cssi/SciSciGPT-SciSciNet huggingface dataset:
Original article: Treatment related psychological distress during adjuvant chemotherapy as a conditioned response

Summary Patients receiving cycles of cytotoxic chemotherapy for cancer often experience noxious side effects following treatments and may develop classically conditioned side effects, such as anticipatory nausea and vomiting (ANV) during the course of repeated infusions. The present study explored the possibility that classical conditioning processes may also contribute to treatment related psychological distress. Sixty-six patients, scheduled for adjuvant chemotherapy for breast cancer (stages I, II, IIIa), agreed to participate. Patients were assessed in the clinic on the first day of every chemotherapy cycle and in their homes three to five days before their final cycle. Patients experienced considerable psychological distress during the course of chemotherapy, and particularly before the first infusion. Prior to the last cycle of chemotherapy, psychological distress was significantly higher in the clinic environment than in patients' homes. Consistent with classical conditioning, psychological distress did not escalate over the days before treatment, but rather increased abruptly when patients returned to the clinic. The results of the present study indicate that several factors are involved in patients' anticipatory psychological distress and highlight the potential contribution that conditioning processes may make to patients' emotional distress in the clinic environment.
Characterization of Oscillations in Closed Drift Thrusters

The nature of oscillations in the 1 kHz-60 MHz frequency range that have been observed during operation of closed drift thrusters (CDT), such as the stationary plasma thruster (SPT) and the anode layer thruster (ALT), is quantitatively discussed. We use contours of various plasma parameters measured inside the accelerating channel of an SPT[1, 2] as the starting point of our investigation and calculate the magnitude and spatial distribution of various associated natural and collision frequencies, characteristic lengths and velocities. This leads to a thorough characterization of the plasma in the channel under typical operation. This detailed picture is then used to evaluate the stability criteria and dispersion relations of oscillations that are suspected to occur. Using various dispersion relations, we present a band by band overview of the oscillations with a description of their observed behavior and discuss their nature and dependencies through comparison of the calculated contours to reported observations. In particular we discuss the excitation of low frequency azimuthal drift waves that can form a rotating spoke at lower values of B∗ r , axially propagating “transit-time” oscillations, high frequency azimuthal drift waves, ionization instability-type waves, and wave emission peculiar to weakly ionized inhomogeneous plasma in crossed electric and magnetic fields.
Determining sensitivity/specificity of virtual reality-based neuropsychological tool for detecting residual abnormalities following sport-related concussion.

OBJECTIVE: Computer-based neuropsychological (NP) evaluation is an effective clinical tool used to assess cognitive function which complements the clinical diagnosis of a concussion. However, some researchers and clinicians argue its lack of ecological validity places limitations on externalizing results to a sensory rich athletic environment. Virtual reality-based NP assessment offers clinical advantages using an immersive environment and evaluating domains not typically assessed by traditional NP assessments. The sensitivity and specificity of detecting lingering cognitive abnormalities was examined on components of a virtual reality-based NP assessment battery to cohort affiliation (concussed vs. controls). METHOD: Data were retrospectively gathered on 128 controls (no concussion) and 24 concussed college-age athletes on measures of spatial navigation, whole body reaction, attention, and balance in a virtual environment. Concussed athletes were tested within 10 days (M = 8.33, SD = 1.06) of concussion and were clinically asymptomatic at the time of testing. RESULTS: A priori alpha level was set at 0.05 for all tests. Spatial navigation (sensitivity 95.8%/specificity 91.4%, d = 1.89), whole body reaction time (sensitivity 95.2%/specificity 89.1%, d = 1.50) and combined virtual reality modules (sensitivity 95.8%,/specificity 96.1%, d = 3.59) produced high sensitivity/specificity values when determining performance-based variability between groups. CONCLUSIONS: Use of a virtual reality-based NP platform can detect lingering cognitive abnormalities resulting from concussion in clinically asymptomatic participants. Virtual reality NP platforms may compliment the traditional concussion assessment battery by providing novel information. Language: en
Orbital Ultrasound and S100 Protein Monitoring during Unilateral and Bilateral Antegrade Selective Cerebral Perfusion in Total Aortic Arch Replacement

