cssi/SciSciGPT-SciSciNet huggingface dataset:
Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic microangiopathies: a cohort study

Summary Background Among the syndromes characterised by thrombotic microangiopathy, thrombotic thrombocytopenic purpura is distinguished by a severe deficiency in the ADAMTS13 enzyme. Patients with this disorder need urgent treatment with plasma exchange. Because ADAMTS13 activity testing typically requires prolonged turnaround times and might be unavailable in resource-poor settings, a method to rapidly assess the likelihood of severe ADAMTS13 deficiency is needed. Methods All consecutive adult patients presenting to three large academic medical centres in Boston, MA, USA, with thrombotic microangiopathy and a possible diagnosis of thrombotic thrombocytopenic purpura between Jan 8, 2004, and Dec 6, 2015, were included in an ongoing multi-institutional registry (the Harvard TMA Research Collaborative). Univariate analysis was used to identify covariates for a logistic regression model predictive of severe ADAMTS13 deficiency (≤10% activity). A clinical point score was generated, and its diagnostic performance was assessed using internal and external validation cohorts and compared to clinical assessment alone. Findings 214 patients with thrombotic microangiopathy were included in the derivation cohort. A seven-component clinical prediction tool, termed the PLASMIC score, was developed and found to reliably assess the pretest probability of severe ADAMTS13 deficiency ( C statistic 0·96, 95% CI 0·92–0·98). Our diagnostic model was reproducibly accurate in both the internal (0·95, 0·91–0·98) and external (0·91, 0·85–0·95) validation cohorts. The scoring system also more consistently diagnosed thrombotic microangiopathy due to severe ADAMTS13 deficiency than did standard clinical assessment, as measured by C statistic (0·96, 95% CI 0·92–0·98 for PLASMIC vs 0·83, 0·77–0·88 for clinical assessment; p vs 0·111 for clinical assessment; mean paired difference 0·05, 95% CI 0·01–0·08; p Interpretation We have developed and validated a clinical prediction tool—the PLASMIC score—to stratify patients with thrombotic microangiopathy according to their risk of having severe ADAMTS13 deficiency. We have shown that this scoring system is superior to standard clinical assessment in addressing the diagnostic challenge presented by thrombotic microangiopathy. Its use, together with clinical judgment, may facilitate treatment decisions in patients for whom timely results of ADAMTS13 activity testing are unavailable. Funding The Luick Family Fund of Massachusetts General Hospital.
Design of low-latency uplink MAC scheduling for Massive MIMO-OFDM systems

Massive MIMO is a promising technology for 5G due to its huge extended multi-user spatial multiplexing and beamforming capability, but its high complexity makes the associated MAC scheduling suffer from long processing time in practice. To solve such problem, this paper designs a low-latency uplink MAC scheduling scheme for Massive MIMO-OFDM systems. Specifically, first, a framework enabling processing parallelization is put forward in which the scheduling for multiple resource blocks (RB) are executed concurrently with the common pre-processing and post-processing. Second, a power-based weight is introduced into the per-RB scheduling, by which the link adaptation could be completed simultaneously with per-RB processing, no longer requiring reduplicate post-scheduling processing. Third, a low-complexity calculation method is applied to the per-layer recursive user selection algorithm for each RB, in which the matrix inversion is substituted by the recursion with vector inner-productions based on Hermitian Matrix Blockwise Inversion Lemma. Finally, performance simulation results demonstrate that the designed MAC scheduling scheme outperforms random scheduling in terms of both cell sum throughput and cell edge throughput.
Abstract 5074: Therapeutic targeting of bromodomain and extra-terminal proteins degradation in triple-negative breast cancer

Triple negative breast cancer represents the most clinically challenging subtypes of breast cancer for which targeted therapeutics are still lacking. BET proteins have emerged as new therapeutic targets for human cancer and other diseases.We have developed a highly potent BET degrader, BETd-246, with an exceptional selectivity based upon a new class of BET inhibitor, BETi-211, and investigated its therapeutic potential and mechanisms of action in TNBC. BETd-246 induces degradation of BET proteins at low nanomolar concentrations within 1 hour, leading to potent anti-proliferative activity and strong apoptosis induction in the majority of TNBC cell lines, and is much more effective than the BETi-211 treatment. RNA-seq analysis reveals that degradation of BET proteins by BETd-246 elicits distinct transcriptional response than BET BD inhibition in TNBC cell lines. Transcriptomic analysis also shows a number of proliferation and survival-related genes were differentially regulated by BETd-246 and BETi-211 which were confirmed by quantitative RT-PCR. Mechanistically, down-regulation of MCL1 by BETd-246 plays a key role in the robust apoptosis induction in TNBC cell lines. In in vivo models, BETd-246 effectively degrades BET proteins and suppresses MCL1 expression in xenograft tumor tissues and exhibits a strong antitumor activity at well-tolerated dose-schedules in mice. Our data strongly suggest that targeting BET protein degradation is an exciting therapeutic strategy for TNBC. Citation Format: Longchuan Bai, Bing Zhou, Chao-Yie Yang, Jiao Ji, Donna McEachern, Sally Przybranowski, Shaomeng Wang. Therapeutic targeting of bromodomain and extra-terminal proteins degradation in triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5074. doi:10.1158/1538-7445.AM2017-5074
NanoVipa: a miniaturized high-resolution echelle spectrometer, for the monitoring of young stars from a 6U Cubesat

