cssi/SciSciGPT-SciSciNet huggingface dataset:
The impact of proton beam therapy on blood cell count nadir during neoadjuvant chemoradiation therapy for esophageal cancer.

137Background: To analyze the blood cell count nadir, particularly grade 4 hematologic toxicities, in patients with esophageal cancer who were treated with neoadjuvant chemoradiation (nCRT) with either Proton Beam Therapy (PBT) or Intensity Modulated Radiation Therapy (IMRT) in a propensity-matched pair analysis. Methods: Esophageal cancer patients (n = 480) treated from 2005-2016 with nCRT with (n = 167) or without (n = 313) induction chemotherapy (ICT) were analyzed. White blood cell, neutrophil, lymphocyte and platelet counts nadir during ICT and CRT were obtained, and graded according to the CTCAE v.4.0. Univariate and multivariable logistic regression models to identify factors associated with increased risk of grade 4 lymphopenia were fitted. By propensity score matching, 136 PBT cases and 136 propensity score matched IMRT controls were selected for comparison. Results: In the entire study cohort during CRT (n = 480), 2 (0.4%), 1 (0.2%), 159 (33%), and 2 (0.4%) patients experienced grade 4 leukopeni...
Prognosis of post-cardiac-arrest anoxic encephalopathy using felbamate: A case report

Reliable prognostic methods for cerebral functional outcome of post cardiac-arrest anoxic encephalopathy (AAE) are necessary. Evolution of the Electroencephalogram (EEG) background pattern is a rob...
Abstract 064: The Lipoxigenase Inhibitor Nordihydroguaiaretic Acid Prevents the Development of Hypoxia-Induced Pulmonary Hypertension in Mice

Pulmonary hypertension (PH) is a chronic lung disease characterized by progressively elevated pulmonary arterial pressures and severe pulmonary vascular remodeling resulting from interactions between oxidized lipoprotein deposition and increased endothelial proliferation. Previously we have shown increased plasma levels of biological oxidation products such as hydroxyoctadecadienoic acids (HODEs) and hydroxyeicosatetraenoic acids (HETEs) in the rat monocrotaline model of PH. Here we investigated the role of HETEs and HODEs in the development of PH and whether their inhibition with the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) attenuates the progression of PH. Mice were placed in a hypoxic chamber with O2 concentrations of ≤10% for 21 days and either left untreated to develop PH (n=7) or treated with NDGA daily (10mg/kg/day, i.p., n=4) from day 1. Direct RV catheterization was terminally performed to record RV pressure (RVP). Pulmonary arteriolar thickening and oxidized lipid deposition were assessed by staining lung sections with Masson’s Trichrome or with α-smooth muscle actin and E-06 (marker for oxidized low-density lipoproteins). In vitro, human pulmonary artery smooth muscle cell (hPASMC) proliferation was assessed by MTT assays in the absence or presence of 12-HETE (100ng/ml), 9-HODE (1µg/ml) and 13-HODE (1µg/ml) alone or together with NDGA (10, 25 and 50µM). In-vitro, HETE/HODE treatment increased hPASMC proliferation ~ 2-fold when compared to untreated cells and NDGA significantly inhibited the proliferative effects of all three oxidized lipids. In-vivo, NDGA treatment prevented the development of PH. RVP was lower in the NDGA-treated group vs. the PH group (24.01±1.39mmHg vs. 36.91±5.74mmHg, p
A Four-Hundred Kilowatt Pressurized Arc Imaging Furnace

The pressurized arc imaging facility at Southwest Research Institute (SwRI) was designed, built, and tested in preliminary fashion during 1956–1958 under the sponsorship of the National Aeronautics and Space Administration (1). A subsequent objective of the NASA program was to conduct ablation studies of materials under extremely rapid heating, in connection with atmospheric re-entry problems (2). In 1959, other programs were begun for the Wright Air Development Division and the Sandia Corporation, which were concerned, respectively, with heat conduction in materials and spectrographic studies of ablation products. These three programs (3–5) were completed in 1960. Since then, additional studies of ablation have been conducted for a private sponsor and SwRI has supported a variety of short experimental studies in the facility, particularly its use as a high-intensity light source for continuously pumping ruby lasers (6). A program of determining dynamic thermal and thermoelastic properties of materials is currently underway for the Air Force Office of Scientific Research. Incidental to its use as a research tool, the facility has been subject to extensive modifications and improvements throughout its five years of operation. Many more improvements are possible and are needed.
Safety enforcement for the verification of autonomous systems

