cssi/SciSciGPT-SciSciNet huggingface dataset:
The neurobiology of depression: An integrated view

Major Depressive Disorder (MDD) is one of the most common and debilitating mental disorders; however, its etiology remains unclear. This paper aims to summarize the major neurobiological underpinnings of depression, synthesizing the findings into a comprehensive integrated view. A literature review was conducted using Pubmed. Search terms included "depression" or "MDD" AND "biology", "neurobiology", "inflammation", "neurogenesis", "monoamine", and "stress". Articles from 1995 to 2016 were reviewed with a focus on the connection between different biological and psychological models. Some possible pathophysiological mechanisms of depression include altered neurotransmission, HPA axis abnormalities involved in chronic stress, inflammation, reduced neuroplasticity, and network dysfunction. All of these proposed mechanisms are integrally related and interact bidirectionally. In addition, psychological factors have been shown to have a direct effect on neurodevelopment, causing a biological predisposition to depression, while biological factors can lead to psychological pathology as well. The authors suggest that while it is possible that there are several different endophenotypes of depression with distinct pathophysiological mechanisms, it may be helpful to think of depression as one united syndrome, in which these mechanisms interact as nodes in a matrix. Depressive disorders are considered in the context of the RDoC paradigm, identifying the pathological mechanisms at every translational level, with a focus on how these mechanisms interact. Finally, future directions of research are identified.
Perspectives on the specific targeting of Fusarium graminearum for the development of alternative head blight treatment approaches

Diseases of agricultural crops caused by fungi have devastating economic and health effects. Fusarium head blight (FHB) is one of the most damaging diseases of wheat and other small grain cereals. FHB reduces agricultural yield while also affecting food supply and safety through deposition of toxins (mycotoxins/phytotoxins). Control of FHB growth and toxin accumulation in grains remain major challenges. While the ultimate goal in the battle against FHB is the development of resistant wheat varieties, the actual use of fully resistant plants that preclude any need for treatment with fungicides remains out of sight. Current antifungals being applied against FHB are generally azole-based inhibitors. However, usage of these azole-based fungicides is being complicated by the facts that these are active only during specific short-lived developmental time periods, fungi are developing increased resistance to them and they are having significant environmental impacts. As such, there is a great need for more targeted, specific and effective antifungal agents to address the significant threat of FHB. This review provides an overview of some of the more promising fungal targets that are currently being investigated for antifungal development.
Effects of feeding alfalfa stemlage or wheat straw for dietary energy dilution on nutrient intake and digestibility, growth performance, and feeding behavior of Holstein dairy heifers

Feeding high-quality forage diets may lead to excessive weight gains and over-conditioning for dairy heifers. Restriction of energy density and dry matter intake by using low-energy forages, such as straw, is a good approach for controlling this problem. Alfalfa stems contain high fiber and moderate protein content and have the potential to be used to replace straw to reduce dietary energy. The objective of this study was to compare nutrient intakes, digestibilities, growth performance, and feeding behaviors of dairy heifers offered an alfalfa silage/corn silage high-energy diet (HE; 13.1% crude protein, 65.4% total digestible nutrients, 39.7% neutral detergent fiber) with 2 energy-diluted diets that replaced various proportions of the corn or alfalfa silages with either alfalfa stemlage (STM; 12.6% crude protein, 59.1% total digestible nutrients, 46.4% neutral detergent fiber) or chopped wheat straw (WS; 12.6% crude protein, 61.9% total digestible nutrients, 43.7% neutral detergent fiber). Seventy-two pregnant Holstein heifers (16.8 ± 1.3 mo) were stratified into 3 blocks (24 heifers/block) by initial body weight (light, 440 ± 18.0 kg; medium, 486 ± 18.6 kg; heavy, 534 ± 25.1 kg), with each block composed of 3 pens (8 heifers/pen), with diets assigned randomly to 1 pen within the block. Diets were offered in a 56-d feeding trial. Both dry matter intake and energy intake were decreased with the addition of low-energy forages to the diets, but no differences in dry matter intake were observed across diluted diets. Digestibility of dry matter, organic matter, neutral detergent fiber, and apparent N were greater for HE compared with diluted diets, and for WS compared with STM. Total body weight gain (74 vs. 56 kg) and average daily gain (1.32 vs. 1.00 kg/d) were greater for heifers offered HE compared with diluted diets. Feed efficiency tended to be less for heifers offered the diluted diets compared with HE (10.7 vs. 8.6 kg of feed/kg of gain). Heifers did not sort for or against particles when offered HE. However, increased sorting behavior was observed for diluted diets. Compared with ad libitum feeding dairy heifers a diet with high nutrient content forages (corn silage and alfalfa silage), use of diet diluted with alfalfa stemlage or wheat straw is an effective feeding management strategy to control total daily dry matter and energy intake by increasing gut fill, and maintain desirable body condition and growth rates, even though the diluted diets had greater sortability.
Status of Resident Attrition From Surgical Residency in the Past, Present, and Future Outlook.

