cssi/SciSciGPT-SciSciNet huggingface dataset:
Mechanisms of the interaction of nitroxyl with mitochondria

It is now thought that NO* (nitric oxide) and its redox congeners may play a role in the physiological regulation of mitochondrial function. The inhibition of cytochrome c oxidase by NO* is characterized as being reversible and oxygen dependent. In contrast, peroxynitrite, the product of the reaction of NO* with superoxide, irreversibly inhibits several of the respiratory complexes. However, little is known about the effects of HNO (nitroxyl) on mitochondrial function. This is especially important, since HNO has been shown to be more cytotoxic than NO*, may potentially be generated in vivo, and elicits biological responses with some of the characteristics of NO and peroxynitrite. In the present study, we present evidence that isolated mitochondria, in the absence or presence of substrate, convert HNO into NO* by a process that is dependent on mitochondrial concentration as well as the concentration of the HNO donor Angeli's salt. In addition, HNO is able to inhibit mitochondrial respiration through the inhibition of complexes I and II, most probably via modification of specific cysteine residues in the proteins. Using a proteomics approach, extensive modification of mitochondrial protein thiols was demonstrated. From these data it is evident that HNO interacts with mitochondria through mechanisms distinct from those of either NO* or peroxynitrite, including the generation of NO*, the modification of thiols and the inhibition of complexes I and II.
Pseudephemerum, new to the United States and Mexico

Pseudephemerum is newly reported from Oregon, U.S.A. and Tlaxcala, Mexico. With examination of available specimens including types, Pleuridium tenellum is proposed as a new synonym of Pseudephemerum nitidum.
Nonleptonic Decays of Hyperons and Current Algebra

Nonleptonic decays of baryons are studied within the framework of current algebra, current-current interaction, and hard pions. A formalism which avoids the usual ambiguity of off-mass-shell extrapolation for the $P$-wave decays is developed, from which formulas for the decay amplitudes can be derived. Two models are discussed. The first model contains the equal-time commutator and the baryon pole terms, but allows for the $\mathrm{SU}(3)$ symmetry breaking through the presence of the parity-violating spurion matrix elements between baryons. The second model adds the $\frac{3}{2}+$ decuplet and ${{Y}_{0}}^{*}(1405)$ contributions to the first model, but the $\mathrm{SU}(3)$ symmetry-breaking matrix elements are not considered. Reasonable agreement with experiment is obtained in both models.
Emplotment as Epic in Archaeological Writing: The Site Monograph as Narrative

To emplot a narrative as epic is to present a story of vast scope and multiple plots as a legitimate member of a tradition of other such stories. This article argues that emplotment as epic is the broadest of three levels of plot in archaeological writings. At that level, the site monograph emerges as a characteristically archaeological form of narrative, fundamental to archaeology as a discipline and a source of chronic anxiety for archaeologists. The ‘stories’ told in site monographs are epic in length, diversity of materials covered and multiplicity of themes, plots and authors. Indeed, the more complexities of that sort the better, since those are features that help to emplot the work as good archaeology.
Integrated Damping Systems for Tall Buildings

This paper investigates the potential of double skin facades (DSF), which are composed of two layers of facades with substantial gaps between them, as an integrated damping system for tall buildings. The connectors between the inner and outer skins of the DSF system are designed to have low axial stiffness with a damping mechanism. Through this design, the vibration of the primary building structure can be substantially reduced. However, the excessive movements of the DSF outer skin masses are a critical design limitation. In order to mitigate this limitation, the tuned mass damper (TMD)/DSF damping (DSFD) interaction system is studied. Compared to the conventional TMD system, the TMD/DSFD interaction system requires a significantly reduced TMD mass ratio. Compared to the DSFD system, the movements of the DSF outer skin masses can be substantially reduced in the TMD/DSFD interaction system.
74 METFORMIN-DIET AMELIORATES CORONARY HEART DISEASE RISK FACTORS AND FACILITATES RESUMPTION OF REGULAR MENSES IN ADOLESCENTS WITH POLYCYSTIC OVARY SYNDROME.

In 35 postmenarchal adolescent females (17 ± 2 years, range 14-19) with polycystic ovary syndrome (PCOS), in a case-series prospective description, we assessed effectiveness of metformin-diet for 1 year for reduction of weight, insulin, HOMA insulin resistance (IR), cholesterol, triglycerides, and resumption of regular menses. By selection, all 35 girls met the 2003 consensus criteria for diagnosis of PCOS; all 35 had clinical hyperandrogenism, 37% were amenorrheic, and 60% oligomenorrheic. Pretreatment median weight was 82.7 kg, BMI 30.8 kg/m2, and 19 (54%) girls had BMI > the CDC age-gender-specific 95th percentile (overweight). Calories (26% protein, 44% carbohydrate) were targeted to 1,500-1,800/day if BMI was
The coevolution of recognition and social behavior

