cssi/SciSciGPT-SciSciNet huggingface dataset:
Gemcitabine, Fludarabine, and Melphalan for Reduced-Intensity Conditioning and Allogeneic Stem Cell Transplantation for Relapsed and Refractory Hodgkin Lymphoma

Abstract Forty patients (median age, 31 years; range, 20 to 63) with Hodgkin lymphoma underwent an allogeneic stem cell transplant with the gemcitabine–fludarabine–melphalan reduced-intensity conditioning regimen. Thirty-one patients (77%) had undergone a prior autologous stem cell transplant, with a median time to progression after transplant of 6 months (range, 1 to 68). Disease status at transplant was complete remission/complete remission, undetermined (n = 23; 57%), partial remission (n = 14; 35%), and other (n = 3; 8%). Twenty-six patients (65%) received brentuximab vedotin before allotransplant. The overall complete response rate before allotransplant was 65% in brentuximab-treated patients versus 42% in brentuximab-naive patients (P = .15). At the latest follow-up (October 2015) 31 patients were alive. The median follow-up was 41 months (range, 5 to 87). Transplant-related mortality rate at 3 years was 17%. Pulmonary, skin toxicities, and nausea were seen in 13 (33%), 11 (28%), and 37 (93%) patients, respectively. At 3 years, estimates for overall and progression-free survival were 75% (95% CI, 57% to 86%) and 54% (95% CI, 36% to 70%). Overall incidence for disease progression was 28% (95% CI, 16% to 50%). We believe the gemcitabine–fludarabine–melphalan regimen allows moderate dose intensification with acceptable morbidity and mortality. The inclusion of gemcitabine affected nausea, pulmonary, and likely skin toxicity. Exposure to brentuximab vedotin allowed more patients to reach allogeneic stem cell transplantation in complete remission. With over 50% of patients progression-free at 3 years, allogeneic stem cell transplantation with reduced-intensity conditioning remains an effective and relevant treatment option for Hodgkin lymphoma in the brentuximab vedotin era.
Vacuolar H+-ATPase: An Essential Multitasking Enzyme in Physiology and Pathophysiology

Vacuolar H+-ATPases (V-ATPases) are large multisubunit proton pumps that are required for housekeeping acidification of membrane-bound compartments in eukaryotic cells. Mammalian V-ATPases are composed of 13 different subunits. Their housekeeping functions include acidifying endosomes, lysosomes, phagosomes, compartments for uncoupling receptors and ligands, autophagosomes, and elements of the Golgi apparatus. Specialized cells, including osteoclasts, intercalated cells in the kidney and pancreatic beta cells, contain both the housekeeping V-ATPases and an additional subset of V-ATPases, which plays a cell type specific role. The specialized V-ATPases are typically marked by the inclusion of cell type specific isoforms of one or more of the subunits. Three human diseases caused by mutations of isoforms of subunits have been identified. Cancer cells utilize V-ATPases in unusual ways; characterization of V-ATPases may lead to new therapeutic modalities for the treatment of cancer. Two accessory proteins to the V-ATPase have been identified that regulate the proton pump. One is the (pro)renin receptor and data is emerging that indicates that V-ATPase may be intimately linked to renin/angiotensin signaling both systemically and locally. In summary, V-ATPases play vital housekeeping roles in eukaryotic cells. Specialized versions of the pump are required by specific organ systems and are involved in diseases.
Pulse shape discrimination properties of plastic scintillators incorporating a rationally designed highly soluble and polymerizable derivative of 9,10-diphenylanthracene

Abstract A highly soluble and polymerizable derivative of 9,10-diphenylanthracene was designed and synthesized specifically to be capable of achieving very high loadings (at least 50 wt.%) when copolymerized with a polyvinyltoluene (PVT) matrix. The resulting heavily crosslinked plastics are mechanically hard and robust, and were found to have exceptional clarity with no sign of dye precipitation. Samples of these plastics both with and without added wavelength shifter were characterized for light yield, scintillation decay, and pulse shape discrimination (PSD) performance for α / γ discrimination, and the results were compared to that of a commercially available PSD plastic, EJ-299-34. The best performing formulation, with a primary dye loading of 50 wt.%, had a measured light yield of 9950 photons/MeV, and achieved a PSD figure-of-merit (FOM) of 1.05, the latter indicating that while the present material is not suited for practical applications, the overall approach demonstrates a proof-of-concept of PSD in highly loaded plastics stabilized through copolymerization of the primary dye, and suggests that further improvements through better dye choice/design may yet be achievable.
Effects of Voice-Adaptation and Social Dialogue on Perceptions of a Robotic Learning Companion