Verifying that the behavior of an autonomous systems is safe is fundamental for safety-critical properties like preventing crashes in autonomous vehicles. Unfortunately, exhaustive verification techniques fail to scale to the size of real-life systems. Moreover, these systems frequently use algorithms whose runtime behavior cannot be determined at design time (e.g., machine learning algorithms). This presents another problem given that these algorithms cannot be verified at design time. Fortunately, a technique known as runtime assurance can be used for these cases. The strategy that runtime assurance uses to verify a system is to add small components (known as enforcers) to the system that monitor its output and evaluate whether the output is safe or not. If the output is safe, then the enforcer lets it pass; if the output is unsafe, the enforcer replaces it with a safe output. For instance, in a drone system that must be restricted to fly within a constrained area (a.k.a. geo-fence) an enforcer can be used to monitor the movement commands to the drone. Then, if a movement command keeps the drone within the geo-fence, the enforcer lets it pass, but if the command takes the drone outside of this area, the enforcer replaces it with a safe command (e.g., hovering). Given that enforcers are small components fully specified at design time, it is possible to use exhaustive verification techniques to prove that they can keep the behavior of the whole system safe (e.g., the drone flying within the geo-fence) even if the system contains unverified code.
Coaxial wires coax energy from water

Inexpensive, earth-abundant photoabsorbers for solar water splitting have, so far, not demonstrated notable performance. Now, voltage gained from a coaxial heterojunction coupled with nanostructure-enhanced photocurrent results in Cu2O photocathodes demonstrating benchmark water-splitting performance.
Solving Sign Problems with Meron Algorithms

A new approach to the solution of sign problems in Monte-Carlo methods, based on cluster algorithms, has emerged recently. The underlying idea is to identify clusters that help match configurations of equal weight but opposite signs and hence do not contribute to the path integral. Avoiding these clusters, called merons, alleviates the sign problem and in certain cases solves it completely. Among the variety of problems that can be solved using these techniques there also exist some severe fermion sign problems. A pedagogical discussion of the above ideas is presented here with an emphasis on applications to fermionic systems.
Uncertainty as a Resource for Managing Complexity

Several novel theories of uncertainty, which either extend or complement probability theory, are overviewed. It is shown that three types of uncertainty are involved in these theories. Well-established measures of these types of uncertainty are overviewed and their utility in three methodological principles of uncertainty is explained.
Preliminaries: Concepts, Trends, and Frameworks

This chapter presents background that will provide context for the rest of the report, including key concepts and frameworks, recent trends in the emergence of production sharing, and a discussion on the potential benefits and risks of joining global supply chains.
Poly(Imidazoleamides): A New Class of Heteroaromatic Polyamides

The introduction of heteroaromatic units into polymer backbones has played a major role in the advancement of high performance materials. This strategy has resulted in a number of aromatic heterocyclic polymers and aromatic-heteroaromatic polyamides. For example, Marvel’sl preparation of polybenzimidazole or Kvenzel’s2 work in which oxadiazole rings were incorporated in aromatic polyamides. We now report the preparation of poly(imidazoleamides), a new class of heteroaromatic polyamides based on cyanoimidazoles.
Intuition and rigor and Enriques's quest

I n the preceding article we have seen that Enriques and, indeed, the whole Italian school of algebraic geometry in the first half of the twentieth centurywere frustratedbyone glaring gap in their theory of algebraic surfaces. This magnificent theory answered essentially all the basic questions about algebraic surfaces and hadbeenconstructedusingpurely geometric tools. But one of its central theorems seemed to defy all their attempts to give it a geometric proof. It had been proven by analytic means by Poincare with his theory of “normal functions”, so the theory was sound—but this approach was alien to their intuitions. It wasmuch like the need for analysis in proving the prime number theorem before Selberg found his elementary proof. In my own education, I had assumed they were irrevocably stuck, and it was not until I learned of Grothendieck’s theory of schemes and his strong existence theorems for the Picard scheme that I saw that a purely algebrogeometric proof was indeed possible. I say here “algebro-geometric”, not “geometric”, because the first requirement in moving ahead had been the introduction of new algebraic tools into the subject first by Zariski and Weil and subsequently by Serre and Grothendieck. When Professors Babbitt and Goodstein wrote me about Enriques’s work in the 1930s, I realized that the full story was more complex. As I see it now, Enriques must be credited with a nearly complete geometric proof using, as did
Birth Certificate Validity and the Impact on Primary Cesarean Section Quality Measure in New York State

In New York (NY), birth certificate data are routinely used for assessing quality of care and health outcomes such as primary cesarean section (PCS) rates. However rare events are often underreported. This study compared birth certificates to medical records, and examined the impact of underreporting on risk adjustment variables for PCS. We conducted an internal validation study using a random sample of 702 NY births in 2009. Sensitivity and positive predictive value (PPV) of rare events reported on birth certificates were determined using abstracted and matched medical records as the gold standard. To assess the impact, we calculated PCS odds ratios for variables in the risk-adjustment model before and after correcting for measurement error. The sensitivity and PPV of birth certificate data elements including those in the PCS risk model varied from 0 to 100. After correction for measurement error, PCS odds ratios increased for most variables. For example, the PCS odds ratio for those with no prior live births was 3.03 (95% CI 2.94, 3.13), but after correction of measurement error increased to 3.46 (95% CI 3.22, 3.67). A composite negative event variable including abruptio placenta, eclampsia, or infection was the only variable that decreased after correction and was no longer significant (uncorrected OR 3.06, 95% CI 2.86, 3.29; corrected OR 1.42, 95% CI 0.79, 2.59). Underreporting on birth certificates remains concerning and impacts the risk adjustment for quality measures. Without improved data validity, health plans’ quality metrics do not fully account for patient case-mix.
Scalable honeycomb top contact to increase the light absorption and reduce the series resistance of thin film solar cells