Recognition of behavioral types can facilitate the evolution of cooperation by enabling altruistic behavior to be directed at other cooperators and withheld from defectors. While much is known about the tendency for recognition to promote cooperation, relatively little is known about whether such a capacity can coevolve with the social behavior it supports. Here we use evolutionary game theory and multi-population dynamics to model the coevolution of social behavior and recognition. We show that conditional harming behavior enables the evolution and stability of social recognition, whereas conditional helping leads to a deterioration of recognition ability. Expanding the model to include a complex game where both helping and harming interactions are possible, we find that conditional harming behavior can stabilize recognition, and thereby lead to the evolution of conditional helping. Our model identifies a novel hypothesis for the evolution of cooperation: conditional harm may have coevolved with recognition first, thereby helping to establish the mechanisms necessary for the evolution of cooperation.
Bounded intention planning

We propose a novel approach for solving unary SAS+ planning problems. This approach extends an SAS+ instance with new state variables representing intentions about how each original state variable will be used or changed next, and splits the original actions into several stages of intention followed by eventual execution. The result is a new SAS+ instance with the same basic solutions as the original. While the transformed problem is larger, it has additional structure that can be exploited to reduce the branching factor, leading to reachable state spaces that are many orders of magnitude smaller (and hence much faster planning) in several test domains with acyclic causal graphs.
The Association between the Intertwin Interval and Adverse Neonatal Outcomes

Objective Previous data examining the association between the interval between the delivery of the first and second twin (intertwin interval) and adverse neonatal outcomes are conflicting. We sought to evaluate whether intertwin interval is associated with adverse neonatal outcomes for the second twin in a contemporary U. S. cohort. Methods This is a cohort study of women who delivered twins at or after 32 weeks gestation between 2006 and 2014 and whose first twin was delivered vaginally vertex. The intertwin interval was dichotomized as Results Of the 171 subjects, 61 (35.7%) had an intertwin interval of ≥ 10 minutes. There were no differences in maternal characteristics. Intertwin interval of ≥ 10 minutes was associated with an increased frequency of arterial pH ≤ 7.1 (22.0 vs. 8.2%, p = 0.03), which persisted after adjusting for confounders (adjusted odds ratio, 2.94; 95% confidence interval, 1.04–8.33). Other adverse outcomes did not differ. Conclusion Intertwin interval of ≥ 10 minutes was associated with increased frequency of arterial pH ≤ 7.1 in the second twin, but no other adverse neonatal outcomes.
Burned by the Hangman: Puritan Agency and the Road Not Taken

The Meritorious Price of Our Redemption, by William Pynchon. 1650. Facsimile ed. Ed. and intro. Michael W. Vella, Lance Schachterle and Louis Mackey. New York: Peter Lang, 1992. 170 pp. $89.95.
Normal and Osteoarthritic Articular Cartilage

Summary A self-perpetuating cycle of events occurs in articular cartilage subjected to increased stress that eventually leads to progressive osteoarthritic changes (Fig. 10). Increased stress on cartilage (physical, chemical, or metabolic) sufficient to injure chondrocytes leads to the release of lysosomal and other degradative enzymes. These enzymes degrade the cartilage matrix. Loss of cartilage matrix leads to both degenerative and reparative reactions. Chondrocytes are stimulated both to replicate and to synthesize matrix components as well as to release degradative enzymes. The reparative response is inadequate to compensate for the degradative activity, and continued loss of proteoglycan and loss of collagen architecture lead to loss of the elastic and resilient properties of cartilage. The loss of elasticity leads to further stress on the articular surface causing erosions. As increased stress is transmitted to the subchondral bony plate, microfractures occur and trabeculae increase in thickness and stiffness; thus more force is transmitted back to the overlying articular cartilage. There are a number of sites where this cycle may be interrupted. Current drug therapy is aimed principally at decreasing inflammation, and many drugs act to stabilize the lysosomal membranes and thereby hinder the release of these degradative enzymes. Current research on new drugs has been aimed at specific enzyme inhibitors capable of preventing activation of these endogenous degradative enzymes. Physiotherapeutic aids (e.g., braces and canes) can limit some of the stress on the articular cartilage, and many surgical procedures (e.g., osteotomies) function to limit stress on particular osteoarthritic areas of joints by altering the weight bearing alignment. In our laboratory with Dr. Balazs, we have recently undertaken clinical trials using intraarticular injections of purified hylauronic acid. This has resulted in a return to normal of the reduced viscosity and molecular size of the hyaluronic acid found in arthritic joints. This more nomal fluid may serve to protect the articular surfaces from increased stress. Clinically this drug also appears to decrease pain in these joints. Perhaps the day is not too far off when both the pain and the underlying degenerative disease may be controlled by drugs capable of inhibiting the degenerative response and enhancing the reparative phenomena in articular cartilage.
Crossmatch conundrums: Can we guess which graft will not be rejected?