With a growing number of applications involving social human-robot interactions, there is an increasingly important role for socially responsive speech interfaces that can effectively engage the user. For example, learning companions provide both task-related feedback and motivational support for students with the goal of improving learning. As a learning companion's ability to be socially responsive increases, so do learning outcomes. This paper presents a socially responsive speech interface for an embodied, robotic learning companion. We explore two methods of social responsiveness. The first method introduces social responses into the dialogue, while the second method augments these responses with voice-adaptation based on acoustic-prosodic entrainment. We evaluate the effect of a social, voice-adaptive robotic learning companion on social variables such as social presence and rapport, and we compare this to a companion with only social dialogue and one with neither social dialogue nor voice-adaptions. We contrast the effects against those of individual factors, such as gender. We find (1) that social presence is significantly higher with a social voice-adaptive speech interface than with purely social dialogue, and (2) that females feel significantly more rapport and are significantly more persistent in interactions with a robotic learning companion than males.
UNEQUAL INTERVAL GREY FORECAST OF THE HIGH TEMPERATURE ABRASION RATE FOR WATER-WALL TUBES IN CFB BOILERS

Directing against the abrasion behavior of water-wall tubes in circulating fluidized bed(CFB)boilers,an unequal interval grey forecast model GM(1.1)has been established on the basis of grey system theory and the measured data of high-temperature abrasion in CFB boilers,and during the process of consecutively increasing or decreasing the original data,the method of weighting being used for the time interval.The accuracy and feasibility of the model have been verified through comparison of calculated values with measured ones.This model needn't to consider complex affecting factors of abrasion,only few original data being needed,and comparatively accurate prediction can be made under condition of small samples,being convenient in calculation,the result of prediction can provide with basis and guidance for condition-based repair of the water-wall tubes in CFB boilers.
Visualizing teacher tweets: finding professional learning networks in topical networks

The data for this study is part of #teachertweets, an interdisciplinary quantitative and qualitative study that examines the networks that US-based teachers form on Twitter, the conversations they are having there, and the content of individual tweets. This poster uses data visualization to explore teachers tweeting about teaching as a topical network toward more understanding of the ways that teachers engage in professional learning on Twitter.
Gamete intrafallopian transfer with spinal anesthesia

Objective To investigate the feasibility of performing GIFT under spinal anesthesia administered through a thin (27-gauge) needle. Design Prospectively studied case series. Setting A tertiary care center staffed by a 260 physician multispecialty group. Patients Twenty-seven consecutive fertility patients underwent 28 laparoscopic GIFT procedures, electing to receive spinal anesthesia administered through a thin (27-gauge) needle. Interventions Laparoscopic GIFT and thin-needle spinal anesthesia. Main Outcome Measures Assessment of anesthetic complications and reproductive outcome. Results Satisfactory anesthesia was obtained in 27 of the 28 cases (96%). One patient required additional general anesthesia because of failed spinal anesthesia. All patients were discharged from the hospital on the day of surgery and no postdural headache, persistent back pain, meningitis, or neurological deficit was reported on a 7-day follow-up. Of the 12 clinical pregnancies (43%), 9 ongoing/delivered pregnancies occurred (32%). Six patients had livebirths, and three patients have ongoing second or third trimester pregnancies; there were three spontaneous abortions. Conclusions Spinal anesthesia administered through a 27-gauge needle is an attractive option for laparoscopic GIFT. The risk of serious morbidity because of an anesthetic-related complications may be reduced, and the oocytes are not exposed to the potentially deleterious effects of the drugs associated with general anesthesia.
p66shc and gender-specific dimorphism in acute renal injury.

Background/aim Acute renal injury (AKI) is more prevalent in males than in females perhaps due to adverse effects of testosterone. The oxidant sensor p66shc is regulated by testosterone, hence may be responsible for the aforementioned gender disparity. Materials and methods Wild-type or p66shc-knockdown renal proximal tubule cells were treated with 400 μM H2O2 in the presence or absence of 100 nM dihydrotestosterone (DHT); the production of reactive oxygen species and cell injury were determined. The impact of DHT on p66shc expression and promoter activity as well as gender-dependent expression of p66shc in the mouse kidney was also determined. Results DHT increased H2O2-dependent oxidative stress and injury via p66shc and expression of p66shc via promoter activation. Renal expression of p66shc was higher in male compared to female kidneys. Conclusion Higher sensitivity of the male kidney to AKI may be due to the testosterone-dependent increase in p66shc expression.
Anticholinergic properties of medications.

As a person ages they aremore susceptible to the adverse effects of medications for a variety of reasons including decreased renal and hepatic function, the presence of multiple health conditions and increasing sensitivity of pharmacologic receptors in the body.1 In this column I will review the subject of anticholinergic properties of medications and will discuss how they can result in adverse effects. First, let’s examine the term “anticholinergic.”While it is quite a mouthful to pronounce, it simply refers to a property that counters the effect of the important neurotransmitter acetylcholine. Thus, an anti-acetylcholine effect is referred to as “anticholinergic.” Our bodies are a complex organism largely run by naturally occurring neurotransmitters such as acetylcholine that relay conduction throughout the central and peripheral nervous systems to send messages and instructions to the rest of our bodily tissues and organs. The more well-known neurotransmitters include dopamine, epinephrine, norepinephrine, serotonin and acetylcholine. While each neurotransmitter plays a unique and important role, acetylcholine innervates many organs including the heart, intestines, airways, urinary system and the eyes. Stimulation of the organ by acetylcholine will have one effect and blocking acetylcholine will generally have the opposite effect. For example, acetylcholine stimulation generally slows heart rate while blocking acetylcholine will typically result in a faster heart rate. Many medications possess properties that either mimic or block the effect of acetylcholine. Those that block or antagonize acetylcholine are said to have anticholinergic properties. Anticholinergic activity is not inherently good or bad. It may be beneficial in some situations and in others it may be undesirable. For example, certain antiparkinsonian medications such as benztropine (Cogentin )
Examination of carnitine palmitoyltransferase 1 abundance in white adipose tissue: implications in obesity research