OBJECTIVE To compare the serum S100 protein concentration and blood flow in the central retinal artery and retrobular vessels between unilateral and bilateral antegrade selective cerebral perfusion during total aortic arch replacement.METHODS From June 2003 to March 2004, 16 patients who underwent total arch replacement were randomly allocated to one of two methods of brain protection: unilateral antegrade selective cerebral perfusion (unilateral group, n=8 ) or bilateral antegrade cerebral perfusion (bilateral group, n=8). Preoperative and postoperative brain CT scans were performed. During the operation, the blood flow in the central retinal artery and retrobular vessels was monitored with orbital ultrasound. Serum S100 protein was assayed before skin incision, immediately after thoracotomy, 30 minutes after the cardiopulmonary bypass, as well as 6 hours, 24 hours and 48 hours post-operatively. RESULTS All patients survived and were discharged from hospital. No new brain infarction occurred. Transient neurologic dysfunction occurred in 1 patient from each group. During antegrade selective cerebral perfusion, blood flow in the right central retinal artery was detectable in the unilateral group, butnot detectable in the left central retinal artery. In the bilateral group, the blood flow on both sides was detectable during antegrade selective cerebral perfusion. The blood flow in the retrobular vessels was detectable in all of the patients during antegrade selective cerebral perfusion. There were no intergroup differences in serum S100 protein concentration in all phases (P0.05). CONCLUSION Both methods of brain protection had a similar effect upon S100 protein concentration providing the circle of Willis was patent and collateral flow was adequate. Blood flow in bilateral antegrade selective cerebral perfusion was more uniform, whilst unilateral antegrade selective cerebral perfusion has the advantage of simplicity.
Synthesis and Characterization of 3,6-Dihydrazine-1,2,4,5-tetrazine and its Energetic Salts

3,6-Dihydrazine-1,2,4,5-tetrazine and its energetic salts were synthesized from the easily available starting materials like triaminoguanidine and 2,4penatanedione.The synthesis route in literature was magnified properly.Moreover,the synthesized(compounds)were characterized by spectra analysis(IR,NMR,EA and MS) and the explosive properties(impact and friction sensitivity) and thermal properties(TGA/DTG) were studied.
Government Subsidies and Household Debt Burden After the Great Recession

During the recent Great Recession, US households, especially those with low incomes, faced severe financial distress. Households experiencing economic hardship may turn to receiving government assistance to alleviate the hardship or distress. Receiving government assistance may improve a household’s financial situation as it could be decreasing its reliance on debt or even improving a household’s ability to repay their current debt. We investigated how households’ financial debt obligations were affected by receiving government assistance, as has not been previously analyzed. Given the focus of this research, we included households under 185 % of poverty threshold released by the 2012 US Census Bureau. Results from the 2010 and 2013 Survey of Consumer Finances indicate that government assistance was positively related to the odds of meeting debt-to-income ratio guidelines, implying that government assistance plays an important role in financial security of low-income households. This study provides important insights for researchers and policymakers in the areas of poverty and household finance.
Positron Emission Tomography Scanning: Applications in Newborns

Positron emission tomography (PET) is an imaging technique that allows local chemical and physiologic functions in various body organs to be measured. Studies of local cerebral glucose metabolism in infants and children using PET have provided important information on human brain functional development and plasticity. In the neonate, PET studies have provided important clues into the pathophysiology of hypoxic-ischemic injury. Patterns of cerebral glucose utilization in various clinical subtypes of cerebral palsy associated with perinatal brain injury are discussed and contrasted to metabolic patterns seen in cerebral palsy without clear etiology. Expanding PET technology provides a new approach that holds great promise in the diagnosis and management of brain disorders affecting the neonate.
The Treatment of Neuropathic Pain

Neuropathic pain is responsible for a significant amount of the morbidity associated with generalized and focal peripheral neuropathies. It is a consequence of alterations in neuronal function, chemistry, and structure that occur secondary to nerve injury. These manifestations of neuronal plasticity occur in the peripheral nerve, spinal cord, and brain. A variety of agents from diverse pharmacologic classes, the so-called adjuvant analgesics, have been used to treat neuropathic pain. These include antidepressants, first- and second-generation anticonvulsants, antiarrhythmic agents, topical agents, N-methyl-D-aspartate receptor antagonists, and opioid analgesics. The use of these adjuvant analgesics, either alone or in combination, should result in the alleviation of neuropathic pain in most patients. Recent advances in the understanding of pain mechanisms at multiple central nervous system levels should pave the way toward more effective treatment modalities.
Comparative Research on the Zahir and Batin Thought

This research paper makes an attempt to expound the Muslim concepts of al-zahir [the evident] and the al-batin [the intrinsic] which touch deeply upon both spiritual and secular practices to ascertain possible similarities and differences between the Muslim and the non-Muslim realms. Despite centuries of economic and cultural relationships, recent times have been loaded with political and media stereotyping of Islam as a “warring” religion whose militants “threaten” the regional peace and international order. Almost nothing is mentioned about the “intrinsic” motives that underlie “evident” dictions of all parties of the conflict. To establish corrective understanding between the Muslims and the non-Muslims as a unified human family, comparative research is critically needed to educate and to disseminate the facts about Islam and the Muslim heritage to expand the peaceful co-existence and the full enjoyment of freedoms and human rights to all humans. In this context, the paper analyzes key concepts of the al-zahir and al-batin to appreciate the meanings of the Muslim Truth and the Hikmat al-Ta’aruf teachings, in comparison with non-Muslim beliefs and secular thought. To conclude, systematic research is crucial to help reconcile the parties by the establishment of comparable ontologies for the Muslim and non-Muslim thought.
Fragile-X Syndrome

A characteristic epileptogenic EEG pattern is described in five of 12 male subjects with fragile-X syndrome evaluated at the Instituto Oasi, via C. Ruggero, Troina, Italy, and Clinica Neurologica, II Universita Roma and Bologna, Italy.
Barbara Epstein, AHIP, FMLA, Medical Library Association President, 2017-2018.

