cssi/SciSciGPT-SciSciNet huggingface dataset:
Obesity-related changes in prolonged repetitive lifting performance.

Despite the rising prevalence of obesity, little is known about its moderating effects on injury risk factors, such as fatigue, in occupational settings. This study investigated the effect of obesity, prolonged repetitive lifting and their interaction on lifting performance of 14 participants, 7 obese (mean body mass index (BMI): 33.2 kg m(-2)) and 7 non-obese (mean BMI: 22.2 kg m(-2)) subjects. To present a physically challenging task, subjects performed repetitive lifting for 1 h at 120% of their maximum acceptable weight of lift. Generalized linear mixed models were fit to posture and acceleration data. The obese group bent to a ∼10° lower peak trunk sagittal flexion angle, had 17% lower root mean square (RMS) jerk and took 0.8 s longer per lift. Over time, the obese group increased their trunk transverse and sagittal posterior accelerations while the non-obese maintained theirs. Although the majority of lifting variables were unaffected by BMI or its interaction with prolonged lifting duration, the observed differences, combined with a greater upper body mass, necessitate a more cautious use of existing psychophysical lifting limits for individuals who are obese, particularly when fatigued.
The Effects of Age of Male and Female Parents on the Life Cycle of Drosophila melanogaster

The durations of the egg, larval, and pupal stages remained constant regardless of parental age. As parental age increased, the longevity of adult progeny decreased, more so in female than in male offspring. Reciprocal crosses between young and old flies indicated that the decreased longevity of adults may have been correlated with increased age of the female rather than the male parent. The number of offspring generally decreased as the parental age increased, but a noticeable increase was observed when the female parent was 15 days old.
Abstract 4091: Epigenetic silencing of microRNA in the pathobiology of CLL

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC MicroRNAs (miRs, miRNA) are a class of non-coding RNA that control gene expression at a post-transcriptional level. Specific and aberrant miRNA signatures distinguish indolent and relapsed forms of chronic lymphocytic leukemia (CLL). In this study, we focused on the expression and cellular targets of a set of microRNA (miR15a, miR-16, miR-29b and miR-101) that are differentially expressed in indolent and refractory disease. The tumor suppressor microRNAs, miR-15a and miR-16, are downregulated in 68% of all CLL and associated with an indolent course. These miRNA are located on an intron of the dleu2 gene within a genomic locus (chr13q) that is frequently deleted in leukemia. However, deletions in 13q usually involve only one allele and do not adequately account for the low expression levels of miR-15a and miR-16. We hypothesized that aberrant recruitment of the histone deacetylases could be a novel mechanism that drives the silencing of miR-15a and miR-16 in CLL. Correspondingly, exposure to a variety of small molecule histone deacetylase inhibitors led to the re-expression of miR-15a and miR-16 in 30% of samples that undergo silencing. We then evaluated the cellular targets of miR-15a and miR-16 in CLL. Ectopic expression of miR-15 and miR-16 in primary leukemia cells led to a loss of Bcl-2 and Mcl-1. However, pharmacological re-expression of these miRNA led to decreases in Mcl-1 protein, with no loss in Bcl-2. Losses in the levels of Mcl-1 were associated with induction of cell death in these leukemia cells. In contrast to miR-15a and miR-16, the microRNAs miR-29b and miR-101 are well expressed in indolent disease but become silenced in relapsed/refractory disease by unknown mechanisms. We identified that exposure to a variety of histone deacetylase inhibitors induced the re-expression of miR-29b and miR-101 in 30-50% of the downregulated samples. Chromatin immunoprecipitation experiments demonstrated that deacetylase inhibition led to an increase in permissive chromatin marks at the gene promoters for these miRNA. miR-29b is known to target Mcl-1, Tcl-1 as well as the DNA methyltransferases 3a and 3b. Ectopic expression of miR-29b in CLL cells led to the decrease of Mcl-1 protein. In parallel, expression of miR-101 led to the inhibition of EZH2 expression. Correspondingly, pharmacological re-expression of miR-29b and miR-101 was associated with losses in Mcl-1 and EZH2 in CLL cells and apoptotic death of these leukemia cells. These results identify a role for epigenetic mechanisms in the pathological silencing of miRNA in both indolent and relapsed CLL. They also offer a novel therapeutic strategy by which to reverse epigenetic silencing of miRNA for therapeutic benefit. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4091.
Hydrogeochemistry and coal-associated bacterial populations from a methanogenic coal bed