We introduce to astrophysical instrumentation and space optics the use of virtually imaged phased array (VIPA) to shrink echelle spectrometers and/or increase their resolution. Here, we report on both a concept of an echelle spectrometer with resolution $$R=50{,}000$$ (@653nm), which fits a 6U nanosatellite platform ( $${{1{\rm U}= 10\,{\rm cm} \times 10\,{\rm cm} \times 10\,{\rm cm}}}$$ ), and on our laboratory tests on a $$R=200{,}000$$ demonstrator. The outline of our paper is as follows: Sect. 1 introduces our concept of a 6U payload comprising an echelle spectrometer based on the VIPA. We present also the science cases of monitoring young stars, and the wider science landscape amenable with larger telescopes. Section 2 gives a more detailed description of the VIPA and of its implementation in a cross-dispersed spectrometer. Section 3 shows the first results at $$R=200{,}000$$ we already achieved at the Institut de Planetologie et d’Astrophysique de Grenoble (IPAG). Finally, Sect. 4 is a discussion on the remaining technical points to study.
Qualitative Research Methods to Advance Research on Health Inequities among Previously Incarcerated Women Living with HIV in Alabama.

Justice-involved HIV-positive women have poor health outcomes that constitute health inequities. Researchers have yet to embrace the range of qualitative methods to elucidate how psychosocial histo...
Three-phase AC optimal power flow based distribution locational marginal price

Designing market mechanisms for electricity distribution systems has been a hot topic due to the increased presence of smart loads and distributed energy resources (DERs) in distribution systems. The distribution locational marginal pricing (DLMP) methodology is one of the real-time pricing methods to enable such market mechanisms and provide economic incentives to active market participants. Determining the DLMP is challenging due to high power losses, the voltage volatility, and the phase imbalance in distribution systems. Existing DC Optimal Power Flow (OPF) approaches are unable to model power losses and the reactive power, while single-phase AC OPF methods cannot capture the phase imbalance. To address these challenges, in this paper, a three-phase AC OPF based approach is developed to define and calculate DLMP accurately. The DLMP is modeled as the marginal cost to serve an incremental unit of demand at a specific phase at a certain bus, and is calculated using the Lagrange multipliers in the three-phase AC OPF formulation. Extensive case studies have been conducted to understand the impact of system losses and the phase imbalance on DLMPs as well as the potential benefits of flexible resources.
Mushroom cultivation in the developing world: A comparison of cultivation technologies

Food and financial insecurity are becoming prominent issues facing much of the developing world. As population densities in these already resource constrained regions continue to increase, it is inherent that a source of sustainable income and a reliable food source be provided, especially to rural populations. Mushroom cultivation is an environmentally benign, sustainable source of nourishment that is rapidly growing to become a profitable sector of agriculture. In high-resource settings, technological advancements have enabled farmers to maximize mushroom yields and quality while minimizing cost and input resources. However, these same benefits have not yet been realized in low- and middle-income settings and challenges characteristic to those contexts have hindered the development of mushroom cultivation. In order to better understand current efforts and their challenges, this article reviews cultivation technologies in both high- and low-resource settings. The outcomes of this review are then synthesized into a comparison of different cultivation technologies on the basis of cost, required resources, and overall success. Challenges and opportunities associated with mushroom cultivation in the developing world are also identified. For example, two prominent challenges in the developing world are spore production and post-harvest transportation and storage. Future practitioners, researchers, and entrepreneurs will be able to use this comparison to identify innovative ways in which the technological advancements of mushroom cultivation in high-resource settings can be applied to resource constrained environments.
Teaching Responsible Drinking Skills

Prevent alcoholism by teaching responsible drinking? Is that a sensible idea? Consider the following multiple choice analogy. There is no one right or wrong answer, but probably one analogy will fit best or seem most true to you.
When Given a Lemon, Make Lemonade: Revising Cardiovascular Risk Prediction Scores.

Yadlowsky and colleagues evaluated 2 approaches for improving the pooled cohort equations to estimate cardiac risk. The editorialists discuss the findings and the need to develop increasingly accur...
A Term Paper Project in Large Survey Courses.

THE OBJECTIVE OF INTRODUCTORY COURSES in history ought not be merely disseminating facts or even deepening insights into our collective past but also teaching tools of the liberal arts--research, analysis, organization, and skill at communicating ideas in clear, correct and forceful writing. These skills are fundamental not only to success in upper division courses but in the later careers of most college graduates. For many years I have been disheartened by the poor quality of many term papers written in my upper division courses, and I suspect that professors of history at most American colleges or universities have had the same experience. Some students do not know or use the mechanics of proper format, even though they may have been taught these in freshman writing courses. Many students spend too much time and effort finding and narrowing a topic that they can handle in a paper of ten to twenty pages. More serious, many students cannot write well. One reason forbad writing is lack of practice; another is the gap between freshmen English courses which teach writing and upper division humanities courses which regularly require term papers. A remedy for both is to require term papers in introductory courses so that freshmen put what they have been learning in their writing courses into immediate practice and therefore do not compartmentalize correct writing as something that applies only to freshman English.
A Class of Association Sensitive Multidimensional Welfare Indices