Carnitine palmitoyltransferase 1 (CPT1) is essential for the transport of long-chain fatty acids into the mitochondria for oxidation. Recently, it was reported that decreased CPT1b mRNA in adipose ...
Allometric scaling of STEALTH® liposomal anticancer agents

1394 Introduction: STEALTH® liposomal (SL) formulations contain lipid conjugated to polyethylene glycol. SL formulations of anticancer agents have been designed to prolong the drug circulation time, increase tumor delivery, and improve the therapeutic index. The disposition of SL-encapsulated drug is dictated by the composition of the liposome, thus altering the pharmacokinetic (PK) profile of the drug. Allometric scaling (AS) is based on a power-law relationship between body weight (BW) and drug clearance (CL) among mammals and has been used to compare the disposition of nonliposomal drugs across species. The objectives of this study were to use AS to do the following: 1) compare the disposition of SL drugs across species, and 2) predict the CL of SL drugs in humans. Methods: The PK of SL doxorubicin (Doxil®), SL cisplatin (SPI-077) and SL CKD-602 (S-CKD602; a camptothecin analogue) were compared. Data for Doxil and SPI-077 in humans were available at clinically relevant doses. For S-CKD602, PK data were available in rats and dogs, with preliminary data from an ongoing dose escalation trial in humans. Plasma samples were analyzed for forms of encapsulated plus released (sum total) of S-CKD602 total (lactone + hydroxy acid), Doxil, and SPI-077. The allometric equation used to evaluate the relationship between BW and CL in each species was CL = a(BW)m (a = empirical coefficient; m = allometric exponent). For each agent, a log regression of the log BW (kg) vs log CL (L/h) in available species was used to estimate parameters in the allometric equation. The Complex Dedrick Plot (CDP) was used to normalize interspecies exposure and time by dividing the plasma concentration (ng/mL) by the dose (mg/kg) and by dividing the time (h) interval by BW0.25. Results: Doxil CL values measured in humans and predicted in humans from the log regression of log CL vs log BW from rats, rabbits, and dogs were 0.053 and 0.076 L/h, respectively. SPI-077 CL values measured in humans and predicted in humans from mice, rats, and dogs were 0.021 and 0.086 L/h, respectively. The allometric equations from plots of log BW versus log CL in rats, dogs, and humans for S-CKD602, Doxil, and SPI-077 were CL = 0.0051(BW)1.07, CL = 0.0017(BW)0.86, and CL = 0.0014(BW)0.73, respectively. Based on the CDP, the disposition of S-CKD602 in rats is not allometrically comparable to dogs and humans. The disposition of S-CKD602 and Doxil is similar in rats but different in dogs and humans. Conclusions: S-CKD602 CL was greater in rats and dogs compared to Doxil or SPI-077, but PK data were not yet available at clinically meaningful doses for S-CKD602 to compare the disposition of the 3 formulations in humans. Using the AS approach described here, the disposition of STEALTH liposome formulations was not predictive across species. Supported by ALZA Corporation, Inc.
Correlation-Aware Multi-Label Active Learning for Web Service Tag Recommendation

Tag recommendation has gained significant popularity for annotating various web-based resources including web services. Compared with other approaches, tag recommendation based on supervised learning models usually lead to good accuracy. However, a high-quality training data set is needed, which demands manual tagging efforts from domain experts. While we could leverage the tags of existing web services assigned by their developers, the quality of these tags may not be good enough to build accurate classifiers for tag recommendation. In this paper, a novel multi-label active learning approach is proposed for web service tag recommendation. The proposed approach is able to identify a small number of most informative web services to be tagged by domain experts. We further minimize the domain expert efforts by learning and leveraging the correlations among tags to improve the active learning process. We conduct a comprehensive experimental study on a real-world data set and results demonstrate the effectiveness of our approach.
The Development of Diagnostic Inference About Uncertain Causes

Young children can engage in diagnostic reasoning. However, almost all research demonstrating such capacities has investigated children’s inferences when the individual efficacy of each candidate c...
Host Control of Fungal Infections: Lessons from Basic Studies and Human Cohorts

In the last few decades, the AIDS pandemic and the significant advances in the medical management of individuals with neoplastic and inflammatory conditions have resulted in a dramatic increase in the population of immunosuppressed patients with opportunistic, life-threatening fungal infections. The parallel development of clinically relevant mouse models of fungal disease and the discovery and characterization of several inborn errors of immune-related genes that underlie inherited human susceptibility to opportunistic mycoses have significantly expanded our understanding of the innate and adaptive immune mechanisms that protect against ubiquitous fungal exposures. This review synthesizes immunological knowledge derived from basic mouse studies and from human cohorts and provides an overview of mammalian antifungal host defenses that show promise for informing therapeutic and vaccination strategies for vulnerable patients.
No-reflow phenomenon in the heart and brain

