cssi/SciSciGPT-SciSciNet huggingface dataset:
Polyneuropathy from Wild Transthyretin Amyloidosis: An Important New Variety (P3.156)

Objective: Recognizing that wild type transthyretin (TTR) cardiomyopathy may be associated with polyneuropathy, we have begun a systematic study of the association between "senile cardiomyopathy" and peripheral polyneuropathy. Background: Mutant TTR is an important cause of familial amyloidotic polyneuropathy [FAP]. More than 100 point mutations of TTR cause polyneuropathy [FAP], cardiomyopathy, and other organ involvement. Orthotopic liver transplantation and protein stabilizing drugs are known to slow FAP disease progression. Oligonucleotide therapies which block the formation of TTR [Isis, Inc. and Alnylam, Inc.] are undergoing phase 2 and 3 pharmaceutical trials. In research of FAP patients it has become known that both mutant and wild transthyretin are constituents in amyloid deposits. Additionally, wild type TTR is known to be implicated in development of “senile cardiomyopathy.” Methods: Patients with wild type TTR causing senile cardiomyopathy were screened for peripheral neuropathy by use of clinical history and neurological examination, neurophysiological tests and skin and nerve biopsies. Results: In the first two patients studied we have found wild type transthyretin deposits in nerve or in skin biopsies, making it likely that polyneuropathy is due to wild type TTR amyloid deposition. Conclusion: By the time of the AAN meeting, we plan to have evaluated more than 25 patients with TTR cardiomyopathy looking for coexisting peripheral neuropathy. We will report on the neurologic examination findings [neuropathy impairment score], Smart Somatotopic QSTing, Nerve Conduction studies, autonomic Tests, nerve or skin biopsies and molecular genetic studies. Our study will answer whether senile cardiomyopathy due to wild TTR is associated with polyneuropathy and whether the associated polyneuropathy is due to “wild” TTR. Disclosure: Dr. Dyck has nothing to disclose. Dr. Grogan has nothing to disclose. Dr. Klein has nothing to disclose. Dr. Litchy has nothing to disclose. Dr. Engelstad has nothing to disclose. Dr. Davies has nothing to disclose. Dr. Dyck has nothing to disclose.
A Comparison between Two Ten-Point Designs for Studying Three-Component Mixture Systems

Three-component mixture experiments are very common. Reasons for their popularity are: (1) ease in selecting the component combinations to run experiments on, (ii) ease in fitting empirical models to the data collected, as well as interpreting the coeff..
Shaking the tyrant's bloody robe

Group violence, despite much study, remains enigmatic. Its forms are numerous, its proximate causes myriad, and the interrelation of its forms and proximate causes poorly understood. We review its evolution, including preadaptations and selected propensities, and its putative environmental and psychological triggers. We then reconsider one of its forms, ethnoreligious violence, in light of recent discoveries in the behavioral and brain sciences. We find ethnoreligious violence to be characterized by identity fusion and by manipulation of religious traditions, symbols, and systems. We conclude by examining the confluence of causes and characteristics before and during Yugoslavia's wars of disintegration.
Nonconvulsive Seizures and Brain Damage

Possible brain damage resulting from nonconvulsive seizures is debated “for” by Young GB and Jordan KG (Department of Clinical Neurological Sciences, 375 South St, London, Ontario, Canada N6A 4G5), and “against” by Aminoff MJ (Box 0114, Room M-794, Department of Neurology, School of Medicine, University of California, San Francisco, CA 94143).
Border Tax Adjustments and Developing Countries: A Perspective from China

It is no hyperbole to say that climate change is one of the most urgent crises all humans face together. Among the many ways that governments have attempted to curb carbon emissions, border tax adjustments (BTAs) have majorly aimed to restore the competitiveness of developed countries with more stringent carbon control policies. This article carefully examines the proposal under the tests of international environmental laws to evaluate the implications of BTAs in international legal system. The article argues that the imposition of BTAs will be inconsistent with set principles of the common but differentiated responsibility (CBDR), sustainable development and polluter pays and cause environmental injustice due to the adaptation and vulnerability of developing countries.
Personalized Semantic Word Vectors

Distributed word representations are able to capture syntactic and semantic regularities in text. In this paper, we present a word representation scheme that incorporates authorship information. While maintaining similarity among related words in the induced distributed space, our word vectors can be effectively used for some text classification tasks too. We build on a log-bilinear document model (lbDm), which extracts document features, and word vectors based on word co-occurrence counts. First, we propose a log-bilinear author model (lbAm), which contains an additional author matrix. We show that by directly learning author feature vectors, as opposed to document vectors, we can learn better word representations for the authorship attribution task. Furthermore, authorship information has been found to be useful for sentiment classification. We enrich the author model with a sentiment tensor, and demonstrate the effectiveness of this hybrid model (lbHm) through our experiments on a movie review-classification dataset.
Identification of a Conserved Histidine As Being Critical for the Catalytic Mechanism and Functional Switching of the Multifunctional Proline Utilization A Protein.