Aim Recent years have witnessed remarkable advances in the ability to detect and characterize HLA antibodies and ability to predict results of flow crossmatch virtually. In this study we compare the crossmatch results and HLA antibody profile among one heart and one kidney transplant recipients. Methods Pre-Tx and serial post-Tx HLA antibody testing was performed using Luminex based assays (One Lambda Thermo fisher) for detection of total HLA IgG, IgG subclasses, IgM, C1q. Sera were tested for total IgG at neat and 1:8 dilution. Antibody testing results were used to predict virtual crossmatch results. Crossmatches were performed by flow cytometry and extended incubation CDC. Results The following table shows pre-Tx and most recent post-Tx DSA characteristics, crossmatch results, biopsy results and graft outcomes in the 2 cases. Conclusion These data provide a cautionary note that pre-Tx DSA characteristics and virtual crossmatch predictions even when consistent with physical crossmatch results (both Pos and Neg), may not correlate with clinical outcomes particularly in highly allosensitized patients. Download : Download full-size image
Who matters for memory: Sources of institutional memory in international organization crisis management

Scholarship on organizational learning has explored how international organizations (IOs) reform but has paid little attention to the origins of institutional memory. For IOs engaged in crisis management operations, acquiring knowledge about strategic errors is necessary for adopting reforms that could save lives. This study seeks to identify the sources that affect whether or not IO elites will contribute knowledge to an IO’s institutional memory in crisis management. The study employs a survey experiment in the field on 120 NATO elites who decide on and plan operations. Findings indicate that when the United States introduces knowledge of a strategic error, NATO elites are significantly less likely to share it. This deterrent effect on knowledge-sharing illustrates an unexpected way in which the US influences international crisis management. The study also finds that an IO’s secretariat can somewhat increase elites’ likelihood of contributing to the IO’s institutional memory.
Physicochemical and Nutritional Requirements for Axenic Replication Suggest Physiological Basis for Coxiella burnetii Niche Restriction.

Bacterial obligate intracellular parasites are clinically significant animal and human pathogens. Central to the biology of these organisms is their level of adaptation to intracellular replication niches associated with physicochemical and nutritional constraints. While most bacterial pathogens can adapt to a wide range of environments, severe niche restriction - an inability to thrive in diverse environments - is a hallmark of bacterial obligate intracellular parasites. Herein the physicochemical and nutritional factors underlying the physiological basis for niche restriction in the zoonotic bacterial obligate intracellular parasite and Q fever agent Coxiella burnetii are characterized. Additionally, these factors are reviewed in the context of C. burnetii evolution and continued (patho)adaptation. C. burnetii replication was strictly dependent on a combination of moderately acidic pH, reduced oxygen tension and presence of carbon dioxide. Of macronutrients, amino acids alone support replication under physicochemically favorable conditions. In addition to utilizing gluconeogenic substrates for replication, C. burnetii can also utilize glucose to generate biomass. A mutant with a disruption in the gene pckA, encoding phosphoenolpyruvate carboxykinase (PEPCK), the first committed step in gluconeogenesis, could be complemented chemically by the addition of glucose. Disruption of pckA resulted in a moderate glucose-dependent growth defect during infection of cultured host cells. Although C. burnetii has the theoretical capacity to synthesize essential core metabolites via glycolysis and gluconeogenesis, amino acid auxotrophy essentially restricts C. burnetii replication to a niche providing ample access to amino acids. Overall, the described combination of physiochemical and nutritional growth requirements are strong indicators for why C. burnetii favors an acidified phagolysosome-derived vacuole in respiring tissue for replication.
Acoustic Investigations of the Strained State of Hydrogenated 09G2S Steel

We study the acoustic properties of inhomogeneous plastically deformed specimens made of 09G2S steel. The specimens with residual strains were successively subjected to heat treatment and hydrogenation from the gas phase. After each procedure, we measured the space distributions of the velocity of longitudinal acoustic waves. We also analyzed the mechanisms of changes in the velocity in the course of hydrogenation in the region of the specimen with residual strains.
Effects of Using an Advancing Care Excellence for Seniors Simulation Scenario on Nursing Student Empathy: A Randomized Controlled Trial

Abstract Background Low levels of empathy among nursing students can adversely impact patient-centered care (PCC) and patient outcomes. Methods An Advancing Care Excellence for Seniors simulation scenario was delivered to 50 nursing students to improve empathy and PCC by improving active listening and self-awareness. Results Active listening, empathy, and PCC scores in the intervention group compared with the control group and baseline significantly differed at postintervention and four-week follow-up (ps Conclusions Using the Advancing Care Excellence for Seniors simulation scenario was effective in improving the four variables.
Chasing the Unicorn? Evaluating Methodologies for Researching the Positive and Extraordinary

The last fifteen years have seen the emergence of positive psychology and positive organizational scholarship as new and increasingly popular areas of social science inquiry. However, there is litt...
The use of Ki-67 labeling index to grade pulmonary well-differentiated neuroendocrine neoplasms: current best evidence.