The no-reflow phenomenon refers to the observation that when an organ is made ischemic by occlusion of a large artery supplying it, restoration of patency in that artery does not restore perfusion ...
The Pharmacology of the Human Sphincter of Oddi

The human sphincter of Oddi is a complex, difficult to assess organ that regulates bile and pancreatic flow into the duodenum. Currently, the best way to measure the effects of drugs and hormones on the sphincter is by retrograde cannulation with a water- perfused manometry catheter. The effects of glucagon, cholecys- tokinin, secretin, pentagastrin, and somatostatin have been evaluated, but not fully. Some drugs and hormones have potential for use as diagnostic agents, but none have been found that have demonstrated a clinical benefit for patients with sphincter of Oddi dysfunction.
Evaluation of a multi-parent advanced generation inter-cross (MAGIC) introgressed line population for Verticillium wilt resistance in Upland cotton

Verticillium wilt (VW, caused by Verticillium dahliae Kleb) is a destructive fungal soil-borne disease in Upland cotton (Gossypium hirsutum L.). High levels of VW resistance can be transferred into Upland from Pima cotton (G. barbadense L.) through interspecific introgression breeding. In this greenhouse study, VW resistance was evaluated in a multi-parent advanced generation inter-cross (MAGIC) introgressed line (IL) population, derived from a random mated Barbadense Upland population with five generations of intermating (called RMBUP-C4) between three Upland cotton cultivars and 18 CS-B Upland lines each carrying a pair of G. barbadense chromosome or arm in the TM-1 background. The objectives of this study were to, (1) evaluate VW resistance of 530 MAGIC ILs in the greenhouse; and (2) to identify lines with VW resistance in the MAGIC population based on a total of three replicated greenhouse tests. Approximately 8 plants for each line in each replicate were grown and screened for VW resistance using three parameters i.e., disease leaf severity rating, percentage defoliated leaves, and percentage infected plants, with a total of ~ 25,190 plants evaluated. A correlation analysis indicated that the three parameters were significantly and positively correlated with one another in each test. The disease leaf severity rating was the best parameter to assess VW resistance due to its relatively low coefficient of variation and its higher resolution to differentiate resistant genotypes from susceptible ones. Of the 530 genotypes, 5 showed resistance to VW, namely, NMIL348, NMIL518, NMIL405, NMIL290, NMIL307 and had higher levels of resistance to VW with mean disease leaf severity ratings, percentage of defoliated leaves, and percentage of infected plants across three tests ranging from 0.58–1.46, 9.46–26.74, and 25–95%, respectively. These lines can be used as parental lines to improve VW resistance in cotton breeding programs.
Tetralogy of Fallot (TOF)

Tetralogy of Fallot is a complex congenital heart anomaly that includes varying degrees of right ventricular outflow obstruction, a ventricular septal defect, right ventricular hypertrophy, and an aorta that overrides ventricular outflow tracts. This section will review the physiology of tetralogy of Fallot and the anesthetic considerations for parturients who present with this congenital heart anomaly.
Neurological Complications Associated with Epidural Steroid Injections

Multiple case reports of neurological complications resulting from intraarterial injection of corticosteroids have led the Food and Drug Administration (FDA) to issue a warning, requiring label changes, warning of serious neurological events, some resulting in death. The FDA has identified 131 cases of neurological adverse events, including 41 cases of arachnoiditis. A review of the literature reveals an overwhelming proportion of the complications are related to transforaminal epidural injections, of which cervical transforaminal epidural injections constituted the majority of neurological complications. Utilization data of epidural injections in the Medicare population revealed that cervical transforaminal epidural injections constitute only 2.4 % of total epidural injections and <5 % of all transforaminal epidural injections. Multiple theories have been proposed as the cause of neurological injury including particulate steroid, arterial intimal flaps, arterial dissection, dislodgement of plaque causing embolism, arterial muscle spasm, and embolism of a fresh thrombus following disruption of the intima.
Ocular and Adnexal T-Cell Lymphoma

Ocular and adnexal T-cell lymphoma represents a rare non-Hodgkin’s lymphoma and is mostly secondary to systemic malignancies. The known etiology is mainly due to genetic predisposition and/or viral infections in different subsets of T-cell lymphoma. Both primary and metastatic T-cell lymphoma can invade intraocular and adnexal tissues. Clinical presentations vary largely based on the different intraocular and adnexal sites that are affected. Pathology based on intraocular/adnexal biopsies is the gold standard for diagnosis. Other diagnostic techniques, including ocular/orbital imaging, immunogenotyping, and molecular diagnosis, are also useful adjuncts to pathological diagnosis and subclassification. Current treatment is based on localized radiotherapy and chemotherapy in patients with local disease and combined with systemic high-dose methotrexate chemotherapy and/or stem cell transplantation in patients with systemic malignancy.
Impact of Hospital Volume on Outcomes of Elective Pneumonectomy in the United States