Proline utilization A from Escherichia coli (EcPutA) is a multifunctional flavoenzyme that oxidizes proline to glutamate through proline dehydrogenase (PRODH) and Δ1-pyrroline-5-carboxylate dehydrogenase (P5CDH) activities, while also switching roles as a DNA-bound transcriptional repressor and a membrane-bound catabolic enzyme. This phenomenon, termed functional switching, occurs through a redox-mediated mechanism in which flavin reduction triggers a conformational change that increases EcPutA membrane binding affinity. Structural studies have shown that reduction of the FAD cofactor causes the ribityl moiety to undergo a crankshaft motion, indicating that the orientation of the ribityl chain is a key element of PutA functional switching. Here, we test the role of a conserved histidine that bridges from the FAD pyrophosphate to the backbone amide of a conserved leucine residue in the PRODH active site. An EcPutA mutant (H487A) was characterized by steady-state and rapid-reaction kinetics, and cell-based ...
Evaluating single-point quantitative magnetization transfer in the cervical spinal cord: Application to multiple sclerosis.

Spinal cord (SC) damage is linked to clinical deficits in patients with multiple sclerosis (MS), however, conventional MRI methods are not specific to the underlying macromolecular tissue changes that may precede overt lesion detection. Single-point quantitative magnetization transfer (qMT) is a method that can provide high-resolution indices sensitive to underlying macromolecular composition in a clinically feasible scan time by reducing the number of MT-weighted acquisitions and utilizing a two-pool model constrained by empirically determined constants. As the single-point qMT method relies on a priori constraints, it has not been employed extensively in patients, where these constraints may vary, and thus, the biases inherent in this model have not been evaluated in a patient cohort. We, therefore, addressed the potential biases in the single point qMT model by acquiring qMT measurements in the cervical SC in patient and control cohorts and evaluated the differences between the control and patient-derived qMT constraints (kmf, T2fR1f, and T2m) for the single point model. We determined that the macromolecular to free pool size ratio (PSR) differences between the control and patient-derived constraints are not significant (p > 0.149 in all cases). Additionally, the derived PSR for each cohort was compared, and we reported that the white matter PSR in healthy volunteers is significantly different from lesions (p < 0.005) and normal appearing white matter (p < 0.02) in all cases. The single point qMT method is thus a valuable method to quantitatively estimate white matter pathology in MS in a clinically feasible scan time.
Guardians of the Earth: Teaching Children to Care for All Living Things

Across cultures, people show affinity to nature, but today’s children have little contact to develop a strong bond. Children’s ways of knowing differ from the abstract, logical ways of adults, focusing instead on sensory and emotional perceptions. Children need to develop a love for nature through unstructured access to natural areas before learning about endangered species. Many factors affect human attitudes toward organisms: media portrayal, physical and behavioral attributes, genetic closeness to humans, cultural and religious factors, and perceived danger. Learning about local fauna and flora can influence preferences from charismatic species to appreciating more modest local organisms. Familiar animals are generally valued with education affecting these attitudes. Humane education programs of several approaches (curriculum-blended, literature-focused, and animal project-based) abound, but their efficacy has not been well documented in the literature. A recent humane education program by the authors is discussed along with examples of animal poetry that the author developed for use with first and second grade students.
Twins actin' differently.

In this issue of Blood , Stritt et al describe how twinfilin 2a (Twf2a), an actin-binding protein, negatively regulates platelet reactivity and turnover in a manner that is intriguingly different from other cytoskeleton-related proteins. 1
Contemporary Best Practice Urolithiasis in Pregnancy

Urolithiasis is the most common nonobstetric complication in the gravid patient. The experience can provoke undue stress for the mother, fetus, and management team. The physiologic changes of pregnancy render the physical exam and imaging studies less reliable than in the typical patient. Diagnosis is further complicated by the need for careful selection of imaging modality in order to maximize diagnostic utility and minimize obstetric risk to the mother and ionizing radiation exposure to the fetus. Ultrasound remains the first-line diagnostic imaging modality in this group, but other options are available if results are inconclusive. A trial of conservative management is uniformly recommended. In patients who fail spontaneous stone passage, treatment may be temporizing or definitive. While temporizing treatments have classically been deemed the gold standard, ureteroscopic stone removal is now acknowledged as a safe and highly effective definitive treatment approach. Ultimately, a multidisciplinary, team-based approach involving the patient, her obstetrician, urologist, radiologist, and anesthesiologist is needed to devise a maximally beneficial management plan.
Auditory sensitivity to spectral modulation phase reversal as a function of modulation depth.

The present study evaluated auditory sensitivity to spectral modulation by determining the modulation depth required to detect modulation phase reversal. This approach may be preferable to spectral modulation detection with a spectrally flat standard, since listeners appear unable to perform the task based on the detection of temporal modulation. While phase reversal thresholds are often evaluated by holding modulation depth constant and adjusting modulation rate, holding rate constant and adjusting modulation depth supports rate-specific assessment of modulation processing. Stimuli were pink noise samples, filtered into seven octave-wide bands (0.125-8 kHz) and spectrally modulated in dB. Experiment 1 measured performance as a function of modulation depth to determine appropriate units for adaptive threshold estimation. Experiment 2 compared thresholds in dB for modulation detection with a flat standard and modulation phase reversal; results supported the idea that temporal cues were available at high rates for the former but not the latter. Experiment 3 evaluated spectral modulation phase reversal thresholds for modulation that was restricted to either one or two neighboring bands. Flanking bands of unmodulated noise had a larger detrimental effect on one-band than two-band targets. Thresholds for high-rate modulation improved with increasing carrier frequency up to 2 kHz, whereas low-rate modulation appeared more consistent across frequency, particularly in the two-band condition. Experiment 4 measured spectral weights for spectral modulation phase reversal detection and found higher weights for bands in the spectral center of the stimulus than for the lowest (0.125 kHz) or highest (8 kHz) band. Experiment 5 compared performance for highly practiced and relatively naive listeners, and found weak evidence of a larger practice effect at high than low spectral modulation rates. These results provide preliminary data for a task that may provide a better estimate of sensitivity to spectral modulation than spectral modulation detection with a flat standard.
Dormancy-breaking and germination requirements of seeds of the Hawaiian endemic Dianella sandwicensis (Xanthorrhoeaceae)