This paper presents a novel design for the top contact of thin film photovoltaic (PV) solar cells. The new top contact is formed by fabricating a 20nm thin honeycomb shaped silver mesh on top of an ultra-thin 13nm of indium tin oxide. The new top contact offers the potential to reduce the series resistance of the cell while increasing the light current via plasmonic resonance. Using the nano-bead lithography technique the honeycomb top contact was fabricated and electrically characterized. The experimental results verified the new contact reduces the sheet resistance by about 40%. Numerical simulations were then used to analyze the potential performance enhancement in the cell. The results suggest the proposed top contact integrated with a typical thin film hydrogenated amorphous silicon PV device would lead to more than an 8% improvement in the overall efficiency of the cell.
Cryopreserved Cd34 Cells: Measuring Viability Pre-Thaw and Viability over Time Post-Thaw

Common practices associated with the use of cryopreserved hematopoietic progenitor cells (HPC) include measuring the viability of the thawed cells from a sample derived from the thawed product, and thawing cells at the patient's bedside out of concern for possible toxicity of DMSO in the post-thaw liquid cell suspension. The former practice carries the risk of discovering excess cell death when it is too late to correct, and the concomitant risk of non-engraftment. The latter practice carries all of the risks associated with manipulating cells in a non-controlled environment including risk of contamination and lack of suitable containment in the event of failure of a cryostorage container. In an effort to reduce risks associated with cell cryostorage, we are currently examining the validity of measuring CD34 viability from cells frozen in retention vials concomitantly with product freezing. We are also examining the stability of HPC being held in cryostorage medium from 1 to 24 hours post thaw. We present here our results from a pilot study performed on six bags of cells, previously identified for discard due to death of the intended recipients. Six bags of HPC and associated retention vials, frozen for 5 to 12 years, were selected at random from the pool of discarded products and de-identified per guidelines for discard of medical waste. CD34+ cells were identified using a modification of the ISHAGE method, and dead cells were identified by infiltration with the fluorochrome dye 7-AAD. CD34+ cells stored in retention vials were 94±11 percent viable, and CD34+ cells stored in bags were 96±7 percent viable. A Wilcoxan matched pairs test yielded p=0.6, indicating that these results were not different. Percent viable CD34+ cell recovery, relative to the known number of CD34+ cells per mL originally frozen, was determined immediately following thawing, and following 1, 2, 4 and 24 hours remining in thawed cryostorage medium, with recoveries (mean ± std. dev.) of 88 ± 31, 76 ± 33, 62 ± 28, 88 ± 41, and 49 ± 26 percent respectively. These preliminary results suggest that viable CD34 percent as measured from a retention vial may serve as a predictor of viability at thawing of it's associated product, and also that HPC held in cryostorage medium post thaw retain viability for at least four hours post thawing. Based on these results we are continuing these studies.
Assessing the feasibility of a chatbot after ureteroscopy

Background: Patients experience common symptoms and/or complications after undergoing ureteroscopy, which is a common procedure used to treat kidney stones. Current methods for patient education regarding these complications include counseling and discharge materials. This study aimed to assess chatbot usage and their ability to deliver information to patient post-ureteroscopy. Methods: Patients who underwent ureteroscopy at the University of Michigan were given instructions to activate the chatbot. Within one to four weeks of their surgery, semi-structured interviews were conducted regarding post-surgical recovery and chatbot usage. Results: Twenty patients were interviewed, seven of whom activated the chatbot. Frequent reasons for not activating the chatbot included misplacing instructions for chatbot use (n=6), relying on follow-up with clinic or discharge materials (n=4), inability to activate chatbot (n=2), and inability to text (n=1). Perceived benefits included alleviation of concerns surrounding common symptoms and quick access to information for non-emergent issues. Conclusions: These results suggest that chatbots are a convenient method to address common concerns post-ureteroscopy. However, better integration in the flow of care delivery and improved usability are needed to increase patient engagement.
Trends in obesity prevalence among total hip arthroplasty patients and the effect on surgical outcomes, 2008-2016.

Abstract Introduction The prevalence of obesity continues to rise in parallel with demand for total hip arthroplasty (THA). This study aims to report obesity trends in primary THA and its effects on procedure outcomes in the United States, stratifying based on Body Mass Index (BMI). Methods Primary THA procedures were identified in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database (2008–2016). Patient demographic (including BMI), primary outcomes (death; serious morbidity), and secondary outcome variables were analyzed. Using BMI comparison groups (Obese: BMI > 30 [O]; Morbidly Obese: BMI > 40 [MO]) for case populations, univariate, propensity score-matched, and multivariate logistic regression analyses were performed. Results The prevalence of obesity increased among primary THA (2008: 546/1200 [45.5%], 2016: 16,078/34,137 [47.1%]) cases. Data on 135,013 primary THA cases were analyzed. Propensity score-matched analyses demonstrated that both serious morbidity (O: OR = 0.73, p Conclusion Both obese and morbidly obese primary THA patient populations were associated with variably increased complication risks; morbidly obese patients had higher complication rates relative to obese patients. Orthopaedic surgeons should continue to consider obesity as a risk factor for THA complications. However, given similar functional outcomes and satisfaction levels as non-obese patients, denying patients THA surgery based on BMI alone may merit reconsideration.
Diagnostic value of CD34 and calretinin immunostaining in the diagnosis of proliferating tricholemmal tumor and trichoblastoma.