Objective To investigate the current rate of attrition in general surgery residency, assess the risk factors, and identify prevention strategies. Design A literature review of the PubMed and MEDLINE databases, from January 1, 1980 to February 1, 2016, for relevant articles. The calculated attrition rate and the statistically significant influencing factors were the main measures and outcomes. Selection All English language articles that described attrition from a general surgery residency were included. Articles that performed an assessment of attrition rates, academic performance, reasons for resident loss, and demographics were identified and data from these studies were collected. Random-effect meta-analysis and meta-regression based on a generalized mixed-effects model was performed. Results A total of 26 studies were included. Reported attrition rates ranged from 2% to 30% over the course of residency training. Random-effect meta-analysis is indicative of a yearly attrition rate of 2.4% (95% CI: 1.3%-3.5%) and a cumulative 5-year attrition rate of 12.9% (95% CI: 7.9%-17.8%). Most of them leave residency during their first 2 years, and the rate significantly decreases with increasing postgraduate year (p Conclusion Attrition in general surgery most commonly occurs within the first 2 years of training and, in contrast to previous findings, is not related to female sex. Restrictions on work hours seem to have increased the rate, whereas remediation practices can prevent it. Training programs should direct efforts towards attrition-prevention strategies.
Phosphate Recovery from Human Waste via the Formation of Hydroxyapatite during Electrochemical Wastewater Treatment.

Electrolysis of toilet wastewater with TiO2-coated semiconductor anodes and stainless steel cathodes is a potentially viable onsite sanitation solution in parts of the world without infrastructure for centralized wastewater treatment. In addition to treating toilet wastewater, pilot-scale and bench-scale experiments demonstrated that electrolysis can remove phosphate by cathodic precipitation as hydroxyapatite at no additional energy cost. Phosphate removal could be predicted based on initial phosphate and calcium concentrations, and up to 80% total phosphate removal was achieved. While calcium was critical for phosphate removal, magnesium and bicarbonate had only minor impacts on phosphate removal rates at concentrations typical of toilet wastewater. Optimal conditions for phosphate removal were 3 to 4 h treatment at about 5 mA cm–2 (∼3.4 V), with greater than 20 m2 m–3 electrode surface area to reactor volume ratios. Pilot-scale systems are currently operated under similar conditions, suggesting that ph...
Enhanced removal of natural organic matter via peroxidase-mediated oxidative coupling

Oxidative coupling reactions mediated by horseradish peroxidase in solutions containing natural organic matter (NOM) comprised by model fulvic acids were performed in completely mixed batch and flow reactors. The subsequent removal of NOM by ultrafiltration was found to be significantly enhanced for solutions subjected to oxidative coupling. Spectroscopic examinations revealed that the fulvic acid molecules were effectively reconfigured by substantial conversion of aromatic hydroxyl groups into ether bonds via oxidative coupling. These conversions apparently result in cross-linking of NOM moieties to form stable species of greater molecular size, thus rendering them more readily removable by ultrafiltration. The results of this study suggest that catalyzed oxidative coupling reactions in combination with ultrafiltration can be developed into an effective scheme for NOM removal in water treatment operations.
Business Analysis in Information Systems Curriculum: Implications of Business Analysis Professionalization

Within the Information Systems Discipline, business analysis has traditionally been considered a part of system development, and is usually taught as a part of systems analysis and design courses. Recent years however, have seen professionalization of business analysis which has culminated in the establishment of the International Institute of Business Analysis (IIBA). Since its incorporation in 2006, IIBA released a Guide to the Business Analysis Body of Knowledge (BA BOK) and now offers a Certified Business Analysis Professional (CBAP) certification. This paper examines the implications of such professionalization of the field of business analysis for IS education, identifies the gaps between the BA BOK and the traditional core IS curriculum and suggests directions for closing such gaps. Broader implications of BA professionalization for the IS discipline identity are also discussed.
Rhabdomyosarcoma: Case report

Summary A case of rhabdomyosarcoma of the gastrocnemius group of muscles with extensive metastases to the lungs is reported. This case is particularly interesting because of the age and race of the child and the location of the tumor with its marked metastases.
Gender Shifts in the History of English: Defining English gender

Introduction In the fifth century BC, according to Aristotle's account, Protagoras first created the labels masculine, feminine , and neuter for Greek nouns, and language scholars have been trying to explain the relationship of grammatical gender categories to the world around them ever since. Protagoras himself, apparently anxious that the grammatical gender of nouns and the sex of their referents did not always correspond in Greek, is said to have wanted to change the gender of Greek menis ‘anger’ and peleks ‘helmet,’ both of which are feminine nouns, to masculine because he felt the masculine was more appropriate given the words' referents (Robins 1971 [1951]: 15–16). Despite Aristotle's subsequent proposal of grammatical reasons for nominal gender classes, the original labels persisted in the descriptions of gender in classical grammars – and, therefore, in all the later Western grammars modeled on them – and these labels have created the pervasive misperception that grammatical gender categories in a language reflect a connection between male and female human beings and masculine and feminine inanimate objects. The terms deceptively imply a link between the categories in the natural gender system of Modern English – in which there is a clear correlation between masculine and feminine nouns and biological traits in the referent – and the categories in the grammatical gender systems of other Indo-European languages; in fact, these two types of systems are distinct.
A Finite Element Model for Viscoelastic Foundations Supporting Plate Structures