One problem with including some wild plant species in restoration projects is that seeds are dormant and fail to germinate. Thus, information on the dormancy-breaking and germination requirements facilitates propagation of species, such as the Hawaiian endemic Dianella sandwicensis Hook. & Arn., for conservation. In seeds of this species the embryo is shorter than the endosperm, and seeds sown in early summer in Hawai‘i did not germinate until autumn. Thus, we hypothesised that seeds have morphophysiological dormancy (MPD) and that germination is promoted by low (autumn) temperatures. Studies on embryo growth and the temperature requirements for dormancy-break and germination were conducted on seeds of D. sandwicensis collected on three Hawaiian Islands. Prior to germination the embryo length : seed length ratio increased 16.3 to 17.6%; thus, seeds have MPD. Since both embryo growth and germination occurred at 25/15°C, seeds have a simple level of MPD. Seeds germinated to 90–100% at both 20/10 and 25/15°C, but germination was faster at 20/10°C. However, seeds incubated for 12 weeks at 25/15°C then moved to 20/10°C reached 100% germination as rapidly as seeds kept at 20/10°C. Our results show that exposure of seeds to relatively cool autumn (20/10°C) conditions facilitates propagation of this species from seeds.
Seven reasons family doctors get sued and how to reduce your risk.

By adopting a risk-management mind-set, physicians can avert not only malpractice claims but also patient injury.
Influence of verapamil on cellular integrity and electrolyte concentrations of ischemic myocardial tissue in the cat.

Verapamil, at a dose of 1 mg/kg, was given intravenously to anesthetized cats one hour after coronary artery occlusion. Verapamil significantly reduced mean arterial blood pressure, but produced an increase in heart rate, partially offsetting the reduction in myocardial oxygen demand resulting from the reduction in pressure. Verapamil failed to prevent the elevations in the S-T segment of the electrocardiogram observed in cats subjected to myocardial ischemia (MI) and given only the vehicle for verapamil (i.e., 0.9% NaCl). Moreover, verapamil also did not prevent the accumulation of creatine phosphokinase (CPK) activity in the circulating blood after MI. Nevertheless, verapamil significantly prevented the loss in CPK and in amino-nitrogen observed in the ischemic region of the myocardium, indicating some protective effect on myocardial integrity. The major effects of verapamil on electrolyte content of ischemic myocardial tissue were a decrease in sodium and an increase in potassium. However, calcium gain by the heart was not prevented by verapamil. Verapamil, therefore, exerts a partial degree of protection of the ischemic myocardium but exerts some other effects which do not help prevent the spread of ischemic damage in the myocardium.
Partial Compensation for Mismatched Uncertain Discrete Systems

Control design of nonlinear discrete-time uncertain systems with (possibly fast) uncertain parameters is considered. We study the effect of only partially compensating the uncertainty. The optimal choice of a design parameter, which indicates the amount of compensation, is recommended.
Cholinergic aspects of carotid body chemotransduction

Neurotransmitters have always been seen as an integral part of the carotid body transducing hypoxia, hypercapnia, and acidosis into increased neural output. Acetylcholine (ACh) was one of the first to be delivered exogenously with a resultant increase in neural output. Hence, ACh was proposed as the principal excitatory neurotransmitter during physiological challenges. A significant amount of data supported this notion, especially studies from Sweden. However, data from other studies was not consistent with this hypothesis. It was reported, for example, that though cholinergic blockers could reduce or abolish an increase in ventilation due to exogenously delivered ACh, they did not block the increase due to hypoxia.
The Current Role of Surgical Therapy in Ewing’s Sarcoma

The role of surgical therapy as an adjunct in the treatment of patients with Ewing’s sarcoma of bone is becoming increasingly clear. Since Ewing’s original description of the use of a radium pack in treating a patient with Ewing’s sarcoma of the ulna, surgery has been reserved primarily for the management of bulky and destructive lesions or for amputation following local failures of radiation therapy. It was well recognized that radiation therapy could most often control the primary tumor; however, the majority of patients developed systemic disease and died within two years.
BEST LINEAR INVARIANT ESTIMATION OF WEIBULL PARAMETERS: SAMPLES CENSORED BY TIME AND TRUNCATED DISTRIBUTIONS

Abstract A method is derived for estimating Weibull parameters from ordered observations selected from time-censored samples or from truncated distributions. The method depends on computer-generated tabulated values, does not require the use of a computer once these values are available and is applicable to all distributions with unknown location and scale parameters. It is particularly useful in cases in which maximum-likelihood solutions require iterative procedures. Tables for estimating Weibull parameters are given for time-censored samples.
Neurobiological Basis of Drug Reward and Reinforcement