The last few decades have seen increased theoretical and empirical interest in multidimensional measures of welfare. This paper develops a two-parameter class of welfare indices that is sensitive to two distinct forms of inter-personal inequality in the multidimensional framework. The first form of inequality pertains to the spread of each dimensional achievement across the population, as would be reflected in the multidimensional version of the usual Lorenz criterion. The second one regards association or correlation across dimensions, reflecting the key observation that inter-dimensional association may alter evaluation of individual as well as overall inequality. Most existing multi-dimensional welfare indices are, however, either completely insensitive to inter-personal inequality or are only sensitive to the first. The class of indices developed in this paper is sensitive to both forms of multidimensional inequality. An axiomatic characterization of the class is provided, and it is shown that other multidimensional indices, such as the ones developed by Bourguignon (1999) and Foster, Lopez-Calva, and Szekely (2005), are sub-classes of this new broader class. Finally, essential statistical tests are constructed to verify the reliability of the evaluations generated by the indices.
Horizontal Dispersion and Critical Scales for Phytoplankton Patches

Planktonic organisms in the sea are subject to physical processes in addition to biological processes. It can be seen that physical effects become important in the distribution of organisms when the time scale of the process is comparable to (or smaller than) that of biological factors such as the time scale of organism reproduction.
Implications of Pragmatic and Cognitive Theories on the Design of Utterance-Based AAC Systems

Utterance-based AAC systems have the potential to significantly speed communication rate for someone who relies on a speech generating device for communication. At the same time, such systems pose interesting challenges including anticipating text needs, remembering what text is stored, and accessing desired text when needed. Moreover, using such systems has profound pragmatic implications as a prestored message may or may not capture exactly what the user wishes to say in a particular discourse situation. In this paper we describe a prototype of an utterance-based AAC system whose design choices are driven by findings from theoretically driven studies concerning pragmatic choices with which the user of such a system is faced. These findings are coupled with cognitive theories to make choices for system design.
College students’ use of self-generated tagclouds for knowledge integration: evidence from reflections

Student-generated tagclouds provided an intuitive overview of a group of learners’ collective knowledge. Although such tagclouds may have the potential to be used as effective learning tools, it has not been clear how students use this tool for knowledge construction. In this paper, we report a two-stage study that investigated college students’ experiences of using tagclouds for developing their domain knowledge, culminating in individual concept maps and research papers. Based on the results of the qualitative analyses of students’ reflections from the first stage, an intervention was introduced: group discussions on tagclouds generated from different groups. The result of Study Stage II showed that group discussions highlighted the utility of the tagclouds. Treatment group participants were more likely to use tagclouds as metacognitive strategies for planning, searching, retrieving, and organizing their learning. The two-stage study also underscored the importance of collecting students’ reflections earlier in the learning process when introducing a new technology tool to promote learning.
Fish oil-rich lipid emulsion modulates neuroinflammation and prevents long-term cognitive dysfunction after sepsis.

Abstract Objectives Sepsis is a severe organic dysfunction caused by an infection that affects the normal regulation of several organ systems, including the central nervous system. Inflammation and oxidative stress play crucial roles in the development of brain dysfunction in sepsis. The aim of this study was to determine the effect of a fish oil (FO)-55–enriched lipid emulsion as an important anti-inflammatory compound on brain dysfunction in septic rats. Methods Wistar rats were subjected to sepsis by cecal ligation and perforation (CLP) or sham (control) and treated orally with FO (600 µL/kg after CLP) or vehicle (saline; sal). Animals were divided into sham+sal, sham+FO, CLP+sal and CLP+FO groups. At 24 h and 10 d after surgery, the hippocampus, prefrontal cortex, and total cortex were obtained and assayed for levels of interleukin (IL)-1β and IL-10, blood–brain barrier permeability, nitrite/nitrate concentration, myeloperoxidase activity, thiobarbituric acid reactive species formation, protein carbonyls, superoxide dismutase and catalase activity, and brain-derived neurotrophic factor levels. Behavioral tasks were performed 10 d after surgery. Results FO reduced BBB permeability in the prefrontal cortex and total cortex of septic rats, decreased IL-1β levels and protein carbonylation in all brain structures, and diminished myeloperoxidase activity in the hippocampus and prefrontal cortex. FO enhanced brain-derived neurotrophic factor levels in the hippocampus and prefrontal cortex and prevented cognitive impairment. Conclusions FO diminishes the negative effect of polymicrobial sepsis in the rat brain by reducing inflammatory and oxidative stress markers.
Synthesis and properties of a high solids triethoxysilane-modified alkyd coatings