A profile of Barbara Epstein, AHIP, FMLA, Medical Library Association President, 2017–2018.
The Systemic and Splanchnic Circulations

In liver cirrhosis, splanchnic and systemic hemodynamic abnormalities are common in patients with portal hypertension. Portal hypertension leads to progressive vasodilatation of the arteries of the splanchnic and systemic circulations, a key event which in turn exacerbates portal hypertension by increasing splanchnic blood flow. Since portal hypertension is central to the development of complications observed in patients with liver disease, the mechanisms underlying this arterial vasodilatation have been an important area of investigation. While nitric oxide (NO) has been shown to be the primary vasodilator molecule, other molecules are also involved in the complex mechanisms of arterial vasodilatation in the systemic and particularly splanchnic circulation. In recent years, it has been suggested that sensory mechanisms in the intestinal microcirculation prompt the initiation of vasodilatation and the progression of portal hypertension. This chapter will summarize the etiology and molecular mechanisms of arterial vasodilatation observed in the intestinal, splanchnic, and systemic circulations in portal hypertension with cirrhosis.
Pre-hospital Therapeutic Hypothermia

Mild therapeutic hypothermia (TH) maintained at 32–34°C for 12–24 h has been shown in clinical trials to significantly improve neurological outcomes for patients recovering from out-of-hospital cardiac arrest (OHCA), as reviewed elsewhere in this book [1, 2]. Though guidelines now recommend cooling for all patients who remain comatose after resuscitation from ventricular fibrillation OHCA, the optimal time to initiate a cooling protocol has not been specified. The question of whether it is advantageous and safe for emergency medical services (EMS) personnel to begin TH immediately post-resuscitation in the pre-hospital setting remains controversial [3]. This chapter will review the evidence on pre-hospital TH and propose an operational guide for program development among interested EMS agencies.
Defining the caudal hypothalamic arcuate nucleus with a focus on anorexic excitatory neurons

Key points Excitatory glutamate neurons are sparse in the rostral hypothalamic arcuate nucleus (ARC), the subregion that has received the most attention in the past. In striking contrast, excitatory neurons are far more common (by a factor of 10) in the caudal ARC, an area which has received relatively little attention. These glutamate cells may play a negative role in energy balance and food intake. They can show an increase in phosphorylated Stat-3 in the presence of leptin, are electrically excited by the anorectic neuromodulator cholecystokinin, and inhibited by orexigenic neuromodulators neuropeptide Y, met-enkephalin, dynorphin and the catecholamine dopamine. The neurons project local axonal connections that excite other ARC neurons including proopiomelanocortin neurons that can play an important role in obesity. These data are consistent with models suggesting that the ARC glutamatergic neurons may play both a rapid and a slower role in acting as anorectic neurons in CNS control of food intake and energy homeostasis. Abstract Here we interrogate a unique class of excitatory neurons in the hypothalamic arcuate nucleus (ARC) that utilizes glutamate as a fast neurotransmitter using mice expressing GFP under control of the vesicular glutamate transporter 2 (vGluT2) promoter. These neurons show a unique distribution, synaptic characterization, cellular physiology and response to neuropeptides involved in energy homeostasis. Although apparently not previously appreciated, the caudal ARC showed a far greater density of vGluT2 cells than the rostral ARC, as seen in transgenic vGluT2-GFP mice and mRNA analysis. After food deprivation, leptin induced an increase in phosphorylated Stat-3 in vGluT2-positive neurons, indicating a response to hormonal cues of energy state. Based on whole-cell recording electrophysiology in brain slices, vGluT2 neurons were spontaneously active with a spike frequency around 2 Hz. vGluT2 cells were responsive to a number of neuropeptides related to energy homeostasis; they were excited by the anorectic peptide cholecystokinin, but inhibited by orexigenic neuropeptide Y, dynorphin and met-enkephalin, consistent with an anorexic role in energy homeostasis. Dopamine, associated with the hedonic aspect of enhancing food intake, inhibited vGluT2 neurons. Optogenetic excitation of vGluT2 cells evoked EPSCs in neighbouring neurons, indicating local synaptic excitation of other ARC neurons. Microdrop excitation of ARC glutamate cells in brain slices rapidly increased excitatory synaptic activity in anorexigenic proopiomelanocortin neurons. Together these data support the perspective that vGluT2 cells may be more prevalent in the ARC than previously appreciated, and play predominantly an anorectic role in energy metabolism.
Argument-Based Validation in Practice: Examples From Mathematics Education

This article provides a brief introduction to the set of four articles in the special issue. To provide a foundation for the issue, key terms are defined, a brief historical overview of validity is provided, and a description of several different validation approaches used in the issue are explained. Finally, the contribution of the articles to further articulating argument-based validation approaches is discussed, along with questions for the field to consider.
Hungry for free trade? Food trade and extreme hunger in developing countries