Drugs of abuse interact with brain circuitry involved in reward and reinforcement, and it is thought that through these interactions drugs can gain influence over brain function, leading to maladaptive behavior. This chapter reviews the basic concepts of reward and reinforcement, with particular emphasis on positive and negative reinforcement and the differences between goal-directed and stimulus-driven “habitual” behavior. The role of particular neurotransmitters and neural circuitry, most notably cortico-basal ganglia circuits, in reward, reinforcement, and drug addiction is then discussed. Several laboratory animal models of drug use are considered along with critical consideration of what constitutes an adequate “addiction” model. The actions of addictive drugs within the brain reinforcement and reward circuitry are then reviewed, including information about the molecular targets of abused drugs, their actions on relevant circuitry, and their actions in the aforementioned laboratory animal models. Finally, the neurobiological underpinnings of drug use, abuse, and addiction are discussed, and some ideas are put forward about future research in this field.
God and Ultimate Reality: An Analytical Interpretation of Śaņkara’s Philosophy

The chief objective of this paper is to offer an analytical clarification of the central concepts of Śaṇkara’s Advaita Vedanta: adhyāsa (superimposition), māyā, avidyā (ignorance), appearance, Īśvara (God), and ultimate reality. Appropriate comparisons are made between Śaṇkara and Kant, Nagarjuna and Śaṇkara, and Yogacara and Śaṇkara. Contrary to the widespread view that Śaṇkara is a metaphysician, this essay demonstrates that Śaṇkara is not a metaphysician but an analytical phenomenologist. For Śaṇkara, all claims about the world and ultimate reality are to be phenomenologically certified; claims not so certifiable are metaphysical.
The Ataxia telangiectasia-mutated and Rad3-related protein kinase regulates cellular hydrogen sulfide concentrations

The ataxia telangiectasia-mutated and Rad3-related (ATR) serine/threonine kinase plays a central role in the repair of replication-associated DNA damage, the maintenance of S and G2/M-phase genomic stability, and the promotion of faithful mitotic chromosomal segregation. A number of stimuli activate ATR, including persistent single-stranded DNA at stalled replication folks, R loop formation, hypoxia, ultraviolet light, and oxidative stress, leading to ATR-mediated protein phosphorylation. Recently, hydrogen sulfide (H2S), an endogenous gasotransmitter, has been found to regulate multiple cellular processes through complex redox reactions under similar cell stress environments. Three enzymes synthesize H2S: cystathionine-β-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate sulfurtransferase. Since H2S can under some conditions cause DNA damage, we hypothesized that ATR activity may regulate cellular H2S concentrations and H2S-syntheszing enzymes. Here we show that human colorectal cancer cells carrying biallelic knock-in hypomorphic ATR mutations have lower cellular H2S concentrations than do syngeneic ATR wild-type cells, and all three H2S-synthesizing enzymes show lower protein expression in the ATR hypomorphic mutant cells. Additionally, ATR serine 428 phosphorylation is altered by H2S donor and H2S synthesis enzyme inhibition, while the oxidative-stress induced phosphorylation of the ATR-regulated protein CHK1 on serine 345 is increased by H2S synthesis enzyme inhibition. Lastly, inhibition of H2S production potentiated oxidative stress-induced double-stranded DNA breaks in the ATR hypomorphic mutant compared to ATR wild-type cells. Our findings demonstrate that the ATR kinase regulates and is regulated by H2S.
Ecological continuity and transformation after the Permo-Triassic mass extinction in northeastern Panthalassa

The Permo-Triassic mass extinction (PTME) is often implicated in the transition from the Paleozoic evolutionary fauna (PEF) to the modern evolutionary fauna (MEF). However, the exact timing and details of this progression are unknown, especially regarding the vacating and filling of functional ecological space after the PTME. Here, we quantify the functional diversity of middle Permian and Early Triassic marine paleocommunities in the western US to determine functional re-organization in the aftermath of the PTME. Results indicate that while the PTME was selective in nature, many new Triassic taxa either re-filled functional roles of extinct Permian taxa or performed the same functional roles as Permian survivors. Despite this functional overlap, Permian survivors and new Triassic taxa differed significantly in their relative abundances within those overlapping functions. This shift in numerical emphasis, driven by an increase in abundance towards more MEF-style traits, may represent a first step in the transition between the PEF and MEF. We therefore suggest that the extreme impact of the PTME had significant and permanent re-organizational effects on the intrinsic structure of marine ecosystems. Early Triassic ecosystems likely bridged the gap between the Paleozoic and modern evolutionary faunas, as newly originated Triassic taxa shared ecospace with Permian survivors, but shifted functional emphasis.
Transitions to Adulthood in Immigrant America: Barriers and Opportunities