Abstract Alkoxysilane modified linseed oil alkyds (TESLOA) were prepared using 3-(triethoxysilyl)propyl isocyanate (TESPIC). TESLOA was formulated as a high solids coating substituting up to 40% of an unmodified long oil linseed oil alkyd in increments of 10%. All the resulting high solids alkyds had a viscosity below 5000 cP. Toxicity and volatile organic compounds (VOCs) were reduced using an iron based primary drier and VOC-exempt acetone, respectively. An increase in adhesion was observed when TESLOA was used in formulations. The chemical resistance, appearance, and flexibility were examined using standard coating tests. An increase in chemical resistance and hardness was observed, while maintaining the flexibility and appearance. The surface energy was measured using contact angle. The TESLOA surface energy exhibited a hydrophobic shift in terms of surface wetting. The additional crosslinking sites of the TESLOA alkyds were evident in a higher glass transition temperature and crosslink density. Tensile properties also exhibited an increase in modulus. Fracture toughness testing showed up to a 50% increase in stress intensity factor at fracture, KIC, and the elastic energy release rate, GIC, when 20 wt.% of TESLOA in the formulation. Corrosion protection was studied using electrochemical impedance spectroscopy (EIS). The EIS data suggested that some self-healing properties could be obtained when using TESLOA as an additive.
Successful catheter ablation of premature ventricular contractions triggering torsade de pointes in a small infant with histiocytoid cardiomyopathy: a case report.

Background A short-coupled variant of torsade de pointes (ScTdP) is rare and resistant to medical treatment. There has not been a reported catheter ablation (CA) of a short-coupled premature ventricular contraction (PVC) triggering ScTdP in an infant. Case summary A neonate was referred to our hospital on the day of birth for Wolff-Parkinson-White syndrome, repeated episodes of supraventricular tachycardia, and a left ventricular non-compaction. She underwent CA of an accessory pathway at 72 days of age. On the 5th day after ablation, she had recurrent TdP episodes resistant to various antiarrhythmic drugs and received extracorporeal membrane oxygenation at 86 days of age. She underwent CA of PVCs triggering TdP at 122 days of age and a weight of 3.4 kg. Two types of PVCs triggering TdP were successfully ablated, which originated from the right ventricle (RV). Pre-potentials were recorded at the earliest ventricular activation sites of the targeted PVCs. After the ablation, she had no TdP episodes and the cardiac assist device was removed. However, she died of uncontrolled heart failure at 6 months of age. The histological findings were compatible with histiocytoid cardiomyopathy and abnormal cells were distributed throughout both ventricles. At the ablation site, fibrotic transmural lesions were noted in the RV wall. Discussion The PVCs triggering TdP were successfully ablated in a 4-month-old girl with histiocytoid cardiomyopathy. The PVCs were likely caused by triggered activity and associated with abnormal Purkinje cells.
Dual-Task Walking Capacity Mediates Tai Ji Quan Impact on Physical and Cognitive Function.

PURPOSE Emerging evidence indicates exercise training improves mobility and cognition and reduces falls in older adults, but underlying mechanisms are not well understood. This study tested the hypothesis that change in dual-task walking capacity mediates the positive effect of Tai Ji Quan and multimodal exercise on physical performance, activity confidence, global cognition, and falls among community-dwelling older adults at high risk of falling. METHODS We conducted a secondary analysis of a 6-month randomized clinical trial comparing Tai Ji Quan: Moving for Better Balance (TJQMBB) and multimodal exercise to stretching exercise in a sample of 670 adults older than 70 yr who had a history of falls or impaired mobility. Distal outcome measures, ascertained at a 12-month follow-up, were the Short Physical Performance Battery, Activities-Specific Balance Confidence, Montreal Cognitive Assessment, and falls. The mediator hypothesized to account for the intervention effects was dual-task cost estimated by calculating changes in gait speed from single-task to dual-task walking from baseline to the end of intervention. RESULTS At 12 months, compared with stretching exercise, multimodal exercise significantly improved Short Physical Performance Battery and Activities-Specific Balance Confidence outcomes and reduced the number of falls (P < 0.05). However, it did not lower dual-task cost or mediate the intervention effects on distal outcomes. In contrast, TJQMBB significantly reduced dual-task cost relative to multimodal and stretching exercises (P < 0.05) which in turn resulted in improvements in lower-extremity physical performance, activity confidence, global cognitive function, and reductions in falls (P < 0.05) during follow-up. CONCLUSIONS Enhanced dual-task walking capacity as a result of Tai Ji Quan training mediated improvements in physical and cognitive outcomes in older adults at high risk of falling.
Effect of feed intake and exogenous porcine somatotropin on longissimus muscle fiber characteristics of pigs weighing 55 kilograms live weight.

Thirty two barrows were used in a 2 x 3 factorial arrangement to evaluate the effects of porcine somatotropin (pST) administration (USDA-pGH-B1; 0 and 100 micrograms.kg BW-1.d-1) and feed intake (FI; ad libitum [A], 1.64 [R1:80% of A] and 1.38 [R2:60% of A] kg/d) on longissimus (LM) muscle fiber characteristics of pigs growing from 25 to 55 kg live weight. The administration of pST resulted in an increase (P less than .05) in muscle fiber size (all three fiber types) and shear-force (17.1%). The percentage of muscle fiber types was not affected by pST treatment. Feeding of the diet at restricted levels (R1 and R2) resulted in smaller (P less than .05) beta R and alpha W fibers compared with feeding ad libitum. Pigs with ad libitum access to their diet had fewer alpha R fibers and more alpha W fibers in the LM compared with those fed at R1 and R2 levels. Restricted feed intake (R1 and R2) resulted in lower (P less than .05) shear-force values compared with ad libitum feeding. The present study indicates that pST administration of young barrows results in an increase in muscle hypertrophy. Restricted FI reduces both transformation from alpha R to alpha W fibers and muscle fiber hypertrophy.
Gingival histoplasmosis: An atypical presentation of African histoplasmosis in three baboons (Papio spp).