Although Ki-67 labeling index (Ki-67%) is not a diagnostic or grading criterion in the World Health Organization classification of pulmonary carcinoid tumor, oncologists often request this test. A survey was administered at a North American Society for Neuroendocrine Tumors meeting to understand how Ki-67% is used in oncologic practices. A systematic literature review was performed to gather best evidence regarding the use of Ki-67%. Consecutive pulmonary carcinoids were stratified into pulmonary typical carcinoids with Ki-67% <5% (group A, n = 187), typical carcinoids with Ki-67% ≥5% (group B, n = 38) and atypical carcinoids irrespective of Ki-67% (group C, n = 31). Overall survival, progression-free survival, recurrence proportions and time to recurrence were compared, by group, using the log-rank test, chi-square statistics and ANOVA, respectively. Our survey confirmed that Ki-67% is frequently used by specialists caring for these patients. Ki-67% of 1–7% significantly correlated with overall survival in the literature but we found no information about Ki-67% cut-off values that would accurately distinguish pulmonary typical from atypical carcinoids or estimate the prognosis of patients stratified by World Health Organization diagnosis and Ki-67% cut-off. Overall survival was significantly different in our 3 patient groups (p < 0.001), with survival probabilities decreasing from groups A to C. Progression-free survival was significantly longer in group A than B (p < 0.007). Our results support the concept that by combining World Health Organization diagnosis and Ki-67%, pulmonary carcinoids can be stratified into 3 grades: G1 (typical carcinoids with Ki-67% <5), G2 (typical carcinoids with Ki-67% ≥5%) and G3 (atypical carcinoids) with different prognoses.
Higher Use of Surgery Confers Superior Survival in Stage I Non-Small Cell Lung Cancer.

Background Lobar resection is the gold standard therapy for medically fit patients with stage I non-small cell lung cancer (NSCLC). However, considerable variability exists in the use of surgical therapy. This study tested the hypothesis that center-based variation in the use of surgical therapy affects survival in NSCLC. Methods We queried the National Cancer Database for patients with stage I NSCLC. Mixed-effects multivariable models were developed to establish the per-center adjusted rate of surgical therapy. Patients were stratified into quartiles based on the treating center’s adjusted rate of surgical therapy. Survival was estimated and then tested by using Kaplan-Meier and the log-rank test. Multivariable Cox proportional hazard models were developed to estimate the effect of rate of surgical therapy on overall survival. Results A total of 139,802 patients met the criteria. There was wide variation in the per-center rate of surgical resection in the highest (80.8%) versus lowest (41.4%, p Conclusions Treatment at a center with a higher rate of surgical therapy confers a considerable survival advantage, even after adjustment for hospital volume, surgical approach, and other confounders. Targeted efforts to improve adherence to guidelines about provision of surgical therapy in early-stage NSCLC may represent a meaningful opportunity to improve outcomes.
Criticism, Reasoning, and Judgment in Science

In his autobiography, physicist Otto R. Frisch tells the following revealing anecdote about Niels Bohr. Bohr, we are told, “never trusted a purely formal or mathematical argument. ‘No, no’ he would say ‘You are not thinking; you are just being logical”’ (Frisch, 1979, p. 95).1 It would be arbitrary and uncharitable to interpret Bohr’s point as implying that being logical is not a form of thinking. Rather it seems obvious that he is distinguishing between two types of thinking, logical thinking and another kind which may be appropriately labeled critical thinking. By logical thinking here Bohr seems to mean a mental activity which progresses from one thought to another in accordance with strict rules, namely rules that are clear, distinct, and exact. It might be better to call such thinking formal, or algorithmic, or deductive, in order not to limit the concept of logic to a one–sided and prejudicial conception. However, I do not want to focus on that, but rather on the other type of thinking. It is obvious from the context that critical thinking is different from logical thinking, not in the sense of being illogical, but rather in the sense that either it follows no rules or it follows rules that are not formal.2 One may speak of informal judgment to refer to this feature of critical thinking being suggested here.
Biomarkers in toxicology and risk assessment

Over the last 30 years, the field of biomarkers has greatly expanded as early and specific endpoints for monitoring cellular responses to various disease states and exposures to drugs and chemical agents. They have enjoyed some success as predictors of health outcomes for a number of clinical diseases, but the application to chemical exposure risk assessments has been more limited. Biomarkers may be classified into categories of markers of exposure, effect, and susceptibility. Currently, “omics” biomarkers (i.e., genomic, proteomic, and metabolomic/metabonomic) are the major classes of biomarkers under development. These markers represent a continuum of cellular responses to drug or chemical exposures and provide linkages to mechanisms of cell injury/cell death or carcinogenic transformation. On the other hand, translation and application of these biomarkers for risk assessment has been limited due to validation and interpretation issues that need to be addressed in order for these potentially extremely valuable endpoints to reach their full potential as predictive tools for public health. This short chapter will briefly review these three “omics” biomarker classes and examine some validation/translation aspects needed in order for them to reach their full potential and acceptance as valuable tools for application to risk assessment.
Systemic circularity: working with individuals for family-level change

Circularity in therapeutic relationships is a commonly encountered topic in the family literature. When the client is a family, circular interviewing questions and statements enable the systemic nurse therapist to encourage reflexive contemplation within the larger relational system. However, family visits often are difficult or impossible to initiate. When this situation occurs, nurse therapists need systemic approaches that can be used to promote growth within the larger system. Circular interviewing questions and statements can be used with individuals to promote family change.
Multiple Representations of Space by the Cockroach, Periplaneta americana.