Approximately 30 percent of the more than 68 million young adults aged 18 to 34 in the United States today are either foreign born or of foreign parentage. As these newcomers make their transitions to adulthood, their experiences and readiness to progress to adulthood differ significantly from one another, and from their native-parentage counterparts. For many ethnic groups, significant progress takes place from the first to the second generation. But for millions of young immigrants, a lack of legal permanent residency status blocks their prospects for social mobility. Immigrant groups experience gaps in social, economic, and legal status that are even greater than the gaps between native whites and blacks. These social and economic divides reflect three very different ways immigrants enter the country: through regular immigration channels, without legal authorization, or as state-sponsored refugees. Having an undocumented status has become all the more consequential with the failure of Congress to pass comprehensive federal immigration reforms. In the 2011 Pastora Cafferty Lecture on Race and Ethnicity in American Life, professor Ruben G. Rumbaut described how generation, national origin, and the contexts in which they are coming of age in America shape the experiences of these newcomers as they become adults.Figures and Data Tables are available at: http://ssrn.com/abstract=2187630
The Radiopharmaceutical Chemistry of the Radioisotopes of Copper

There are five radioisotopes of copper that are suitable for use in nuclear imaging or targeted radionuclide therapy: copper-67, copper-64, copper-62, copper-61, and copper-60. The diverse nuclear properties of these radionuclides include half-lives ranging from 10 min to 62 h and decay pathways via positron (β+) and beta-minus (β−) emission. Single-photon emission computed tomography (SPECT) as well as radionuclide therapy can be performed using copper-67, while the quartet of other radioisotopes decays via positron emission for positron emission tomography (PET). Two current foci of research into the radiopharmaceutical chemistry of copper are the creation of new coordination architectures for the radiometal and the development of relatively simple radiolabeling techniques that will lead to agents that remain stable in vivo. This chapter will discuss the production of the various radionuclides, the development of chelators for copper(II), and the applications of copper radiopharmaceuticals in both imaging and therapy.
Retrosynthetic design of metabolic pathways to chemicals not found in nature

Abstract Biology produces a universe of chemicals whose precision and complexity is the envy of chemists. Over the last 30 years, the expansive field of metabolic engineering has many successes in optimizing the overproduction of metabolites of industrial interest, including moving natural product pathways to production hosts (e.g., plants to yeast). However, there are stunningly few examples where enzymes are artificially combined to make a chemical that is not found somewhere in nature. Here, we review these efforts and discuss the challenges limiting the construction of such pathways. An analogy is made to the retrosynthesis problem solved in chemistry using algorithmic approaches, recently harnessing artificial intelligence, noting key differences in the needs of the optimization problem. When these issues are addressed, we see a future where chemistry and biology are intertwined in reaction networks that draw on the power of both to build currently unobtainable molecules across consumer, industrial, and defense applications.
The Visual Turn in Mobile Communication: Notes about Travel Experiences

Joachim Hoflich has been a seminal contributor to the field of mobile communication and indeed, it was through this work that I had my first personal encounter with him. The occasion was a meeting hosted in Budapest by Kristof Nyiri at the Hungarian Academy of Sciences in 2002. In my mind’s eye, I can still see him standing beneath bucolic murals of Hungarian landscapes in the palace’s capacious meeting rooms, reading with gusto his paper to the assembled scholars.
Wound Healing and Plastic Surgery Principles

Successful surgery relies on proper wound healing and tissue repair. When these processes do not follow their normal pattern, urological surgeons may be faced with complications including skin separation, wound dehiscence, tissue necrosis, and breakdown of vascular, urinary and parenchymal structures. Determinants of proper surgical healing include preservation of critical anatomical structures; restoration of tissue integrity and homeostasis; and the regenerative potential of tissues. In addition, the surgeon must have a detailed knowledge of previous surgical, traumatic, infectious, and radiation related perturbations to normal anatomy and physiology, along with an understanding of the time course and vulnerability of tissues after injury in order to properly plan for successful primary repair or tissue transfer to achieve restoration of function.
The trends of socioeconomic inequities in full vaccination coverage among children aged 12-23 months from 2000 to 2017: evidence for mitigating disparities in vaccination service in Zhejiang province.

This study aimed to evaluate the trends and changes in inequities in the completeness of the primary vaccination (CPV) scheduled before the first year of age among children aged 12–23 months, from ...
How fisher behavior can bias stock assessment: insights from an agent-based modeling approach

During stock assessment, fishery-dependent observations are often used to develop indices of abundance or biomass from catch per unit of effort (CPUE) and contribute catch at size or age informatio...
RNA sequencing of whole blood in dogs with primary immune-mediated hemolytic anemia (IMHA) reveals novel insights into disease pathogenesis

Immune-mediated hemolytic anemia (IMHA) is a life-threatening autoimmune disorder characterized by a self-mediated attack on circulating red blood cells. The disease occurs naturally in both dogs and humans, but is significantly more prevalent in dogs. Because of its shared features across species, dogs offer a naturally occurring model for studying IMHA in people. In this study, we used RNA sequencing of whole blood from treatment-naive dogs to study transcriptome-wide changes in gene expression in newly diagnosed animals compared to healthy controls. We found many overexpressed genes in pathways related to neutrophil function, coagulation, and hematopoiesis. In particular, the most highly overexpressed gene in cases was a phospholipase scramblase, which mediates the externalization of phosphatidylserine from the inner to the outer leaflet of cell membranes. This family of genes has been shown to be critically important for programmed cell death of erythrocytes as well as the initiation of the clotting cascade. Unexpectedly, we found marked underexpression of many genes related to lymphocyte function. We also identified groups of genes that are highly associated with the inflammatory response and red blood cell regeneration in affected dogs. We did not find any genes that distinguished dogs that lived vs. those that died at 30 days following diagnosis, nor did we find any relevant genomic signatures of microbial organisms in the blood of affected animals. Future studies are warranted to validate these findings and assess their implication in developing novel therapeutic approaches for dogs and humans with IMHA.
Association of Patterns of Glaucomatous Macular Damage With Contrast Sensitivity and Facial Recognition in Patients With Glaucoma.