In this paper a numerical approach for the analysis of elastic plate on viscoelastic foundations is developed. The effects of foundation responses are introduced by an analogy to mechanical plate vibrations. The differential and integral types of viscoelastic foundation responses are formulated by particular forms of finite difference equations to analyze the time effects. The structural responses are modeled by the finite element displacement method. The present method combines these two formulations for the response of elastic plates on visco- elastic foundations. The technique is validated by comparing the finite element results to the analytical solution of an infinite elastic beam on a Kelvin foundation. Numerical results are also included for a simply supported elastic plate on Maxwell and Kelvin foundations.
Fibrinogen receptor antagonist-induced thrombocytopenia in chimpanzee and rhesus monkey associated with preexisting drug-dependent antibodies to platelet glycoprotein IIb/IIIa

Most clinical trials with fibrinogen receptor antagonists (FRAs) have been associated with thrombocytopenia. This report describes the occurrence of thrombocytopenia in one chimpanzee and one rhesus monkey upon administration of potent FRAs. Chimpanzee A-264 experienced profound thrombocytopenia on two occasions immediately upon intravenous administration of two different potent FRAs, L-738,167 and L-739,758. However, an equally efficacious antiaggregatory dose of another potent antagonist, L-734,217, caused no change in platelet count. These compounds did not affect platelet count in five other chimpanzees or numerous other nonhuman primates. Flow cytometric analysis showed drug-dependent antibodies (DDAbs) in the plasma of chimpanzee A-264 that bound to platelets of chimpanzees, humans, and all other primates tested only in the presence of the compounds that induced thrombocytopenia. Rhesus monkey 94-R021 experienced thrombocytopenia upon administration of a different antagonist, L-767,679, and several prodrugs that are converted into the active form, L-767,679, in the blood. More than 20 other FRAs, including those that induced thrombocytopenia in chimpanzee A-264, had no effect on platelet count in this monkey. Flow cytometric measurements again identified DDAbs that reacted with platelets of all primates tested and required the presence of L-767,679. Screening for DDAbs in the plasma of 1,032 human subjects with L-738,167 and L-739,758 demonstrated that the incidence of these preexisting antibodies in this population was 0.8% ± 0.6% and 1.1% ± 0.6%, respectively.
Synthetic Spectra For Accretion Discs: The UV Absorption Spectrum

With my collaborators (Ivan Hubeny, NASA/Goddard Space Flight Center; Marcos Diaz, Catherine Grant, and Darren Williams, all of Penn State), I am computing the structure of discs and their corresponding UV spectra for a large grid of choices of the white dwarf mass M wd and the mass transfer rate M. In our approach, we divide the problem into a number of parts, each corresponding to a particular FORTRAN-implemented computer program.
Philosophical trilogy in critical visual analysis – Case of refugee discourse

Abstract Through Critical Visual Analysis (CVA) using the theoretical lens of social semiotics, this paper critically analyzes two images of the Syrian boy who was washed ashore during a refugee journey. The images resulted in a debate and shaped a serious discourse around the Middle Eastern refugee crises. However, the same image from different angle, was used by Daesh/ISIS (in Dabiq Magazine) to present a different kind of ‘reality’/ideology, signifying the possibility of depiction of diverging ideologies through identical images. This research adopts a Conceptual Analytical Approach blending the work of three of the 18th and 19th Century philosophers through their ideas of Genius, Fine Art, Tragedy and Pessimism. To this end, considering Kant, Schopenhauer and Nietzsche's philosophy of arts, this paper critically analyses the images in an effort to reinforce the significance of philosophical analysis in CVA, through deconstruction. In doing so, the article embraces a Logical Analytical Approach, overlaying these selected concepts on contemporary issue within broader refugee discourse. Integrating the contemporary social semiotic concepts with philosophical concepts signifies the need for such Integrative Analytical Approach.
Introduction: Theorizing Transcultural Queer Bodies and Their Appropriation of Frenchness

Navarro-Ayala examines France as a nation and an imagined cultural space. His introduction theorizes that Frenchness plays a significant role in the construction of a queer identity in both Latin America and North Africa. Rather than approaching these cultures as a residual depository of European thought, colonization, and linguistic dominance—as has often been demonstrated to prove problematic in queer theory and literary criticism—Navarro-Ayala’s research takes a transcultural approach to homo/sexual identities and subjectivities. He compares these two marginal regions from the global South in order to further the discussion about bodily image, sexuality, masculinity, marginality, ethnicity, and class within the discipline of queer studies, paying particular attention to the ways in which these sociological factors are associated with France in different cultural contexts.
iGYM: A Wheelchair-Accessible Interactive Floor Projection System for Co-located Physical Play