When cockroaches are trained to a visual-olfactory cue pairing using the antennal projection response (APR), they can form different memories for the location of a visual cue. A series of experiments, each examining memory for the spatial location of a visual cue, were performed using restrained cockroaches. The first group of experiments involved training cockroaches to associate a visual cue (CS - green LED) with an odor cue (US) in the presence or absence of a second visual reference cue (white LED). These experiments revealed that cockroaches have at least two forms of spatial memory. First, it was found that during learning, the movements of the antennae in response to the odor influenced the cockroaches’ memory. If they use only one antenna, cockroaches form a memory that results in an APR being elicited to the CS irrespective of its location in space. When using both antennae, the cockroaches resulting memory leads to an APR to the CS that is spatially confined to within 15° of the trained position. This memory represents an egocentric spatial representation. Second, the cockroaches simultaneously formed a memory for the angular spatial relationships between two visual cues when trained in the presence of a second visual reference cue. This training provided the cockroaches an allocentric representation or visual snapshot of the environment. If both egocentric and the visual snapshot were available to the cockroach to localize the learned cue, the visual snapshot determined the behavioral response in this assay. Finally, the split-brain assay was used to characterize the cockroach’s ability to establish a memory for the angular relationship between two visual cues with half a brain. Split-brain cockroaches were trained to unilaterally associate a pair of visual cues (CS - green LED and reference - white LED) with an odor cue (US). Split-brain cockroaches learned the general arrangement of the visual cues (i.e. the green LED is right of the white LED), but not the precise angular relationship. These experiments provide new insight into spatial memory processes in the cockroach.
Genetic Analysis of Nuclear Migration and Anchorage to Study LINC Complexes During Development of Caenorhabditis elegans

Studying nuclear positioning in developing tissues of the model nematode Caenorhabditis elegans greatly contributed to the discovery of SUN and KASH proteins and the formation of the LINC model. Such studies continue to make important contributions into both how LINC complexes are regulated and how defects in LINC components disrupt normal development. The methods described explain how to observe and quantify the following: nuclear migration in embryonic dorsal hypodermal cells, nuclear migration through constricted spaces in larval P cells, nuclear positioning in the embryonic intestinal primordia, and nuclear anchorage in syncytial hypodermal cells. These methods will allow others to employ nuclear positioning in C. elegans as a model to further explore LINC complex regulation and function.
Phenotypic Diversity of Colored Phytochemicals in Sorghum Accessions With Various Pericarp Pigments

Abstract Sorghum is a versatile grain generally consumed in Asia and Africa countries but is gaining interest in the United States due to its gluten-free and bioactive compound-enriched health benefits. There are many varieties of sorghum that come in a wide range of colors. Various phytochemical pigments that reside within different components of the sorghum kernel, especially in pericarp and endosperm, contribute to these genetic factor-dependent phenotypic colors. Various pericarp pigments are reflective of the certain phytochemical levels, which may include anthocyanins, carotenoids, and condensed tannins, etc. This chapter reviews recent studies on the association of the pericarp pigments in various sorghum accessions with anthocyanins and carotenoids, respectively. It covers aspects of the potential health benefits of these colored dietary constituents, however, further investigations are warranted to clarify the diversity of theses bioactive constituent interactions with genetic and environmental factors. How these phytochemicals correlate to the sorghum pericarp pigments could be important in future use of sorghum as a functional food for potential health benefits.
Free space optical non-orthogonal multiple access experimentation

Free Space Optical (FSO) multi-user communication provides high aggregate bandwidth and link robustness attributable to spatial diversity. The primary challenge for this technology is interference among multiple users at the receiver. A non-orthogonal multiple access (NOMA) technique multiplexes numerous users in the power domain at the same time and frequency resource. Thus, different users simultaneously transmit their signals with various power levels. The receiver then decodes user data individually from the overlapped signal using successive interference cancellation (SIC). This paper reports the use of NOMA in an FSO link with two users and details an investigation of the effects of power allocation and channel estimation on the user’s signals demodulation accuracy. Analysis of varying data rate and system capacity gain are explored. Experimental results indicate that accurate channel estimation and optimum power allocation ratio can improve the accuracy of signal reconstruction. Difference in data rate tested proved negligible to signal demodulation quality.
Implications for the Inclusion of Echo Intensity for Athlete Monitoring: A Mini Review

Sport practitioners (i.e., sport scientists, strength and conditioning coaches, sport coaches, and sports medicine staff) must implement appropriately planned annual training regimens, recovery strategies, and use both accepted and novel athlete monitoring protocols to continually progress athletic performance.
reply: Parameters for global ecosystem models

Tian et al. reply — Our model-based analysis of the effects of interannual climate variability and increasing atmospheric CO2concentration on carbon storage in Amazonian ecosystems focused on CO2exchanges between the atmosphere and undisturbed forests and other upland eco-systems of the region1. Crutzen et al. urge us to add the emissions of isoprene and other volatile organic compounds (VOCs) to our analysis. They argue that ignoring these emissions could lead to an overestimation of annual net carbon storage (net ecosystem production) in the Amazon Basin.
Dynamics of vitamin A uptake, storage, and utilization in vocal fold mucosa.

