and limbic system are important components of the neural circuit that underlies stress and anxiety. These brain regions are connected by white matter tracts that support neural communication including the cingulum, uncinate fasciculus, and the fornix/stria-terminalis. Determining the relationship between stress reactivity and these white matter tracts may provide new insight into factors that underlie stress susceptibility and resilience. Therefore, the present study investigated sex differences in the relationship between stress reactivity and generalized fractional anisotropy (GFA) of the white matter tracts that link the prefrontal cortex and limbic system. Diffusion weighted images were collected and deterministic tractography was completed in 104 young adults (55 men, 49 women; mean age = 18.87 SEM = 0.08). Participants also completed self-report questionnaires (e.g., Trait Anxiety) and donated saliva (later assayed for cortisol) before, during, and after the Trier Social Stress Test. Results revealed that stress reactivity (area under the curve increase in cortisol) and GFA of the cingulum bundle varied by sex. Specifically, men demonstrated greater cortisol reactivity and greater GFA within the cingulum than women. Further, an interaction between sex, stress reactivity, and cingulum GFA was observed in which men demonstrated a positive relationship while women demonstrated a negative relationship between GFA and cortisol reactivity. Finally, trait anxiety was positively associated with the GFA of the fornix/stria terminalis – the white matter pathways that connect the hippocampus/amygdala to the hypothalamus. These findings advance our understanding of factors that underlie individual differences in stress reactivity.
The Hidden Cost of Hemolyzed Blood Samples in the Emergency Department.

Background On average, patients with hemolyzed potassium samples spend about 1 h longer in the emergency department (ED), regardless of acuity level or disposition. We aimed to quantify the direct expenses associated with poor-quality preanalytic blood samples collected in the ED. Methods We created a simple table with a range of direct expenses (i.e., costs) and rates of hemolyzed sample draws, allowing for identification of potential high-level cost-of-care impact analysis. We included a range of costs informed by review of literature on the topic. Those costs range from $600 to $3000 per bed-hour. This amount was inflation adjusted from 1996 to 2020 (1.68 × [direct cost per visit] × [100 000 visits per year/365 days/24 h]). We provided a range of hemolysis incidence based on previously reported data. Results We showed that for an ED with 100 000 annual visits, a 40% draw rate for routine chemistries (including potassium), and a 10% hemolysis incidence, the direct cost impact of hemolysis waste is approximately $4 million/year as a result of the 1 h of added length of stay on average for a patient with a hemolyzed blood sample. This amount represents an annualized estimated cost of caring for a patient in the ED with an avoidable extended length of stay. Conclusions The financial burden of poor-quality blood samples can be estimated using cost per bed-hour and rate of sample failure. Similar methodology may identify additional QC issues with previously invisible financial implications.
The paradigm of hematological malignant versus non-malignant manifestations, driven by primary immunodeficiencies: a complex interplay

Hematological malignancies (HM) developed on underlying primary immunodeficiencies (PID) are rare and of unusual features. Differentiating between malignant and non-malignant lymphoproliferation in cases of pediatric hematology and oncology and revealing their molecular predisposition demonstrate the complex interplay between PID and HM. We retrospectively studied a case series of seven pediatric patients, all with PID with manifestations raising suspicion for HM or hypereosinophilic syndrome (HES) or confirmed HM of lymphoid origin. Combined immunodeficiency (CID) without detection of a known mutated gene or with ataxia-telangiectasia (AT), STAT3 gain of function (GOF), DOCK8 deficiency, and CTLA4 deficiency were diagnosed in three, one, one, one, and one patient, respectively. Acute lymphoblastic leukemia and Hodgkin lymphoma followed by second primary Burkitt lymphoma were diagnosed in one patient with CID each, while lymphomatoid granulomatosis in one patient with AT. Lymphoproliferative disease occurred in STAT3 GOF, CTLA4 deficiency and CID, one patient each, and idiopathic HES in DOCK8 deficiency (median age at presentation of PID or any hematological manifestation: four years). Four patients underwent hematopoietic cell transplantation (HCT) for STAT3 GOF, DOCK8 deficiency and CID in one, one, and two cases, respectively (median age: 10 years). At the last follow-up, all transplanted patients were alive. Reporting on patients’ phenotype, genotype and course of disease shed light on the prevalence, characteristics, and pathophysiology of HM complicating PID. Discriminating the non-yet malignant lymphoproliferation from its malignant equivalent on the same pathophysiology background proved of additional value. Outcomes of PID after HCT, herein reported, are favorable.
Recurrent acute kidney injury in preterm neonates is common and associated with worse outcomes and higher mortality.