Physical play opportunities for people with motor disabilities typically do not include co-located play with peers without disabilities in traditional sport settings. In this paper, we present a prototype of a wheelchair-accessible interactive floor projection system, iGYM, designed to enable people with motor disabilities to compete on par with, and in the same environment as, peers without disabilities. iGYM provides two key system features-peripersonal circle interaction and adjustable game mechanic (physics)-that enable individualized game calibration and wheelchair-accessible manipulation of virtual targets on the floor. Preliminary findings from our pilot study with people with motor disabilities using power wheelchairs, manual wheelchairs, and people without disabilities showed that the prototype system was accessible for all participants at higher than anticipated target speeds. Our work has implications for designing novel, physical play opportunities in inclusive traditional sport settings.
Party Formation and Proliferation on Senegal’s Uneven Playing Field

This chapter analyzes the sources of party formation and proliferation in Senegal. First, the author argues that electoral rules, social cleavages, and ideology do not account for party proliferation by themselves; President Wade also used the uneven playing field to encourage party formation but made survival in the opposition difficult enough that most party leaders minimized their involvement in elections and negotiated forms of patronage that did not require vote-seeking. Subsequently, the author presents an in-depth account of the logics of party creation among a chronological subset of politicians who contributed to the initial acceleration in party formation. While the logics of party creation are multiple, and various opposition parties in Senegal are created to contest elections, many other party leaders run organizations that function primarily to obtain patronage that does not depend on regularized vote-seeking. This research is based on archival research on all registered parties; semi-structured interviews conducted with the 46 people who created parties during 1998–2003, the six years surrounding Senegal’s first presidential turnover in 2000; vignettes of pre- and post-alternance party formation; and analysis of the types and frequencies of new parties’ electoral activity and performance, as well as their leaders’ declared motivations.
Detection of intussusception by point-of-care ultrasound at emergency department: a case report

Case Report A 80-year-old man, with hypertension, hyperlipidemia, and secondary parkinsonism, presented to our ED due to intermittent periumbilical pain for hours. Initial vital signs were stable except high blood pressure (T:36.3’C P:62 beats/min R:18 breaths/min BP:178/91mmHg). Physical examination showed right side abdominal tenderness and positive peritoneal sign. He denied fever, dyspnea, nausea/vomiting, diarrhea, tarry or bloody stool passage, nor trauma history. Point-of-care Ultrasound (POC-US) was performed by ED physician revealing the target sign (Figure 1) and the pseudokidney sign (Figure 2) over right side abdomen without obvious fluid accumulation in the peritoneum. Abdominal computerized tomography (CT) with contrast enhancement was further done reporting highly suspecting ileocolic intussusception (Figure 3). Emergent laparotomy revealed ileocecal intussusception with one polypoid tumor on terminal ileum which might be the leading point. Right hemicolectomy with LN dissection and ileo-transverse anastomosis were done. He was discharged days later and had follow-up at Outpatient Department. Discussion Intussusception refers to a process in which a segment of intestine invaginates into the adjoining intestinal lumen.In adults, intussusception accounts only for less than 5 percent of mechanical bowel obstructions.12Typically, it's owing to pathologic lead point within the bowel, which is 50 percent due to malignancy. 34Among adults, intermittent abdominal pain may be the most common presentation. Due to low incidence rate and unspecified presentation among adults, the diagnosis isn't often made until abdominal computerized tomography (CT) was done. In this situation, point-of-care ultrasound (POC-US) can be helpful to have early diagnosis of intussusception and early intervention in order to avoid necrosis or perforation of intestines. In our patient, intermittent periumbilical pain was the initial presentation. POC-US was performed by ED physician and under impression of intussusception, further abdominal CT and GS consultation were arranged right away. Early diagnosis and early intervention may avoid further necrosis or perforation of intestines. By using POC-US, ED physicians could rapidly detect specified lesions by real-time images and could detect the dynamic changes. And, most important, POC-US is a non-invasive and radiation-free tool that may be used as the primary tool to screen acute abdominal emergencies.
Perioperative Outcomes and Complications After Primary Total Hip Arthroplasty in Patients With Disproportionately Short Stature: A Matched Cohort Analysis.

Abstract Background This study compared (1) perioperative outcomes, (2) postoperative complications, and (3) reoperation rates after primary total hip arthroplasty (THA) between short stature patients and matched control patients. Methods A review of primary THA patients from 2012 to 2017 using an institutional database was conducted. This yielded 12,850 patients of which 108 were shorter than 148 cm. These patients were matched 1:1 by age (P = .527), gender (P = .664), and body mass index (P = .240) to controls. The final study population with minimum 1-year follow-up that was included for analysis comprised 47 patients in the short stature cohort and 57 patients in the control cohort. The following outcomes/complications were compared: operative times, lengths of stay (LOSs), intraoperative fractures, minor complications, 90-day readmissions, and revisions. Results Operative times were significantly longer in the short stature cohort than in the matched control cohort (133 ± 65 minutes vs 104 ± 30 minutes, P = .005). In addition, hospital LOS was slightly longer in the short stature group than in the matched control groups (3.2 ± 1.5 days vs 2.6 ± 1.0, P = .017). Rates of intraoperative fractures (P = 1.000), minor complications P = .406), 90-day readmissions (P = .5000), and revision (P = .202) were similar between the short stature and control cohorts. Conclusion Patients with disproportionately short stature had longer operative times and slight longer LOS. However, complication and readmission rates were similar. Future studies with larger sample sizes are warranted to confirm these findings and further evaluate implant survivorship in this unique THA patient population.
``Who'': Perception of talker properties