Background Despite advances in surgical technique and perioperative management, pneumonectomy remains associated with significant morbidity and mortality. The purpose of this study was to examine the impact of annual institutional volume of anatomic lung resections on outcomes after elective pneumonectomy. Methods We evaluated all patients who underwent elective pneumonectomy from 2005 to 2014 in the National Inpatient Sample. Patients less than 18 years of age, or with trauma-related diagnoses, mesothelioma, or a nonelective admission were excluded. Hospitals were divided into volume quartiles based on annual institutional anatomic lung resection caseload. We studied the effect of institutional volume on inhospital mortality, complications, and failure to rescue, as well as costs and length of stay. Results During the study period, an estimated 22,739 patients underwent pneumonectomy, with a reduction in national mortality from 7.9% to 5.5% (P trend = .045). Compared with the highest volume centers, operations performed at the lowest volume hospitals were associated with 1.74 increased odds of mortality (95% confidence interval, 1.14 to 2.66). Despite similar odds of postoperative complications, low volume hospital status was associated with increased failure to rescue rates (18.3% vs 12.7%, P = .024) and adjusted odds of mortality (1.70; 95% confidence interval, 1.09 to 2.64) after any complication. Conclusions High volume hospital status is strongly associated with reduced mortality and failure to rescue rates after pneumonectomy. Efforts to centralize care or disseminate best practices may lead to improved national outcomes for this high-risk procedure.
Effect of random deferral of percutaneous coronary intervention in patients with diabetes and stable ischaemic heart disease

Background In stable ischaemic heart disease (SIHD), measurement of fractional flow reserve (FFR) to guide selection of lesions for percutaneous coronary intervention (PCI) reduces death and myocardial infarction (MI) compared with angiographic guidance. However, it is unknown if the improved outcomes are due to avoidance of stenting of physiologically insignificant lesions or are a by-product of placing fewer stents. Methods We developed a Monte Carlo simulation using the PCI strata of the Bypass Angioplasty Revascularization Investigation 2 Diabetes study to investigate how random deferral of PCI impacts outcomes. To simulate deferral, a randomly selected group of patients randomised to PCI were removed and replaced by an equal number of randomly selected patients randomised to intensive medical therapy (IMT) using a random number generator in Python’s NumPy module. The primary endpoint was the rate of death or non-fatal MI at 1 year. Results Death/MI at 1 year occurred in 8.3% of 798 patients in the PCI group and 5.1% of 807 patients in the IMT control group (p=0.02). Following 10 000 iterations of random replacement of 10%, 20%, 30% or 40% of PCI patients with randomly selected IMT patients, the rate of death/MI at 1 year progressively declined from 8.3% to 8.0%, 7.6%, 7.3% and 7.0%, respectively. Conclusions In this simulation model, random deferral of PCI procedures in SIHD progressively reduced death/MI as the percentage of procedures deferred increases. FFR-guided deferral of PCI may improve outcomes as a result of placing fewer stents and be unrelated to the haemodynamic severity of lesions.
Looking beyond Language: An Examination of College Literacy Readiness of Students from Refugee Backgrounds.

For people who have experienced forced migration, postsecondary education provides a way to look forward instead of backward. Despite a high prevalence of college aspirations, refugee-background st...
MIMO and Waveform-Diversity Techniques Applied to Real-World Radar Settings [Book/Software Reviews]

This book is geared toward both active radar researchers and practicing radar engineers and managers interested in learning more about the benefits of incorporating MIMO and waveform- diversity techniques into their work and applying the technology to real-world radar settings. The authors have developed a website (www.islinc .com) that includes color versions of some of the graphics in the book as well as MATLAB tools implementing some of the discussed in the text. The book attempts to present a fair analysis of MIMO radar technology in a way that clearly highlights its benefits and pitfalls and gives radar engineers the analysis tools they need to work on trade studies and final system designs. This text collects the newest MIMO technology, from basic theory to ad - vanced MIMO analysis. Many examples and real-world test data and analysis provide for a comprehensive resource on MIMO technology. This is a must-have text for MIMO radar scientists and designers and students in college radar classes. MIMO is not a cure-all radar technology; without careful analysis, its use can lead to performance degradation.
Murine cancer cachexia models replicate elevated catabolic pembrolizumab clearance in humans.