One of the greatest challenges of the twenty-first century is to ensure that the world population has reliable access to adequate, affordable and nutritious food sufficient to avoid hunger. Agricultural trade liberalization is often considered a central element of economic strategies aiming at improving food security in developing countries. Many, however, argue that most developing countries may not benefit from freer agricultural trade and that liberalization may accentuate food insecurity. From an empirical perspective, little is known about the effects of trade on food security in developing countries. We estimated the effects of food trade openness on extreme hunger in developing countries using a novel two-step approach. First, we estimated the reverse causal impacts of hunger on food trade openness using rainfall anomalies as instrumental variables to generate exogenous variation in hunger. In a second step, we estimated the effect of food trade openness on hunger using the residual food trade openness that is not driven by hunger as an instrument. We found that a 10% increase in food trade openness would increase the prevalence of undernourishment by about 6%. We also found evidence that developing countries reduce food trade openness as a response to increased hunger, suggesting protectionist policies. A percentage point increase in undernourishment prevalence would decrease food trade openness by 0.9%. Our results suggest that countries may be better off adopting food self-sufficiency for some time, despite such actions clashing with World Trade Organization’s regulations and current agenda.
Some Problems for Physicists in First Order Diffusional Phase Transformations in Crystalline Solids

Although the homogeneous nucleation kinetics of precipitates formed during first order diffusional phase transformations now appear to be well understood when the precipitate has the same crystal structure and orientation as the matrix, analysis of homogeneous nucleation involving a significant change in crystal structure has just begun. The core problem is evaluation of the chemical interfacial energy as a function of boundary orientation with a fixed lattice orientation relationship for coherent interphase boundaries. Quantitative understanding of nucleation at dislocations requires analysis of strain energy interactions between faceted nuclei and the dislocations, using anisotropic, inhomogeneous elasticity theory. Diffusional growth of precipitates whose crystal structure differs from that of their matrix can be qualitatively understood in terms of interphase boundaries which have a partially coherent structure. These boundaries are immobile in the direction normal to themselves and can migrate only by means of the ledge mechanism. Theory of the origin of ledges, and also of kinks on the risers of ledges, is the main gap to be filled in order to place this approach to diffusional growth on a quantitative basis. Theory of morphological instability and of growth of the unstable products at the point of instability appears applicable in the large to precipitation from solid solution but must be reworked in terms of the ledge mechanism in order to make such applications more realistic.
Notes on the geometry of the space of polynomials

We show that the symmetric injective tensor product space is not complex strictly convex if E is a complex Banach space of dim E ≥ 2 and if n ≥ 2 holds. It is also reproved that l∞ is finitely represented in if E is infinite-dimensional and if n ≥ 2 holds, which was proved in the other way in [3]. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
Distributed Global Optimization by Annealing

The paper considers a distributed algorithm for global minimization of a nonconvex function. The algorithm is a first-order consensus + innovations type algorithm that incorporates decaying additive Gaussian noise for annealing, converging to the set of global minima under certain technical assumptions. The paper presents simple methods for verifying that the required technical assumptions hold and illustrates it with a distributed target-localization application.
Survival Analysis of Anaplastic Large Cell Lymphoma, Systemic and Cutaneous-Types: Report from the International T-Cell Lymphoma Project.

Abstract The WHO (World Health) Organization Classification recognizes two distinct subtypes of anaplastic large cell lymphoma: Primary systemic and Primary cutaneous types, which have differences in immunophenotype, genetics, and clinical behavior. It is now known that approximately 60% of systemic ALCLs express the anaplastic lymphoma kinase (ALK) protein (ALK-pos) and have a significantly superior survival to ALK-neg cases. Since ALK-neg ALCL appear to have a prognosis similar to peripheral T-cell lymphoma unspecified (PTCL-U), it has been suggested that they should be classified as PTCL-U. Herein, we report the clinical features of newly diagnosed systemic and cutaneous ALCL from the International T-cell Lymphoma Study Group. Materials and Methods: 186 cases of ALCL were identified by the WHO disease definitions: systemic ALCL 163 (88%) (ALK-pos 91 (56%), 72(44%) ALK-neg), and 23 (17%) cutaneous ALCL (cut ALCL). The median age of ALK-pos, ALK-neg and cut ALCL was 32, 57.5 and 54, respectively. There was a male predominance for all subtypes. Most cases of systemic ALCL presented with stage III or IV disease (64% ALK-pos, 58% ALK-neg) and in contrast, 87% of cut ALCL had localized disease. The majority of patients with systemic ALCL were treated with CHOP-type chemotherapy. Most patients with cut ALCL (91%) received additional therapy: 13 (62%) CHOP-type chemotherapy, 11(52%) chemoradiation, 4 (19%) radiation alone. Results: The 5y failure free survival (FFS) and overall survival (OS) was superior for ALK-pos ALCL (70.5% and 58%) compared to ALK-neg ALCL (49% and 36%) (p=.022 and p=.014 for FFS and OS, respectively). Comparison of ALK-pos (n=16) and ALK-neg ALCL (n=23) patients with limited stage disease (defined as stage I or II, no B symptoms and non-bulky) failed to demonstrate a significant difference in FFS (p=.54) or OS (p=.21). Both ALK-pos and ALK-neg ALCL had a superior FFS (ALK-pos p Conclusions: Similar to prior reports, ALK-pos ALCL has a superior outcome to ALK-neg ALCL. For limited stage patients, this survival difference is not apparent, suggesting that a small subgroup of patients with ALK-neg ALCL may have a more favorable prognosis, similar to ALK-pos ALCL. The IPI is effective in both ALK-neg and ALK-pos ALCL at risk stratification. Finally, contrary to prior reports, ALK-neg ALCL patients appear to have a superior outcome to PTCL-U and an apparent plateau in the FFS curve. These results suggest that ALK-neg ALCL should still be distinguished from both ALK-pos ALCL and PTCL-U.
School Shootings in the U.S. – Where to Begin