Gingival lesions as the sole manifestation of African histoplasmosis (Histoplasma capsulatum var. duboisii) have never been reported in baboons. Grossly, lesions can be indistinguishable from bacterial ulcerative gingivitis or gingival hyperplasia. Clinical outcomes of primary gingival histoplasmosis in baboons are unknown, and, may complicate colony management decisions.
Protease-Activated Receptor-2 (PAR-2) as a Novel Target for Modulating Immune Responses to Neo Antigens Following In Vivo Gene Transfer.

Abstract The safety of several strategies using novel adeno-associated viral (AAV) vectors (serotypes-1,-5,-7,and -8) to skeletal muscle of large animals have been hampered by the immune response to the transgene ( Blood 103: 85, 3303, and 3330). Dendritic cells (DC) are potent antigen-presenting cells that govern the immune responses. The involvement of proteases is critical to DC antigen processing and presentation. Proteases' effects on cells are mediated by protease-activated receptor (PAR) a group of four G-protein-coupled receptors. Bone marrow-derived DC from PAR-2 knockout mice do not spontaneously develop to mature state and only do so upon stimulations of inflammatory signals, therefore, PAR-2 proved critical for DC activation. Work with selective PAR-2 agonists and knockout animals suggests a in vivo contribution of this receptor to several chronic inflammatory diseases and tumor development. In fact, small peptides functioning as PAR-2 antagonists are now being tested as anti-angiogenic agents. We sought to determine whether inhibiting specific targets on the T-cell activation cascade would provide a strategy to prevent the development of antibody following IM injection of AAV. To do this we evaluated the risk of inhibitior formation to clotting factor IX (FIX) in PAR-2 deficient mice compared with heterozygous (+/−) or normal (+/+) genotypes. Mice received IM injection of AAV-1 encoding human FIX (hFIX) at two different doses (low and high cohorts). FIX and antibody levels were monitored weekly. PAR-2(−/ −) mice(n=4) given the low dose exhibited circulating FIX levels of 500± 99ng/ml which remained stable for the duration of the experiment(10 weeks), and no antibody for FIX was detected. In three PAR-2(+/+) mice, FIX expression was transiently detected at week 2 followed by a period of 4 weeks with undetectable levels. This was due to the formation of FIX specific IgG-1 antibody, which results from activation of CD4+ T-cell mainly of Th2 subset, that peaked at week 6. These antibodies inhibit FIX clotting activity as determined by a functional assay at titre of 3–5.5BU (Bethesda Unit) in all 3 mice. High dose AAV-1 treated PAR-2(−/ −) mice(n=6) resulted in continuous expression of FIX(1,500±353ng/ml) in the absence of FIX antibody. In contrast, inhibitors of FIX were detected in all mice(5 per group) PAR-2(+/−) or PAR-2(+/+). All animals develop IgG-1 antibodies to FIX through 10 weeks of observation. At week 6 post-injection, FIX inhibitors were detected in 3/10 mice at levels of ~1 BU. Continuous follow-up showed that a decrease in antibody titers to FIX was associated with slowly increasing FIX antigen. In addition, splenocytes from PAR-2 (+/+) mice exhibit significant increase (p
Ion specific fluorescence modulation of polyvinyl alcohol-boronate matrices

Borylated polymers are emerging as valuable chemosensors that can report analyte binding through an array of responses. Fluorescent materials are particularly valuable in this regard, as modulation of their photophysical properties can facilitate rapid substrate detection and quantitation. Here, we report that condensing aryl boronic acids onto polyvinyl alcohol (PVA) affords fluorescent polymers, a phenomenon that has been widely overlooked. Importantly, selective modulation of the photophysical properties was observed in the presence of borophilic anions (e.g. fluoride, hydroxide, and cyanide). Density functional theory (DFT) calculations suggested that a combination of covalent and non-covalent interactions were crucial for anion binding. Time-dependent DFT computations were also performed to explain the appearance of a distinct peak in the polymer's absorbace profile. Finally, films of these PVA-aryl boronates were employed in ion extraction studies. Given the ease with which these polymers can be accessed, they could serve as general platforms for developing ion selective membranes or detectors.
Chapter 30 – Derivation and Differentiation of Human Embryonic Germ Cells

Human embryonic germ (EG) cells can be derived from primordial germ cells (PGCs) by using methods similar to those used to derive mouse EG cultures. Like mouse embryonic stem (ES) and EG cells, human EG cells require leukemia inhibitory factor (LIF) for proliferation as undifferentiated stem cells. Unlike mouse EG cells, however, human EG cells retain dependence on exogenous cytokines and factors supplied by the feeder layer, and spontaneously differentiate into embryoid bodies (EBs) more frequently. Although EBs are not pluripotent, they express phenotypic markers found on progenitor, precursor, and mature cells. Cells retaining a capacity for cell proliferation and express makers of multiple lineages can be isolated from EBs, and can be used in a variety of in vitro and in vivo differentiation paradigms. Current challenges are to match individual EB-derived (EBD) cultures to desired endpoints, and to enrich or purify specific populations of cells within EBD cultures.
Body Composition as an Independent Predictive and Prognostic Biomarker in Advanced Urothelial Carcinoma Patients Treated with Immune Checkpoint Inhibitors.