Background Proliferating tricholemmal tumor (PTT) is a rare neoplasm of controversial biological behavior for which distinction from other more common tumors is essential. Similarly, trichoblastoma (TB) remains a debatable entity that may represent a variation of basal cell carcinoma (BCC). Our goal is to correlate the staining pattern of calretinin and CD34 in these two follicular tumors vs. their major differential diagnoses, invasive squamous cell carcinoma (ISCC) and BCC. Method Descriptive study of 68 cases: 6 PTT, 22 TB, 20 ISCC, and 20 BCC in a period of 15 years. The diagnosis was confirmed with H&E. The immunohistochemistry results were analyzed and scored positive (weak +, moderate ++, and strong +++) or negative. Results Calretinin was expressed in 4/6 cases of PTT and negative in all TB. Only one malignant case of PTT was positive for CD34 (1/2) and negative in all TB cases. Calretinin and CD34 were negative for all ISCC and BCC. The intensities are shown in tables. Conclusion The diagnosis of these neoplasms is a morphologic diagnosis. However, in those cases where the morphologic aspect is difficult to interpret, calretinin may assist in the diagnosis of PTT, distinguishing the hair follicle tumors with an outer root sheath differentiation. Likewise, CD34 showed significant affinity for the malignant subset of PTT. Calretinin and CD34 did not add any value to the differentiation between TB and BCC. However, this might suggest that both are the same entity with a different morphological permutation.
Intranasal tPA Application for Axonal Remodeling in Rodent Stroke and Traumatic Brain Injury Models

Stroke and traumatic brain injury (TBI) are the major causes of adult long-term disability worldwide. Unfortunately, there are no efficacious therapies available for the vast majority of stroke and TBI patients during their convalescence. As a thrombolytic agent, recombinant tissue plasminogen activator (tPA) is the only FDA approved therapeutic agent for treatment of acute ischemic stroke; however, the application of tPA is limited by the narrow therapeutic time window and potential adverse side effects on brain edema and hemorrhage. In addition to vascular endothelium derived tPA in the circulation, neuroendocrine tissue synthesized tPA is widely distributed in the CNS and is involved in axonal path finding, synaptic plasticity and dendritic remodeling during development, and axonal outgrowth after stroke and injury. We have investigated the therapeutic effect of tPA on neurological recovery and corticospinal axonal remodeling in rodent subacute stroke and TBI models administered intranasally, to bypass the blood-brain barrier and avoid the rapid inactivation and clearance of tPA in the circulation. The neurorestorative benefits of tPA in subacute stroke and TBI treatments and the potential underlying mechanisms are discussed in this chapter.
Total Anterior Uncinatectomy During Anterior Discectomy and Fusion for Recurrent Cervical Radiculopathy: A Two-dimensional Operative Video and Technical Report

A common cause of cervical radiculopathy from degenerative foraminal stenosis is severe uncovertebral hypertrophy. It is difficult to accomplish complete foraminal decompression in these cases with posterior techniques without the removal of a large portion of the facet joint. Total removal of the uncovertebral joint from an anterior approach allows for complete decompression of the exiting cervical nerve root and has been shown to be a safe technique. In this surgical video and technical report, we demonstrate the surgical anatomy and operative technique of a two-level anterior uncinatectomy during anterior discectomy and fusion (ACDF) for recurrent cervical radiculopathy after a previous multi-level posterior foraminotomy. The patient is a 67-year-old male with a progressive left arm and neck pain with radiographic, clinical, and electrophysiologic diagnostic evidence of active C6 and C7 radiculopathies from degenerative foraminal stenosis at the C5-6 and C6-7 levels. Posterior foraminotomies had been performed without significant improvement in his radicular pain. A repeat MRI demonstrated lateral foraminal stenosis from severe uncovertebral joint hypertrophy at the C5-6 and C6-7 levels. After acquiring informed consent from the patient, an anterior approach was performed with complete removal of the uncovertebral joints at both levels with discectomy and fusion. Postoperatively, the patient had complete resolution of his radicular pain and remained pain-free at the latest follow-up. Complete uncinatectomy and ACDF is an effective technique for complete foraminal decompression in cases of refractory radiculopathy and neck pain after unsuccessful posterior decompression.
Intracellular and Intercellular Aspects of Macrophage Immunometabolism in Atherosclerosis