This paper focuses on a four-phase approach for describing the process whereby a school shooter realizes the activities leading up to the attack Desire to Act, Authority to Act, Means to Act, and Opportunity to Act. Greater emphasis is given to the first two phases, and the concept of ‘Authority to Act’ is examined closely. Confronted with the awful reality of a school shooting, one of the most difficult questions in everyone’s mind is, “How could they do such a thing”? The answer lies in the belief that they have the authority to act and a better understanding of this component may one day provide enhanced tools for prevention. A systems thinking approach is used to discover key relationships within the problem set that lead to new insights into the true nature of the problem. This paper will use this modern set of tools to investigate the causal factors which influence school shooters.
Abstract 14290: Treadmill Exercise Training Reduces the Systolic Blood Pressure Response to Walk Exercise in Patients With Peripheral Artery Disease

Introduction: Supervised exercise therapy (SET) improves functional capacity in people with peripheral artery disease (PAD). However, the effects of SET on improving cardiovascular health remain un...
Utility of the Pectoral Nerve Block (PECS II) for Analgesia Following Transaxillary First Rib Section.

Abstract Introduction The transaxillary approach to resection of the first rib is one of several operative techniques for treating thoracic outlet syndrome. Unfortunately, moderate to severe postoperative pain is anticipated for patients undergoing this particular operation. While opioids can be used for analgesia, they have well described side effects, which has led investigators to search for clinically relevant alternative analgesic modalities. We hypothesized that a regional analgesic procedure, commonly called a pectoral nerve (PECS II) block, which anesthetizes the second through sixth intercostal nerves as well as the long thoracic nerve and the medial and lateral pectoral nerves, would improve postoperative analgesia for patients undergoing a transaxillary first rib resection. Methods We performed a retrospective study by reviewing the charts of all patients that had undergone a transaxillary first rib resection for thoracic outlet syndrome during the defined study period. Patients that received a PECS II block were compared to those that did not. The primary outcome was a comparison of numeric rating scale pain scores during the first 24-hours following the operation. Secondary outcomes included cumulative opioid consumption during the same time period. Results Pain scores during the first 24-hours following the operation were not statistically different between groups (Block Group: 3.9 [2.1-5.3] [median (IQR 25-75%)] vs. Non-block Group: 3.6 [2.4-4.1]; P = 0.40. In addition, opioid use through the first 24-hours after the operation was not significantly different (43.5 [22.0-81.0] [median morphine equivalents in mg's] vs. 42.0 [12.5-75.0]; P = 0.53). Conclusion An ultrasound-guided PECS II nerve block did not reduce postoperative pain scores or opioid consumption for patients undergoing a transaxillary first rib resection. However, a prospective, randomized, study with improved power would be beneficial to further explore the potential utility of a PECS II block for patients presenting for this surgical procedure.
Designing Immersive Stories for Health: Choosing Character Perspective Based on the Viewer’s Modality

This study investigates how different character perspectives (a main vs. supporting character) impact story-consistent attitudes and beliefs and how that effect varies as a function of modality (mo...
Molecular Actions Underlying Wolffian Duct Regression in Sexual Differentiation of Murine Reproductive Tracts

Sexually dimorphic establishment of the reproductive tract system requires sex-specific regression of the Wolffian duct and Mullerian duct in the mesonephros. In an XX embryo, the Wolffian duct regresses under the control of the mesenchymal transcription factor COUP-TFII. To understand cellular and molecular actions underlying Wolffian duct regression, we performed transcriptomic analyses of XX mesonephroi with or without Coup-tfII and genome-wide analysis of COUP-TFII chromatin occupancy in XX mesonephroi. The integrative analysis of COUP-TFII genome-wide binding and transcriptomic analysis revealed the suppression of muscle differentiation and extracellular matrix genes by COUP-TFII and identified a group of potential transcriptional partners of COUP-TFII in the mesenchyme that potentially facilitate Wolffian duct regression. These findings provide insights into the molecular action of COUP-TFII in the Wolffian duct mesenchyme and identify a list of biologically relevant candidate genes and pathways for future functional analyses in sexual differentiation of reproductive tracts.
Abstract 1175: Identification of novel combination therapies with the LSD1 inhibitor SP-2577 (Seclidemstat) in Ewing's Sarcoma using a complete druggable CRISPR library approach