Abstract Objective Extrahepatic vitamin A is housed within organ-specific stellate cells that support local tissue function. These cells have been reported in the vocal fold mucosa (VFM) of the larynx; however, it is unknown how vitamin A reaches and is disseminated among VFM target cells, how VFM storage and utilization vary as a function of total body stores, and how these parameters change in the context of pathology. Therefore, in this study, we investigated fundamental VFM vitamin A uptake and metabolism. Methods Using cadaveric tissue and serum from human donors representing the full continuum of clinical vitamin A status, we established a concentration range and analyzed the impact of biologic and clinical covariates on VFM vitamin A. We additionally conducted immunodetection of vitamin A-associated markers and pharmacokinetic profiling of orally dosed α-retinyl ester (a chylomicron tracer) in rats. Results Serum vitamin A was a significant predictor of human VFM concentrations, suggesting that VFM stores may be rapidly metabolized in situ and replenished from the circulatory pool. On a vitamin A-sufficient background, dosed α-vitamin A was detected in rat VFM in both ester and alcohol forms, showing that, in addition to plasma retinol and local stellate cell stores, VFM can access and process postprandial retinyl esters from circulating chylomicra. Both α forms were rapidly depleted, confirming the high metabolic demand for vitamin A within VFM. Conclusion This thorough physiological analysis validates VFM as an extrahepatic vitamin A repository and characterizes its unique uptake, storage, and utilization phenotype.
Effect of concurrent organic cation transporter blockade on norepinephrine clearance inhibiting- and antidepressant-like actions of desipramine and venlafaxine

Abstract Depression is a major health problem for which most patients are not effectively treated. This underscores a need to identify new targets for the development of antidepressants with improved efficacy. Studies have shown that blockade of low-affinity/high-capacity transporters, such as organic cation transporters (OCTs) and the plasma membrane monoamine transporter (PMAT), with decynium-22 can produce antidepressant-like effects and inhibit serotonin clearance in brain when the serotonin transporter is pharmacologically or genetically compromised. In vitro studies show that OCTs/PMAT are also capable of norepinephrine transport, raising the possibility that decynium-22 might enhance the antidepressant-like effects of norepinephrine transporter inhibitors. Using in vivo electrochemistry, we show that local administration of decynium-22 into dentate gyrus of hippocampus enhanced the ability of the norepinephrine transporter blocker, desipramine, but not the dual norepinephrine/serotonin transporter blocker venlafaxine, to inhibit norepinephrine clearance. In parallel, systemic administration of decynium-22 (0.32 mg/kg) enhanced the antidepressant-like effects of desipramine (32 mg/kg), but not those of venlafaxine, in the tail suspension test, underscoring the heterogeneous response of mice to antidepressants, including those that share similar mechanisms of action. Systemic administration of normetanephrine, a potent blocker of OCT3, failed to potentiate the antidepressant-like effects of desipramine, suggesting that the actions of decynium-22 to augment the antidepressant-like effects of desipramine are likely mediated by another OCT isoform and/or PMAT. Taken together with existing literature, concurrent blockade of OCTs and/or PMAT merits further investigation as an adjunctive therapeutic for desipramine-like antidepressant drugs.
A transformation-based method for auditing the IS-A hierarchy of biomedical terminologies in the Unified Medical Language System.

Objective The Unified Medical Language System (UMLS) integrates various source terminologies to support interoperability between biomedical information systems. In this article, we introduce a novel transformation-based auditing method that leverages the UMLS knowledge to systematically identify missing hierarchical IS-A relations in the source terminologies. Materials and methods Given a concept name in the UMLS, we first identify its base and secondary noun chunks. For each identified noun chunk, we generate replacement candidates that are more general than the noun chunk. Then, we replace the noun chunks with their replacement candidates to generate new potential concept names that may serve as supertypes of the original concept. If a newly generated name is an existing concept name in the same source terminology with the original concept, then a potentially missing IS-A relation between the original and the new concept is identified. Results Applying our transformation-based method to English-language concept names in the UMLS (2019AB release), a total of 39 359 potentially missing IS-A relations were detected in 13 source terminologies. Domain experts evaluated a random sample of 200 potentially missing IS-A relations identified in the SNOMED CT (U.S. edition) and 100 in Gene Ontology. A total of 173 of 200 and 63 of 100 potentially missing IS-A relations were confirmed by domain experts, indicating that our method achieved a precision of 86.5% and 63% for the SNOMED CT and Gene Ontology, respectively. Conclusions Our results showed that our transformation-based method is effective in identifying missing IS-A relations in the UMLS source terminologies.
Clinical Outcomes of Lung Transplants From Donors With Unexpected Pulmonary Embolism.