Abstract Biogenic coalbed methane (CBM), a microbially-generated source of natural gas trapped within coal beds, is an important energy resource in many countries. Specific bacterial populations and enzymes involved in coal degradation, the potential rate-limiting step of CBM formation, are relatively unknown. The U.S. Geological Survey (USGS) has established a field site, (Birney test site), in an undeveloped area of the Powder River Basin (PRB), with four wells completed in the Flowers-Goodale coal bed, one in the overlying sandstone formation, and four in overlying and underlying coal beds (Knoblach, Nance, and Terret). The nine wells were positioned to characterize the hydraulic conductivity of the Flowers-Goodale coal bed and were selectively cored to investigate the hydrogeochemistry and microbiology associated with CBM production at the Birney test site. Aquifer-test results indicated the Flowers-Goodale coal bed, in a zone from about 112 to 120 m below land surface at the test site, had very low hydraulic conductivity (0.005 m/d) compared to other PRB coal beds examined. Consistent with microbial methanogenesis, groundwater in the coal bed and overlying sandstone contain dissolved methane (46 mg/L average) with low δ 13 C values (− 67‰ average), high alkalinity values (22 meq/kg average), relatively positive δ 13 C-DIC values (4‰ average), and no detectable higher chain hydrocarbons, NO 3 − , or SO 4 2 − . Bioassay methane production was greatest at the upper interface of the Flowers-Goodale coal bed near the overlying sandstone. Pyrotag analysis identified Aeribacillus as a dominant in situ bacterial community member in the coal near the sandstone and statistical analysis indicated Actinobacteria predominated coal core samples compared to claystone or sandstone cores. These bacteria, which previously have been correlated with hydrocarbon-containing environments such as oil reservoirs, have demonstrated the ability to produce biosurfactants to break down hydrocarbons. Identifying microorganisms involved in coal degradation and the hydrogeochemical conditions that promote their activity is crucial to understanding and improving in situ CBM production.
RESEARCH ON THE EFFECT OF AIR DISINFECTION BY A KIND OF HERB ESSENTIAL OIL SLICE

Objective To observe the effect of air disinfection by a kind of air disinfection slice to the indoor air in the hospital. Methods Plate sampling and bacterial culture method were used to detect the disinfection effect of the indoor air by heating fumigating the air disinfection slice,and compared with the ultraviolet irradiation. Results The effective components of the air disinfection slice are essential oil of Schizonepeta and other Chinese herb. Each piece is 290 mg. Put 2 pieces in a 20m2room and heat fumigate them for 1h. In the condition of the people-absence,the average removal rate of natural bacteria in indoor air was 93. 37%,the average number of natural bacteria in air is 200 cfu / m3. After Ultraviolet irradiates for 1h,the average removal rate of natural bacteria in indoor air is 65. 43%. Conclusion By heating and fumigating,the air disinfection slice which contains Chinese herbal medicine plant essential oil can disinfect the natural bacteria in indoor air to achieve disinfection requirements without bad smell.
Studying α7 nicotinic receptor anti-inflammatory signaling

α7 nicotinic receptors (α7 AChRs) reportedly play anti-inflammatory roles in innate immune function, in part by blocking the transcription factor NFkB. We tested whether heterologously expressed α7...
Suppression of blood flow autoregulation plateau during nitric oxide blockade in canine kidney

We examined the autoregulation of renal blood flow (RBF) and renal function in anesthetized dogs during nitro-L-arginine (NLA)-induced blockade of endothelium-derived nitric oxide (EDNO). Intrarena...
The Immunotherapeutics & Vaccine Summit--CHI's fourth annual meeting. Preclinical/clinical development of immunotherapies and vaccines. 17-19 August 2009, Providence, RI, USA.

The Immunotherapeutics & Vaccine Summit held in Providence, RI, USA included topics covering new preclinical and clinical developments in the field of immunotherapies and vaccines. This conference report highlights selected presentations on the iSBTc-FDA-NCI taskforce findings on immunotherapy biomarkers, clinical assay development and optimization, and bioassays to measure immune responses. Investigational vaccines discussed include a fusion protein adjuvant vaccine (Research by Discovery), a novel intradermal particle delivery device (Universite de Sherbrooke) and a Hsp-based vaccine for meningitis (ImmunoBiology Ltd).
TH-CD-207A-04: Optimized Respiratory Gating for Abnormal Breathers in Pancreatic SBRT

Purpose: Pancreatic SBRT is uniquely challenging due to both the erratic/unstable motion of the pancreas and the close proximity of the radiosensitive small bowel. Respiratory gating can mitigate this effect, but the irregularity of motion severely affects traditional phase-based gating. The purpose of this study was to analyze real-time motion data of pancreatic tumors to optimize the efficacy and accuracy of respiratory gating, with the overall goal of enabling dose escalated pancreatic SBRT. Methods: Fifteen pancreatic SBRT patients received 30–33 Gy in 5 fractions on a Varian TrueBeam STx unit. Abdominal compression was used to reduce the amplitude of tumor motion, and daily cone-beam computed tomography (CBCT) scans were acquired prior to each treatment for target localization purposes. For this study, breathing data (phase and amplitude) were collected during each CBCT scan using Varian's Real-Time Position Management system. An in-house template matching technique was used to track the superior-inferior motion of implanted fiducial markers in CBCT projection images. Using tumor motion and breathing data, phase-based or amplitude-based respiratory gating was simulated for all 75 fractions, targeting either end-exhalation or end-inhalation phases of breathing. Results: For the average patient, gating at end-exhalation offered the best reductions in effective motion for equal duty cycles. However, optimal central phase angle varied widely (range: 0–92%, mean±SD: 49±12%), and phase-based gating windows typically associated with end-exhalation (i.e., “30–70%”) were rarely ideal. Amplitude-based gating significantly outperformed phase-based gating, with average effective ranges for amplitude-based gating 25% lower than phase-based gating ranges (as much as 73% lower). Amplitude-based gating was consistently better suited to accommodate abnormal breathing patterns. For both phase-based and amplitude-based gating, end-exhalation provided significantly better results than end-inhalation. Conclusion: Amplitude-based gating reliably outperformed phase-based gating, and end-exhalation was more suitable than end-inhalation. These results will be used to guide future dose-escalation trials. Research funding provided by Varian Medical Systems to Miften and Jones.
Safety assessment of dicamba mono-oxygenases that confer dicamba tolerance to various crops