Introduction: Ewing9s Sarcoma (ES) is a rare and aggressive pediatric bone tumor that is driven by a chromosomal translocation and fusion between EWS and FLI1 genes resulting in a chimeric protein. Nearly 85% of ES cases express the EWS/FLI protein which functions as a transcription factor and drives oncogenesis. It has been previously observed in ES patient samples have high levels of the histone lysine specific demethylase 1 (LSD1). LSD1 is recruited by EWS/FLI as a member of the nucleosome remodeling and histone deacetylase (NuRD) complex to repress the critical EWS/FLI targets LOX and TGFBR2. Treatment with the potent LSD1 reversible inhibitor, SP-2577 (Seclidemstat), causes de-repression of these genes and impaired tissue culture cell viability in multiple ES cell lines. In this study we investigated new targeted therapies to use in combination with SP-2577 to help increase the cytotoxicity of the drug within ES cell types. Methods: Synthego® arrayed CRISPR screening platform was used to knock down genes associated with known druggable interactions in the ES cell line SK-N-MC. Genes were knocked down singularly either in the presence/absence of SP-2577. Viability screening was used to determine genes that increased the cytotoxicity of SP-2577. Statistical analysis, z-score, and IPA analysis was performed to investigate correlations between loss of gene effect and LSD1 pathway. Hit-gene validation was performed using siRNA and/or sgRNA knockdown/knockout, and other methods such as qPCR, and western blot assay for protein expression. Results: Arrayed CRISPR screening identified 103 gene deletions that resulted in increased SP-2577 cytotoxicity in SK-N-MC cell line. Among those, the top 19 hits were selected by identifying a FDA approved drug-gene interaction. Two high- interest hits were seen to have significant interaction with the LSD1 pathway: ABL2 and SH2B3. Drug combination treatment of SP-2577 with either Ruxolitinib or Dasatinib in ES cell lines showed high synergy at low dose ratio. Downstream pathways analysis confirmed the efficacy of the drugs combination. Detailed data will be presented. Conclusion: Our data support the validity of the arrayed CRISPR screening to identify new therapeutic strategies in ES, and highlights the potential for Ruxolitinib or Dasatinib treatment in combination with SP-2577 in ES patients. Citation Format: Samuel Sampson, Trason Thode, Mohan Kaadige, Alexis Weston, Serina Ng, Kevin Drenner, Raffaella Soldi, Sunil Sharma. Identification of novel combination therapies with the LSD1 inhibitor SP-2577 (Seclidemstat) in Ewing9s Sarcoma using a complete druggable CRISPR library approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1175.
Evaluation of glucose absorption rates following intracoelomic or subcutaneous administration in experimentally dehydrated inland bearded dragons (Pogona vitticeps).

OBJECTIVE To evaluate glucose absorption rates as an indirect measure of fluid absorption after SC or intracoelomic (ICe) administration of 2.5% dextrose solution to experimentally dehydrated inland bearded dragons (Pogona vitticeps). ANIMALS 9 adult bearded dragons. PROCEDURES In a randomized, blinded, placebo-controlled, crossover design study, bearded dragons were experimentally dehydrated with a previously described protocol and then received 2.5% dextrose solution (a 1:1 mixture of 5% dextrose in isotonic multiple electrolytes solution; 20 mL/kg), SC or ICe, or a control treatment (the same electrolytes solution without added glucose; 20 mL/kg). Blood glucose (BG) concentrations were measured at predetermined times up to 24 hours after fluid administration. There was a ≥ 14-day washout period between treatments. Mean changes in BG concentration from baseline were compared among treatments. RESULTS Administration of 2.5% dextrose solution by either route increased BG concentration with a significantly greater change in values within 5 minutes, compared with control treatment results. The mean change in BG concentration after ICe administration was significantly greater than that after SC administration 15 and 30 minutes after injection, with mean differences of -50 and -36 mg/dL, respectively, for the SC treatment. Within 1 hour after fluid administration, there was no significant difference in BG values between the 2 dextrose administration routes. CONCLUSIONS AND CLINICAL RELEVANCE Findings supported that fluid therapy by SC administration, which carries a lower risk of iatrogenic complications, can provide results similar to those achieved with ICe administration.
Concrete Failure Related to Constituent Properties

A failure criterion for common grades of concrete is proposed on the basis of a critical value of the irrecoverable work associated with internal crack formation. An expression is given for the critical value with explicit dependence on aggregate size and implicit dependence on volume and shape of aggregate, as well as bond characteristics. An empirical relationship is then used to write the failure criterion in terms of ultimate stress with explicit dependence on size and volume of aggregate.
Receptors for Coxsackieviruses and Echoviruses