Importance Facial recognition is a critical activity of daily living that relies on macular function. Glaucomatous macular damage may result in impaired facial recognition that may negatively affect patient quality of life. Objective To evaluate the association of patterns of glaucomatous macular damage with contrast sensitivity and facial recognition among patients with glaucoma. Design, Setting, and Participants In this prospective cohort study at a single tertiary care center, 144 eyes of 72 consecutive patients with glaucoma with good visual acuity (20/40 or better in each eye) were studied. Data were collected from March to April 2019. Exposures Eyes with macular damage were categorized as having focal, diffuse, or mixed (focal and diffuse) damage based on optic disc and macular spectral-domain optical coherence tomography and 10-2 visual field (VF) damage. Only eyes with focal or diffuse damage were included. Higher-acuity and lower-acuity eyes were determined by 10-2 VF mean deviation (MD). Facial disability was defined as facial recognition scores at the 2% level of normal participants. Main Outcomes and Measures (1) Monocular contrast threshold as measured by the Freiburg Visual Acuity and Contrast Test and (2) binocular facial recognition as measured by the Cambridge Face Memory Test. Results Of the 72 included patients, 49 (68%) were White and 41 (57%) were female, and the mean (SD) age was 67.0 (11.6) years. Eyes with diffuse damage had greater contrast impairment compared with eyes with focal damage (β = -0.5; 95% CI, -0.6 to -0.4; P < .001) after adjusting for 10-2 VF MD, 24-2 VF MD, age, presence of an early cataract, and number of drops. Similarly, Cambridge Face Memory Test scores were significantly lower in patients with diffuse rather than focal macular damage, regardless of eye (better-seeing eye: β = 10.0; 95% CI, 2.0 to 18.2; P = .001; worse-seeing eye: β = 5.5; 95% CI, 0.8 to 10.0; P = .23). Relative risk of facial disability was greater for patients with diffuse but not focal macular damage in the better-seeing eye (relative risk, 86.2; 95% CI, 2.7 to 2783.3; P = .01). Conclusions and Relevance In this cohort study, diffuse rather than focal glaucomatous macular damage was associated with diminished facial recognition and contrast sensitivity. Evaluation of macular optical coherence tomography and 10-2 VF and resultant detection of diffuse macular damage may help minimize glaucoma-related visual disability.
Early technical pancreas failure in Simultaneous Pancreas-Kidney Recipients does not impact renal allograft outcomes.

Early pancreas loss in simultaneous pancreas-kidney (SPK) transplants has been associated with longer perioperative recovery and reduced kidney allograft function. We assessed the impact of early pancreas allograft failure on transplant outcomes in a contemporary cohort of SPK patients (n = 218). Early pancreas allograft loss occurred in 12.8% (n = 28) of recipients. Delayed graft function (DGF) was more common (21.4% vs. 7.4%, p = 0.03) in the early pancreas loss group, but there were no differences in hospital length of stay (median 6.5 vs. 7.0, p = 0.22), surgical wound complications (p = 0.12), or rejection episodes occurring in the first year (p = 0.87). Despite differences in DGF, both groups had excellent renal function at 1 year post-transplant (eGFR 64.1 ± 20.8 vs. 65.8 ± 22.9, p = 0.75). There were no differences in patient (HR 0.58, 95% CI 0.18-1.87, p = 0.26) or kidney allograft survival (HR 0.84, 95% CI 0.23-3.06, p = 0.77). One- and 2-year protocol kidney biopsies were comparable between the groups and showed minimal chronic changes; the early pancreas loss group showed more cv changes at 2 years (p = 0.04). Current data demonstrate good outcomes and excellent kidney allograft function following early pancreas loss.
Towards Contactless Monitoring of Blood Pressure at Rest and During Exercise Using Infrared Imaging

Blood pressure monitoring have been shown to improve management of chronic health conditions. However, devices used for automated monitoring of blood pressure at home provide reliable measurements only at rest and cannot be used during exercise for continuous blood pressure monitoring. Image-based analysis of skin color changes has been introduced to capture pulse transit time which correlates with blood pressure. In this project we assess feasibility of using infrared imaging to support continuous contactless blood pressure monitoring at rest and during exercise. In order to utilize image-based photoplethysmogram (iPPG) and image-based pulse transit time (iPTT) without blinding effect of high intensity visible light source, a light source outside visible spectrum had to be employed. Thus, we introduced a high-speed camera to measure iPPG and iPTT with the infrared light source. The feasibility of this approach that was unclear at the beginning of the study was fully supported by our initial analysis.
Under-Prosecution Too