Abstract Dicamba tolerant (DT) soybean, cotton and maize were developed through constitutive expression of dicamba mono-oxygenase (DMO) in chloroplasts. DMO expressed in three DT crops exhibit 91.6–97.1% amino acid sequence identity to wild type DMO. All DMO forms maintain the characteristics of Rieske oxygenases that have a history of safe use. Additionally, they are all functionally similar in vivo since the three DT crops are all tolerant to dicamba treatment. None of these DMO sequences were found to have similarity to any known allergens or toxins. Herein, to further understand the safety of these DMO variants, a weight of evidence approach was employed. Each purified DMO protein was found to be completely deactivated in vitro by heating at temperatures 55 °C and above, and all were completely digested within 30 s or 5 min by pepsin and pancreatin, respectively. Mice orally dosed with each of these DMO proteins showed no adverse effects as evidenced by analysis of body weight gain, food consumption and clinical observations. Therefore, the weight of evidence from all these protein safety studies support the conclusion that the various forms of DMO proteins introduced into DT soybean, cotton and maize are safe for food and feed consumption, and the small amino acid sequence differences outside the active site of DMO do not raise any additional safety concerns.
Thin Die Fabrication and Applications to Wafer Level System Integration

Thin die fabrication is an essential part of wafer processes in 3D IC, interposer, and fan-in and fan-out wafer level packaging technologies. A review on the available process technologies including temporary bonding, de-bonding, wafer thinning, thin wafer handling, thin wafer backside processes, and die singulation are discussed and summarized in this chapter. The fabricated thin dies are integrated and assembled using wafer level system integration (WLSI) processes. A brief summary on two important WLSI technology platforms, namely Chip-on-Wafer-on-Substrate (CoWoS™) and Integrated Fan-Out (InFO) are presented as a conclusion for thin die fabrication and wafer level system integration chapter.
Orthostatic Tremor and Orthostatic Myoclonus: Weight-bearing Hyperkinetic Disorders: A Systematic Review, New Insights, and Unresolved Questions.

Background: Orthostatic tremor (OT) and orthostatic myoclonus (OM) are weight-bearing hyperkinetic movement disorders most commonly affecting older people that induce “shaky legs” upon standing. OT is divided into “classical” and “slow” forms based on tremor frequency. In this paper, the first joint review of OT and OM, we review the literature and compare and contrast their demographic, clinical, electrophysiological, neuroimaging, pathophysiological, and treatment characteristics. Methods: A PubMed search up to July 2016 using the phrases “orthostatic tremor,” “orthostatic myoclonus,” “shaky legs,” and “shaky legs syndrome” was performed. Results: OT and OM should be suspected in older patients reporting unsteadiness with prolonged standing and/or who exhibit cautious, wide-based gaits. Surface electromyography (SEMG) is necessary to verify the diagnoses. Functional neuroimaging and electrophysiology suggest the generator of classical OT lies within the cerebellothalamocortical network. For OM, and possibly slow OT, the frontal, subcortical cerebrum is the most likely origin. Clonazepam is the most useful medication for classical OT, and levetiracetam for OM, although results are often disappointing. Deep brain stimulation appears promising for classical OT. Rolling walkers reliably improve gait affected by these disorders, as both OT and OM attenuate when weight is transferred from the legs to the arms. Discussion: Orthostatic hyperkinesias are likely underdiagnosed, as SEMG is often unavailable in clinical practice, and thus may be more frequent than currently recognized. The shared weight-bearing induction of OT and OM may indicate a common pathophysiology. Further research, including use of animal models, is necessary to better define the prevalence and pathophysiology of OT and OM, in order to improve their treatment, and provide additional insights into basic balance and gait mechanisms.
Incremental value of 3D over 2D echocardiography in a patient with multiple ICD leads in the right ventricle

A 65-year-old male with dyspnoea and oedema from severe tricuspid regurgitation was referred for tricuspid valve (TV) surgery. He had undergone placement of a dual-chamber implantable cardioverter defibrillator (ICD) 15 years prior for dilated cardiomyopathy that was upgraded to a biventricular system with placement of a new right ventricular lead 3 years ago. Intraoperative 2D …
Sonoran Desert rodent abundance response to surface temperature derived from remote sensing

Abstract Nocturnal rodents play a key role in the Sonoran Desert ecosystem as consumers, prey and reservoirs of disease-yet rodent distribution remains poorly mapped. We use surface temperature extracted from the Landsat Thematic Mapper thermal infrared band to model rodent abundance obtained from trapping data at the Organ Pipe Cactus National Monument in southwest Arizona. We produce response curves that describe the effects of surface temperature on species abundance. Daytime surface temperature derived from images collected in June across thirty rodent trapping grids ranged from 318 K (45.0 °C) to 332 K (59.2 °C). Results show peak seasonal surface temperature splits high species abundances into two groups: Merriam's kangaroo rat, Arizona pocket mouse, desert pocket mouse and southern grasshopper mouse species prefer habitat characterized by higher surface temperatures; and white-throated wood rat, cactus mouse, rock pocket mouse and Bailey's pocket mouse species prefer habitat characterized by lower temperatures. Abundances for the high and low temperature habitat groupings correlate linearly with surface temperature (r = +0.66 and −0.75, respectively, p
Neoadjuvant and adjuvant chemotherapy without radiation for esophageal cancer