Macrophage immunometabolism, the changes in intracellular metabolic pathways that alter the function of these highly plastic cells, has been the subject of intense interest in the past few years, in part because macrophage immunometabolism plays important roles in atherosclerosis and other inflammatory diseases. In this review article, part of the Compendium on Atherosclerosis, we introduce the concepts of (1) intracellular immunometabolism-the canonical pathways of intrinsic cell activation leading to changes in intracellular metabolism, which in turn alter cellular function; and (2) intercellular immunometabolism-conditions in which intermediates of cellular metabolism are transferred from one cell to another, thereby altering the function of the recipient cell. The recent discovery that the metabolite cargo of dead and dying cells ingested through efferocytosis by macrophages can alter metabolic pathways and downstream function of the efferocyte is markedly changing the way we think about macrophage immunometabolism. Metabolic transitions of macrophages contribute to their functions in all stages of atherosclerosis, from lesion initiation to formation of advanced lesions characterized by necrotic cores, to lesion regression following aggressive lipid lowering. This review article discusses recent advances in our understanding of these different aspects of macrophage immunometabolism in atherosclerosis. With the increasing understanding of the roles of macrophage immunometabolism in atherosclerosis, new exciting concepts and potential targets for intervention are emerging.
Exploration of baseline and early changes in neurocognitive characteristics as predictors of treatment response to bupropion, sertraline, and placebo in the EMBARC clinical trial.

Background Treatment for major depressive disorder (MDD) is imprecise and often involves trial-and-error to determine the most effective approach. To facilitate optimal treatment selection and inform timely adjustment, the current study investigated whether neurocognitive variables could predict an antidepressant response in a treatment-specific manner. Methods In the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial, outpatients with non-psychotic recurrent MDD were first randomized to an 8-week course of sertraline selective serotonin reuptake inhibitor or placebo. Behavioral measures of reward responsiveness, cognitive control, verbal fluency, psychomotor, and cognitive processing speeds were collected at baseline and week 1. Treatment responders then continued on another 8-week course of the same medication, whereas non-responders to sertraline or placebo were crossed-over under double-blinded conditions to bupropion noradrenaline/dopamine reuptake inhibitor or sertraline, respectively. Hamilton Rating for Depression scores were also assessed at baseline, weeks 8, and 16. Results Greater improvements in psychomotor and cognitive processing speeds within the first week, as well as better pretreatment performance in these domains, were specifically associated with higher likelihood of response to placebo. Moreover, better reward responsiveness, poorer cognitive control and greater verbal fluency were associated with greater likelihood of response to bupropion in patients who previously failed to respond to sertraline. Conclusion These exploratory results warrant further scrutiny, but demonstrate that quick and non-invasive behavioral tests may have substantial clinical value in predicting antidepressant treatment response.
The Constraining, Liberating, and Informational Effects of Nonbinding Law

We show that nonbinding law can have a constraining effect on political leaders, because legal compliance is a costly signal to imperfectly informed voters that the leader is unbiased. Moreover, nonbinding law can also have a liberating effect, enabling some leaders to take action when they otherwise would have done nothing. In addition, we illustrate how voters may face a trade-off between the legal standard that induces optimal behavior of the current leader (i.e., that most effectively addresses the moral hazard problem) and the legal standard that optimizes selection of future leaders (i.e., that most effectively addresses the adverse selection problem). We discuss a range of positive and normative implications that follow from our analysis. (JEL D72, K40).
Exercise Cardiovascular Magnetic Resonance: A Review

While pharmacologic stress cardiovascular magnetic resonance imaging (MRI) is a robust noninvasive tool in the diagnosis and prognostication of epicardial coronary artery disease, clinical guidelines recommend exercise-based testing in those patients who can exercise. This review describes the development of exercise cardiovascular MRI protocols, summarizes the insights across various patient populations, and highlights future research initiatives. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.
Critical interactions for SARS-CoV-2 spike protein binding to ACE2 identified by machine learning

Both SARS-CoV and SARS-CoV-2 bind to the human ACE2 receptor. Based on high-resolution structures, the two viruses bind in practically identical conformations, although several residues of the receptor-binding domain (RBD) differ between them. Here we have used molecular dynamics (MD) simulations, machine learning (ML), and free energy perturbation (FEP) calculations to elucidate the differences in RBD binding by the two viruses. Although only subtle differences were observed from the initial MD simulations of the two RBD-ACE2 complexes, ML identified the individual residues with the most distinctive ACE2 interactions, many of which have been highlighted in previous experimental studies. FEP calculations quantified the corresponding differences in binding free energies to ACE2, and examination of MD trajectories provided structural explanations for these differences. Lastly, the energetics of emerging SARS-CoV-2 mutations were studied, showing that the affinity of the RBD for ACE2 is increased by N501Y and E484K mutations but is slightly decreased by K417N.
Cell Fate Decisions in the Wake of Histone H3 Deposition