BACKGROUND Acute kidney injury (AKI) in preterm neonates is associated with poor outcomes that may worsen in the setting of recurrent episodes of AKI. This study defines and studies the incidence, risk factors, and outcomes of recurrent AKI (rAKI). METHODS Retrospective chart review of the neonates born at a gestational age of ≤28 weeks admitted to the neonatal intensive care unit (NICU) between January 2014 and December 2018. We identified AKI based on the serum creatinine (Scr) concentrations using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. rAKI was defined as the occurrence of AKI after Scr from the prior AKI had returned to baseline. RESULTS Forty-nine of the 205 (24%) preterm neonates developed rAKI. An earlier diagnosis (<7 days old) and a higher KDIGO stage (stage 3) at the initial episode of AKI was associated with rAKI (p = 0.03). Preterm neonates with rAKI had higher mortality as compared to those with a single episode of AKI (sAKI) (adjusted odds ratio (aOR) 4.55, 95% confidence interval (CI), 1.12-18.51). Length of stay (LOS) was longer among neonates with rAKI as compared to those with sAKI by 36 days (95% CI 24.9-47.1). CONCLUSIONS Recurrent AKI in preterm neonates was associated with earlier episodes and higher KDIGO stage of the initial AKI episode. Neonates with rAKI had higher mortality and longer LOS compared to those with sAKI. IMPACT Definition and study of the incidence of rAKI and its associated outcomes among preterm neonates. Recurrent AKI is common among preterm neonates and may contribute to worse outcomes for premature neonates in the NICU. Early recognition of the risk factors for AKI, and effective management of initial AKI and early phase of recurrent AKI may improve outcomes of these preterm neonates.
Hepatic Nutrient and Hormonal Regulation of the PANcreatic-DERived Factor (PANDER) Promoter

Abstract PANcreatic-DERived factor (PANDER, FAM3B) has been shown to regulate glycemic levels via interactions with both pancreatic islets and the liver. Although PANDER is predominantly expressed from the endocrine pancreas, recent work has provided sufficient evidence that the liver may also be an additional tissue source of PANDER production. At physiological levels, PANDER is capable of disrupting insulin signaling and promoting increased hepatic glucose production. As shown in some animal models, strong expression of PANDER, induced by viral delivery within the liver, induces hepatic steatosis. However, no studies to date have explicitly characterized the transcriptional regulation of PANDER from the liver. Therefore, our investigation elucidated the nutrient and hormonal regulation of the hepatic PANDER promoter. Initial RNA-ligated rapid amplification of cDNA ends identified a novel transcription start site (TSS) approximately 26 bp upstream of the PANDER translational start codon not previously revealed in pancreatic β-cell lines. Western evaluation of various murine tissues demonstrated robust expression in the liver and brain. Promoter analysis identified strong tissue-specific activity of the PANDER promoter in both human and murine liver-derived cell lines. The minimal element responsible for maximal promoter activity within hepatic cell lines was located between −293 and −3 of the identified TSS. PANDER promoter activity was inhibited by both insulin and palmitate, whereas glucose strongly increased expression. The minimal element was responsible for maximal glucose-responsive and basal activity. Co-transfection reporter assays, chromatin-immunoprecipitation (ChIP) and site-directed mutagenesis revealed that the carbohydrate-responsive element binding protein (ChREBP) increased PANDER promoter activity and interacted with the PANDER promoter. E-box 3 was shown to be critical for basal and glucose responsive expression. In summary, in-vitro and in-vivo glucose is a potent stimulator of the PANDER promoter within the liver and this response may be facilitated by ChREBP.
Byssochlamys spp. and their importance in processed fruits

Publisher Summary This chapter discusses that spoilage of canned and bottled fruits by Byssochlamys spp., first recognized in Great Britain in the 1930s and has since been documented in several countries around the world. The first documented fruit spoilage outbreaks attributed to Byssochlamys occurred in England and it was thought at that time the organism was confined to that country. The mold isolated from spoiled processed fruits in many instances is Paecilomyces. It has been long recognized that a large percentage of any given crop of ascospores of Byssochlamys possesses a dormancy that can be broken by heat treatment. Like bacterial spores, ungerminated ascospores are highly refractile when viewed under the phase microscope, but lose this characteristic on germination before the germ tube(s) emerges. Byssochlamys is a problem in fruit spoilage mainly because of the exceptionally high heat resistance exhibited by its ascospores. In the course of studying the chief metabolic products of B. fulva cultured on a synthetic medium containing glucose as a sole source of carbon, Raistrick and Smith noted that in preliminary tests an ether-soluble precipitate formed upon the addition of hydrochloric acid to 4-week-old Czapek-Dox culturing fluid. Foods, feeds, and grains that become moist during storage may subsequently overheat and provide thermophilic fungi with a competitive growth advantage over other microorganisms. The chapter discusses that it does not seem feasible to eliminate Byssochlamys spp. from fruit refuse and soils which contaminate fruits as they arrive from the field.
Analysis of peripheral doses for base of tongue treatment by linear accelerator and helical TomoTherapy IMRT.