4054 Background: A Phase II trial to evaluate neoadjuvant (NAD) and adjuvant (AD) combination chemotherapy (CT) without radiation therapy (RT), for Stage III esophageal adenocarcinoma. Methods: Sta...
Input Use of Paddy Farming under Owner Cultivated Land and Tenant -Cultivated Land in Batticaloa District

Paddy is a most important food staple and mainstay for the rural population in Batticaloa district. Though, absence of land is prevailed in Batticaloa district. Therefore, farmers have been engaging on both owner – cultivated land and tenant- cultivated land to cultivate paddy. Batticaloa district in which there is a difference in regarding assessing the government assistance.
A robust variant of block Jacobi-Davidson for extracting a large number of eigenpairs: Application to grid-based real-space density functional theory

In this work, we investigate a block Jacobi-Davidson (J-D) variant suitable for sparse symmetric eigenproblems where a substantial number of extremal eigenvalues are desired (e.g., ground-state real-space quantum chemistry). Most J-D algorithm variations tend to slow down as the number of desired eigenpairs increases due to frequent orthogonalization against a growing list of solved eigenvectors. In our specification of block J-D, all of the steps of the algorithm are performed in clusters, including the linear solves, which allows us to greatly reduce computational effort with blocked matrix-vector multiplies. In addition, we move orthogonalization against locked eigenvectors and working eigenvectors outside of the inner loop but retain the single Ritz vector projection corresponding to the index of the correction vector. Furthermore, we minimize the computational effort by constraining the working subspace to the current vectors being updated and the latest set of corresponding correction vectors. Finally, we incorporate accuracy thresholds based on the precision required by the Fermi-Dirac distribution. The net result is a significant reduction in the computational effort against most previous block J-D implementations, especially as the number of wanted eigenpairs grows. We compare our approach with another robust implementation of block J-D (JDQMR) and the state-of-the-art Chebyshev filter subspace (CheFSI) method for various real-space density functional theory systems. Versus CheFSI, for first-row elements, our method yields competitive timings for valence-only systems and 4-6× speedups for all-electron systems with up to 10× reduced matrix-vector multiplies. For all-electron calculations on larger elements (e.g., gold) where the wanted spectrum is quite narrow compared to the full spectrum, we observe 60× speedup with 200× fewer matrix-vector multiples vs. CheFSI.
Hemorrhoids: what are the options in 2018?

Purpose of review Efforts continue to improve the treatment of patients with symptomatic hemorrhoidal disease by interventions designed to improve efficiency and effectiveness, including by reducing intraoperative and postoperative pain, decreasing operating times, minimizing blood loss and controlling symptoms and recurrence rates. Simultaneously, there are also renewed efforts to minimize the number of patients who will require procedural intervention by focusing on conservative measures that encourage better bowel regulation and habits. The purpose of this brief report is to review the current status of the diagnosis and treatment of patients with hemorrhoidal disease. Overall, new procedures or procedural refinements to existing techniques continue to be introduced with promising short-term outcomes - at least in some instances. In most instances, long-term follow-up or equivalency data are still being accumulated such that a definitive, unequivocal answer to what is truly the best alternative to traditional hemorrhoidectomy remains controversial. One of the challenges is heterogeneity as regards diagnosis, intervention and, especially, outcomes measures such that comparing therapies is too difficult. A recent initiative to standardize metrics has promise. Recent findings Recent studies largely appear to suggest that conservative treatment approaches and managing patient expectations are critically important in which a primary objective should be to minimize the progression to symptomatic disease and complications in patients who are diagnosed with hemorrhoids. The pace of change as regards the development of new or improved surgical techniques appears may be accelerating. Summary Progress is being made and the knowledge base is being expanded as regards the treatment options for patients with hemorrhoids and expected outcomes. A key initiative to standardize the approaches to diagnosis and treatment about staging, procedural interventions and outcomes will facilitate comparative analytics, if successful.
Inactivation of tumor suppressor p53 by estrogen receptor: Mechanisms of a novel phenomenon with translational implications