Conventional wisdom holds that the criminal legal system suffers from over-enforcement, including over-prosecution. This account, however, obscures data suggesting that some crimes, including sexual assault, are under-prosecuted. High attrition rates in sexual assault cases are caused not only by insufficient reporting and inadequate police investigation but also by prosecutors’ frequent refusal to file charges due to what they describe as “insufficient evidence.” Yet, studies suggest that the designation “insufficient evidence” is often a pretext, disguising the actual reason for prosecutorial declination decisions - prosecutors’ prediction of the low likelihood that hypothetical juries would convict, a test commonly referred to as the “convictability” standard. The under-prosecution of sexual assault is an especially disconcerting problem because victims of these crimes are often marginalized, including racial and other minorities, who have been under-served by a legal system that has failed to provide them with equal protection of law. The problem, however, has received only scant scholarly attention. This makes two contributions to existing literature. First, it argues that the convictability standard that prosecutors rely on to assess evidentiary sufficiency should be rejected. In its stead, this Article proposes the “reasonable prosecutor” standard for prosecutors to adhere to in deciding whether to bring sexual assault charges. Under this standard, the threshold is whether, as a legal matter, based on the law’s substantive definition of the crime and the likely admissible evidence, the suspect should be found guilty beyond a reasonable doubt. Second, this Article uses the under-prosecution of sexual assault as a case study for making broader arguments about the prosecutor’s role in promoting social justice goals. To send the expressive message that both defendants and victims deserve the law’s protection, this Article develops the Equitable Prosecution Model. The model uses the concept of equitable prosecution to justify a more vigorous prosecution of crimes like sexual assault that have largely been under-prosecuted. Drawing on a civil rights underpinning, and theorizing the roles for progressive prosecutors in curbing sexual violence, this model highlights the prosecutor’s role in bringing criminal charges for historically under-prosecuted crimes. It requires prosecutors to equitably balance defendants’ and victims’ conflicting interests. This model thus reconciles the goals of the BLM and #MeToo movements, demonstrating that they are complementary, rather than contradictory.
683-P: Real-World Evaluation of Once-Weekly Semaglutide (Sema OW) in Patients Newly Initiating GLP-1 Agonist Therapy

Background: This study presents real-world effectiveness of sema OW in a cohort of US commercially insured/Medicare Advantage T2D patients newly initiating a GLP-1 agonist. Methods: Claims and lab result data were used to identify T2D patients who initiated sema OW between 12/1/17 - 6/30/20 (index as first claim). Selected patients had ≥1 A1c result within ≤3 months pre- and ≥3 months post-index. Patients with no claim for any GLP-1 agonist in the 12 months prior to index and persistent on sema OW (those with a sema OW prescription with days supply dispensed overlapping/in proximity of date of post-index A1c) were assessed for A1c changes and stratified by age ( 9%. Results: Of 1,842 patients newly initiating sema OW, 49% were female and 8% were ≥ 65 years of age. The pre/post change in A1c was significant in all patients (-1.3%) and in each age subgroup ( 9%, regardless of age. Attainment of A1c Conclusion: nitiation of sema OW in T2D patients naive to GLP-1 agonists and persistent on sema OW was associated with a significant reduction in A1c and an increase in target attainment of A1c Disclosure N. Shivappa: Other Relationship; Self; Novo Nordisk. C. Swift: Employee; Self; Novo Nordisk Inc. J. Noone: Employee; Self; Novo Nordisk Inc. S. Du: None. Y. M. Paprocki: Employee; Self; Novo Nordisk, Stock/Shareholder; Self; Novo Nordisk. H. Tan: Other Relationship; Self; HealthCore. V. Willey: Employee; Self; HealthCore.
Flame aerosol synthesis of hollow alumina nanoshells for application in thermal insulation

Abstract Commercial implementation of hollow nanoshell materials is often limited by difficult scale-up and high cost. Here we present a scalable, continuous, and potentially low-cost route to hollow nanostructured materials using a High Temperature Reducing Jet flame aerosol reactor. The key advantage of this process over traditional flame aerosol synthesis methods is separation of flame chemistry and particle formation, which allows production of hollow nanoshells from an aqueous salt solution without any template or surfactant. We produced amorphous hollow alumina with an average diameter of 181 nm and shell thickness below 10 nm, and demonstrated the generality of the method by also producing hollow SiO2, ZrO2, Ga2O3, and Co2O3. We characterized the morphology, phase transition, thermal stability, and thermal conductivity of the flame-made hollow alumina by electron microscopy, x-ray diffraction, and thermal analysis methods. As a prototypical application, we incorporated hollow alumina into thermal insulation, combining it with common fiberglass insulation to reduce the thermal conductivity by 30% relative to pure fiberglass, to 0.028 W m−1 K−1 while maintaining robust fire-resistance and elasticity.
The Effect of Diabetes Self-Management Education on Glycemic Control in Minority Patients With Diabetes Mellitus.