Spoken language simultaneously provides listeners with linguistic content and information about the person speaking. Listeners can identify specific individuals from auditory-only speech signals. Furthermore, listeners can identify a range of physical and socio-cultural talker characteristics (indexical characteristics) with above chance accuracy. Listeners are sensitive to relatively stable aspects of a talker's identity, such as their age, height, gender, race/ethnicity, sexual orientation, region of origin, native, and language status. Talkers also transmit more transitory information (e.g., current health status or emotional state). The mental representations that listeners build for individual talkers and speaker groups interact with the processing of linguistic information, such that the same physical acoustic signal can be interpreted in different ways depending on the talker's perceived indexical characteristics. In this talk, I will focus on how these mental models can allow for more efficient and accurate processing of speech signals. For example, listeners are more accurate at identifying words from familiar than unfamiliar talkers. Likewise, listeners more accurately understand speech from non-native speakers after a period of exposure. Research on the “who” of speech perception demonstrates the need for considering the interaction between talker characteristics and listener knowledge when making decisions about speech privacy.Spoken language simultaneously provides listeners with linguistic content and information about the person speaking. Listeners can identify specific individuals from auditory-only speech signals. Furthermore, listeners can identify a range of physical and socio-cultural talker characteristics (indexical characteristics) with above chance accuracy. Listeners are sensitive to relatively stable aspects of a talker's identity, such as their age, height, gender, race/ethnicity, sexual orientation, region of origin, native, and language status. Talkers also transmit more transitory information (e.g., current health status or emotional state). The mental representations that listeners build for individual talkers and speaker groups interact with the processing of linguistic information, such that the same physical acoustic signal can be interpreted in different ways depending on the talker's perceived indexical characteristics. In this talk, I will focus on how these mental models can allow for more efficient an...
Testing Criteria for Mobile Apps Based on Callback Sequences

App quality has been shown to be the most important indicator of app adoption. To assure quality, developers mainly use testing to find bugs in app and apply structural and GUI test coverage criteria. However, mobile apps have more behaviors than the GUI actions, e.g. an app also handles events from sensors and executes long-running background tasks through Android API calls to Services and AsyncTasks. Our studies found that there are important app behaviors via callback interactions that should be covered in testing, as data sharing between callbacks is common and is the cause of many existing bugs. We design a family of test criteria based on callback sequences and use the Callback Control Flow Automata (CCFA) to measure the coverage for testing. Our experiments show that guiding by our criteria, testing can find more bugs and trigger bugs faster than the state-of-the-art tools.
Effect of Flumazenil on Hypoactive Delirium in the ICU: A Double-Blind, Placebo-Controlled Pilot Study.

Author(s): Schomer, Kendra J; Duby, Jeremiah J; Firestone, Rachelle L; Louie, Erin L; Sebat, Christian M; Love, Dawn M; Cocanour, Christine S; Albertson, Timothy E | Abstract: To determine whether the use of flumazenil reverses hypoactive delirium and increases delirium-free days in critically ill patients who were exposed to benzodiazepine therapy during the ICU admission. Design:This was a single-center, double-blinded, randomized placebo-controlled pilot study. Setting:Adult ICUs at a large academic medical center in the United States. Patients:Adult, critically ill patients with benzodiazepine exposure and hypoactive delirium based on the Confusion Assessment Method-ICU and Richmond Agitation Sedation Scale assessments were considered for enrollment. Interventions:Patients received a test dose of flumazenil starting at 0.1 mg intravenously and titrated up every 5 minutes by 0.1 mg increments up to a maximum total dose of 2 mg. Patients who demonstrated a Richmond Agitation Sedation Scale score increase of greater than 1 point were considered responders and randomized to flumazenil (0.05-0.3 mg/hr) or placebo infusion for up to 72 hours. Confusion Assessment Method-ICU scores were assessed twice daily for resolution of delirium. Measurements and Main Results:The trial was stopped early based on the observed size effect and power analysis. Twenty-two of the 25 patients responded to the flumazenil test dose (88%). The median number of delirium-free days alive without coma within 14 days of enrollment was similar between the two infusion groups (12.7 vs 9.2; p = 0.19). There was no difference in the probability of delirium resolution within the first 14 days with 90% versus 70% in the flumazenil and placebo groups, respectively (p = 0.2). There was no statistical difference (odds ratio, 0.17; 95% CI, 0.022-1.23; p = 0.079) in delirium- and coma-free days at the end of the study drug infusion. There was no difference between groups in ICU length of stay (7.8 ± 4.8 vs 7 ± 8; p = 0.74). No serious adverse events occurred. Conclusions:This study found that flumazenil test dose and infusion present a potential option for hypoactive delirium associated with benzodiazepine exposure; however, the possible benefit is unknown. Larger studies are warranted to further evaluate these findings.
Inter/intra-tumoral dose response variations assessed using FDG-PET/CT feedback images: Impact on tumor control and treatment dose prescription.