1580 Mutational inactivation of p53 gene is one of the most frequent events in most cancers. However, p53 mutations are infrequent (20-30%) in breast cancers. In spite of genetically being wild type, why p53 is functionally debilitated in breast cancer has remained unclear. Most (60-80%) breast cancers are estrogen receptor (ER) alpha -positive. Our recent finding that ER alpha binds directly to p53 and inhibits its function has provided a novel mechanism for inactivating genetically wild type p53 in human cancers. Using multiple technical approaches such as immunoprecipitation (IP), chromatin immunoprecipitation (ChIP), GST pull-down assays, gel mobility shift assays, and far western assays, we have demonstrated binding of ER alpha to p53 and have delineated the domains on both the proteins necessary for the interaction. ChIP assays demonstrated that ER interacts with p53 bound to endogenous p21 (CDKN1A) (a prototypic target for transcriptional activation by p53) and survivin and mdr1 (targets for transcriptional repression by p53) resulting in suppression of p53-mediated transcriptional regulation of these genes in human breast cancer cells. Importantly, ionizing radiation disrupted the ER-p53 interaction in vivo both in human cancer cells and human breast tumor xenografts in mice. Intriguingly, 17β-estradiol (E2) has diametrically opposite effects on corepressor recruitment to a p53-target gene promoter versus a prototypic ERE-containing promoter. Sequential ChIP assays and quantitative real-time PCR analysis showed that ER alpha, when bound to p53, recruits transcriptional corepressors such as NCOR resulting in repression of p53-activated genes, as opposed to coactivator recruitment leading to gene activation when ER alpha is bound to ERE on gene promoters. Antiestrogens such as tamoxifen and fulvestrant (ICI 182780) disrupt the ER-p53 interaction and counteract the repressive effect of ER alpha on p53. Thus, we have uncovered a novel mechanism by which estrogen could be providing a strong proliferative advantage to cells by a dual mechanism: enhancing expression of ERE-containing pro-proliferative genes while at the same time inhibiting transcription of p53-dependent anti-proliferative genes. Consistently, ER alpha enhances cell cycle progression and inhibits apoptosis of breast cancer cells. Correlating with these observations, our retrospective clinical study shows that presence of wild type p53 in ER-positive breast tumors is associated with better response to tamoxifen therapy. Thus, our data could provide a new mechanistic basis for resistance to tamoxifen therapy in breast cancer patients. Our findings reveal a novel function of ER alpha and suggest that suppressing p53 function is an important component in the pro-proliferative role of ERα. Further, our observation that antiestrogens disrupted ER-p53 interaction have translational implications.
Reevaluating Order Effects in the Binaural Bithermal Caloric Test.

Purpose The purpose of this study was to determine whether a significant order effect exists in the binaural bithermal caloric test. Method Fifteen volunteers (mean age = 24.3 years, range = 18–38 ...
Relaxing LER requirement in EUV lithography

Low throughput has been a critical issue in extreme ultraviolet (EUV) patterning due to the difficulty in increasing light source power. This limitation has driven the need for photoresists with better throughput which unfortunately come with higher line edge roughness (LER). In this work, the possibility of relaxing LER requirements for metal layer patterned by EUV lithography (EUVL) is studied. Single patterning and litho-etch litho-etch (LELE) patterning with EUVL are considered. To assess the impact of LER on design yield, analytical and simulation based modeling approaches are developed, which consider the LER induced metal wire shorts/opens and the enhanced time dependent dielectrics breakdown (TDDB) for metal wires with different geometries. The impact of LER on wire delay is studied by Elmore’s delay model.
Liver Calcifications and Calcified Liver Masses: Pattern Recognition Approach on CT.

OBJECTIVE. Because of the ubiquitous use of radiologic imaging, particularly with CT, the detection of focal hepatic calcifications has increased. Calcifications can be seen in cystic and solid mas...
Approximation by Positive Sublinear Operators

Here we study the approximation of functions by positive sublinear operators under differentiability. We produce general Jackson type inequalities under initial conditions. We apply these to a series of well-known Max-product operators. So our approach is quantitative by producing inequalities with their right hand sides involving the modulus of continuity of a high order derivative of the function under approximation. It follows Anastassiou, Coroianu, Gal (J. Comput. Anal. Appl. 12(2):396–406, 2010, [3]).
Multiple Stages of Virus-Receptor Interactions as Shown by Simian Virus 40

None of the many antibiotics that are clinically effective in the fight against bacteria are active against viruses. Furthermore, the search for clinically effective antiviral agents has thus far produced relatively few useful drugs. Nevertheless, adhesion based therapies may be particularly promising in the fight against viruses. First, whereas adhesion may enhance the infectivity of certain bacteria, the interaction of a virus with its receptor is absolutely critical for infection. Furthermore, since virus-receptor interactions are highly specific, a virus can not easily mutate its receptor binding site and remain viable. Thus, the anti-adhesion approach to antivirals is not likely to lead to drug resistant variants. Also, whereas viruses were once thought to interact with a single cell membrane component, an increasing number of viruses are appearing to interact sequentially with multiple distinct cell surface components (Haywood, 1994; Norkin, 1995). Initial binding may be followed by secondary interactions that strengthen adhesion, promote entry, or both. This complexity may be a cause for optimism since it produces additional opportunities for the rational development of drugs that might target initial binding, adhesion strengthening, or entry.
ADRTrace: detecting expected and unexpected adverse drug reactions from user reviews on social media sites

We automatically extract adverse drug reactions (ADRs) from consumer reviews provided on various drug social media sites to identify adverse reactions not reported by the United States Food and Drug Administration (FDA) but touted by consumers. We utilize various lexicons, identify patterns, and generate a synonym set that includes variations of medical terms. We identify "expected" and "unexpected" ADRs. Background (drug) language is utilized to evaluate the strength of the detected unexpected ADRs. Evaluation results for our synonym set and ADR extraction are promising.
Improved error bounds for a certain class of Newton-like methods