Background Diabetes self-management education (DSME) plays a vital role in diabetes control yet is highly underutilized, especially in the minority population. The efficacy of DSME on glycemic control among the Hispanic and non-Hispanic black population is not as well established as it is compared to the non-Hispanic White population. Methodology In this retrospective cohort study, patients who participated in both group and one-to-one DSME classes at Saint Francis Medical Center, Trenton, New Jersey, from 2017 to 2019 were identified. Mean hemoglobin A1c levels before DSME and after DSME were compared using paired t-test. Results A total of 344 patients were included in the study. Out of 344 patients, 200 (58%) patients were Hispanic and 97 (28%) were non-Hispanic black, 42 (12%) were Caucasian, and five (2%) were from other races. The mean hemoglobin A1c was reduced by an average of 1.08% among patients who participated in group DSME (DSME done in group settings) and by an average of 1.95% among patients who participated in one-to-one DSME (DSME done in individualized settings). Conclusion DSME is effective in reducing hemoglobin A1c levels in Hispanic and non-Hispanic black majority patients. One-to-one DSME is more effective than group DSME in reducing hemoglobin A1c in this patient population.
Mechanomyogram amplitude vs. isometric ankle plantarflexion torque of human medial gastrocnemius muscle at different ankle joint angles.

Abstract The purpose of this study was to investigate the influence of changes in ankle joint angle on the mechanomyogram (MMG) amplitude of the human medial gastrocnemius (MG) muscle during voluntary isometric plantarflexion contractions. Ten healthy individuals were asked to perform voluntary isometric contractions at six different contraction intensities (from 10% to 100%) and at three different ankle joint angles (plantarflexion of 26°; plantarflexion of 10°; dorsiflexion of 3°). MMG signals were recorded from the surface over the MG muscle, using a 3-axis accelerometer. The relations between root mean square (RMS) MMG and isometric plantarflexion torque at different ankle joint angles were characterized to evaluate the effects of altered muscle mechanical properties on RMS MMG. We found that the relation between RMS MMG and plantarflexion torque is changed at different ankle joint angles: RMS MMG increases monotonically with increasing the plantarflexion torque but decreases as the ankle joint became dorsiflexed. Moreover, RMS MMG shows a negative correlation with muscle length, with passive torque, and with maximum voluntary torque, which were all changed significantly at different ankle joint angles. Our findings demonstrate the potential effects of changing muscle mechanical properties on muscle vibration amplitude. Future studies are required to explore the major sources of this muscle vibration from the perspective of muscle mechanics and muscle activation level, attributable to changes in the neural command.
“The Heart is a House”: A Heuristic for Generating Cardiac Differential Diagnoses:

BACKGROUNDDifferential diagnosis (DDx) is a core clinical reasoning skill that all medical students and physicians must acquire and develop. Metamemory techniques (MMTs), including mnemonic devices...
Tissue distribution and histopathological effects of titanium dioxide nanoparticles after intravenous or subcutaneous injection in mice.

Nanoparticles can be formed following degradation of medical devices such as orthopedic implants. To evaluate the safety of titanium alloy orthopedic materials, data are needed on the long-term distribution and tissue effects of injected titanium nanoparticles in experimental animals. In this study, we evaluated the tissue distribution and histopathological effects of titanium dioxide (TiO2) nanoparticles (approximately 120 nm diameter) in mice after intravenous (i.v.; 56 or 560 mg kg−1 per mouse) or subcutaneous (s.c.; 560 or 5600 mg kg−1 per mouse) injection on two consecutive days. Animals were examined 1 and 3 days, and 2, 4, 12 and 26 weeks after the final injection. When examined by light microscopy, particle agglomerates identified as TiO2 were observed mainly in the major filtration organs – liver, lung and spleen – following i.v. injection. Particles were still observed 26 weeks after injection, indicating that tissue clearance is limited. In addition, redistribution within the histological micro-compartments of organs, especially in the spleen, was noted. Following s.c. injection, the largest particle agglomerates were found mainly in the draining inguinal lymph node, and to a lesser extent, the liver, spleen and lung. With the exception of a foreign body response at the site of s.c. injection and the appearance of an increased number of macrophages in the lung and liver, there was no histopathological evidence of tissue damage observed in any tissue at any time point. Published 2011. This article is a US Government work and is in the public domain in the USA.
Antiviral Activity of Selected Catharanthus Alkaloids

Thirty-six alkaloids isolated either from Catharanthus roseus or C. lanceus were evaluated for in vitro activity against vaccinia and polio type III viruses. Nine of these alkaloids were effective as antiviral agents, with pericalline being the most effective.
Cerium (III) Methanesulfonate

[77998-20-0] (·2H2O) C3H9CeO9S3 (MW 425.42) InChI = 1S/3CH4O3S.Ce/c3*1-5(2,3)4;/h3*1H3,(H,2,3,4);/q;;;+3/p-3 InChIKey = XPQVQIJYDXCEKC-UHFFFAOYSA-K [73640-09-2] C3H13CeO11S3 (MW 461.46) InChI = 1S/3CH4O3S.Ce.2H2O/c3*1-5(2,3)4;;;/h3*1H3,(H,2,3,4);;2*1H2/q;;;+3;;/p-3 InChIKey = CSCZHPRFXJAVNZ-UHFFFAOYSA-K (stable, soluble cerium(III) salt used as a mediator for organic oxidation) Alternate Name: cerous methanesulfonate. Physical Data: white crystalline solid. Solubility: very sol water, aqueous methanesulfonic acid, and aqueous acetonitrile; sol methanol; insol acetone. Preparative Methods: prepared by the reaction of methanesulfonic acid with an aqueous suspension of cerium(III) carbonate. Solids can be precipitated with acetone or a large excess of methanesulfonic acid. Handling, Storage, and Precautions: best used in aqueous solution as prepared. Cerium(III) salts are generally believed to be of low toxicity.