BACKGROUND Several immune checkpoint inhibitors (ICIs) are approved for the treatment of advanced urothelial carcinoma (UC). There are limited biomarkers for ICI-treated patients with UC. We investigated the association between body composition and clinical outcomes in ICI-treated UC patients. MATERIALS AND METHODS We conducted a retrospective analysis of 70 ICI-treated patients with advanced UC at Winship Cancer Institute from 2015 to 2020. Baseline computed tomography images within 2 months of ICI initiation were collected at mid-L3 and muscle and fat compartments (subcutaneous, intermuscular, and visceral) were segmented using SliceOMatic v5.0 (TomoVision, Magog, Canada). A prognostic body composition risk score (high: 0-1, intermediate: 2-3, or low-risk: 4) was created based on the β coefficient from the multivariate Cox model (MVA) following best-subset variable selection. Our body composition risk score was skeletal muscle index (SMI) + 2 × attenuated skeletal muscle (SM) mean + visceral fat index (VFI). Concordance statistics (C-statistics) were used to quantify the discriminatory magnitude of the predictive model. RESULTS Most patients (70%) were men and the majority received ICIs in the second- (46%) or third-line (21%) setting. High-risk patients had significantly shorter overall survival (OS; hazard ratio [HR], 6.72; p < .001), progression-free survival (HR, 5.82; p < .001), and lower chance of clinical benefit (odds ratio [OR], 0.02; p = .003) compared with the low-risk group in MVA. The C-statistics for our body composition risk group and myosteatosis analyses were higher than body mass index for all clinical outcomes. CONCLUSION Body composition variables such as SMI, SM mean, and VFI may be prognostic and predictive of clinical outcomes in ICI-treated patients with UC. Larger, prospective studies are warranted to validate this hypothesis-generating data. IMPLICATIONS FOR PRACTICE This study developed a prognostic body composition risk scoring system using radiographic biomarkers for patients with bladder cancer treated with immunotherapy. The study found that the high-risk patients had significantly worse clinical outcomes. Notably, the study's model was better at predicting outcomes than body mass index. Importantly, these results suggest that radiographic measures of body composition should be considered for inclusion in updated prognostic models for patients with urothelial carcinoma treated with immunotherapy. These findings are useful for practicing oncologists in the academic or community setting, particularly given that baseline imaging is routine for patients starting on treatment with immunotherapy.
Polyetheretherketone (PEEK) Post and Core Restorations: A 3D Accuracy Analysis between Heat-Pressed and CAD-CAM Fabrication Methods.

Purpose The purpose of this study was to evaluate the accuracy of polyetheretherketone (PEEK) based post and core restorations using heat-pressed and computer-aided design and computer-aided manufacturing (CAD-CAM) methods. Materials and methods Post and core patterns (n=10) were fabricated using an acrylic pattern resin and each pattern was scanned to generate a resin pattern standard tessellation file (STL-R) to be used as the standard control group for the 3D profilometric analysis. The STL-R files were loaded into a computer-aided manufacturing (CAM) machine and a milling disk made of a modified PEEK-based polymer with 20% ceramic fillers was milled into post and core restorations. Each original post and core resin pattern was sprued, invested and pressed using pellets made of the same PEEK material and a PEEK pressing unit. The resulting post and core restorations from the CAD-CAM and heat-pressed methods were scanned to generate STL-M (milled) and STL-P (heat-pressed) files, respectively. STL-M and STL-P files were digitally aligned and compared to STL-R files using a 3D analysis software. The 3D spatial distribution deviation was exported, and the statistical analysis was performed using the 95% CI deviation distribution from the Gaussian function subtraction. The statistical outcome for each group was merged and a 3D color-coded map was created showing the average deviation (α = 0.05). Results The heat-pressed post and core restoration showed 79 ±6 % of the areas within ±50 μm while the CAD-CAM post-and-core restoration showed 66 ±9 %. The CAD-CAM post and core restorations show 6 ±5 % of the areas above the ideal for marginal adaptation limit threshold of 200μm, while only 0.7 ±0.7 % was found for the heat-pressed. Conclusions The heat-pressed method to manufacture PEEK-based post and core restorations showed higher accuracy than the CAD-CAM method. This article is protected by copyright. All rights reserved.
Dos o tres cosas que sé sobre el concepto de cultura