Background Monoclonal antibody (mAb) immune checkpoint inhibitor (ICI) therapies have dramatically impacted oncology this past decade. However, only about one-third of patients respond to treatment, and biomarkers to predict responders are lacking. Recent ICI clinical pharmacology data demonstrate high baseline drug clearance (CL0) significantly associates with shorter overall survival, independent of ICI exposure, in patients receiving ICI mAb therapies. This suggests CL0 may predict outcomes from ICI therapy, and cachectic signalling may link elevated CL0 and poor response. Our aim was to determine if mouse models of cancer cachexia will be useful for studying these phenomena and their underlying mechanisms. Methods We evaluated pembrolizumab CL in the C26 and Lewis lung carcinoma mouse models of cancer cachexia. A single treatment of vehicle or pembrolizumab, at a dose of 2 or 10 mg/kg, was administered intravenously by tail vein injection. Pembrolizumab was quantified by an ELISA in serial plasma samples, and FcRn gene (Fcgrt) expression was assessed in liver using real-time quantitative reverse transcription PCR. Non-compartmental and mixed-effects pharmacokinetics analyses were performed. Results We observed higher pembrolizumab CL0 and decreased Fcgrt expression in whole liver tissue from tumour-bearing vs. tumour-free mice. In multivariate analysis, presence of tumour, total murine IgG, muscle weight and Fcgrt expression were significant covariates on CL, and total murine IgG was a significant covariate on V1 and Q. Conclusions These data demonstrate increases in catabolic clearance of monoclonal antibodies observed in humans can be replicated in cachectic mice, in which Fcgrt expression is also reduced. Notably, FcRn activity is essential for proper antigen presentation and antitumour immunity, which may permit the study of cachexia's impact on FcRn-mediated clearance and efficacy of ICI therapies.
Culturally Relevant Education: Think Local Within a Holistic Orientation

Students bring valuable cultural ways of knowing and worldviews to the classroom. Teachers who build on student cultures are able to motivate and make learning more meaningful. We believe that teac...
KEEPING PACE WITH 21ST CENTURY HEALTHCARE: A FRAMEWORK FOR TELEHEALTH RESEARCH, PRACTICE, AND PROGRAM EVALUATION IN OCCUPATIONAL THERAPY

The use of telehealth to deliver occupational therapy services rapidly expanded during the COVID-19 pandemic. There are frameworks to evaluate services delivered through telehealth; however, none are specific to occupational therapy. Therefore, occupational therapy would benefit from a framework to systematically evaluate components of telehealth service delivery and build evidence to demonstrate the distinct value of occupational therapy. The PACE Framework outlines four priority domains to address areas of need: (1) Population and Health Outcomes; (2) Access for All Clients; (3) Costs and Cost Effectiveness; and (4) Experiences of Clients and Occupational Therapy Practitioners. This article describes the development and expert reviewer evaluation of the PACE Framework. In addition, the PACE Framework's domains, subdomains, and outcome measure examples are described along with future directions for implementation in occupational therapy research, practice, and program evaluation.
Mast cells in human disease

In this review, I have presented the possible involvements of mast cells in some human diseases. It is not intented to be all-encompassing, and descriptions have sometimes been relatively brief for the sake of conciseness. As is apparent in these discussions, evidence for the role of mast cells in human diseases is frequently indirect and circumstantial. However, the recent development of techniques permitting isolation of mast cells from human tissues with up to 90% purity30 gives promise of more definitive studies of mast cells isolated from diseased as well as healthy human organs. Therefore, we can look forward to learning more about the role in disease of this cell which has fascinated and puzzled us all.
Prior event rate ratio adjustment: numerical studies of a statistical method to address unrecognized confounding in observational studies.

Purpose The purpose of this study was to evaluate a statistical method, prior event rate ratio (PERR) adjustment, and an alternative, PERR-ALT, both of which have the potential to overcome “unmeasured confounding,” both analytically and via simulation. Methods Formulae were derived for the target estimates of both PERR methods, which were compared with results from simulations to ensure their validity. In addition to the theoretical insights gained, relative biases of both PERR methods for estimating exposure effects were also investigated via simulation studies and compared empirically with electronic medical record database study results. Results Theoretical derivations closely matched simulated results. In simulation studies, both PERR methods significantly reduce bias from unmeasured confounding compared with the standard Cox model. When there is no interaction between unmeasured confounders and time intervals, the estimate from PERR-ALT is unbiased, whereas the estimate from PERR has well-controlled relative bias. When interactions exist, relative biases tend to increase but not greatly, especially when the exposure effect is relatively large in comparison with the interaction effects. When the event rate is low and the sample size is limited, PERR is more computationally stable than PERR-ALT. In empiric study comparisons with randomized controlled trials, both PERR methods show potential to reduce bias from the standard Cox model similarly when unmeasured confounding is present. Conclusions Extensive simulation studies and theoretical derivation show that PERR-based methods may reduce bias from unmeasured confounders when the exposure effect is relatively large in comparison with confounder–exposure interaction. The rare study event situation warrants further investigation. Copyright © 2012 John Wiley & Sons, Ltd.
Primary effusion lymphoma in women: report of two cases of Kaposi's sarcoma herpes virus-associated effusion-based lymphoma in human immunodeficiency virus-negative women