Abstract Purpose To quantify inter/intra-tumoral variations of baseline metabolic activity and dose response. To evaluate their impact on tumor control and treatment dose prescription strategies. Methods and materials Tumor voxel baseline metabolic activity, SUV0, and dose response matrix, DRM, quantified using the pre-treatment and weekly FDG-PET/CT imaging feedback for each of 34 HNSCC patients (25 HPV+ and 9 HVP−) were evaluated. Inter/intra-tumoral variations of tumor voxel (SUV0, DRM) for each of the HPV− and HPV+ tumor groups were quantified and used to evaluate the variations of individual tumor control probabilities and the efficiency of uniform vs non-uniform treatment dose prescription strategies. Results Tumor voxel dose response variation of all tumor voxels assessed using FDG-PET/CT imaging feedback had the mean(CV) = 0.47(47%), which was consistent with those of previously published in vitro tumor clonogenic assay. The HPV− tumors had the mean(CV) dose response, 0.53(49%), significantly larger than those of the HPV+ tumors, 0.45(43%). However, their baseline SUVs were opposite, 6.5(56%) vs 7.7(65%). Comparing to the inter-tumoral variations, both HPV−/+ tumor groups showed larger intra-tumoral variations, (53%, 58%) vs (20%, 31%) for the baseline SUV and (38%, 37%) vs (31%, 21%) for the dose response. Due to the large dose response variations, treatment dose to control the tumor voxels has very broad range with CV of TCD50 = 97% for the HPV− and 67% for the HPV+ tumor group respectively. As a consequence, heterogeneous prescription dose could potentially reduce the treatment integral dose for 92% of the HPV+ tumors and 78% of the HPV− tumors. Conclusions The study demonstrates that tumor dose response assessed using FDG-PET/CT feedback images had a similar distribution to those assessed conventionally using in vitro tumor clonogenic assay. Inter-tumoral dose response variation seems larger for HPV− tumors, but intra-tumoral dose response variations are similar for both HPV groups. These variations cause very large variation on the individual tumor control probability and limit the efficacy of dose escalation and de-escalation in conventional clinical practice. On the other hand, heterogeneous dose prescription guided by metabolic imaging feedback has a potential advantage in radiotherapy.
Abstract PR-10: Identifying new risk factors for early-onset CRC in population under 50 years old using EHR-based machine learning

Objective: Colorectal cancer (CRC) is the 3rd most common cancer in the United States. Despite declining incidence in patients older than 50, there has been an increasing trend of CRC in patients under the age of 50. Some risk factors such as inflammatory bowel disease and inherited genetic syndromes can lead to early onset of CRC; yet incidence of these disorders is not concomitant with the increase of CRC under 50 years old. This study utilizes machine learning models with electronic health records (EHR) data from the OneFlorida network—a clinical research network contributing to the national PCORnet to demonstrate a potential avenue for investigation of the rise in incidence. Methods: This study applied four machine learning algorithms on a cohort of 1,227 CRC cases and matched 34,157 controls, all under the age of 50 extracted from the OneFlorida network. Colon cancer (CC) and rectal cancer (RC) were modeled separately. For each case patient, we created a prediction window starting from the first recorded encounter in their EHR to end dates of 0, 1, 3, and 5 years prior to the case CC/RC index date. For each control patient we matched them to cases based on age at an encounter date to close to the case index date. The data was split into a training set (80%) for training the models, and a testing set (20%) used to measure model performance. SHapley Additive exPlanations (SHAP) was used to analyze significant features. Results: Notable trends in model prediction results were decreased sensitivity across prediction windows as data per patient decreased, in both RC and CC cohorts. Zero-year and 1-year prediction area under the curve (AUC) was significant at 0.64 to 0.75 for all algorithms across RC and CC. As the prediction window widened, the prediction performance dropped to as low as 0.35 (i.e., 5-year prediction). The best performing algorithm across all experiments was the support vector machine (SVM). Top predictors identified in the CC cohort include hypertension, cough/asthma, chronic sinusitis, anxiety d/o, and atopic dermatitis, while top predictors in the RC cohort include obesity, female gender, HIV, anxiety d/o and asthma. Conclusions: Disorders with chronic immunosuppression (e.g., HIV) or inflammation (e.g., obesity, asthma, sinusitis, dermatitis) may represent immune-axis derangements contributing to a favorable state for CRC. This preliminary study provides early insight into the capacity of artificial intelligence to uncover new risk factors in the population of patients with onset of young-onset CRC with more algorithm refinement and risk factor exploration underway. Citation Format: Michael B. Quillen, Taylor M. Parker, Jiang Bian, Thomas George. Identifying new risk factors for early-onset CRC in population under 50 years old using EHR-based machine learning [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PR-10.
The effects of teacher-delivered behavior skills training on paraeducators' use of a communication intervention for a student with autism who uses AAC