Using the majorant theory for the solutions of nonlinear operator equations we deduce better error bounds for the solution than the ones already in the literature under similar assumptions.
Calcimimetics and Bundled Reimbursement

Since 2011, the Centers for Medicare & Medicaid Services has provided reimbursement for renal dialysis services furnished to Medicare beneficiaries through a bundled payment system known as the Prospective Payment System. Medications that have no injectable equivalent, known as "oral-only medications," are currently excluded from the bundle and are paid separately through Medicare Part D. Thus, before the development of etelcalcetide, the first injectable calcimimetic, calcimimetics were reimbursed outside the bundle. Etelcalcetide's introduction and approval for use in Medicare triggered a transition payment for a minimum of 2 years that will eventually result in the incorporation of calcimimetics into the dialysis bundle. Consequently, providers may face incentives to reduce calcimimetic use when the transition period has expired. The complexity of bone-mineral management in conjunction with the paucity of evidence-based recommendations in this area makes it difficult to predict the impact of this transition. Because these medications are expensive, a poor transition could have financial ramifications for dialysis organizations and potentially patient health. To ensure that patients are not adversely affected, it is critical that Medicare incorporate these medications into the bundle carefully, with close monitoring of outcomes.
A Single Institution Retrospective Analysis of Outcomes in Multiple Myeloma Patients Aged 50 and Younger Undergoing Autologous HCT

Introduction and Objectives Multiple myeloma (MM) is a disease of the elderly with the median age of diagnosis being 66 years and rare in the population younger than 50 years. Younger patients generally undergo autologous HCT as part of their treatment once they achieve an adequate response. Overall survival in patients with MM has dramatically improved over the last 2 decades with the advent of novel agents. The purpose of this retrospective analysis was to evaluate the disease behavior and transplant outcomes in patients younger than 50 years. Methods We retrospectively reviewed the charts of 29 patients aged ≤50 who underwent autologous HCT between May 2003 and Dec 2017 at our institution. All patients received Melphalan as their conditioning regimen. 28% (n=8) of the patients had renal insufficiency at the time of diagnosis (serum Creatinine ≥ 2.0 mg/dl). Results 38 auto-HCTs were performed in this group of patients. 7 patients underwent salvage transplant and 2 patients underwent planned tandem auto-HCT. Nearly 80% (n=23) patients had Salmon Durie stage 3 disease at the time of auto-HCT. Overall survival for the entire cohort was 109 months and PFS was 51 months. Median age at diagnosis was 46 years. The median age of the first transplant is 47 years. Median time to relapse/progression was 31 months after auto-HCT for the entire cohort. For patients with high-risk cytogenetics (28%, n=8) median time to relapse was 13 months compared to 72 months in standard risk patients. There was total of 12 deaths in the entire cohort with the majority of deaths (10/12) due to disease progression/relapse and 1 died from a secondary malignancy. Median time to relapse/progression after salvage HCT was 16 months. Of the 7 patients who underwent salvage HCT, 3 died secondary to disease progression with a median time to death is 12.6 months. Conclusion Despite recent advances in the treatment of multiple myeloma, younger patients with high-risk disease status continue to have poor outcomes. Aggressive induction regimens and possible planned tandem Auto-PBSCT may be a reasonable approach to improve outcomes in younger patients with high-risk disease status. Further studies with a larger cohort are warranted to corroborate our findings and also find ways to improve survival in this high-risk group.
Bicultural stress, coping, and psychological functioning among Mexican-descent and White college students.

OBJECTIVE The present study investigates associations between bicultural stress, coping, and responses to stress (RTS) in relation to depressive symptoms and self-esteem for Mexican-descent and non-Latinx White college students. METHOD With a sample of 268 Mexican-descent and non-Latinx White college students, two multiple-mediation path models and two moderation models are examined. RESULTS The hypothesized mediation models were both supported indicating higher bicultural stress is associated with higher reporting of engaged and disengaged forms of coping and RTS. Engaged coping was associated with mental health resiliency while disengaged coping and RTS contributed to vulnerability. Disengaged and secondary engaged coping were mediators in the depressive symptoms and self-esteem models. In terms of moderation, disengaged coping and RTS were both moderators in the bicultural stress-depressive symptoms relationships. CONCLUSIONS College students' reactions to bicultural stress may either promote mental health resiliency through engaged strategies or increase vulnerability through disengaged coping and involuntary RTS.
Dynamic airway constriction in rats: heterogeneity and response to deep inspiration.

Airway narrowing due to hyperresponsiveness severely limits gas exchange in patients with asthma. Imaging studies in humans and animals have shown that bronchoconstriction causes patchy patterns of...
Mapping the literature of dental hygiene: an update.