An expanding repertoire of histone variants and specialized histone chaperone partners showcases the versatility of nucleosome assembly during different cellular processes. Recent research has suggested an integral role of nucleosome assembly pathways in both maintaining cell identity and influencing cell fate decisions during development and normal homeostasis. Mutations and altered expression profiles of histones and corresponding histone chaperone partners are associated with developmental defects and cancer. Here, we discuss the spatiotemporal deposition mechanisms of the Histone H3 variants and their influence on mammalian cell fate during development. We focus on H3 given its profound effect on nucleosome stability and its recently characterized deposition pathways. We propose that differences in deposition of H3 variants are largely dependent on the phase of the cell cycle and cellular potency but are also affected by cellular stress and changes in cell fate. We also discuss the utility of modern technologies in dissecting the spatiotemporal control of H3 variant deposition, and how this could shed light on the mechanisms of cell identity maintenance and lineage commitment. The current knowledge and future studies will help us better understand how organisms employ nucleosome dynamics in health, disease, and aging. Ultimately, these pathways can be manipulated to induce cell fate change in a therapeutic setting depending on the cellular context.
Using Virtual Simulations in Online Laboratory Instruction and Active Learning Exercises as a Response to Instructional Challenges during COVID-19

The onset of the COVID-19 pandemic in the spring of 2020 thrust instructors into a world of frenzy, presenting unique challenges to delivering course content A particular challenge was determining suitable substitutes for wet lab experiments that are often comprised in science labs Recognizing that this problem was not short-term, I started to look into virtual substitutions to be implemented in the 2020-2021 academic year Virtual simulations can replace labs, be incorporated as pre-lab assignments, or used as active-learning or experiential learning exercises in a traditional classroom setting while providing low-cost, safe, and acceptable solutions to the current problem Virtual simulations were examined on different platforms, including Labster, McGraw Hill Connect Virtual Labs, HHMI BioInteractive, Learn Genetics, Virtual Interactive Bacteriology Laboratory, and Biology Corner The goal was to provide faculty around the world with a reference list of virtual simulations that are aligned to specific AAAS and ASM student learning outcomes These simulations are discussed in terms of content, features, and advantages of use A list of lab exercises aligned to biology courses (microbiology, genetics, and cell biology) is also provided
Optimizing On-Chip Decoupling Capacitors to Improve Power Supply Noise Induced Jitter and ESD Robustness

The designs of power delivery network (PDN) and electrostatic discharge (ESD) protection are increasingly challenging and crucial in today's highly complicated silicon chips. The budgets of supply noise and PSIJ are significantly reduced. These stringent budgets and CDM ESD protection demand low-ESR on-chip decoupling capacitors to mitigate the problems. MIMcap usually provides an order of magnitude larger capacitance than any other on-die capacitance implementation. However, MIMcap typically has large ESR, which significantly reduces its effectiveness and hence needs to be optimized. MIMcap frequency response is extremely layout-dependent. In this paper, the methodologies of MIMcap optimization for various processes in different foundries are described. The methodologies are applied for the first time in three Intel FPGA silicon chips. The applications prove that the optimized MIMcap reduces ESR, PDN noise, PSIJ, and improves the ESD robustness. MIMcap optimization methodologies enable higher-performance and cost-competitive designs.
A bidirectional relationship between anxiety, depression and gastrointestinal symptoms in Parkinson's disease.

Abstract Introduction Anxiety, depression and gastrointestinal (GI) symptoms are common non-motor symptoms in Parkinson’s disease (PD). Past studies provide evidence of a disrupted microbiome-gut-brain axis in PD, which is associated with certain motor and non-motor symptoms in PD. Additionally, there is evidence of a bidirectional association between mental health and gut health among individuals with GI disorders. The current study examined the bidirectional association between GI symptoms and anxiety/depression among individuals newly diagnosed with PD. Methods We conducted a secondary data analysis of the Parkinson’s Progression Markers Initiative. This included 487 individuals newly diagnosed with PD and followed for up to 5 years. Participants completed questionnaires of anxiety, depression and GI symptoms (Scales for Outcomes in Parkinson’s Disease Autonomic; SCOPA-AUT) at each annual visit. Multilevel models examined the bidirectional-lagged relationship between GI symptoms and anxiety/depression. Results Models provided evidence for a bidirectional relationship between GI symptoms and anxiety/depression. Specifically, more severe GI symptoms predicted more severe anxious/depressive symptoms within the same year and at the following year. There was also evidence of the inverse directionality, meaning that more severe anxiety/depression predicted more severe GI symptoms concurrently and in the following year. Discussion Findings provide preliminary evidence for a cyclical relationship among gut health and mental health in PD. Future studies are needed to examine if the microbiome-gut-brain axis plays a mechanistic role.
Sociodemographic, Clinical, and Treatment-Related Factors Associated With Hyperglycemic Crises Among Adults With Type 1 or Type 2 Diabetes in the US From 2014 to 2020.