Special education teachers are often responsible for training their staff how to support children with autism spectrum disorder in their classrooms. In addition to academic and behavioral interventions, paraeducators also need to be prepared to support students with complex communication needs. This study was designed to investigate the effects of a paraeducator-implemented communication intervention in a public school. A multiple probe design across participants was used to evaluate a communication intervention that included providing opportunities to initiate with least-to-most prompting for a 10-year-old student with autism who used an augmentative and alternative communication (AAC) device. Prior to the intervention, the student was rarely observed initiating interactions with her AAC device, and paraeducators were rarely observed offering opportunities to initiate or providing supports to help the student initiate. Following training, data from each paraeducator indicated an increased rate when providing the communication intervention and as a result, the student displayed an increase in the targeted intervention, initiation. Findings from the intervention highlight the need for explicit teaching when promoting initiation among students with autism who use AAC.
Epimutation of MMACHC compound to a genetic mutation in cblC cases.

Background Methylmalonic aciduria (MMA) combined with homocystinuria, cobalamin(cbl)C deficiency type (OMIM 277400), is the most common autosomal recessive inherited disorder of intracellular cobalamin metabolism caused by mutations in the MMACHC gene (OMIM 609831), of which more than 100 mutations have been identified to date. In this study, we only identified a coding mutation in one allele at the MMACHC gene locus, and no large fragments deletion or duplication were found. Up to now, only three epimutation cblC cases were reported. We hypothesized whether the MMACHC was hypermethylated. Methods To address this hypothesis, the entire coding region and adjacent splice sites of the panel genes involved in metabolic diseases were sequenced using the Illumina HiSeq X platform, followed by confirmation via Sanger sequencing in their parents and brothers. Methylation analysis of the MMACHC was performed using an EpiTect Bisulfite Kit and methylation-specific PCR (MSP) to investigate the role of epimutations in cblC disease. Results We identified a clearly pathogenic single heterozygous c.658_660del, p. (K220del) mutation, which was also identified in the mother. Analysis of the MMACHC indicated a heterozygous epimutation consisting of 34 hypermethylated CpG sites in a CpG island encompassing the promoter and first exon of the MMACHC, which was also identified in the father. Furthermore, we identified a single heterozygous c.*2C>T mutation in the sixth exon of the PRDX1 (OMIM 176763) in patients and their fathers, which was the only sequence variation that segregated with the MMACHC methylation. Neither c.658_660del and epimutation in MMACHC nor c.*2C>T in PRDX1 was discovered in her brother. Conclusion We report compound heterozygotes in MMACHC for a genetic mutation and an epimutation in cblC cases. To our best knowledge, this is the first report of two cblC cases from China caused by compound heterozygous mutations with a coding mutation in one allele and an epimutation in the other at the MMACHC locus.
Mild traumatic brain injury/ concussion initiates an atypical astrocyte response caused by blood-brain barrier dysfunction

Abstract Mild traumatic brain injury/ concussion (mTBI) account for 70-90% of all reported TBI cases and cause long lasting neurological consequences in 10 to 40% of patients. Recent clinical studies revealed increased blood-brain barrier (BBB) permeability in mTBI patients, which correlated with secondary damage after mTBI. However, the cascade of cellular events initiated by exposure to blood-borne factors resulting in sustained damage are not fully resolved. We previously reported that astrocytes respond atypically to mTBI rapidly downregulating many proteins essential to their homeostatic function while classic scar formation does not occur. Here, we tested the hypothesis that mTBI -induced BBB damage causes atypical astrocytes through exposure to blood-borne factors. Using a mTBI mouse model, 2-photon imaging, an endothelial cell-specific genetic ablation approach, and serum-free primary astrocyte cultures, we demonstrated that areas with atypical astrocytes coincide with BBB damage and that exposure of astrocytes to plasma proteins is sufficient to initiate downregulation of astrocyte homeostatic proteins. While mTBI resulted in frequent impairment of both physical and metabolic BBB properties and leakage of small-sized blood-borne factors, deposition of the coagulation factor fibrinogen or vessel rupture were rare. Surprisingly, even months after mTBI BBB repair did not occur in areas with atypical astrocytes. Together, these findings implicate that even relatively small BBB disturbances are sustained long-term and render nearby astrocytes dysfunctional, likely at the cost of neuronal health and function.
A Systematic Survey of Text Worlds as Embodied Natural Language Environments.

Text Worlds are virtual environments for embodied agents that, unlike 2D or 3D environments, are rendered exclusively using textual descriptions. These environments offer an alternative to higher-fidelity 3D environments due to their low barrier to entry, providing the ability to study semantics, compositional inference, and other high-level tasks with rich high-level action spaces while controlling for perceptual input. This systematic survey outlines recent developments in tooling, environments, and agent modeling for Text Worlds, while examining recent trends in knowledge graphs, common sense reasoning, transfer learning of Text World performance to higher-fidelity environments, as well as near-term development targets that, once achieved, make Text Worlds an attractive general research paradigm for natural language processing.
Catalytic and noncatalytic growth of ZnO nanostructures on different substrates, and Sb-doped ZnO nanostructures on Au-catalyzed Si(100): Components for potential utilization in three-dimensional dye-sensitized solar cells