E L TEMA CENTRAL DE ESTA CONFERENCIA TRATA SOBRE LA PERMANENCIA DEL SIGNIFICADO de cultura como concepto antropologico y del de su permanencia entre los pueblos que estudian los antropologos. Cuestiona el rechazo que el funcionalismo superficial hace de la afirmacion de la diferencia cultural de los pueblos –la llamada invencion de la tradicion– y la vigencia de tales distinciones –la inventiva de la tradicion–. Sostiene, ademas, que precursores como Boas, Linton, etcetera, lejos de ser responsables de las criticas contemporaneas sobre su trabajo, aportaron ideas acerca de la cultura que aun son pertinentes para la comprension de las formas y procesos culturales actuales. La diferencia es que, en aquel entonces, ellos tuvieron una ventaja sobre la mayoria de nosotros: no tuvieron el temor paralizante de la discusion posestructuralista
Evolution und das bewußte Selbst

Wir nehmen am Evolutionsprozes des Lebens teil, doch ist der Mensch sich erst in den letzten 100 Jahren seines evolutionaren Ursprungs klar geworden. Die Folgen, die die Reorientierung von Mensch zur Natur mit sich bringt, sind noch nicht lange genug Teil seines Lebens gewesen, um in das menschliche begriffliche Denken uber sich selbst aufgenommen worden zu sein. Die emotionellen Kontroversen des letzten Jahrhunderts setzten sich in dieses Jahrhundert fort und haben eine vernunftige Einschatzung der Entwicklungsgeschichte in Beziehung zum Menschen verzogert. In den letzten Jahren gab es jedoch ein paar Veroffentlichungen von fuhrenden Biologen (Dobzhansky, 1962, 1967; Simpson, 1964; Lack, 1961; Thorpe, 1962), die den Beginn einer evolutionaren Philosophie zeigen, die auf einem ausgewogenen Verstandnis des evolutionaren Prozesses beruht, so wie er heutzutage dargestellt wird.
Demonstration of Systems for the Recovery of Materials and Energy from Solid Wastes

This paper reviews the U.S. Environmental Protection Agency program to demonstrate new and innovative systems to recover materials and energy from municipal solid waste. The following resource recovery projects are described: (a) the use of shredded solid waste as a coal substitute, (b) the wet pulping of solid waste for materials recovery, (c) the pyrolysis of solid waste to produce a fuel oil, (d) the pyrolysis of solid waste for steam generation, (e) recovery of materials from incinerator residue, and (f) the use of shredded solid waste as a fuel in an oil-fired boiler. The extent to which this program has been successful in promoting the implementation of resource recovery systems by state and local governments and by the private sector is discussed.
Cultural Transmission and Material Culture: Breaking Down Boundaries

Reviewed Medium: book Year: 2008 Pages: 320 Publisher: University of Arizona Press ISBN: 978-0-8165-2675-8 (hard cover). Prices: $49.95 USD(hard cover).
Synchronization of master-slave chaotic system with coupling time-varying delay based on sampled-data control

The problem of synchronization for master-slave chaotic system with coupling time-varying delay and sampled-data is researched in this paper. The time interval between two sampled processes is time-varying and the time interval is bounded. We used the input delay method to transform the sampled control system into a continuous system with time-varying delay. The synchronization criterion, which can be solved effectively by using Matlab, is given to ensure the slave systems synchronize with master the systems. Finally, the simulation results show the effectiveness of the design method.
Rescuing the Dignitary Torts from the Constitution

The rights of individuals to recover for dignitary torts has been withering for the past forty years, since the Supreme Court constitutionalized the state common law tort of defamation in New York Times v. Sullivan in 1964. The Court announced in that case that the First Amendment required it to impose high standards for individual defamation claims in order to protect robust speech. As that principle has taken hold, it has in effect squeezed the rights of individuals to recover for invasion of privacy and intentional infliction of emotional distress as well as defamation. Just last Term, the Court held in Snyder v. Phelps that the free speech rights of funeral protesters barred an intentional infliction recovery by a grieving parent, a result dictated by the Constitution’s ostensible choice to vault speech interests over individual dignitary interests. The Article questions whether that ordering is constitutionally compelled by examining whether the Ninth Amendment provides a textual counterweight to the First. That provision, which specifies that enumerated rights should not be construed to “deny or disparage” “rights retained by the people,” may prohibit a constitutional trampling of the dignitary torts if they vindicate rights “retained by the people.” Given the lengthy history of the dignitary torts, traceable to Roman law, dignitary rights are properly classified as rights retained under most theories of the Ninth Amendment.
Solving mathematical problems: a personal perspective

Feel like writing a review for The Mathematical Intelligencer? You are welcome to submit an unsolicited review of a book of your choice; or, if you would welcome being assigned a book to review, please write us, telling us your expertise and your predilections.
Culture and Neuroscience in Developmental Psychology: Contributions and Challenges

Even with the recent exponential growth in neuroscience research, relatively little attention has been given to cultural influences on brain maturation. In the case of psychological processes that are culturally vari- able, work in cultural developmental neuroscience is vital in determining the degree of generality that can be attrib- uted to neuroscientific findings and in providing unique insight into how developmental neurobiology interacts with sociocultural parameters. The present article high- lights contributions of cultural research in developmental neuroscience in identifying both common and culturally variable brain-behavior pathways and in understanding the nature and extent of brain plasticity. It also points to the importance of cultural work in highlighting the consti- tutive role of collective meanings in psychological phe- nomena and in preventing the drawing of unwarranted deterministic conclusions from neurological evidence.
A Perturbation Refinement Method for Nonholonomic Motion Planning