Studies in the late 1950s demonstrated that homogenates of particular tissues could adsorb picornaviruses, including some echoviruses and coxsackieviruses, and correlated virus adsorption with susceptibility to infection. The understanding of the receptors for group B coxsackieviruses (CVBs) is largely based on work carried out in the beginning of 1960s, and culminating in the identification of two receptor molecules within the past 5 years. Attachment-interference studies, in which saturation of cellular receptors by one virus was found to prevent attachment of a related virus, identified several picornavirus receptor families, whose members were likely to share receptors. Decay-accelerating factor (DAF) is expressed on many cell types and functions to protect cells from lysis by autologous complement. DAF is a member of a family of complement regulatory proteins composed of homologous short consensus repeat (SCR) domains. Consistent with the original observation that all six CVB serotypes compete for a single receptor, Coxsackievirus and adenovirus receptor (CAR) has been shown to mediate infection by laboratory and clinical isolates belonging to all six serotypes, including viruses like CVB3-rhabdomyosarcoma (RD) that also interact with DAF. The observation that CAR-transfected rodent cells become infected, while DAF-transfected CHO cells do not, suggests that DAF cannot perform some postattachment function essential for virus infection. Recent experiments confirm that ICAM-1 is in fact a receptor for group A coxsackieviruses (CVA)21. Infection by a variety of echovirus serotypes, as well as by CVA9, was reportedly inhibited by a monoclonal antibody to a 44-kDa cell surface protein.
The Effect of Conflicting Consumer Reviews on the Accuracy of a Purchase Decisions

Online consumer review plays an important role in customers’ purchase decisions. However, conflicting online reviews can confuse potential customers. As a result, he/she will take a risk of either selecting a product that is not able to satisfy their needs or not select an appropriate product. This error in purchasing can impose significant tangible and intangible costs on the supply chain. In this paper, a conceptual framework will be proposed to model the effect of three types of conflict among online consumer reviews: including Conflicting opinions among product attributes, Conflicting star ratings and the Disagreement intensity among reviewers (CCD model) on the perceived informativeness and accuracy of a purchase decision. Result of this study may help sellers to analyze and categorize online reviews and publish reviews that would improve the accuracy of a purchase decision, thereby decreasing the overall cost of a wrong purchase.
Abstract 13072: Bivalirudin versus Heparin Monotherapy in Percutaneous Coronary Intervention Patients: a Comparison of Acute Adverse Outcomes and Long Term Mortality

Introduction: Bivalirudin compared with heparin has been shown to reduce rates of bleeding and death in patients undergoing primary percutaneous coronary intervention (PCI). In light of recent literature showing the opposite, the aim of the current study is to compare the acute and long-term outcomes of a contemporary population of patients undergoing PCI. Hypothesis: There is no statistically significant difference in acute and long-term outcomes between heparin monotherapy and bivalirudin in PCI patients. Methods: Prospective data from 1/1/11 till 3/31/13 at 2 tertiary care centers in the New York area was obtained. Univariate, bivariate and propensity score adjusted analyses were performed. The primary endpoint was acute adverse outcome (composite of death, MI, CVA, bleeding, and transfusion). The secondary one was long term all-cause mortality. Results: Among the 6,719 PCI patients (1,209 heparin including 258 with bailout glycoprotein IIb/IIIa inhibitor, median follow up 19 months) heparin monotherap...
The Arabidopsis splicing factor SR1 is regulated by alternative splicing

The serine-arginine (SR)-rich splicing factors play essential roles in general splicing and regulate alternative splice site utilization in a concentration-dependent manner. SR1 is a plant homologue of the human general/alternative splicing factor SF2/ASF. We report here that alternative splicing regulates SR1 itself. Of the five detected SR1 transcripts only one encodes the full-length protein, while the other four are different variants of the essential arginine-serine-rich domain. The data suggest that SR1 pre-mRNA could be committed to two alternate splicing pathways. One, dependent on the alternative utilization of competing 3' splice sites in intron 9, generates SR1, SR1B and SR1C. The other, regulated by suppression of intron 9 5' splice site utilization, generates SR1D and SR1E. The splicing pattern and molecular structure of SR1D indicates an evolutionary conservation of splicing-based regulation between plants and vertebrates and suggests that the various isoforms perform important functions. Results from transient gene expression assays indicate that alternative splicing is not an autoregulatory mechanism used to control the transcript level of the full-length protein. The ratio of SR1/SR1B transcripts, which are generated by alternative 3' splice site utilization in intron 9, is under temperature control. The temperature-dependent increase in SR1B/SR1 ratio suggests a role of SR1B in the adaptation to high-temperature environments. In addition, based on the regulated co-expression of SR1 transcripts, it is possible that some SR1 functions could be determined by the combinatorial action of the various isoforms.
The Potential of Fast Ignition and Related Experiments with a Petawatt Laser Facility