Objective: This study updates Haaland’s 1999 dental hygiene mapping study. By identifying core journals and estimating database coverage, it characterizes changes in dental hygiene research and aids librarians in collection development and user education. Method: Cited references from a three-year (2015–2017) sample of core dental hygiene journals were collected, categorized into five formats, and analyzed by format and publication year according to Bradford’s Law of Scattering. CINAHL Complete, MEDLINE, and EMBASE were surveyed to determine the indexing coverage of cited journals. Results: The number of cited journal titles increased from 389 in 1999 to 1,675 in 2018. Core Zone 1 titles increased from 5 to 11. Journal article citations increased from 69.5% of all citations in 1999 to 78.4% in the present study, whereas book citations decreased from 18.1% to 5.1%. A newly added category, “Internet sources,” accounted for 8.4% of citations. Overall, 68.6% of citations were 10 years or younger versus 71.4% in 1999. Most Zone 1 and Zone 2 journals were specific to dentistry or dental hygiene. Conclusion: Notable changes since 1999 were an increased volume of literature and a shift from print to online sources, reflecting improved accessibility of the literature and greater Internet use. From 1999 to 2018, citations to journal articles increased, books decreased, websites appeared, and government publications increased slightly. These findings indicate that dental hygiene research is growing and that indexing coverage for this field has improved dramatically in the past two decades.
“I Never Know What to Expect”: Aleatory Identity Play in Fortnite and Its Implications for Multimodal Composition

Abstract In game and composition studies, an increased scholarly attention has been paid to affect as it relates to the formation of habits. However, the current discussion of affect has not been extended to gamers’ identity performance in multimodal composition practices. In this article, I argue that aleatory procedure—one type of affective game design that centers on the random and unknown processes of rhetorical invention—has the potential to transform gamers’ gender and racial identity performance in flux. To explore the value of aleatory procedure in modulating the affective relations of game play, I conducted screencast recordings, stimulated recalls, in-depth interviews, and observations with Fortnite gamers who were randomly assigned avatars of different genders and races. Findings suggests that aleatory procedure invites players to engage in a fluid affective identity play that is not restricted to individual players and their desires, but rather is in a constant process of transformation both within and across affective assemblages. Based on the findings, I conclude this article by discussing the implications of the aleatory method for critical literacies and multimodal composition.
Underrepresented in Surgery: (Lack of) Diversity in Academic Surgery Faculty.

Abstract Background A call to increase diversity among academic surgery faculty (ASF) was made in 2008, after recognizing the lack of surgeons considered underrepresented in medicine (URM). We aimed to quantify and assess trends among URM ASF in the interval since that call to action. Methods Publicly available data on ASF were reviewed. We calculated the percentage of ASF in 2018 by URM group, then stratified by academic rank of assistant professor, associate professor, and full professor. We compared 2005-2018 ASF of Hispanic or Latino (HL) and African American (AA) background; 2005 data were unavailable for other URM groups. Results In 2018, URM surgeons accounted for 7.06% (n = 1013/14,340) of ASF (AA: n = 492, 3.43%; HL: n = 485, 3.38%; American Indian or Alaskan Native: n = 23, 0.16%; and Native Hawaiian/Pacific Islander: n = 13, 0.09%). When comparing 2005-2018, AA ASF remained stable across ranks (total: n = 298, 3.12% versus n = 492, 3.43%; P = 0.09), whereas HL ASF decreased across ranks (total: n = 415, 4.35% versus n = 485, 3.38%; P = 0.00007). Conclusions Surgeons from URM backgrounds account for 7% of ASF. No increase in AA and a decrease in HL ASF occurred from 2005 to 2018. There is a paucity of data for other URM groups. Active strategies to increase diversity and inclusion in academic surgery are necessary.
Navigating the Global Refugee Regime: Law, Myth, Story

This article engages in a cultural study of refugee law “from below,” that is, from the perspective of refugees. Bringing to bear insights from critical refugee studies, I argue that today’s global...
Time course of pupillary response to threat words before and after attention bias modification for transdiagnostic anxiety disorders: A randomized controlled trial.

INTRODUCTION Altered attention to threatening stimuli at initial and sustained stages of processing may be dissociable dimensions that influence the development and maintenance of transdiagnostic symptoms of anxiety, such as vigilance, and possibly require distinct intervention. Attention bias modification (ABM) interventions were created to implicitly train attention away from threatening stimuli and have shown efficacy in treating anxiety. ABM alters neurocognitive functioning during initial stages of threat processing, but less is known regarding effects of ABM on neural indices of threat processing at sustained (i.e., intermediate and late) stages, or if ABM-related neural changes relate to symptom response. The current study utilized pupillary response as a temporally sensitive and cost-effective peripheral marker of neurocognitive response to ABM. MATERIALS AND METHODS In a randomized controlled trial, 79 patients with transdiagnostic anxiety provided baseline data, 70 were randomized to receive eight sessions of twice-weekly ABM (n = 49) or sham training (n = 21), and 65 completed their assigned treatment condition and returned for post-training assessment. RESULTS Among ABM, but not sham, patients, pupillary response to threat words during initial and intermediate stages decreased from pre- to post-training. Pre- to post-training reductions in intermediate and late pupillary response to threat were positively correlated with reductions in patient-reported vigilance among ABM, but not sham, patients. CONCLUSIONS All measured stages of threat processing had relevance in understanding the neural mechanisms of ABM, with overlapping yet dissociable roles exhibited within a single neurophysiological marker across an initial-intermediate-late time continuum. Pupillometry may be well suited to measure both target engagement and treatment outcome following ABM.
The SARS-CoV-2 Spike mutation D614G increases entry fitness across a range of ACE2 levels, directly outcompetes the wild type, and is preferentially incorporated into trimers