The kinematic path planning problem of a nonholonomic system can be posed as a point-to-point control problem of a nonlinear system. This system has the property that it is not locally stabilizable but is globally controllable. In this paper, we present a new algorithm for constructing a feasible path between specified initial and final configurations. Polyhedral constraints in both configuration and non-configuration spaces (possibly non-convex) can also be incorporated in this framework. The algorithm is based on the assumption that the system is usually controllable about a non-trivial trajectory, which is true for many cases. An initial trajectory is iteratively warped until the desired final configuration is reached. Examples of a front-wheel driven car, and tractors with one, two, and three trailers are included to illustrate the efficacy of the proposed algorithm.
Conditional viral tracing reveals that steroidogenic factor 1‐positive neurons of the dorsomedial subdivision of the ventromedial hypothalamus project to autonomic centers of the hypothalamus and hindbrain

Excitation of neurons in the ventromedial hypothalamus (VMH), especially those residing in the dorsomedial part of the nucleus (VMHdm), evokes sympathetic nervous system (SNS) outflow, modulating a number of physiological functions including feeding and blood glucose homeostasis. However, the anatomical basis of VMH-mediated SNS activation has thus far proved elusive. To understand how VMH neurons exercise output functions and describe an anatomical link between these neurons and the SNS, we identified downstream neural targets of the VMHdm by injecting an adenoviral vector encoding Cre recombinase (Cre)-regulated farnesylated green fluorescent protein (GFPf ) into the VMHdm of mice that express Cre in neurons expressing the VMH-specific transcription factor steroidogenic factor 1 (SF1). We confirm previously described projection patterns of the VMHdm and report the existence of a formerly unidentified projection pathway to a number of autonomic centers in the brainstem. These VMH efferents travel caudally through the periaqueductal gray (PAG) and then ventrally through the lateral lemniscus to the ventral surface of the brain, where they eventually reach caudal autonomic centers including the C1 catecholamine cell group of the rostral ventrolateral medulla (RVLM) and the nucleus of the solitary tract (NTS), where VMH efferents make close contacts with catecholaminergic neurons. We also found that VMHdm fibers reach a number of brainstem areas, including the retrotrapezoid nucleus (RTN), which are important in regulating respiration. Thus, the present study indicates that the VMH may modulate sympathetic and autonomic activity via synaptic contacts in the RTN, NTS, and RVLM and provides significant anatomical evidence to support a role of the VMH in respiratory regulation.
Thyroid hormones are associated with longitudinal cognitive change in an urban adult population.

Recent evidence indicates that thyroid hormones may be closely linked to cognition among adults. We investigated associations between thyroid hormones and longitudinal cognitive change, within and outside of reference ranges, stratifying by sex and race. This longitudinal study used data from the Healthy Aging in Neighborhoods of Diversity Across the Lifespan study, set in Baltimore City, MD, 2004-2013, on adults aged 30-64 years at baseline visit, with a length of follow-up between visits 1 and 2 ranging from <1 to 8 years; mean ± standard deviation: 4.64 ± 0.93. The final analytic sample sizes ranged from 1486 to 1602 participants with 1.6-1.7 visits per participant (total visits: 2496-2757), depending on the cognitive test. Eleven cognitive test scores spanning domains of learning or memory, language or verbal, attention, visuospatial and/or visuoconstruction, psychomotor speed, executive function, and mental status were used. Mixed-effects regression models were conducted, interacting time of follow-up with several thyroid exposures. Whites performed better than African Americans, with only 4 cognitive test scores of 11 declining significantly over time. Importantly, above reference range thyroid stimulating hormone (vs. reference range, thyroid stimulating hormone, above reference range [TSHarr]) was linked to faster rates of decline on the digits span backwards test, reflecting working memory (TSHarr × time γ ± standard error: -0.14 ± 0.05, p = 0.006) and clock-command, at test of visuospatial and/or visuoconstruction abilities (TSHarr × Time γ ± standard error: -0.10 ± 0.04, p = 0.004). The latter finding was replicated when comparing normal thyroid function to "subclinical hypothyroidism". Within-reference ranges, a higher thyroid stimulating hormone was related to faster decline on the clock-command test scores in women. In sum, higher baseline thyroid stimulating hormone was associated with faster cognitive decline over-time among urban US adults, specifically in domains of working memory and visuospatial and/or visuoconstruction abilities.
In vitro–in vivo correlation: Perspectives on model development

In vitro-in vivo correlation (IVIVC) allows prediction of the in vivo performance of a drug based on the in vitro drug release profiles. To develop an effective IVIVC, the physicochemical and biopharmaceutical properties of the drug as well as the physiological environment in the body must be taken into consideration. Key factors include drug solubility, pK(a), drug permeability, octanol-water partition coefficient and pH of environment. In general, construction of an IVIVC involves three stages of mathematical manipulation: construct a functional relationship between input (in vitro dissolution) and output (in vivo dissolution); establish a structural relationship using data collected; parameterize the unknowns in the structural model. Some key mathematical relationships used in IVIVC development are presented. The establishment of an effective IVIVC has important implications in quality control and regulatory compliance.