A model of energy gain induced by fast ignition of thermonuclear burn in compressed deuterium-tritium fuel, is used to show the potential for 300× gain with a driver energy of 1 MJ, if the National Ignition Facility (NIF) were to be adapted for fast ignition. The physics of fast ignition has been studied using a petawatt laser facility at the Lawrence Livermore National Laboratory. Laser plasma interaction in a preformed plasma on a solid target leads to relativistic self-focusing evidenced by x-ray images. Absorption of the laser radiation transfers energy to an intense source of relativistic electrons. Good conversion efficiency into a wide angular distribution is reported. Heating by the electrons in solid density CD2 produces 0.5 to 1 keV temperature, inferred from the D-D thermo-nuclear neutron yield.
R&D Risk Management

Risk is a major concern in functional R&D organizations, and can arise from any number of sources from simple misunderstandings to natural disasters. Yet despite its importance and prevalence, risk is typically loosely described and poorly characterized. What exactly do we mean by the word “risk”? What distinguishes big risks from small ones? In this work, we discuss the notion and the depiction of risk from the perspective of an R&D organization. We first focus on the two fundamental determinants of risk: uncertainty and unwantedness. We provide a means for decomposing risk into context-relevant categories to improve understanding and communication among R&D stakeholders. We then offer a graphical approach to visualize project risk over time before closing with a general discussion of portfolio level risk. Keywords: RD technical risk; commercial risk; execution risk; portfolio risk
Double sampling in switched-capacitor delta-sigma A/D converters

The achievable signal-to-noise ratio is switched-capacitor delta-sigma modulation analog-to-digital converters is set by the oversampling clock frequency divided by twice the signal bandwidth. The use of double sampling in the switched-capacitor integrators to achieve a factor of two increase in the oversampling factor without reducing the settling time of the operational amplifier is proposed. Detailed simulations have shown that for sufficiently small capacitor mismatch, the double-sampling schemes provide a significant increase in SNR. The larger the desired SNR, the more sensitive the circuit is to capacitor mismatch. It is concluded that the random gain implementation is preferred over the alternating gain scheme, because the former spectrally spreads the effect of the capacitor mismatch. >
Food Systems in an Unequal World: Pesticides, Vegetables, and Agrarian Capitalism in Costa Rica

Political ecology of the 1990s was heavily influenced by Blaikie and Brookfield's (1987) structural “chain of expianation” that examined environmental problems starting with the land manager and mo...
State and Regional Water Supply

Integrated watershed management (IWM) seeks to combine interests, priorities, and disciplines as a multistakeholder planning and management process for natural resources within a watershed ecosystem, centered on water quantity and water quality. Driven bottom-up by local needs and priorities and top-down by regulatory responsibilities, it must be adaptive, evolving dynamically as conditions change. Water resource spatial and political scales range from local/municipal, subregional, state, regional (multistate), national, multinational (‘regional’ in a global sense) to continental and global. Large watersheds occupy state and regional spatial scales, presenting considerable challenges for IWM and water supply, in particular, because of the number and diversity of human consumers and biodiverse habitat needs. A watershed spatial scale is often used by ecologists to analyze species distribution and biogeochemical cycling. Watersheds can be characterized by the proportions of land area taken up by five main land use/land cover categories: urban land, agricultural land, rangeland, forestland, and water. It is arguable whether a watershed or ecoregion scale (region of relative homogeneity based on soil, climate, and vegetative criteria) is most appropriate for managing water quality and aquatic habitats. Even in terms of water stocks and flows, the differences between precipitation and evapotranspiration in one watershed that determine the runoff and infiltration that can be used for water supply are influenced by regional climatic and hydrological processes. Keywords: watershed management; institutions; planning; consumption; treatment; distribution; health risks; ecosystem; agriculture; energy
A comparison of radiated emissions testing to European Directive 95/54/EC using an open field test site and a semi-anechoic chamber

Most automotive component level testing, and in particular European Directive 95/54 requires that under some (in practice most) conditions radiated emissions measurements from electrical/electronic sub-assemblies (ESAs) are made with the ESA under test mounted on an elevated ground plane 1 m high on a wooden table. It is shown that how this ground plane is connected to the test sites ground is very important, and that this is in fact a key issue in obtaining correlation between different open field sites and also in obtaining correlation to test results obtained in a semi-anechoic chamber.
Evidence for trifluoromethyltin(II) compounds

Abstract The products of several reactions between (CF 3 ) 2 Cd · glyme and SnI 2 in tetrahydrofuran have been examined by 19 F NMR. Resonances representing the new compounds CF 3 CdI, CF 3 SnI and (CF 3 ) 2 Sn were assigned based on NMR parameters and 119 Sn Mossbauer spectra.
A chloroquine-like molecule designed to reverse resistance in Plasmodium falciparum.

A class of hybrid molecules which we term ‘reversed chloroquines' (RCQs) was designed, and a prototype molecule, N‘-(7-chloroquinolin-4-yl)-N-[3-(10,11-dihydrodibenzo[b,f]azepin-5-yl)propyl]-N-methylpropane-1,3-diamine (1), was synthesized and tested against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. An in vitro assay against the two strains indicated that 1 was effective at low-nM concentrations against both strains. A preliminary study in mice demonstrated oral efficacy against P. chabaudi and the absence of obvious toxicity. The RCQ approach therefore appears to be feasible.