The purpose of this study was to compare the peripheral doses to various organs from a typical head and neck intensity-modulated radiation therapy (IMRT) treatment delivered by linear accelerator (linac) and helical TomoTherapy. Multiple human CT data sets were used to segment critical structures and organs at risk, fused and adjusted to an anthropomorphic phantom. Eighteen contours were designated for thermoluminescent dosimeter (TLD) placement. Following the RTOG IMRT Protocol 0522, treatment of the primary tumor and involved nodes (PTV70) and subclinical disease sites (PTV56) was planned utilizing IMRT to 70Gy and 56 Gy. Clinically acceptable treatment plans were produced for linac and TomoTherapy treatments. TLDs were placed and each treatment plan was delivered to the anthropomorphic phantom four times. Within 2.5 cm (one helical TomoTherapy field width) superior and inferior to the field edges, normal tissue doses were on average 45% lower using linear accelera­tor. Beyond 2.5 cm, the helical TomoTherapy normal tissue dose was an average of 52% lower. The majority of points proved to be statistically different using the Student's t-test with p > 0.05. Using one method of calculation, probability of a secondary malignancy was 5.88% for the linear accelerator and 4.08% for helical TomoTherapy. Helical TomoTherapy delivers more dose than a linac immediately above and below the treatment field, contributing to the higher peripheral doses adjacent to the field. At distances beyond one field width (where leakage is dominant), helical TomoTherapy doses are lower than linear accelerator doses.
Antioxidant Role of Glutathione S-Transferases: Protection Against Oxidant Toxicity and Regulation of Stress-Mediated Apoptosis

It has been known that glutathione S-transferases (GSTs) can reduce lipid hydroperoxides through their Se-independent glutathione peroxidase activity and that these enzymes can also detoxify lipid peroxidation end products such as 4-hydroxynonenal (4-HNE). In this article, recent studies suggesting that the Alpha class GSTs provide a formidable defense against oxidative stress are critically evaluated and the role of these enzymes in the regulation of oxidative stress-mediated signaling is reviewed. Available evidence from earlier studies together with results of recent studies in our laboratories strongly suggests that lipid peroxidation products, particularly hydroperoxides and 4-HNE, are involved in the mechanisms of stress-mediated signaling and that it can be modulated by the Alpha class GSTs through the regulation of the intracellular concentrations of 4-HNE.
Model order reduction for discrete-time LTI systems using the alignment distance

The alignment distance is a recently introduced (differential-geometric) distance on the manifold of LTI systems of fixed order n and output-input dimension (p,m). In this paper, we formulate model order reduction for discrete-time LTI (MIMO) systems in terms of the alignment distance. The intuition behind our formulation is to consider systems of orders lower than n as boundary points of the mentioned manifold in an appropriate ambient space, and the goal is to find a system of order at most r (on the boundary) closest to a given system of order n, where closeness is measured in the alignment distance. We introduce an algorithm for this minimization problem and give some a-priori error bounds in terms of the Hankel singular values of the system. Interesting relations and resemblances emerge with the popular balanced truncation reduction, which is a method not based on any optimality criterion. We show that in certain cases (but not always) balanced truncation provides a good approximation to reduction based on the alignment distance. In fact, our approach can be considered as a principled attempt to put balanced truncation in an optimization framework, and in doing so we allude to a shortcoming of balanced truncation that highlights an advantage of our approach. The proposed approach is general and can be extended to other classes of systems.
Working Safe: How to Help People Actively Care for Health and Safety, Second Edition

Orientation and Alignment Choosing the Right Approach Starting with Theory Paradigm Shifts for Total Safety Human Barriers to Safety The Complexity of People Sensation, Perception, and Perceived Risk Stress vs. Distress Behavior-Based Psychology Basic Principles Identifying Critical Behaviors Behavioral Safety Analysis Behavior-Based Intervention Intervening with Activators Intervening with Consequences Intervening as a Behavior-Change Agent Intervening with Supportive Conversation Actively Caring for Safety Understanding Actively Caring The Person-Based Approach to Actively Caring Increasing Actively Caring Behaviors Putting It All Together Promoting High-Performance Teamwork Evaluating for Continuous Improvement Obtaining and Maintaining Involvement Reviewing the Principles
A Fuzzy Diagnostic Model and Its Application in Automotive Engineering Diagnosis

This paper describes a fuzzy diagnostic model that contains a fast fuzzy rule generation algorithm and a priority rule based inference engine. The fuzzy diagnostic model has been implemented in a fuzzy diagnostic system for the End-of-Line test at automobile assembly plants and the implemented system has been tested extensively and its performance is presented.