Recent molecular evidence suggests an association with a new herpes virus, Kaposi's sarcoma-associated herpes virus (KSHV/HHV-8), and primary effusion lymphomas (PEL). PELs have a characteristic morphology, phenotype, and clinical presentation with malignant effusions in the absence of a contiguous solid tumor mass. Most cases of PEL have occurred in human immunodeficiency virus (HIV)-positive male patients who are coinfected with Epstein-Barr virus (EBV). This report describes two cases of PEL in HIV- and EBV-negative women. In one patient, a pleural cavity PEL was preceded by classic Kaposi's Sarcoma (KS) of the lower extremities. In the second patient, PEL developed in an artificial cavity related to the capsule of a breast implant. Both cases had the characteristic morphologic appearance of high-grade anaplastic/B-cell immunoblastic lymphomas, with loss of B-cell differentiation antigens, clonal immunoglobulin heavy chain gene rearrangements, and expression of activation antigen CD30. Both cases were negative for EBV, herpes virus simplex, and cytomegalovirus (CMV). DNA extracted from both lymphomas and skin KS specimen showed KSHV sequences by molecular analysis. This report expands the spectrum of KSHV-associated disease to include PEL in HIV-negative women.
the theory of meaning and the practice of communication

Etude de la conception conventionnelle du langage, de la competence linguistique et de la methode d'interpretation que Davidson refute au profit d'une theorie systematique de la signification du langage naturel qui prendrait la forme ideale d'une theorie recursive de la verite. Rejetant le role des conventions, des regles et des regularites couramment admises par les philosophes et les linguistes, l'A. montre que Davidson defend une approche de la communication ou la signification du dire s'accompagne de la comprehension du faire, dans le sens de la theorie de la signification de Dummett et dans le sens du sceptcisme de Wittgenstein repris par Kripke
Elution of Exocellular Enzymes from Saccharomyces fragilis and Saccharomyces cerevisiae

Weimberg, Ralph (Northern Regional Research Laboratory, Peoria, Ill.), and William L. Orton. Elution of exocellular enzymes from Saccharomyces fragilis and Saccharomyces cerevisiae. J. Bacteriol. 91:1-13. 1966.-Invertase and acid phosphatase are repressible exocellular enzymes in Saccharomyces fragilis and S. cerevisiae. The conditions for eluting these enzymes from both organisms were compared. Either KCl or beta-mercaptoethanol eluted the enzymes from S. fragilis, and the amounts eluted varied quantitatively according to the physiological age of the organism. In addition to eluting enzymatic activity from the cells, these reagents also caused a large increase in the amount of activity that remained associated with the cells of S. fragilis. Invertase and acid phosphatase were not removed from cells of S. cerevisiae by KCl or beta-mercaptoethanol. These enzymes were separated from S. cerevisiae cells only when there was some degree of cell-wall digestion by snail gut fluid.
Community Gardening and Education Outreach Expand Students Dietetics Practice Skills

As part of their professional training, dietetics students participate in a community-based gardening initiative that fosters skills for effective public health practice. Students complete a 6-week training course in basic gardening and applied skills with Master Gardeners to build on new knowledge and reinforce their practical experience while working in a community garden. Following training, students outreach as educators to local community agencies and learn how to integrate applications in nutrition and dietetics with gardening as a community-building strategy for enhancing food security and sustaining communities.
Free vibration of plate by integral method

Abstract This paper addresses a new computer-aided implementation of classical analytical procedure to treat free vibration of rectangular plates supported at arbitrary interior points. An integral method which has been successfully applied to the analysis of transient heat conduction is adopted. This procedure is based on the Galerkin method but takes advantage of symbolic algebra software such as REDUCE or MACSYMA. For free vibration of plates, the lateral displacement is expressed as a series of polynomials each of which satisfies both the free boundary conditions and the supporting constraint conditions. Coefficients of these polynomials are determined by the standard Galerkin method. Symbolic algebra software is essential to perform necessary algebraic operations to generate admissible trial functions and generalized mass and stiffness matrices for the eigenvalue problem. The obtained expression is in closed form and unlike purely numerical methods such as finite element or finite difference methods, this method does not require excessive computational time nor huge memory storage. Numerical examples are presented and compared with existing data.
Fabrication and characterization of Tl-Ba-Ca-Cu-O superconducting films on LaAlO 3 substrates

A multi-step process is used to fabricate Tl2Ba2Ca1Cu2O8 films on (100) LaA103 substrates. Submicron thick precursor films of Ba-Ca-Cu-O are rf magnetron sputter deposited from a single target. Film stoichiometry is measured by ion beam backscattering spectroscopy. Deficiencies of the alkaline earths that are found in the precursor films are then compensated for by the addition of appropriate CaF2 and/or BaF2 films onto the surface of the precursor film. Post deposition annealing of the films is then done in an atmosphere of thallium oxide and oxygen in order to form the superconducting phases. The annealed films are examined using x-ray diffraction (XRD), an ac inductance technique, and critical current in an external magnetic field. XRD shows the c-axis length of the superconducting phase to increase as the overall film stoichiometry approaches 2212. The transition widths measured by inductive coupling weakly correlate with 77 K critical current measurements. Our best critical current results are 1.5*106 amps/ cm2 for a film measured at 4 K in an 8 T magnetic field (parallel to the films' c-axis).
Cancer recurrence and survival rates after anatomic radical retropubic prostatectomy for prostate cancer: intermediate-term results.