Abstract Early in the current pandemic, the D614G mutation arose in the Spike protein of SARS-CoV-2 and quickly became the dominant variant globally. Mounting evidence suggests D614G enhances viral entry. Here we use a direct competition assay with single-cycle viruses to show that D614G outcompetes the wildtype. We developed a cell line with inducible ACE2 expression to confirm that D614G more efficiently enters cells with ACE2 levels spanning the different primary cells targeted by SARS-CoV-2. Using a new assay for crosslinking and directly extracting Spike trimers from the pseudovirus surface, we found an increase in trimerization efficiency and viral incorporation of D614G protomers. Our findings suggest that D614G increases infection of cells expressing a wide range of ACE2, and informs the mechanism underlying enhanced entry. The tools developed here can be broadly applied to study other Spike variants and SARS-CoV-2 entry, to inform functional studies of viral evolution and vaccine development.
Physical therapists' attitudes are associated with their confidence in and the frequency with which they engage in prescription opioid medication misuse management practices with their patients. A cross-sectional study.

BACKGROUND In the US, prescription opioid medication misuse (POMM) necessitates engagement of physical therapists (PTs). We (1) evaluated the attitudes of (PT) related to their management of patients with POMM and (2) examined the association between these attitudes and PTs confidence in POMM-related management abilities and the frequency with which they engaged in POMM-related management practices. Methods: We conducted a national survey of PTs that included a modified Drug and Drug Problems Perception Questionnaire (DDPPQ). Confidence in POMM-related abilities and the frequency of engaging in POMM-related management practices were measured. Logistic regression evaluated the association between the DDPPQ subscales (role adequacy, role legitimacy, role self-esteem, role support, job satisfaction) and confidence and frequency outcomes. Results: The analysis included 402 respondents. Role adequacy and legitimacy subscales were associated with confidence and frequency outcomes (p<.05), indicating that more favorable role adequacy and legitimacy attitudes are associated with greater odds of having more confidence in POMM-related management abilities and of engaging in more frequent POMM-related management practices. Conclusions: PTs with a greater sense of preparedness to engage in POMM-related management were more likely to report greater confidence in POMM-related management abilities and engage in POMM-related management practices with greater frequency.
The Clp1 R140H mutation alters tRNA metabolism and mRNA 3' processing in mouse models of pontocerebellar hypoplasia.

Homozygous mutation of the RNA kinase CLP1 (cleavage factor polyribonucleotide kinase subunit 1) causes pontocerebellar hypoplasia type 10 (PCH10), a pediatric neurodegenerative disease. CLP1 is associated with the transfer RNA (tRNA) splicing endonuclease complex and the cleavage and polyadenylation machinery, but its function remains unclear. We generated two mouse models of PCH10: one homozygous for the disease-associated Clp1 mutation, R140H, and one heterozygous for this mutation and a null allele. Both models exhibit loss of lower motor neurons and neurons of the deep cerebellar nuclei. To explore whether Clp1 mutation impacts tRNA splicing, we profiled the products of intron-containing tRNA genes. While mature tRNAs were expressed at normal levels in mutant mice, numerous other products of intron-containing tRNA genes were dysregulated, with pre-tRNAs, introns, and certain tRNA fragments up-regulated, and other fragments down-regulated. However, the spatiotemporal patterns of dysregulation do not correlate with pathogenicity for most altered tRNA products. To elucidate the effect of Clp1 mutation on precursor messenger RNA (pre-mRNA) cleavage, we analyzed poly(A) site (PAS) usage and gene expression in Clp1 R140H/- spinal cord. PAS usage was shifted from proximal to distal sites in the mutant mouse, particularly in short and closely spaced genes. Many such genes were also expressed at lower levels in the Clp1 R140H/- mouse, possibly as a result of impaired transcript maturation. These findings are consistent with the hypothesis that select genes are particularly dependent upon CLP1 for proper pre-mRNA cleavage, suggesting that impaired mRNA 3' processing may contribute to pathogenesis in PCH10.
Chapter 28. New Directions in Positron Emission Tomography-Part II

Publisher Summary This chapter describes the positron emission tomography (PET) method and its recent use in studies of the brain, metabolism, heart disease, and tumors. It also covers PET studies with therapeutic drugs and substances of abuse, and the rapidly emerging use of PET in clinical diagnosis. PET is a unique tracer method that can be used to measure the spatial and temporal concentration of radioactivity in a volume element of tissue in a living system. PET can be extremely valuable in the quantitative determination of the biodistribution of drugs in human and their short term pharmacokinetics in any body tissue. No other technology is capable of answering these questions as quickly, as safely, and as precisely as PET. It has been most widely applied to the study of CNS drugs. Other applications with diagnostic potential are emerging. With PET, it is possible to directly correlate the cognitive function, metabolism, and structural integrity in the brain. In Alzheimer's disease, PET has been used to identify the characteristic deficits in brain metabolism that, in certain cases, have been shown to precede clinical presentation. PET has also been used to study the psychiatric diseases, such as schizophrenia, affective disorders, obsessive compulsive disorders, anxiety disorders, violence, and substance abuse.