Importance Hyperglycemic crises (ie, diabetic ketoacidosis [DKA] and hyperglycemic hyperosmolar state [HHS]) are life-threatening acute complications of diabetes. Efforts to prevent these events at the population level have been hindered by scarce granular data and difficulty in identifying individuals at highest risk. Objective To assess sociodemographic, clinical, and treatment-related factors associated with hyperglycemic crises in adults with type 1 or type 2 diabetes in the US from 2014 to 2020. Design, Setting, and Participants This retrospective cohort study analyzed administrative claims and laboratory results for adults (aged ≥18 years) with type 1 or type 2 diabetes from the OptumLabs Data Warehouse from January 1, 2014, through December 31, 2020. Main Outcomes and Measures Rates of emergency department or hospital visits with a primary diagnosis of DKA or HHS (adjusted for age, sex, race/ethnicity, and region, and for year when calculating annualized rates) were calculated separately for patients with type 1 diabetes and type 2 diabetes. The associations of sociodemographic factors (age, sex, race/ethnicity, region, and income), clinical factors (comorbidities), and treatment factors (glucose-lowering medications, hemoglobin A1c) with DKA or HHS in patients with type 1 or type 2 diabetes were assessed using negative binomial regression. Results Among 20 156 adults with type 1 diabetes (mean [SD] age, 46.6 [16.5] years; 51.2% male; 72.6% White race/ethnicity) and 796 382 with type 2 diabetes (mean [SD] age, 65.6 [11.8] years; 50.3% female; 54.4% White race/ethnicity), adjusted rates of hyperglycemic crises were 52.69 per 1000 person-years (95% CI, 48.26-57.12 per 1000 person-years) for type 1 diabetes and 4.04 per 1000 person-years (95% CI, 3.88-4.21 per 1000 person-years) for type 2 diabetes. In both groups, factors associated with the greatest hyperglycemic crisis risk were low income (≥$200 000 vs Conclusions and Relevance In this cohort study, younger age, Black race/ethnicity, low income, and poor glycemic control were associated with an increased risk of hyperglycemic crises. The findings suggest that multidisciplinary interventions focusing on groups at high risk for hyperglycemic crises are needed to prevent these dangerous events.
Somatosensory behavioral alterations in a NGF-induced persistent low back pain model.

Abstract Low back pain (LBP) is a major global burden in part due to the underlying pathophysiological mechanisms being poorly understood. A LBP rat model involving two injections of nerve growth factor (NGF, an endogenous pain-related neurotrophin) into trunk musculature was recently developed. Additional behavioral work in this NGF-LBP rat model is required to better characterize local and remote somatosensory alterations related to NGF-induced peripheral and central sensitization. This work characterizes the time-dependent development of hypersensitivity to trunk and hindpaw cutaneous mechanical stimulation and deep muscle mechanical hyperalgesia in adult male Sprague-Dawley rats (n = 6/group). Behavioral assays were performed at baseline (Day 0, D0), D2, D5 (pre- and 4 h post-2nd NGF or control injection), D7, D10, and D14 in NGF and control groups. Trunk and hindpaw cutaneous mechanical hypersensitivity were tested using von Frey filaments. Deep trunk mechanical hyperalgesia was determined using a small animal algometer. NGF rats demonstrated increased cutaneous sensitivity to ipsilateral trunk mechanical stimuli at D7, D10, and D14. NGF rats also demonstrated ipsilateral deep mechanical hyperalgesia on D2, D5 + 4 h, D7, D10, and D14. Cutaneous hypersensitivity was delayed compared to deep hyperalgesia in NGF rats. No additional sensory changes were noted. Together, these results indicate that male mechanical somatosensory changes develop primarily locally in the ipsilateral trunk following unilateral NGF injections. These findings contrast with a previous report in female rats using this NGF-LBP model showing more widespread (bilateral) hyperalgesia and remote mechanical hypersensitivity. Future studies will examine potential sex-related pain behavioral differences in the NGF model.
Some Neuronal Mechanisms of Simple Behavior

Publisher Summary This chapter discusses on the fields of ethology and neurophysiology as both deals directly with animal behavior, ethology with its origins and causes in intact animals and neurophysiology with its mechanisms. The possible origins of both fields as a source of their basic viewpoints are compared and some of the concepts of neurophysiology that seem relevant to behavior are presented. Neurophysiology has attained a fair understanding of the “grammar and syntax” of communication between individual nerve cells. The so-called Hodgkin-Huxley interpretation of membrane events in a neuron provided a foundation for modern neurophysiology much as was done for ethology by Darwinian evolution. It accounts for the propagation of impulses along nerve fibers (axons), as well as for their genesis in nerve cells through synaptic contacts with other nerve cells. An action potential propagates itself over the electrically excitable membrane of the nerve fiber after the fashion of a spreading forest fire or mountain avalanche. Depolarization, a decrease in the local membrane potential, precipitates an action potential not hyperpolarization or an increase in membrane potential. Spike patterns are discussed that constitute the message. The interests of ethology and neurophysiology can be said to overlap at the skin of an animal. The chapter summarizes the major concepts of neurophysiology, and examines some detail on what seem to be an operational but very minor interface, such minor that whether animal behavior is scrutinized from a neurophysiological or from an ethological viewpoint the boundary of the “skin” must be crossed and re-crossed numerous times, if research on animal behavior and its mechanisms is to give a real intellectual satisfaction.
Do Package Inserts Reflect Symptoms Experienced in Practice