Background Pulmonary embolism (PE) is unexpectedly detected in some donor lungs during organ procurement for lung transplantation. Anecdotally, such lungs are usually implanted; however, the impact of this finding on recipient outcomes remains unclear. We hypothesized that incidentally detected donor PE is associated with adverse short-term and long-term outcomes among lung transplant recipients. Methods We analyzed a prospectively maintained database of all lung donors procured by a single surgeon and transplanted at our institution between 2009 and 2018. A standardized approach was used for all procurements and included antegrade and retrograde flush. Pulmonary embolism was defined as macroscopic thrombus seen in the pulmonary artery during the donor procurement operation. Results A total of 501 consecutive lung procurements were performed during the study period. The incidence of donor PE was 4.4% (22 of 501). No organs were discarded owing to PE. Donors with PE were similar to donors without PE in baseline characteristics and Pa o 2. Recipients in the two groups were also similar. Pulmonary embolism was associated with a higher likelihood of acute cellular rejection grade 2 or more (10 of 22 [45.5%] vs 120 of 479 [25.1%], P = .03). Multivariable Cox modeling demonstrated an association between PE and the development of chronic lung allograft dysfunction (hazard ratio 2.02; 95% confidence interval, 1.23 to 3.30; P = .005). Conclusions Lungs from donors with incidentally detected PE may be associated with a higher incidence of recipient acute cellular rejection as well as reduced chronic lung allograft dysfunction-free survival. Surgeons must use caution when transplanting lungs with incidentally discovered PE. These preliminary findings warrant corroboration in larger data sets.
Rates and Risk Factors of Revision Arthroscopy or Conversion to Total Knee Arthroplasty Within 1 Year Following Isolated Meniscectomy.

Purpose To identify the rates of and risk factors for revision arthroscopy and conversion to total knee arthroplasty (TKA) within 1 year of isolated meniscectomy. Methods Humana and Medicare national insurance databases were queried for patients who underwent isolated meniscectomy. Patients who underwent revision arthroscopy or TKA within 1 year postoperatively were identified by International Classification of Diseases Procedural Codes, Ninth Revision, and Current Procedural Terminology codes. Multivariate binomial logistic regression analysis was used to identify risk factors, and adjusted odds ratios (ORs) and 95% confidence intervals (Cis) were calculated, with P < .05 considered significant. Results A total of 13,142 patients and 407,888 patients underwent isolated meniscectomy in the Humana and Medicare databases, respectively. Of the patients, 395 (3.01%) and 3,770 patients (0.92%) underwent revision arthroscopy, and 629 patients (4.79%) and 38,630 patients (9.47%) underwent TKA within 1 year of meniscectomy in the Humana and Medicare databases, respectively. Obesity (Humana: OR = 1.33, P = 0.003; Medicare: OR = 1.10, P < 0.001) and age < 20 years (Humana: OR = 2.64, P = 0.022), 20-29 years (Humana: OR = 3.30, P = 0.002), 40-49 years (Humana: OR = 3.80, P < 0.001), 50-59 years (Humana: OR = 1.99, P = 0.027), and < 64 years (Medicare: OR = 1.74, P < 0.001) were risk factors for revision arthroscopy. Obesity (Humana: OR = 1.64, P < 0.001; Medicare: OR = 1.37, P < 0.001), morbid obesity (Medicare: OR = 1.20, P < 0.001), age 70-74 (Medicare: OR = 1.12, P < 0.001), 75-79 (Medicare: OR = 1.25, P < 0.001), 80-84 (Medicare: OR = 1.20, P < 0.001), and concomitant osteoarthritis (Humana: OR = 1.42, P < 0.001; Medicare: OR = 1.46, P < 0.001) were risk factors for conversion to TKA. Conclusions Medicare and Humana databases showed that 0.92%-3.01% and 4.79%-9.47% of patients undergo revision arthroscopy or conversion to TKA within a year of isolated meniscectomy. Obesity was a risk factor for early revision arthroscopy and conversion to TKA, whereas concomitant osteoarthritis was a risk factor for conversion to TKA. Level of Evidence Level III, retrospective comparative trial.
A young man with recurrent kidney stones and renal failure.

Dent disease is an inherited proximal renal tubulopathy leading to low molecular weight proteinuria, hypercalciuria with nephrocalcinosis and nephrolithiasis, and progressive renal failure. Two genetic mutations have been identified. The disease usually presents in childhood or early adult life and may be associated with other proximal tubular defects, which can lead to significant morbidity, especially in children. The disorder can extend to interstitial and glomerular cells, which contributes to progression to end-stage kidney disease. The pathophysiologic process remains incompletely understood, and no specific treatment is available. Dent disease is likely under-recognized. It needs to be included in the differential, especially in young males, presenting with recurrent kidney stones, proteinuria, and impaired renal function.
Causes and Prevention of Bovine Abortion

Abortion is a particularly costly and vexing problem for veterinarians and cow/calf producers. Determining the causes of bovine abortion is difficult for several reasons, and despite the advances in diagnostic technology of the past few years, diagnostic success in bovine abortions seldom reaches 50% in laboratories around the world. Table 1 summarizes the results of diagnostic efforts on bovine abortions over the past 3 years at the South Dakota Veterinary Diagnostic Laboratory where specimens from 600 to 1000 aborted calves are examined each year. With the exception of dystocia, twinning, trauma, and anomaly (which in some cases may be caused by infection) all the causes listed are infectious, i.e. bacterial, viral, fungal, or protozoan. Because toxic, metabolic, and hereditary causes of abortion seldom result in a product or lesion readily recognizable in fetal tissues, these causes of abortion usually remain undetected by diagnosticians. Obviously the stockman wants every pregnant cow to go to term and deliver a live, healthy calf. This is an unrealistic expectation, but the level of abortion in a herd that should elicit alarm has not been determined exactly. A maximum loss of 3%, while not desirable, probably is not unreasonable. Some of these losses may result from certain inherited hormonal deficiencies, and routine culling usually keeps this problem to a minimum. As with any average figure, this 3% loss does not occur uniformly each year in every herd. Therefore fewer than 1% "normal" abortions may occur in a herd for several years, and then the number may exceed 3% for 1 or more years. This makes it difficult to set a precise figure for the number of abortions that should be accepted before investigation into the cause is started, but in general, diagnostic efforts should be initiated any time more than 1% of the herd abort.
PD-LI Promotes Retraction Fiber Formation and Determines Persistent Cell Migration by Altering Integrin β4 Dynamics