AbstractPurpose: We evaluate cancer recurrence and survival rates following anatomic radical retropubic prostatectomy.Materials and Methods: From 1983 through August 1997, 1 surgeon performed anatomic radical retropubic prostatectomy in 1,778 men (mean age plus or minus standard deviation 63 +/− 7), using a unilateral or bilateral nerve sparing modification when feasible (93%). Postoperative adjuvant radiation therapy (mean dose 60 Gy.) was given to 4% of patients because of adverse pathological findings. Patients were followed with semiannual prostate specific antigen (PSA) tests and annual digital rectal examinations. Followup PSA 0.3 ng./ml. or greater was considered evidence of cancer recurrence. We used Kaplan-Meier product limit estimates to calculate 7-year cancer recurrence-free probabilities, prostate cancer specific survival and all cause survival (overall, and stratified by age, preoperative PSA, tumor grade and tumor stage). We used multivariate Cox proportional hazards models to determine cli...
Mu Opioid Receptor Binding Correlates with Nicotine Dependence and Reward in Smokers.

The rewarding effects of nicotine are associated with activation of nicotine receptors. However, there is increasing evidence that the endogenous opioid system is involved in nicotine's rewarding effects. We employed PET imaging with [11C]carfentanil to test the hypotheses that acute cigarette smoking increases release of endogenous opioids in the human brain and that smokers have an upregulation of mu opioid receptors (MORs) when compared to nonsmokers. We found no significant changes in binding potential (BPND) of [11C]carfentanil between the placebo and the active cigarette sessions, nor did we observe differences in MOR binding between smokers and nonsmokers. Interestingly, we showed that in smokers MOR availability in bilateral superior temporal cortices during the placebo condition was negatively correlated with scores on the Fagerstrom Test for Nicotine Dependence (FTND). Also in smokers, smoking-induced decreases in [11C]carfentanil binding in frontal cortical regions were associated with self-reports of cigarette liking and wanting. Although we did not show differences between smokers and nonsmokers, the negative correlation with FTND corroborates the role of MORs in superior temporal cortices in nicotine addiction and provides preliminary evidence of a role of endogenous opioid signaling in frontal cortex in nicotine reward.
Effects of testosterone and other steroids on incorporation of glycine-1-C14 into protein by rat and human liver slices.

THE specific role of many hormones in tissue metabolism remains obscure. The simple addition of pure hormones to in vitro systems might be expected to offer some useful information with respect to the mechanism of action of such hormones. Since some steroid hormones are known to influence protein metabolism in the intact animal, such hormones were added directly to liver slices and their effects upon the in: corporation of radioactive glycine into protein were observed. This report presents data which demonstrate a significant depression of incorporation with certain steroids and that the depression is the same for rat and human liver tissue. EXPERIMENTAL Liver tissue was sliced and incubated, the protein precipitated, prepared for counting, counted in a gas-flow counter, and corrected for self-absorption as previously described (Grossman and Hauschildt, 1952). Steroids3 dissolved in ether were added to the incubation flasks and the ether was evaporated by gentle heat before adding buffer and tissue.
A variational principle for wave propagation in random media

We set up a variational integral appropriate for discussing the ‘eigenvalues’ of theexact probability equation describing wave propagation in a turbulent medium. We demonstrate that: (i) Extremal variations of the integral with respect to an adjoint probability field gives the probability equation (which is not self-adjoint) relevant to wave propagation in the random medium. (ii) Extremal variations of the integral with respect to the probability field gives the adjoint probability equations. (iii) Extremal variations of the integral with respect to trial functions for both the probability field and its adjoint gives a variational principle for calculating the normal mode eigenvalues describing wave propagation in the turbulent medium.
1,25-Dihydroxyvitamin D3 targeting of NF-κB suppresses high glucose-induced MCP-1 expression in mesangial cells

Macrophages accumulate in kidney glomeruli and interstitium of patients with diabetic nephropathy in response to monocyte chemoattractant protein-1 (MCP-1); a chemokine produced by both tubular epithelial and mesangial cells (MCs). Vitamin D and its analogs have been shown to have renoprotective effects; however, there are few studies involving diabetic nephropathy. We explored mechanisms by which 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) can be renoprotective by measuring MCP-1 expression in MCs. Using a luciferase reporter assay, we found that high glucose (HG)-induced MCP-1 transcription and that this induction is blocked by 1,25(OH) 2 D 3 . Electrophoretic mobility shift and chromatin immunoprecipitation assays showed that HG increased the p65/p50 binding to the two NF- κ B sites within the promoter. This was suppressed by 1,25(OH) 2 D 3 , but this decrease was reversed by overexpression of p65. 1,25(OH) 2 D 3 was found to stabilize I κ B α leading to an inhibition of p65 translocation to the nucleus and subsequent reduction of NF- κ B binding. In primary MCs prepared from vitamin D receptor knockout animals, basal MCP-1 levels were elevated but not affected by 1,25(OH) 2 D 3. The analog paricalcitol inhibited the induction and activity of MCP-1 while ameliorating glomerulosclerosis in streptozotocin-diabetic mice. Our results suggest that 1,25(OH) 2 D 3 might block hyperglycemia-induced renal injury by blunting NF- κ B activation.