Abstract This study investigates the growth of antimony-doped ZnO nanostructures on Au-catalyzed Si(100) and undoped ZnO nanostructures (nanocolumns, nanowires, nanotubes) on the surfaces of different substrates, including fused silica, sapphire, Si(100), and thin wire electrodes to facilitate the transport of photogenerated electrons, reduce recombination rates, and improve power conversion efficiencies (PCEs) of hybrid metal oxide/polymer solar cells. The novel proposed cylindrical design makes use of existing capillary technology to allow for light propagation through the waveguide versus light exposure normal to a planar surface. In addition, the design may help enhance PCE values by the ability to utilize photons from all directions upon sunlight illumination. Thin capillary (tubular) structure could be properly sealed through only two ends versus planar designs, which would significantly improve retention of liquid electrolyte. Anchoring of the nano metal oxide layers was attained by vapor phase transport synthesis under controlled temperature, pressure, and carrier gas flow. Morphology, structure, composition, and photoelectronic characterization of cell components was performed using scanning electron microscopy, powder X-ray diffraction, and room-temperature photoluminescence.
High resolution muscle measurements provide insights into equinus contractures in patients with cerebral palsy

Muscle contractures that occur after upper motor neuron lesion are often surgically released or lengthened. However, surgical manipulation of muscle length changes a muscle's sarcomere length (Ls ), which can affect force production. To predict effects of surgery, both macro- (fascicle length (Lf )) and micro- (Ls ) level structural measurements are needed. Therefore, the purpose of this study was to quantify both Ls and Lf in patients with cerebral palsy (CP) as well as typically developing (TD) children. Soleus ultrasound images were obtained from children with CP and TD children. Lf was determined and, with the joint in the same position, CP biopsies were obtained and formalin fixed, and Ls was measured by laser diffraction. Since soleus Ls values were not measurable in TD children, TD Ls values were obtained using three independent methods. While average Lf did not differ between groups (CP=3.6±1.2 cm, TD=3.5±0.9 cm; p>0.6), Ls was dramatically longer in children with CP (4.07±0.45 µm vs. TD=2.17±0.24 µm; p<0.0001). While Lf values were similar between children with CP and TD children, this was due to highly stretched sarcomeres within the soleus muscle. Surgical manipulation of muscle-tendon unit length will thus alter muscle sarcomere length and change force generating capacity of the muscle.
Interactions of Diet and Cortisone in the Regulation of Adaptive Enzymes in Rat Liver

Abstract The responses of the adaptive enzymes, serine dehydrase (l-serine hydro-lyase (deaminating), EC 4.2.1.13), ornithine transaminase (l-ornithine: 2-oxoacid aminotransferase, EC 2.6.1.13), glucose 6-phosphate dehydrogenase (d-glucose 6-phosphate:NADP oxidoreductase, EC 1.1.1.49), and glucokinase (ATP:d-glucose 6-phosphotransferase, EC 2.7.1.2), in rat liver were studied in relation to changes in the level of dietary protein and treatments with cortisone. The administration of cortisone markedly altered the responses of the enzymes to the diet, and the effects of the hormone depended both on the route of its administration (intraperitoneal or intramuscular injection) and on the dietary regimen of the rats. The response of each enzyme to the regulatory stimuli (diet and cortisone) showed elements of both uniqueness and similarity with respect to the responses of the other three enzymes to these stimuli. The results indicate that the regulatory system for each enzyme responds to a specific set of effectors (e.g. amino acids or carbohydrate or both, of dietary or endogenous origin) and that cortisone alters the capacity of the regulatory systems to interact with the appropriate effectors.
Automatic measurement of instruction cache capacity

There is growing interest in autonomic computing systems that can optimize their own behavior on different platforms without manual intervention. Examples of successful self-optimizing systems are ATLAS, which generates Basic Linear Algebra Subroutine (BLAS) Libraries, and FFTW, which generates FFT libraries. Self-optimizing systems may need the values of hardware parameters such as the number of registers of various types and the capacities of caches at various levels. For example, ATLAS uses the capacity of the L1 cache and the number of registers in determining the size of cache tiles and register tiles. We have built a system called X-Ray, which uses micro-benchmarks to measure such parameter values automatically. The micro-benchmarks currently implemented in X-Ray can determine the latency of various instructions, the existence of important instructions like fused multiply-add, the number of registers of various kinds, and parameters of the memory hierarchy. In this paper, we discuss how X-Ray determines the capacity of the instruction cache (I-cache), which is needed for important optimizations such as loop unrolling. We present the micro-benchmark used in X-Ray to measure I-cache capacity, the experimental methodology used to obtain accurate estimates, and experimental results on a large number of current platforms.
Notes on the mechanism of ATP synthesis.

The most commonly quoted mechanism of the coupling between the electrochemical proton gradient and the formation of ATP from ADP and Pi assumes that all states of the F1 portion of the ATP synthase have β subunits in “tight,” “loose,” and “open” conformations. Models based on this assumption are inconsistent with some of the available experimental evidence. A mechanism that includes an additional β subunit conformation, “closed,” observed in the rat liver structure overcomes these difficulties.