Background: while the US FDA maintains a voluntary reporting system, postmarketing adverse drug events (ADEs) are underreported, and this case report-based system does not allow accurate determination of incidence.
The Eichler-Shimura Isomorphism on SL2(Z)

In this chapter we describe the Eichler-Shimura theory already mentioned in the preceding chapter.
Effect Propensity: The Distribution of Switchers' Choices in the Reference State as a Determinant of the Direction of Effects on Choice

In a choice between two options, decision makers can often be divided into three segments: those who strongly prefer the first option, those who strongly prefer the second option, and those who might choose either option depending on the particular conditions ("Switchers"). In any reference state, such as the experimental control, most Switchers are likely to favor one of the two options. Thus, the limited growth potential of the option favored by Switchers in the reference state creates "effect propensity" in the opposite direction, whereby any condition or manipulation applied to the reference state is more likely to increase the share of the other option. We test this proposition in a series of studies in the context of choices between safe and risky options and between lower-price/quality and higher-price/quality options. The results indicate that a large majority of conceptually unrelated manipulations tend to increase the choice share of risky and higher-price/quality options. This effect propensity can be reversed when the risky and higher-price/quality options are the status quo alternatives or asymmetrically dominating in the reference state. Alternative explanations for effect propensity are examined. We discuss the implications of effect propensity for the interpretation of research findings, the selection of controls, and theory tests.
Hartree-Fock-Roothaan wavefunctions for diatomic molecules: II. First-row homonuclear systems A2, A2±, and A2∗

Abstract Tables of electronic wavefunctions are presented for 43 homonuclear diatomic systems, A2, A 2 ± , and A 2 ∗ , involving first-row elements Li through F. These wavefunctions were obtained at the experimental (or theoretical) internuclear separation and are expansion solutions of the Restricted Hartree-Fock equations. The various molecular orbitals are expanded in extensive sets of symmetry-adapted Slater-type-functions. The repertory of states includes the experimental ground states of the systems indicated, a few low-lying excited states, and certain positive and negative ions. The calculations are restricted to electronic states involving either closed-shell electron configurations or open-shell configurations with one incompletely filled open shell. The quality, limitations, and gross details of these calculations are briefly discussed.
Human histologic evaluation of HTR polymer and freeze-dried bone allograft. A case report.

Abstract This case report compares the results of placement of HTRTM (Hard Tissue Replacement Synthetic BoneTM) and freeze-dried bone allograft (FDBA) in the same patient. 2 notches were made in each of 6 teeth, 1 at the gingival margin and the other at the most apical level of calculus. Soft tissue reponses with both materials included probing depth reduction, gingival shrinkage and gain in clinical attachment. Histological sections of block extraction sites 30 months after placement of either material showed no signs of new attachment. Little or no inflammation was present with both materials. There was also an absence of all FDBA particles which assumes complete resorption of this material prior to 30 months. Gingival shrinkage resulted in the exposure of the gingival and calculus notch in all FDBA treated sites. Gingival epithelium was found adjacent to the gingival notch in all HTRTM treated sites. The calculus notch in HTRTM treated sites was lined by junctional epithelium with connective tissue and bone opposing the adhesion. HTRTM particles were present and surrounded by connective tissue or bone. HTRTM appears to serve as a scaffold for new bone formation when in close contact with alveolar bone.
Employees amidst welfare reform : TANF employees' overall job- and organizational-role satisfaction

SUMMARY The impact of welfare reform on organizational functioning at the Georgia Division of Family and Children Services (DFCS) is measured between 1999 and 2000 using a longitudinal survey method, a large sample of employees, and multiple regression analysis. During this one year period the agency experienced a change in leadership as well as had to contend with the evolving requirements associated with the Personal Responsibility and Work Opportunity Reconciliation Act of 1996 (PRWORA). The findings indicate that a trusted leadership and an organizational climate that is receptive to and fosters effective communication can improve the chances of successfully implementing large-scale organizational change like that created by the PRWORA.
Osteonecrosis of the femoral head: current concepts and controversies

Despite many investigations into ON of the femoral head, many issues remain unresolved. The pathogenesis in most cases is only speculative and may involve intravascular factors such as microemboli or extravascular factors such as increased interosseous pressure. MRI has emerged as the diagnostic test of choice for suspected early lesions, and radiographs should be used to diagnose and follow advanced lesions. Bone scanning can be useful for early diagnosis and CT scanning or tomography may help plan surgical procedures. The role of the functional exploration of bone is controversial. The natural history of early lesions is unknown; this makes it difficult to evaluate results of treatment. Radiographic ON will usually progress to collapse and arthrosis if treated nonoperatively. The role of core decompression or other joint preserving operations to prevent collapse is controversial, since the reports of success and complication rates have been extremely variable. These procedures are ineffective if used after radiographic collapse. Total hip replacement is the only satisfactory treatment for advanced symptomatic stages, but is relatively contraindicated in young active patients. Further research is needed to assess the natural history of early ON and evaluate the role of surgery in preventing progression.