Although the immune checkpoint function of PD-L1 has dominated its study, its cell autonomous functions are now being realized. Here, we report that PD-L1 localizes in retraction fibers and migrasomes at the rear of migrating cells and it facilitates directionally persistent cell migration, a function that underlies tumor invasion. We also demonstrate that PD-L1 interacts with the β4 integrin in retraction fibers and migrasomes and that this integrin contributes to their formation, a process that is dependent on laminin-332. More specifically, our data reveal that PD-L1 senses low membrane tension at the cell rear during migration, forms lipid rafts that contain the β4 integrin and, consequently, localizes this integrin to sites of retraction fiber formation. Depletion of PD-L1, the β4 integrin or chemical disruption of lipid rafts resulted in reduced retraction fiber formation and stalled directional cell migration. Our findings identify a novel cell autonomous function of PD-L1 in promoting the formation of retraction fibers and migrasomes that is critical for regulating directionally persistent cell migration by interacting with the b4 integrin and altering its dynamics.
Phase II study of the IDH2- inhibitor enasidenib in patients with high-risk IDH2-mutated myelodysplastic syndromes (MDS)

7010Background: Isocitrate dehydrogenase 2 (IDH2) mutations occur in 5% of patients (pts) with MDS. Enasidenib (ENA) is a selective oral inhibitor of the mutant IDH2 enzyme with single-agent activi...
Jury Deliberations – How Do Reasoning Skills Interplay with Decision-Making?

We may well wonder how the Casey Anthony reached its verdict in spite of many of us thought was a raft of compelling evidence. In order to understand some of the nuances at play, it is important to understand some of the issues that confront a jury and how the criminal justice system ensures or attempts to ensure a fair outcome in our trial by jury system. At the risk of stating the obvious, one of the most enduring features of our criminal justice system is the institution of trial by a jury of one’s peers. This constitutionally mandated system is, arguably, the best connection between the ordinary man and the judicial system. It has been argued, and all the evidence point to it, that jury trials allow the law to inject common sense as well as the ordinary man's perspectives into an otherwise, complex and hermetic, process.
Confirmation of infantile spasms resolution by prolonged outpatient EEGs.

OBJECTIVE There is no consensus on the type or duration of the posttreatment EEG needed for assessing treatment response for infantile spasms (IS). We assessed whether outpatient electroencephalograms (EEGs) are sufficient to confirm infantile spasms (IS) treatment response. METHODS Three-year retrospective review identified new-onset IS patients. Only presumed responder to IS treatment at 2 weeks with a prolonged (>90 minutes) outpatient EEG to assess treatment response and at least 3-month follow-up were included. Hypsarrhythmia, electroclinical spasms, and sleep were evaluated for the first hour and for the duration of the EEG. RESULTS We included 37 consecutive patients with new-onset IS and presumed clinical response at 2 weeks posttreatment. Follow-up outpatient prolonged EEGs (median: 150 minutes, range: 90-240 minutes) were obtained 14 days (IQR: 13-17) after treatment initiation. EEGs detected ongoing IS in 11 of 37 (30%) presumed early responders. Prolonged outpatient EEG had a sensitivity of 85% (confidence interval [CI] 55%-98%) for detecting treatment failure. When hypsarrhythmia and/or electroclinical spasms were not seen, EEG had a negative predictive value 92% (CI: 75%-99%) for confirming continued IS resolution. Outpatient EEG combined with clinical assessment, however, identified all treatment failures at 2 weeks. Compared with the entire prolonged EEG, the first-hour recording missed IS in 45% (5/11). While sleep was captured in 95% (35/37) of the full EEG recording, the first hour of recording captured sleep in only 54% (20/37). SIGNIFICANCE Infantile spasms treatment response can be confirmed with a clinical history of spasm freedom and an outpatient prolonged EEG without evidence for ongoing spasms (hypsarrhythmia/electroclinical spams on EEG). Outpatient prolonged EEG, but not routine EEGs, represents an alternative to inpatient long-term monitoring for IS posttreatment EEG follow-up.
Achievability and Impossibility of Exact Pairwise Ranking

We consider the problem of recovering the rank of a set of $n$ items based on noisy pairwise comparisons. We assume the SST class as the family of generative models. Our analysis gave sharp information theoretic upper and lower bound for the exact requirement, which matches exactly in the parametric limit. Our tight analysis on the algorithm induced by the moment method gave better constant in Minimax optimal rate than ~\citet{shah2017simple} and contribute to their open problem. The strategy we used in this work to obtain information theoretic bounds is based on combinatorial arguments and is of independent interest.